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LACTRIMS Abstracts
Mult Scler 2012 18: 1821 DOI: 10.1177/1352458512466528 The online version of this article can be found at: http://msj.sagepub.com/content/18/12/1821
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Abstracts
Multiple Sclerosis Journal 2012; 18: (S5) 18211879
LACTRIMS Abstracts
A1 - Oral presentation A longitudinal study of brainstem involvement in a cohort of NMO Brazilian patients from Rio de Janeiro Marcos Papais Alvarenga, Marina Papais Alvarenga,Claudia Cristina Ferreira Vasconcelos, Gutemberg Augusto Santos Cruz, Regina Maria Papais-Alvarenga Postgraduate Program in Neurology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro; Brazil Hospital da Lagoa - Rio de Janeiro, Brazil Objective: For over a century neuromyelitis optica was considered an acute and severe demyelinating condition characterized by optic neuritis and transverse myelitis with monophasic clinical course. The recurrent form of the disease was recognized in the last decade. A revised criteria for NMO (2006) allow the inclusion of patients with clinical disease outside of the optic nerve and spinal cord. We will describe here the clinical and radiological characteristics of brainstem involvement in recurrent NMO patients. Methods: We ascertained NMO patients retrospectively at a referral unit for MS in Rio de Janeiro (Brazil) who satisfied the revised criteria (2006) and presented a recurrent clinical course. From medical charts demographic, clinical and laboratorial data were recorded. Cases with disease restricted to the optic nerve and spinal cord were compared with those with brainstem (BS) involvement. Results: 76 NMO patients were identified (women [92%] and Afro Brazilians [66%]). Sixteen patients had 35 BS acute events: vestibular syndrome (7/16), trigeminal syndrome (6/16), ophthalmoplegia (6/16), vomiting (5/16), bulbar nerve syndrome (4/16), hiccups (3/16), sensory tract signs (3/16), deafness (2/16), facial palsy (2/16), pyramidal syndrome (1/16), ataxia (1/16). MR confirmed brainstem lesions in 11/16 cases. A few number of acute ON and high recurrences occurred in RNMO-BS group. Conclusions: The application of the revised criteria in an ethnically diverse population allowed the identification of brainstem syndrome in 20% in this cohort. RNMO-BS cases are similar to those in whom the disease is restricted with respect to demographic data, morbidity and mortality. A2 - Oral presentation A role for the Blink Reflex test in the diagnosis and progression of disease assessment in multiple sclerosis Joseph B. B. Brooks1, Yara D. Fragoso2, Marcia Jardim3, Celso L. S. Oliveira4 1UNIMES/UNIRIO; 2UNIMES/UNIRIO; 3UNIRIO; 4UNIMES A role for the Blink Reflex test in the diagnosis and progression of disease assessment in multiple sclerosis. Although neurological anamnesis and examination are cornerstones of multiple sclerosis (MS) diagnoses, judicious
use of paraclinical information enables clinical precision. Among electrophysiological tests, Blink Reflex (BR) provides structural-functional brainstem assessments and may assist in clinically diagnosing MS. The aim was to show the role of BR in investigating structural-functional brainstem pathways. Methods: A prospective case-control study was conducted on 60 patients with MS and clinically isolated syndrome (CIS) and 240 healthy volunteers. Recordings from the orbicularis eye muscles were made bilaterally and simultaneously. Ten stimulations were recorded on each side of the face. Statistical analyses on the variables included risk ratio, odds ratio, Pearson correlation and Student t-test. Results: The control group (1M:2F; mean age 39.5 years) showed BR within international reference values. In the MS group, with equivalent gender ratio and mean age, 41 patients (76%) had relapsing-remitting MS, 5 had secondary progressive MS and 8 had CIS. The mean disease duration was 7 years. The last relapse was typically over a year earlier. Abnormal BR values were observed in older patients with higher EDSS and longer disease duration, as well as patients with SPMS, histories and/or images of brainstem demyelination and brain atrophy, black holes and acute (Gd+) lesions on MRI. Conclusion: BR may be an important tool in diagnosing temporal and/or spatial dissemination of brain lesions, and as a significant marker of disease progression or acute attack. This low-cost, easy-to-perform and noninvasive test should be kept in mind for diagnosis and follow-up purposes. A3 - Oral presentation Acute Disseminated Encephalomyelitis: Presentation in the Adult Population R. Alonso, Fernandez N. Liguori, B. Silva, O. Garcea Divisin Neurologa Hospital Ramos Meja, Ciudad Autnoma de Buenos Aires; Centro Universitario de Neurologa Jos Mara Ramos Meja, Facultad de Medicina, UBA Introduction and Objectives: Acute disseminated encephalo myelitis (ADEM) is a demyelinating inflammatory disease that usually develops after vaccination or infectious processes. The course is usually single and most often affects children. We describe the clinical, radiological, CSF of adult patients with a diagnosis of ADEM in a Demyelinating Disease Center of Buenos Aires. Material and methods: We evaluated medical records of 550 patients diagnosed with demyelinating disease of the central nervous system from the period June 2002 to June 2012. We selected those diagnosed with ADEM (acute neurological event with no history of similar symptoms or illness to explain it, one or multiple MRI demyelinating lesions larger than 2 cm, excluding CSF infection). Different characteristics were evaluated as: gender, age, existence vaccination or infection up
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to 4 weeks before, clinical, MRI, CSF characteristics, prognosis and treatment. Results: We selected 17 patients diagnosed with ADEM, 59% were women, the mean age was 29 years, 47% had medical history, mostly respiratory infection. The first clinical manifestation was motor/sensitive deficit (29%), involvement of mental status (23.5%), posterior fossa (17.6%) . On the other hand 88% of patients had polysymptomatic manifestations at admission. In our serie 23,5% (four patients) had recurrent form of ADEM. In the CSF study, 35% showed raised protein levels. In 13 patients were evaluated BOC and these was negative. 59% of patients showed MRI gadolinium enhancement, 82% showed multiple lesions. In one case, the diagnosis is made by biopsy, 88% of patients had a good response to corticosteroids, one patient died. Conclusions: While ADEM is a rare entity in the spectrum of demyelinating diseases in adults, its recognition and differential diagnosis with other inflammatory CNS must be properly taken into account in this population group. A4 Advanced MRI techniques for the evaluation of demyelinating diseases: what is for research and what is for clinical practice Vanessa G A Itagiba, Fernanda C Rueda-Lopes, Emerson L Gasparetto, Thomas M Doring, Romeu C Domingues, Paulo R V Bahia UFRJ - Universidade federal CDPI - Clinica de Diagnstico por Imagem (DASA) Objective: Advanced MRI techniques plays an essential role in the evaluation of demyelinated diseases. Post-processing programs allows the analysis of the white and gray matter and the normal-appearing white matter damage, and also to quantify brain atrophy. Our exhibit aims to illustrate the advanced MRI techniques utilities in clinical practice and research management of demyelinated diseases. Content Organization 1. MRI protocols Conventional MRI sequences: T1WI, T2WI, FLAIR, Proton density images, postcontrast T1WI. Advanced MRI techniques: Diffusion weighted(DWI), Diffusion tensor(DTI), Blood Oxygenation Level Dependent(BOLD), Double-inversion recovery(DIR), magnetization transfer, Quantitative susceptibility mapping(QSM), Proton Spectroscopy, Perfusion. Post-processing methods: Tract-Based Spatial Statistics (TBSS), FreeSurfer, FMRI Resting State. Usual MRI findings in demyelinated diseases. Clinical applications of Advanced MRI techniques. Relevant research applications of Advanced MRI techniques and post-processing. Summary: Advanced MRI techniques plays an essential role in the differential diagnosis of demyelinated lesions and improve the diagnosis and monitoring of disease progression. They are of great utility in clinical practice and research, and enabled better understanding of the pathophysiology changing the concepts about the evolution of these diseases.
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A5 Anti-aquaporin 4 antibody positive and progressive disease Antonio Pereira Gomes Neto, Paulo Pereira Christo, Renata Brant de Souza Santa Casa de Belo Horizonte- Minas Gerais Objective: Report a case of Neuromyelitis Optica(NMO) in patient with antibody antiaquaporina 4 positive with atypical onset and progression. Methods: Case report. Results: HMO, 30years old,male, who had, from early 2010, paraparesis of insidious and progressive course. In 2011, he began to walk with unilateral support, and in May, to use a wheelchair. In mid2011, began urinary incontinence, dysphagia and important emotional lability. In late 2011 he presented upper limb paresis and bilateral visual deficit, also slowly and insidiously. MRI brain showed the presence of hyperintense lesions on T2 and Flair,nonspecific and MRI of the cervical spine, longitudinal extensive myelitis, affecting spinal segments from C1 to T2 . Research anti-aquaporin 4 was positive. In December 2011, the patient underwent methylprednisolone pulse therapy for five days, with improving his mobility. However, the disease continued to progress, with worsening of motor and cognitive development, even with the repetition of new pulse and the institution of continuous immunosuppressive therapy (azathioprine). Conclusion: This report fits into the spectrum of Neuromyelitis Optica, but presents an entirely different evolution from those known and considered typical of the disease, being slowly progressive from the outset, without the occurrence of relapse, demonstrating that the phenotype of NMO can be, as in this case, more varied than usually cited in the literature. A6 - Oral presentation Application of the Mcdonald 2010 Criteria for the Diagnosis Of Multiple Sclerosis in an Argentinean Cohort of Patients With Clinically Isolated Syndromes Liliana Patrucco, Juan Ignacio Rojas, Edgardo Cristiano MS Center, Hospital Italiano de Buenos Aires Objective: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS) with a sensitivity of 66% and specificity of 88%. We aimed to evaluate these new criteria in a cohort of patients from Buenos Aires, Argentina. Methods: Patients with CIS, in whom MRI was performed within 3 months of onset of symptoms were included between January 2005 and June 2010. Patients were followed and Poser or McDonald 2005 criteria were used as gold standard diagnostic criteria for MS. MRI was assessed by a blind evaluator identifying recently diagnostic MS criteria. New criteria sensibility, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for this cohort were determined. Results: 101 patients were included. 86 converted to MS (McDonald 2005/Poser) while 15 didnt convert during the follow-up. Mean age 35.5 5 years, mean follow-up time was 7.3 3.2 years (range 1.8 -11 years). Sensibility was 84%, specificity 80%, PPV 88%, NPV 71% and accuracy 82%. Discussion: This is the first study assessing McDonald 2010 criteria behavior in a Latin-American population and may contribute to its international validation.

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A7 Application of 2010 Criteria MCDonald in a Clinically Isolated Syndromes group in Buenos Aires Berenice Anabel Silva, Juan Carlos valos, Nora Fernndez Liguori, Orlando Garcea Multiple Sclerosis Clinic and Demyelinating Diseases. Hospital Ramos Meja, University Centre of Neurology, School of Medicine. Buenos Aires University, Argentina Introduction: In 2010 there was a review of the McDonald criteria for diagnosis of Multiple Sclerosis (MS), modifying paraclinical evidence required to demonstrate dissemination of lesions in time (DT) and space (DE) in clinically isolated syndromes (CIS). Objective: to evaluate the diagnosis of MS according to 2010 McDonald criteria in a population of patients with CIS. Materials and Methods: We retrospectively analyzed medical records of 845 patients attending the MS Clinic JM Ramos Mejia Hospital between 2000 and 2011; 91 were presented with a single clinical event; 58 (63.8%) were at high risk of MS conversion. MS diagnosis was assessed according to 2010.Results: 21 patients (36.2%) met the new criteria to DT and DE as gadoliniumenhancing lesion in their first MRI were corroborated, 76.2% were women and 23.8% men, mean age 32, 7 years (SD = 9.3), 85.7% had SCA unifocal, multifocal 14.3%, 52.4% showed clinical sequel; 2 patients progressed to clinically defined MS, with a mean time to the second clinical event of 7 months. Conclusions: In our population applying the 2010 McDonald criteria, sensitivity for earlier diagnosis of MS was significantly increased. A8 Association between clinical parameters and cognitive performance in Relapsing-Remitting Multiple Sclerosis in Buenos Aires Berenice Anabel Silva, Valeria Cores, Angeles Merino, Leticia Fiorentini, Nora Fernndez Liguori, Sandra Vanotti, Orlando Garcea Multiple Sclerosis Clinic and Demyelinating Diseases. Hospital Ramos Meja, University Centre of Neurology, School of Medicine. Buenos Aires University, Argentina Introduction: Cognitive decline in Multiple Sclerosis has a prevalence of 43% in Argentina. Relationship between cognition and clinical variables like physical disability, disease duration, age at onset and amount of registered relapses, is still a matter of discussion. Purpose: to analyze the association between clinical and cognitive parameters in patients with Relapsing Remitting Multiple Sclerosis (RRMS). Subjects and Method: 38 patients (23 female, 15 male) were assessed with a neuropsychological battery. Physical disability, disease duration, age at onset, total relapses, relapses in the first two years after onset and relapses in the last year before evaluation. Results: Media of age was 41 years old (DE = 12.01) and media of education was 12,45 years (DE = 3.1). EDSS significantly correlated (p < 0.01) with the Symbol Digit Modalities Test, (r = -0.46), Semantic Fluency (r = -0.46), Digit Forwards (r = -0.43) and PASAT-3 (r = -0.43). No significant correlations were found between cognitive measures and disease duration, age at onset and relapses. Conclusion: physical disability is associated with cognition in RRMS, especially with attention and verbal fluency. No evidence of association with other disease
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parameters was found. The results suggest the need to consider cognitive decline despite clinical characteristics of the patients. A9 Association study in multiple sclerosis (MS): CIITA gene polymorphism (rs4774*C) in conjunction with the HLADRB1*15:01+ haplotype increases the susceptibility to MS Eduardo Ribeiro Paradela1,2, Andre Luis dos Santos Figueiredo1,2, Luciana Agostinho1,2, Catielly Rocha1,2, Wagner Horta1, Fabola Rachid Malfetano3, Valeria Coelho Santa Rita Pereira3, Isabella DÀndrea Meira3, Carmen Lcia Anto Paiva2 and Soniza Vieira Alves-Leon1,3 1Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Programa de Ps-graduao em Neurologia (PPGNEURO); 2Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Laboratrio de Biologia Molecular; 3Centro de Referncia em Esclerose Mltipla e outras Doenas Inflamatrias Desmielinizantes do Sistema Nervoso Central do Hospital Universtrio Clementino Fraga Filho/Universidade Federal do Rio de Janeiro Multiple sclerosis (MS) has been associated with the Class-II HLA system (6p21.3) and other genes, such as CIITA (16p13). The main objective of this study was to evaluate the relationship between HLA class II (polymorphisms of HLA-DQA1, HLADRB1 and HLA-DQB1 loci) and CIITA polymorphisms -168A/G (rs3087456; promoter region variant) and +1614 G/C (rs4774*C; G500A; exon 12) and susceptibility to MS in a Brazilian sample from Rio de Janeiro State, Brazil. In this study, peripheral blood samples of 52 patients diagnosed with MS, who were registered in the outpatient clinic of neurology at University Hospital Clementino Fraga Filho (UFRJ), as well as samples of 116 healthy controls matched for ancestry, sex and age were analyzed. After DNA extraction, the alleles of HLA-DQA1, HLA-DRB1 and HLA-DQB1 loci were identified by PCR-SSP (Polymerase Chain Reaction Amplification with Sequence-Specific Primers) and genetic sequencing. Polymorphisms -168A/G and +1614 G/C on CIITA gene were analyzed by PCR and sequencing. Our results have indicated that the relative risk (RR) associated with the HLADRB1*15:01 allele was 3.11 [Odds Ratio (OR) = 3.39; Mantel Haenszel corrected p value = 0.0048653]; concerning the HLADQB1*06:02 allele, RR was 2.54 (OR = 2.86; Mantel Haenszel corrected p value = 0.03110396). The rs3087456 polymorphism and HLA-DQA1 allele were not associated with susceptibility to MS in our sample, but the polymorphism +1614G/C, together with HLA-DRB1*15:01+ increased the RR to 4.46 (OR = 4.60, Mantel Haenszel corrected p value = 0.04884730). These findings not only indicate that +1614G/C in conjunction with the HLA-DRB1*15:01+ allele increases the susceptibility to MS in this Brazilian sample but also reinforce the multifactorial and polygenic trait of the disease. A10 ASSOCIATION STUDY OF IL7R (CD127) GENE POLYMORPHISM (T244I) AND HLA CLASS II WITH SUSCEPTIBILITY TO MULTIPLE SCLEROSIS IN A BRAZILIAN SAMPLE Andre Figueiredo1,2, Eduardo Paradela1,2, Wagner Horta1, Fabola Rachid Malfetano3, Valeria Coelho Santa Rita Pereira3, Isabella
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DÀndrea Meira3, Luciana Agostinho1,2, Catielly Rocha1,2, Carmen Lcia Anto Paiva2 and Soniza Vieira Alves-Leon1,3 1Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Programa de Ps-graduao em Neurologia (PPGNEURO); 2Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Laboratrio de Biologia Molecular; 3Centro de Referncia em Esclerose Mltipla e outras Doenas Inflamatrias Desmielinizantes do Sistema Nervoso Central do Hospital Universtrio Clementino Fraga Filho/Universidade Federal do Rio de Janeiro Multiple Sclerosis (MS) is an autoimmune neurologic disorder which mainly affects young adults. MS has been associated with MHC Class II allele HLA-DRB1*15:01. The disease is characterized by destruction of the myelin sheath around the axon of a neuron in the central nervous system. This disease has been associated with several genes, such as IL7R (interleukin 7 receptor gene, 5p14p12), also known as CD127. The aim of this study was to evaluate the relationship between the gene IL7R T244I polymorphism (rs6897932) and susceptibility to MS. In this study, peripheral blood samples were taken from 50 patients diagnosed with MS who were registered with the outpatient Clinic of Neurology, at the University Hospital Clementino Fraga Filho (UFRJ); and from 126 healthy control subjects, matched for ancestry, sex and age. MS patients were classified according to the McDonalds criteria (2001). After DNA extraction by the organic method, the polymorphism T244I was evaluated by PCR followed by capillary electrophoresis in the ABI PRISM 3500 Genetic Analyzer platform (Applied Biosystems). The results indicated that the relative risk (RR) associated with the C allele presence was 1.30 (C/C or C/T); Odds Ratio (OR) was 2.15 (Mantel Haenszel corrected p value = 0.0424395. The association between rs6897932 polymorphism and HLA-DRB1*15:01 allele was RR = 3.34 (OR = 3.52; Mantel Haenszel corrected p value = 0.039823), while the RR associated to HLA-DRB1*15:01 allele alone was 3.11 (OR = 3.39). These findings reinforce the genetic trait of this HLA related disease, indicating a putative relationship between the polymorphism T244I in the IL7R (CD127) gene and susceptibility to MS. A11 - Oral presentation Brain atrophy as a non response predictor to interferon- b in relapsing-remitting multiple sclerosis Juan Ignacio Rojas; Liliana Patucco; Edgardo Cristiano Hospital Italiano de Buenos Aires, Argentina Several predictors for treatment failure to interferon beta (IFN) have been proposed, however brain atrophy has not been well studied. Methods: In this prospective and longitudinal study, all consecutive relapsing-remitting multiple sclerosis (RRMS) patients treated with sc IFN 1 where included. Confirmed disability progression or a new relapse between weeks 48 - 144 after IFN beginning were considered as treatment non response. EDSS progression, relapses, number of active lesions at 1 year (new or enlarging T2-weighted plus gadolinium-enhancing lesions, categorized in >2 or 2) and brain parenchymal fraction (% BPF) volume change within the initial year of treatment were used as predictive factors. Cox regression model was adjusted for age, gender and disease duration.

Results: 71 patients were included (71.8% female) with a followup of 144 weeks. 34 (48%) fulfilled criteria of non response to IFN treatment. The model showed: 1) relapses + disability progression HR=4.6 (p<0.001, IC95% 3.1-6.7); 2) relapses + BPF decrease HR=4.1 (p 0.001, IC95% 3.2-7.3); 3) relapses + disability progression + new active lesions HR=10.1 (p<0.001, IC95% 7.115.2) and 4) relapses + disability progression + new active lesions + BPF decrease HR=14.4 (p<0.001, IC 95% 11.4-21.2). Conclusions: Adding BPF measures to previously described predictive failure factors may increase sensibility to early identify non responder patients to IFN 1 in the second and third year of therapy. A12 - Oral presentation Brain atrophy evaluation in Multiple Sclerosis patients: a comparison study with Clinically Isolated Syndrome and Neuromyelitis Optica Fernanda Miraldi Clemente Pessa, Fernanda Cristina Rueda Lopes, Soniza Vieira Alves-Leon, Emerson Leandro Gasparetto Federal University of Rio de Janeiro; Radiology and Neurology Departamens of Hospital Universitrio Clementino Fraga Filho Introduction: Brain atrophy is quite common in multiple sclerosis (MS) in both grey (GM) and white matter (WM). However, brain atrophy in Clinical Isolated Syndrome (CIS) and in neuromyelitis optica (NMO) is still unclear. The aim of this study is to evaluate brain atrophy in MS patients when compared to CIS and NMO patients using post-processing techniques for T1-weighted imaging (WI) acquired with Magnetic Resonance Imaging (MRI). Methods: We studied 41 MS patients, 19 patients with CIS and 25 NMO. Grey matter (GM), white matter (WM) and wholebrain (WB) volumes were calculated for each group. A t-test was used to compare MS to CIS and MS to NMO. A p-value less than or equal to 0.05 was considered statistical significant. Results: The comparisons showed reduced MS values in GM (p=0.04), WM (p=0.05) and WB (p=0.02) volumes in comparison to CIS. Conclusions: Brain atrophy occurs in both grey and white matter in MS patients, different from CIS, a suggestive early stage where brain volume evaluation showed to be preserved. The lack of difference between MS and NMO may be associated with the same pattern of atrophy in NMO patients. A 13 Brain atrophy in radiolocially isolated syndromes Juan Ignacio Rojas, Liliana Patucco, Edgardo Cristiano Hospital Italiano de Buenos Aires, Argentina MRI lesions suggestive of multiple sclerosis (MS) in the absence of a clinical scenario is a condition named radiologically isolated syndrome (RIS). Scarce data exists about brain atrophy this condition. The aim of this study was to compare brain atrophy in RIS, in clinically isolated syndrome (CIS) and a healthy control sample. Methods: patients with RIS were included prospectively during June 2009 to June 2012. CIS patients (with less than a year of disease onset) and healthy volunteers matched by age and gender and included during the same period of time were used as control groups. An automated analysis tool, SIENAX, was used to obtain

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total brain volume (TBV), gray matter volume (GMV) and white matter volume (WMV). K-Wallis test was used to analyze the data. Results: 12 RIS patients, 43 CIS patients and 29 healthy controls were included. Mean age for RIS was 30 5.4 years vs. 34 7 in CIS patients and 34.4 9 in healthy controls (p=0.29). The TBV in RIS was 1.53 mm3 x 106, 1.51 x 106 in CIS and 1.64 x 106 in healthy controls (p= 0.12 vs. CIS and p=0.003 vs. healthy controls); the GMV in RIS was 0.56 x 106, 0.53 x106 in CIS and 0.71 x 106 in healthy controls (p=0.2 vs. CIS and p=0.003 vs. healthy controls) and the WMV in RIS was 1 x 106, 0.98 inCIS and 1.12 x 106 in healthy controls (p=0.66 vs. CIS and p=0.12 vs. healthy controls). Conclusions: our study showed a decrease in brain volume of RIS patients compared with healthy controls similar to CIS patients. Future studies will help to confirm this finding. A14 Brain atrophy over 1 year of disease onset predicts long-term clinical status in relapsing-remitting multiple sclerosis Juan Ignacio Rojas, Liliana Patucco, Edgardo Cristiano Hospital Italiano de Buenos Aires, Argentina; Cristina Besada - Neurradiology Center, Hospital Italiano de Buenos Aies, Argentina Brain atrophy correlates with neuroaxonal loss in multiple sclerosis (MS) and potentially may reflect disease progression earlier than conventional lesion measures. The objective of this study was to investigate whether brain atrophy changes during the first year of disease in RRMS, independently predict disability on the long term. Methods: We prospectively included RRMS patients with recent onset of the disease (less than 15 months of the first symptom). Brain MRIs performed at onset and after 12 months were used in order to measure the percentage of brain atrophy (SIENA software). EDSS score was used to measure progression. Cox regression test was used to analyze clinical variables and disease progression. Results: 26 patients were included, mean age at onset was 32.89 years and mean follow-up time was 9.35 years. Mean time between first and second MRI scan was 131.5 months. During follow-up, 42.1% of patients reached an EDSS of 4 or higher. Adjusting by age at onset, gender, oligoclonal bands in CSF, MRI Barkhofs criteria and immunomodulatory treatment, only brain atrophy rate during the first year of disease was significantly related to progression during the follow up (p<0.001). Brain atrophy rate in patients that reached EDSS 4 was -1.12% vs. -0.28 (p=0.003) in patients that didnt. Cut-off values higher than -0.8% were significantly associated with higher disability over time (OR 4.2 CI95% 2.2-6.5, p=0.008). Discussion: brain atrophy rates during the first year of disease were predictive of disease progression in our population. A15 Brain volume changes may predict conversion in radiologically isolated syndromes Liliana Patrucco, Jimena Miguez, Vernica Fleitas, Juan Ignacio Rojas, Edgardo Cristiano Hospital Italiano de Buenos Aires, Argentina MRI lesions suggestive of multiple sclerosis (MS) in the absence of a clinical scenario is a condition named radiologically isolated syndrome (RIS). The objective was to determine predictive
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factors for conversion to a clinically isolated syndrome (CIS) or MS in subjects with RIS. Methods: A retrospective review of RIS cases with at least 1 year of follow up was performed. Demographic, MRI findings (brain volumes and brain and spinal cord lesion load) and oligoclonal bands (OB) in CSF were analyzed as potential predictors for clinical progression. Results: 12 subjects with RIS were included (mean follow up time 33.6 12 months). 5 (42%) of them progressed clinically (3 to CIS, 2 to RRMS) over a mean time of 18 5 months from the date of RIS identification. After adjusting for potential confounders, demographic, OB and lesion load in brain and spinal cord were not associated with progression of RIS. RIS subjects that progressed showed a decrease in white matter brain volume (0.9 x106 vs. 1.1x106, p=0.04), grey matter brain volume (0.5 x106 vs. 0.59x106, p=0.005) and total brain volume (1.51 x106 vs. 1.59x106 p=0.02) compared with RIS patients that did not. Conclusion: We observed a decrease in brain volumes of patients with RIS that progressed to CIS or MS. Brain atrophy would be a predictive factor for conversion in RIS if confirms by further studies. A16 Breastfeeding and risk of postpartum relapses in women with multiple sclerosis Nora Fernndez Liguori1, Diana Klajn2, Mara Laura Saladino1, Berenice Silva3, Fernando Cceres4, Orlando Garcea1 1Consultorio Esclerosis Mltiple, Seccin Neurologa, Hospital Enrique Torn, Buenos Aires, Argentina; Clnica Esclerosis Mltiple, Instituto Neurociencias de Buenos Aires, INEBA, Buenos Aires, Argentina; Clnica Esclerosis Mltiple y Enfermedades; 2Seccin Neurologa, Hospital Enrique Torn, Buenos Aires, Argentina; 3Clnica Esclerosis Mltiple y Enfermedades Desmielinizantes, Divisin Neurologa, Hospital J.M.Ramos Meja, Buenos Aires, Argentina; 4Clnica Esclerosis Mltiple, Instituto Neurociencias de Buenos Aires, INEBA, Buenos Aires, Argentina Introduction: Postpartum period is a risk factor for increased activity in Multiple Sclerosis (MS), 20% - 40% of women experience relapses during this period. Recent studies suggest that breastfeeding has a protective effect on postpartum relapses (PPR). Objetive: To determine breastfeeding frequency in patients with definite MS and its association with PPR. Material and Methods: Retrospective, longitudinal, descriptive, analytical, three MS centers. Ad hoc survey, women with definite MS (McDonald) with live births (LB) after MS onset, data obtained on exclusive breastfeeding (EB): no regular formula feeding during the first 2 months postpartum. Fishers exact test: incidence of relapse in the first 6 months postpartum between women with and without EB. Results: Out of 40 pregnancies with LB in 27 women, 18 breastfed, 14 EB: 35% (CI 95%, 18.96 to 51.06). PPR in patients with EB: 35.71%. PPR in patients without EB: 15.38% RR: 2.32 (CI 95% 0.74 to 7.28) (p = 0.14). PPR in patients with relapses the year before pregnancy or pregnancy (RYBP): 46.15%; PRP in patients without RYBP: 11.11%, RR: 4.15 (CI 95% 1.23 to 14.03) (p = 0.038).
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Patients without RYBP (N = 27) RPP in patients without EB: 22.22%. RPP in patients without EB: 5.36% RR = 4.22 (CI 95% 0.43 to 40.69) (p = 0.32). Conclusions: Relapses the year before pregnancy and during pregnancy were predictors.of PPR. We observed a non-significant trend of more RPP in women with exclusive breastfeeding. We cannot confirm a deleterious effect of exclusive breastfeeding on PPR but the trend observed is against a protective effect. A17 Burden of Multiple Sclerosis and Unmet Needs in Brazil: patient preferences for MS treatments Silva NL1, Takemoto MLS2, Damasceno B3, Fragoso Y4, Finkelsztejn A5, Gomes M1 1Novartis Biocincias SA. Sao Paulo, Brazil; 2ANOVA knowledge Tanslation. Rio de Janeiro,RJ; 3UNICAMP Hospital de Clnicas. Campinas, SP; 4UNIMES - Universidade Metropolitana de Santos. Santos,SP; 5Hospital de Clnicas de Porto Alegre. Porto Alegre, RS Objective: This study aimed to examine patient preferences related to current and future MS treatment characteristics. Methods: Cross-sectional study conducted in 8 Brazilian major MS treatment sites. Patients preferences were assessed using a Discrete Choice Experiment (DCE) that consisted in 18 hypothetical treatment scenarios built by altering six different treatment attributes related to the following domains: mode of administration, frequency, duration of administration, monitoring, local and systemic side-effects. For each scenario, patients were asked to state the most acceptable and the least acceptable attribute. Data were analyzed according to the best-worst scaling (BSW) method described by Flynn et al (2007). Results: The study enrolled 210 MS patients and all of them provide information on preferences, mean (standard deviation) age was 40.7 [11.5] years-old and 70.7% were female. Patients with mild disease (Expanded Disability Status Scale [EDSS] score 0-3) represented 40.4% of patients, 43.8% had moderate disease (EDSS 4-6.5) and 15.9% had severe disease (EDSS 7). The most frequently selected attributes as most acceptable were related to the administration mode and frequency. A pill that you take orally was selected as the most preferred attribute, 77.7% of times when available. In the regression model proposed by Flynn et al (2007), oral administration (regression coefficient=2.1) was more preferred than injections (coeff.=-1.0 and 0.3 for intramuscular and subcutaneous, respectively) or infusions (coeff.=-1.5). The least preferred attribute domain was systemic side effects. Conclusion: The results indicate that Brazilian patients prefer oral MS treatments as compared to injections or infusions and the individual impact of this characteristic overcomes other administration and tolerability issues. A18 Burden of Multiple Sclerosis and Unmet Needs in Brazil: work status and productivity loss Silva NL1, Takemoto MLS2, Damasceno B3, Fragoso Y4, Finkelsztejn A5, Gomes M1
1Novartis

Biocincias SA. Sao Paulo, Brazil; 2ANOVA knowledge Tanslation. Rio de Janeiro, RJ; 3UNICAMP Hospital de Clnicas. Campinas, SP; 4UNIMES - Universidade Metropolitana de Santos. Santos, SP; 5Hospital de Clnicas de Porto Alegre. Porto Alegre, RS Objective: This study aimed to investigate the impacts of multiple sclerosis (MS) on productivity and employment of Brazilian patients. Methods: This was a cross-sectional, multicenter, patientreported outcomes study conducted in 8 Brazilian major MS treatment sites. Information regarding demographic and clinical data, disease severity, work status and productivity loss was collected through structured interviews. Results: The study enrolled 210 MS patients and all of them provide information on productivity loss, of which the mean (standard deviation [SD]) age was 40.7 [11.5] years-old and 70.7% were female. Patients with mild disease (Expanded Disability Status Scale [EDSS] score 0-3) represented 40.4% of patients, 43.8% had moderate disease (EDSS 4-6.5) and 15.9% had severe disease (EDSS 7). The self-reported monthly income was BRL 1764.06 (among the 88% of patients that reported income 0), which is slightly above the national average wage for 2011 (BRL 1,629.40). The employment rate was 33.3% (only patients reporting formal, regular and paid current work). Early retirement due to MS was reported by 37.1% of patients (mean time from MS diagnosis to retirement = 3.9 years), ranging from 10.7% among patients with mild disease to 63.6% among severe MS patients. Among those currently employed, 13.4% had sick leaves in the previous 6 months. The frequency of patients with MS-related permanent workload reduction and income reduction was 24.7% and 21.9%, respectively; and 10.8% of patients reported losing their jobs specifically due to the MS. Conclusion: MS can significantly compromise patients work status, both in terms of early retirement, workload reduction and income losses. The economic consequences of MS-related work impairment can adversely affect both patients, families and the society. A19 Cadasil Diagnosis in Patients Treated as Multiple Sclerosis Andrade, P.S., Mazoni, D, Matos, K.C.M, Fajardo, C,
Torres, D.S Pasteur Hospital
Objectives: Report case of a patient with a history of stroke and relapsing-remitting Multiple Sclerosis (RRMS), hospitalized on relapse, which was diagnosed with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy). Methods: Revaluation was performed based on chronology and evolution of signs and symptoms, research about relatives with similar comorbidities and review of previous images, associated with a research involving original articles, systematic reviews and case reports in indexed literature. Case report: Male patient, 51 years old, with a history of mild hypertension, ischemic stroke and RRMS in treatment with Interferon, admitted with hemiparesis and motor aphasia. He underwent pulse therapy with methylprednisolone and intravenous

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human immunoglobulin for 5 days without improvement. MRI findings included sequel of bilateral and diffuse subcortical infarcts, with emphasis on basal ganglia and periventricular regions, sequel of micro hemorrhages in the basal ganglia and a hyper intense lesion on Diffusion Weighted MRI compatible with acute ischemia located in internal capsule. Cerebrospinal fluid was normal, including negative IgG index and absence of oligoclonal bands. There were no embolic etiologies. Revised anamnesis revealed chronic migraine, depressive disorder and acute ischemia before 50 years old. His grandfather and two aunts were reported with similar comorbidities. Imaging studies revealed suggestive changes since onset of signs and symptoms. Conclusion: CADASIL is a hereditary disease that results in infarcts and progressive demyelination on deep white matter by occlusion of small cerebral arteries. It manifests in adulthood with cardinal features as recurrent migraine headache, focal deficits secondary to cerebral ischemia and neuropsychiatric disorders in advanced stages. Family history and typical radiographic changes bring strong clinical suspicion, which is confirmed by the finding of mutations in Notch 3 gene. It must be remembered when young patients have cerebral ischemia, migraine and diffuse demyelination in imaging exams.
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most prevalent was Neuromyelitis Optica. The high prevalence of NMO in this population sample is probably due to the ethnic distribution of population in the eastern of So Paulo City. A21 - Oral presentation Clinical Analysis of malignant MS in a Brazilian reference center for MS Fabrcio da Costa Hampshire de Arajo1, Juliana Calvet Kallenbach Aureno1, Gutemberg Augusto Cruz dos Santos2, Solange Maria das Graas Gomes Camargo3, Cludia Cristina Ferreira Vasconcelos2 1Universidade Federal do Estado do Rio de Janeiro; 2Universidade Federal do Estado do Rio de Janeiro / Hospital Federal da Lagoa; 3Hospital Federal da Lagoa Objective: Analyse the evolutionary clinical factors related to the patients with malignant RRMS. Methods: Retrospective cohort using the databasis of the idiopathic inflammatory demyelinating diseases ambulatory at Lagoa Federal Hospital, Brazil. Two hundred medical records of patients with MS were analysed and 6 patients with malign evolution were included. Results: The average age of the first relapse was 31.83 years, the interval between the first two relapses was 2,48 years, the number of relapses in the first 5 years was 3,51 years, the time to start treatment was 8,25 years, 1 functional system was affected in the first relapse of these patients (50% pyramidal, 33% sensitive, and about 17% with brainstem involvement), the time to reach EDSS 6 was 3,18 years and the average age for the beginning of progression was 37,2 years old. Conclusions: Based on the literature, malignant MS has prevalence around 10% among all cases. In our research, this value was 3%, perhaps because the small sample selected and that we included only patients with RRMS. The average age of the first relapse and the first interval between the relapses in our cohort were similar to the literature, in which the malignant MS has an older age than the patients with reversible EDSS 6 in the first 5 years of disease and the greater risk of malign evolution in patients with interval between the first 2 relapses is around 2 years. The motor involvement in the first relapse was more prevalent, in agree with literature. The recognition of clinical factors is important to early and effective treatment. A22 Clinical and radiological characteristics of patients with MS in the National Police Hospital 2000-2010, Lima Peru Csar Capar Zamalloa Hospital Nacional LNS PNP, Lima, Peru Background: Multiple Sclerosis (MS) is the first cause of neurological disability in young adults. Over 1 million people around the world are affected with MS, in Peru the actual number of people affected is not known. There is an estimation of prevalence of approximately 7,4 cases per 100000 inhabitants. Epidemiological studies in our country are limited. The investigation about this pathology will provide better understanding of the disease, and also a better
A20 - Oral presentation Central Nervous System Demyelinating Diseases: A Prevalence Study in a Public Tertiary Hospital in So Paulo Brazil Rocha, MSG, Piccolo, AC., Brucki, SMD Hospital Santa Marcelina, So Paulo, Brazil Objective: This study aims to demonstrate the punctual prevalence of central nervous system demyelinating diseases in a public tertiary hospital located in the eastern of So Paulo, Brazil. Subjects and methods: One hundred seventy-five patients who received neurological attendance during the year of 2011 in an outpatient clinic from the Hospital Santa Marcelina were included. Statistical analyses included the descriptive data and samples histograms. Results: Ninety-two patients (52.6%) were Multiple Sclerosis (MS) patients according to McDonald criteria, followed by 12 clinically isolated syndrome patients (6.9%) and three cases of MS rare forms (1.7%). Fifty-three patients (30.3%) were Neuromyelitis Optica (NMO) patients according to the 2006 clinical diagnostic criteria. Additionally, there were 16 patients (9.1%) with NMO spectrum syndromes and two cases fulfilling diagnostic criteria for acute disseminated encephalomyelitis. One hundred twenty-nine patients were female (73.7%) with a 2.5-1 female/male proportion. The majority of patients considered themselves as being white (60%), sixty-eight patients (38.9%) assumed an African descendant, and there were only two form Asian origin. Age ranged from 15 to 65 years (mean = 40 years). Mean disease duration was 7.5 years (range: 1 to 37 years). Median EDSS was 3, ranging from zero to 9.5. All patients had fully neuroimagem investigation and CSF laboratory examination. Aquaporin-4 antibody was performed in 86.8% of NMO patients. The proportion of positive test in NMO patients was 43.4%. Conclusion: Multiple Sclerosis was the most prevalent demyelinating disease in our outpatient clinic. The second
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opportunity for the patients to have a better performance in everyday activities. Methods: The present is a descriptive, retrospective and transversal study. The study population was the clinical reports of all the patients with the diagnoses of Multiple Sclerosis in the Hospital Nacional LNS PNP between the years 2000 and 2010. Results: We found a female predominance (52.38%), with an average age of presentation of 42 years old, and a range of 24 to 75 years. The motor manifestations were more frequent (80.95%), followed by sensory manifestations (71.42%), the third clinical manifestation in frequency were fatigue (42.85%). The radiological characteristics show presence of demyelination plaques in brain hemispheres in 100% of cases, in brainstem in 33.33%, in the cerebellum in 19.04% and in the spinal cord in 23.8% of the cases. Conclusions: The clinical characteristics of the patients with Multiple Sclerosis in our hospital are similar to the ones described by others and in other regions. The radiological characteristics of the patients diagnosed with Multiple Sclerosis are also similar to the ones described worldwide by other autors. A23 Clinical comparative study between two Multiple Sclerosis Centres in Spain and Argentina Berenice Anabel Silva1, Nora Fernndez Liguori1, Antonio Len2, Miguel Guerrero2, Oscar Fernndez Fernndez2, Orlando Garcea1 1Multiple Sclerosis Clinic and Demyelinating Diseases, Hospital Ramos Meja, University Centre of Neurology, School of Medicine. Buenos Aires University, Argentina; 2Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Mlaga, Spain Introduction: actually there are no data on differences in the clinical behavior of multiple sclerosis between American and European patients. Objective: to make a comparative analysis of clinical features of MS between two specialized MS public centres, in Spain: Hospital Regional Universitario Carlos Haya, Mlaga (HRUCA) and Argentina: Hospital Ramos Meja, Buenos Aires (HRM). Methods: Cross-sectional study in which a single evaluator randomly collected 190 MS medical records at both centres. Data collected were: age at time of consultation (AC), at diagnosis (AD) and at disease onset (AO); gender, clinical form (CF), time to diagnosis of MS (TD), years of evolution of MS (YE), clinical presentation of the disease (CP), uni or multifocal presentation (UMP) , current clinical characteristics of MS (CC), presence of familial MS (FMS), Expanded disability status score (EDSS), time to reach EDSS equal to 6 (T6). Comparative analysis was performed using t-test and chi square test. Results: Statistically significant differences were found in: CF (p = 0.006) with a higher percentage of 10.5% primary progressive MS in HRM versus 1.6% in HRUCA; CC (p = 0.04) with 58.4% spinal cord involvement in HRM versus 47.8%; presence of FMS (p = 0.03) and T6 (p=0,01) higher in HRUCA; TD (p = 0.01 ), higher in HRM. Conclusion: While this is an analysis of a sample of patients of both centers, it is the first of its kind conducted in Latin America. This opens the door to future research on clinical characteristics of MS compared with other regions.

A24 Clinical Efficacy and Safety of Oral Bg-12 (Dimethyl Fumarate) In RelapsingRemitting Multiple Sclerosis (RRMS): An Integrated Analysis of the Phase 3 Define and Confirm Studies Bar-Or, A1, Gold, R2, Fox, R. J3, Havrdova, E4, Selmaj, K5, Kurukulasuriya, N. C6, Yang, M6, Raghupathi, K6, Novas, M6, Sweetser, M. T6, Viglietta, V6 ,Dawson, K. T6, Phillips, J.T7 1Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; 2St Josef Hospital, Ruhr University, Bochum, Germany; 3Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA; 4Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 5Medical University of Lodz, Lodz, Poland; 6Biogen Idec Inc., Weston, MA, USA; 7Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA Objective: To report clinical efficacy and safety of BG-12 relative to placebo based on an integrated analysis of DEFINE and CONFIRM. Methods: Integrated analysis was conducted in BG-12 240 mg twice (BID) and three times (TID) daily and placebo treatment groups, contingent upon consistent results across studies. Primary efficacy endpoints were proportion of patients relapsed (DEFINE) and annualized relapse rate (ARR) (CONFIRM) at 2 years. Safety assessments included adverse events (AEs) and laboratory parameters. Results: The integrated intent-to-treat analysis population included 2,301 patients. Baseline characteristics were similar between studies and treatment groups. At 2 years, relative to placebo, BG-12 BID and TID reduced ARR by 49% each (both p<0.0001), risk of relapse by 43% and 47% (both p<0.0001) and risk of 12-week confirmed disability progression by 32% (p=0.0034) and 30% (p=0.0059), respectively. In the placebo, BG-12 BID and BG-12 TID groups, the incidence of AEs was 93%, 95% and 94%; serious AEs 21%, 18% and 16%; and AEs leading to treatment discontinuation 12%, 14% and 14%. The most common AEs (10% in any group) with a 5% higher incidence in either BG-12 group than placebo were flushing and gastrointestinal events. There was no increase in the incidence of serious infections or malignancies in the BG-12 groups compared to placebo. Conclusion: The positive efficacy and acceptable safety profile of BG-12 in this integrated analysis support its potential to become a valuable oral treatment option for relapsing MS. A25 Clinical features and multiple sclerosis epidemiological in Rio Grande-RS Cheple Roberto Abib1, Raul Mendonza Sassi2, Leonardo Alves1 1FURG e Santa Casa de Rio Grande-RS; 2FURG Introduction: Epidemiological studies on multiple sclerosis (MS) have suggested that the interaction between genetic susceptibility and environmental factors may be the key to the differences in prevalence between different communities. Objectives: To describe the clinical and epidemiological characteristics of patients enrolled in the city of Rio Grande-RS. Methods: We included 30

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patients with confirmed clinical diagnosis of MS according to the Poser criteria, the clinical form of Lublin et al. and by the inability scale (EDSS) of Kurtze. Results: Of 30 patients, 70% are female, the proportion of women to men was 2.3:1, only 6% were non-Caucasian. The clinical type of relapsing-remitting MS (RRMS) was the most frequently found, being evident in 86% of patients, followed by the secondary progressive form (SPMS), with 6% of patients, with 3% relapsing-progressive form (PRMS) and primary progressive (PPMS). The average age was 45 years. The age distribution was as follows: 25-34 years: 26% of patients, 35-44 years: 20% of patients, 45-54 years: 26% of patients, 55-64 years: 20% of patients, and, 65 years and over: 6.6% of patients. The majority of patients had only one location of the disease, the most frequent was the pyramidal tract, followed by tract sensory, cerebellar and optic pathway. The EDSS found in patients was: 0-3, 53%; 3.5 to 6.5, 36.7%; 7 or higher, 10%. They use 83% of patients medication. Average time evolution related to the date of diagnosis was 7 years; Time evolution of 0-4 years, 30% patients, 5-9 years, 36.7% of patients, 10-14 years, 26.7% of patients, 15-19 years, 3.3% of patients, 20 years or older, 3.3% of patients. Conclusion: The results obtained in Rio Grande-RS of MS patients are in agreement with previous studies conducted in other Brazilian populations. A26 - Oral presentation Clinical profile or recurrent /bilateral optic neuritis in patients from Rio de Janeiro Elizabeth Batista, Silvio Pessanha Netto, Luiz Claudio Pinto, Katiane Marin, Erlane Fernandes, Natalia Matheus, Regina Alvarenga Servio de neurologia do Hospital da Lagoa; Servio de neurofisilologia Luiz Carlos Pinto Abstract Aim: To establish the clinical profile of simultaneous or recurrent idiopathic bilateral optic neuritis in adults, the efficacy of steroid therapy, extent of visual recovery, and neurological outcome. Methods: The authors performed a retrospective review of all cases of inflammatory demyelinating diseases receiving care from 1995-2012 in Hospital da Lagoa (Rio de Janeiro, Brazil) to identified cases of acute recurrent optic neuritis (NORB). Exclusion criteria included previous multiple sclerosis or myelopathy and known systemic disorders. All patients received intravenous methylprednisolone at acute phase. Visual dysfuntion (VD) scores at first ON were recorded from medical records at nadir and at recovery for the worse eye in each patient. The visual function and PEV were evaluated in 2012 for both eyes. The positivity of the antibody anti-AQP4 was analyzed. Results: Among 1278 IIDD records, 21 NORB cases were identified ( ) and 19 were included in this study [14 women and five women, 52,5% Afro descendants and 47,4% white]. The first ON occurred at range of 5- 57 years (median = 32) and affected both eyes in 73% of the cases; the VD score varied at nadir from 3 to 7 (median= 6) and at recovery from zero to 6 (median=4). The VD after six months was severe at least in one eye I 78% and severe in both eyes in 50% . A recurrence occurred after a range of 0,1-2 years (median=1 year) in all patients, except one. At the last evaluation (2012) after a median time of disease of 4 years (3 months 19 years), severe VD was detected in 25/38 eyes
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(65,78%) and no patient developed other neurological problem during this time. The PEV (2012) was pathological in 24/34 eyes. AQP4 antibody was positive in 1 of 15 patients. Conclusion: Idiopathic acute bilateral or recurrent optic neuritis is a rare and severe NMO complex syndrome, more frequently affecting young Afro descendants women. Vision recovers with corticosteroid therapy is poor. A27 Cognition and personality in a sample of Mexican patients with MS Rabago Barajas Brenda Viridiana1, Aguayo Arelis Adriana1,3, Macas Islas Miguel ngel1,2 1University of Guadalajara, University Center for Health Sciences; 2Mexican Social Security Institute, Western National Medical Center; 3University Enrique Daz de Len, Psychology Objective: To analyze the relationship between cognition and personality in Mexican patients with MS. Methods: sixty-eight patients with relapsing-remitting MS. For inclusion did not take into account age, gender, education, evolution, treatment and EDSS. Battery Rao, personality inventory NEO-Five-Factor and Beck Depression Inventory was applied. A p-value <0.05 was considered significant. Results: Forty-six women, 22 men, mean age 35.410.2, 13.75.3 year mean education, age of first symptoms 27.29.2, age at diagnosis 29.59.2, disease duration 5.65.8 years. EDSS 2.31.5. DC 56%, depression 24%, patients with predominance on neurotic characteristics 73%, extroversion 10%, openness 6%, kindness 4%, responsibility 7%. Patients with predominance of neurotic characteristics as compared to all the remaining personality domains, had significant differences in storage memory (p=.027), recovery (p=.002), delayed (p=.044), Processing Speed (Pasat 3) (p=.001), Pasat 2(p=.002) and attention (p=.029). Significant differences were found in memory retrieval (p=.032) and delayed memory (p=.032) between patients with neurotic characteristics and openness, as well as Pasat between patients with neurotic characteristics and extraversion (p=.002). Conclusions: Results indicate that in patients with predominant neurotic characteristics have a lower cognitive performance in relation to prevalence in patients with other predominant personality characteristics. A28 Cognition in Multiple Sclerosis Antonio Pereira Gomes Neto, Paulo Pereira Christo, Renata Brant de Souza Santa Casa de Belo Horizonte-Minas Gerais Objective: Assessing the cognitive profile of a group of patients with multiple sclerosis followed at CAPPEM-BH. Methods: We evaluated 32 patients treated for demyelination diseases, in Santa Casa de Belo Horizonte, and applied a battery of neuropsychological tests that include assessing the following domains: executive, memory,language and visual constructive. Results: Among the cognitive domains assessed, the most prevalent alteration occurred in the executive (87.5%), followed
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by visual constructive (75%), language (65.6%) and memory (59.4%) -. In 81.2% of cases there were combined impacts in the areas assessed. One third of cases showed psychiatric disorders. Only 1 patient had scores within the normal range. Our study revealed significant prevalence of associated psychiatric disorders (31.2%), consistent with data observed in most studies (15 to 50% of patients). Conclusion: Neuropsychological assessment should approach the most frequently affected mental functions in MS. It is important to assess the presence of associated depression. Treatment of commitment includes drug and cognitive behavioral measures, but none of the proposed treatments have been proved effective. In our sample, the most often impaired was the executive, and combined deficits were the most prevalent pattern. A29 Cognition in the initial stage of Multiple Sclerosis a preliminary study Cntia Kirchmeyer1, Dora-Neide Rodrigues2, Renata Alves Paes3, Regina M. P. Alvarenga4 Neuropsicloga e Mestranda em Neurologia da UNIRIO, PPGNEURO; 2Neuropsicloga e Mestre em Neurologia da UNIRIO, PPGNEURO; 3Neuropsicloga e Ps-doutoranda de Neurologia da UNIRIO, PPGNEURO; 4Neurologista, MD, PhD., Professora Associada da Escola de Medicina e Cirurgia - UNIRIO e Coordenadora do Programa de Ps-Graduao em Neurologia da PPGNEURO/UNIRIO Objective: To determine the frequency and pattern of cognitive impairment in early multiple sclerosis (MS) and to correlate it with the mood (depression and anxiety) and with the EDSS. Methodology: 40 patients newly diagnosed with MS (mean disease duration: 21.6 months) and 40 control subjects underwent a brief neuropsychological evaluation consisting of 4 tests: Rey Auditory Verbal Learning test, Hooper Visual Organization Test, COWAT, Digit Symbol and Becks scales for anxiety (BAI) and depression (BDI). Results: Cognitive impairment occurred in 12.5% of MS patients and 5% in controls, so the frequency rate of cognitive impairment of patients was estimated at 7.5%. Cognition was compromised in two trials: RAVLT and HOOPER. Memory functions (recognition, short-term memory and immediate and delayed recall), visuospatial perception and organization were altered. Memory showed the highest sensitivity index. There was no significant correlation between mood (anxiety and depression) and EDSS with cognitive deficits. Conclusion: The frequency rate of cognitive impairment in early MS is low and memory functions and perception/organization visuospatial are the first to suffer alterations. Keywords: Cognitive impairment, early multiple sclerosis, neuropsychological assessment. A30 Cognitive impairment and MRI features in benign multiple sclerosis: preliminary results. G. Santos, N. E. Corra de Arajo, C. C. Ferreira Vasconcelos, L. A. Moreira de Souza, R. Alves Paes, D.-N. Rodrigues Cerqueira, T.C. Monteiro, S. M. G. Gomes Camargo, F.

Hampshire Araujo, J. Calvet Kallembach, L.C. Santos Thuler, R. Papais Alvarenga UNIRIO (Rio de Janeiro, BR); Hospital Da Lagoa (Rio de Janeiro, BR); INCA (Rio de Janeiro, BR); Hospital Quinta DOr; Instituto DOR de Ensino e Pesquisa Background: The definition of benign multiple sclerosis (B-MS) is still controversial. Although in B-MS disability is minimal or even absent, subclinical cognitive impairment seems to be present in many cases. Recent studies have pointed towards the utility of Neuropsychological tests and MRI features in correct define B-MS. Objective: The aim of this study is to correlate the grade of cognitive impairment and MRI features in patients classified as B-MS. Methods: Among 155 patients with 10 years or more of disease duration, 125 (80%) were classified as benign form (EDSS <=3 and disease duration >= 10 years). After 15 years of evolution 78 patients (62,4%) continued as benign. We were able to evaluate 21 (27%) subjects regarding cognitive status by Neuropsychological battery: Rey list (three steps), verbal fluency (two steps), digit symbol (one step), Hooper test (one step). According to their performance, they were classified as: mild, moderate and serious impairment. We reviewed the MRI features of 10 (47%) of these patients at the time of the cognitive evaluation. Results: All patients evaluated were women with mean age of 43 (+/-9.4) years and mean disease duration of 14,9 (+/-3.5) years. Afro descendent represented 20%. Mild cognitive impairment was present in 40% and moderate in the other 60% of patients. All subjects had supra and infratentorial lesions (100% in brain stem, and 80% in cerebellum). Only 2 of the group had confluent lesions, and the others presented a mean diameter lesion of 5-10mm. Corpus callosum (CC) alteration was present in 90% of the sample, while black holes were absent only in 40%. Only 3 patients didnt have focal atrophy, which was present mostly in CC and fronto-parietal topographies. Conclusion: We werent able to identify any aspect statistic significant due to the small sample; however we believe that a study with a larger cohort could be capable of identify the true B-MS patients in the early stages of the disease, influencing at the treatment decision. A31 Cognitive Relapse in Multiple Sclerosis: Report of 3 Cases Frederico Maia Prado, Victor de Almeida Kosac, Andr PC Matta, Henrique Cal, Osvaldo JM Nascimento, Joo Gabriel Dib Federal Fluminense University- Brazil Amato M.P., Portaccio E., Goretti B., Zipoli V., Iudice A., Della Pina D., et al. (2010) Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study. Mult Scler16: 14741482; Sormani M, Stromillo ML, Battaglini M, Signori A, De Stefano N.(2012) Modelling the distribution of cortical lesions in multiple sclerosis. Mult Scler. 2012 Feb;18(2):229-31 Objective: To present 3 cases with an unusual purely cognitive relapse in patients with multiple sclerosis (MS) relapsingremitting. Methods: We selected three patients with MS, diagnosed according to the McDonaldss modified criteria (2010), whose clinical picture include acute changes in distincts areas of

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cognition, lasting more than 24 hours, and complete resolution. They were submitted to complete history, physical examination and imaging. Results: Patient 1: Man, 48y, reported acute memory loss 2 years ago, associated to disorientation with remission after one month. Six months ago he presented with similar relapse lasting one week, also with complete resolution after corticosteroid pulsotherapy. MRI showed hyperintense lesion on FLAIR in the temporal region. Patient 2: Female, 36y, MS diagnosed at 32, with acute onset history of anomia and decreased verbal fluency, with normal repetition and interpretation. MRI showed new juxtacortical lesion at left frontal lobe, near the operculum, and previous detected periventricular and pontine lesions. Patient 3: Female, with history of memory loss and temporo-spatial disorientation lasting 2 weeks. She reported dysnomia and dyscalculia with impaired working memory 2 months ago. MRI compatible with MS. Conclusion: It is increasingly recognized progressive cognitive deterioration in patients with relapsing-remitting MS. However, reports of relapses with purely cognitive impairment are still uncommon. With this evidence, it is essential a careful assessment of the clinical manifestations in MS for proper management. A32 Comparison of fatigue and functional status among multiple sclerosis subtypes and neuromyelitis optica Helcio. Alvarenga-Filho, Leandro.A.C. Nogueira, Sergio. Seixas R.M Papais-Alvarenga, Claudia C F Vasconcelos, Katia.N. Lopes, Felipe.R. Nbrega, Luiz .Claudio.S. Thuler, Sonia.R.S. Carvalho, Ricardo.M Dias Objective: To compare fatigue and functional status between MS and NMO Methods: A descriptive case series study at Lagoa Hospital - Rio de Janeiro, Brazil was carried. The inclusion of the study was to have MS diagnostic with McDonald et al. criteria and NMO diagnostic with Wingerchuk et al. criteria. The main outcome measurements were demographic variables, quality of life (SF-36 v.1), disability by EDSS, motor function of the upper limb (Box & Blocks test), gait (Hauser ambulatory index) and fatigue (Fatigue Severity Scale). Results: One hundred and eighteen patients fulfilled the study criteria. The mean age of patients was 42 years, 73% of patients were female, and the average of disability was moderate (EDSS= 3.9). Primary-progressive MS (PPMS) patients were older than relapsing-remitting MS (RRMS) (OR=4.3; IC 95% [1.512.7], p<0.01) and NMO (OR=5.2; IC 95% [1.518.8], p<0.01). RRMS showed less disability than the others (p<0.01). The fatigue was not statistical difference between the conditions (mean RRMS=40,2; PPMS=41,5; NOM=41,6; p=0.90). PPMS patients had more gait limitation (OR=7.1; IC 95% [2.421.6], p<0.01), more disability (OR=9.8; IC 95% [2.934.5], p<0.01) and decreased of physical function domain (OR=8.2; IC 95% [1.0176.6], p=0.03), than RRMS subjects. PPMS had more gait limitation (OR=2.8; IC 95% [0.89.4], p=0.06) and decreased role emocional (SF-36) (OR=6.4; IC 95% [1.433.6], p<0.01) than NOM patients. The quality of life was reduced in all domains of these subjects. NMO patients had more severe disability than RRMS patients (OR=6.1; IC 95% [2.019.2]; p<0.01).
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Conclusion: Primary-progressive MS patients showed severe disability and more gait limitation than relapsing-remitting MS and NMO patients. The fatigue affected in a similar way all three conditions. The quality of life was reduced in all domains in the study population, been more declined in primary-progressive MS patients. Only the Vitality domain was more decreased in relapsing-remitting MS patients. A33 Continuos excretion of JC virus and BK virus in one multiple sclerosis patient undergoing natalizumab treatment: one year follow up Nali, L.H.S.; Sumita, L.M.; Fink, M.C.D.; Olival, G.S.; Santiago, T.F.; Bermudez, J.E.V.; Moraes, L. 4; Cavenaghi, V.; Tilbery, C.P.; Callegaro, D.4; Casseb, J.S.; Penalva-de-Oliveira, A.C.; Romano, C. M. Laboratrio de Virologia do Instituto de Medicina Tropical, USP; Santa Casa de Misericrdia de So Paulo; Insituto de Infectologia Emlio Ribas; 4Hospital das Clnicas de So Paulo, HCFMUSP This study aimed to investigate one patient undergoing Natalizumab treatment that have continuous excretion of BK and JC Polyomavirus in the urine, to monitor possible viremia and perform molecular characterization of Regulatory Regions in JCV virus. Materials and Methods: Blood and urine samples were collected monthly from a patient undergoing Natalizumab treatment, totaling 12 samples. For detection of Polyomavirus DNA was initially screened using a Polymerase Chain Reaction (PCR) primers complementary to a region common to the JC and BK. Then, the samples with positive reactions were differentiated between JC and BK, via real-time PCR based on TaqMan system. The viral load determination was based on a standard curve. The molecular characterization of the RR JC was made by PCR with specific primers followed by sequencing. Results: All blood samples were negative for JCV and BKV. However all urine samples were positive for JCV. The month by month analysis of JC viral load in the urine revealed an increase of approximately 90 times between the first and 12th collection (770.000 to 6x107 viral copies/ml). BKV was detected only from the 7th collection and remained detectable until the 12th collection. BK viral load increased approximately 13x (1,000 to 130,000 viral copies/ml) between the 6th and 11th month of treatment. The sequence analysis of the JC RR was similar to the archetypal. Conclusions: The results suggest that the viral load of JCV and BKV in the urine of this patient may have increased due to prolonged treatment. However, results of sequencing indicate that so far the JCV is the archetypal form, showing no evidence of viral reactivation. A34 Costs of multiple sclerosis in Latin America and the Caribbean: systematic review of the literature Marina Romano, MD1, Gerardo Machnicki, MSc, PhD2, Juan Ignacio Rojas, MD3, Nadina Frider, MD4, Jorge Correale MD5
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Centro de Educacin Mdica e Investigaciones Clnicas. Norberto Quirno CEMIC. Argentina; 2Global Health Economics and Outcomes Research. Novartis Argentina; 3Neurology Department.MS Clinic. Hospital Italiano de Buenos Aires. Argentina; 4Novartis Regional Medical Director in Neuroscience Latinoamerica & Canada; 5Department of Neurology. Institute for Neurological Research Dr Ral Carrea Multiple sclerosis (MS) is the second most common cause of neurological disability in young adults. Limited information is available about the cost of the disease in Latin America and the Caribbean (LAC). The objective was to assess health economic data of MS in LAC. Methods: We conducted a systematic review of the literature from 1990 to 2011. Outcome measures included: mean cost of disease modifying therapies (DMTs), mean cost of treatment of relapses (steroids and hospitalization), mean cost of disease by stage stratified by EDSS and mean cost of rehabilitation. Results: Nine hundred and thirty nine citations were identified. Seven studies from 3 countries (Brazil, Argentina and Colombia) met predetermined inclusion criteria. The studies were heterogeneous in several aspects. The mean cost of DMTs treatment was reported to be of USD 35,000 per patient-treated for 2004 in Argentina and the total MS expenditure of DMTs rose from U$D 14,011,700 in 2006 to U$D 122,575,000 in 2009 in Brazil. In Sao Paulo, DMTs accounted for 12.9% of high cost medication supplied by the public sector in Brazil. The mean length of hospitalization related to MS was 7.7 days being the mean cost of hospitalizations reported of USD 386 for 2009 in Brazil. Patients cost ranged between USD 10543 (EDSS 8-9.5) and USD 25713 (EDSS 3 5-5). Indirect costs markedly increased for the EDSS 8-9.5 patients. Conclusions: This study represents the first systematic review of the costs of MS in LAC. Further research about the economic burden of MS in LAC is needed. A35 - Oral presentation Cytokine profile in relapsing-remitting multiple sclerosis patients and the association with the progression and the activity of the disease Ana Paula Kallaur, Sayonara Rangel Oliveira, Andra Name Colado Simo, Elaine Regina Delicato de Almeida, Helena Kaminami Morimoto, Damcio Ramon Kaimen-Maciel, Josiane Lopes, Wildea Lice de Carvalho Jennings Pereira, Renato Marques Andrade, Larissa Muliterno Pelegrino, Edna Maria Vissoci Reiche State University of Londrina Cytokines and their receptors have an important role in the multiple sclerosis (MS) and have been correlated with the disease activity. The aims of this study were to evaluate the serum pro-inflammatory (TNF-, IL-1b, IL-6, and IL-12), Th1 (IFN-), Th17 (IL-17), and anti-inflammatory Th2 (IL-4 and IL-10) cytokines levels in relapsingremitting MS (RR-MS) patients; and to evaluate the association between cytokine profile with the clinical disability and disease activity of RR-MS patients. The study enrolled 169 RR-MS patients in the remission clinical phase and in 132 controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium (Gd). The serum cytokine level was assessed using enzyme linked-immunosorbent assay. The IFN-, IL-6, IL-12, and IL-4 levels were higher in RR-MS
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patients than controls (p=0.0009, p=0.0114, p=0.0297, and p=0.0004, respectively) and IL-1 levels trend towards higher in controls than RR-MS patients (p=0.0992). IL-4 were higher in RR-MS patients with mild disability compared to those with moderate and severe disability (p=0.0375). TNF- and IL-10 levels were higher in RRMS patients with negative Gd-enhancing lesions than those with positive Gd-enhancing lesions presented at MRI (p=0.0457 and p=0.0533).. IL-17 levels trend towards higher in RR-MS patients with negative Gd (p=0.0631). Low TNF- and high IFN- levels were independently associated with the RR-MS (p=0.0078 and p=0.0056, respectively) and also with the activity of the disease (p=0.0348 and p=0.0133, respectively). The results underscore that RR-MS patients, even in the remission clinical phase, exhibit a complex system of inflammatory and anti-inflammatory cytokines that may interact to modulate the progression and the activity of the disease. Keywords: cytokines, multiple sclerosis, disease activity, disability, disease progression Financial Support: CAPES, Araucria Foundation, State University of Londrina, Bayer Health Care. A36 Analysis on neonatal newborn results among patients with multiple sclerosis Sandra Maria Garcia de Almeida, Fabola Rachid Malfetano, Gisele AlexandreLoureno Isabella D Andrea Meira, LetciaFzer, Simone Baptista,Valria Coelho Santa Rita Pereira, Yara Fragoso, Soniza Vieira Alves-Leon Hospital Universitrio Clementino Fraga Filho/UFRJ, Programa de Psgraduao em Neurologia (UNIRIO) Objectives: Multiple sclerosis (MS) affects young adults of reproductive age and has a broad spectrum of clinical variations. The ability to have children must be evaluated and depends on the degree of disability. Our objective is to evaluate the neonatal results among MS patients newborns, and compare them with healthy controls. Methods: This case-control study examined data on selected MS patients in accordance with the criteria of McDonald et al.(2001) and included those who became pregnant during or after the MS diagnosis. The control group consisted of healthy women matched by age and parity, with no teratogenic medication, at the rate of two controls for each case. A questionnaire was applied, after obtaining the patients permission, while they were waiting for or after leaving their consultations at the clinical research unit or obstetric ward of the University Hospital of the Federal University of the State of Rio de Janeiro. Comparisons were made between the MS patients newborns and the healthy controls. The variables examined included: gestational age at delivery, prematurity, malformations, mortality, weight, height, head circumference, Apgar score variations at the 1st and 5th minutes and complications in the nursery after childbirth. The data were entered into Excel worksheets and subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS), version 13.0 for Windows. Results: 115 women were interviewed: 33 with MS and 82 in the control group, yielding a total of 129 pregnancies: 43 with MS and 86 in the control group. In the MS group, 18.6% (n=8) became pregnant while exposed to medication for their MS. The average gestational age of the MS patients newborns was 38.3

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weeks (SD2 .89), versus 38.9 weeks in the control group (SD1 .38). There were no significant differences in the frequencies of prematurity (0% for MS patients versus 2.3% for controls), malformation absence (90.7% for MS patients newborns versus 97.7% for controls) and mortality rate (2.3% for MS patients newborns versus 1.2% for controls).The average weight of MS mothers newborns was 3171 g (SD 634.136) versus3284 g (SD 502.854) for controls. The average height of MS patients newborns was 48 cm (SD 4) versus 49.5 cm (SD 2.4) for controls. The average cephalic perimeter of MS patients newborns was 34.1 (SD 2.6) versus34.4 cm(SD 1.4)for controls. The average Apgar score at the firstminute for MS patients newborns was 8.7 (SD0.49) and at the fifthminute 9.6 (SD0.56) versus first minute 8.0 (SD 1.61) and fifth minute 9.1 (SD1.31) for controls. In 81.4% of the MS patients newborns, there were no complications in the nursery versus 83.7% for controls. No statistically significant associations were found between these variables. Conclusions: Our results indicate that the intrauterine environment for fetal development is favorable in MS patients. The neonatal variables analyzed showed results within the normal range, in comparison with the newborns of healthy controls. We conclude that MS patients can obtain good results with multidisciplinary neonatal monitoring of the pregnancy cycle. A37 Demographic and clinic characteristics of patients treated with Natalizumab a Brazilian preliminary study M. Papais Alvarenga, C. Vasconcelos, G. Santos, E. Batista, S. Camargo, J. Calvet, M. Deslandes, R. Papais Alvarenga. Hospital Federal da Lagoa e Hospital Universitrio Gaffre e Guinle Objectives: The aims of this study are to analyze demographic and clinical data of patients from Rio de Janeiro (Brazil) with relapsing MS (Relapsing-remitting MS and Secondary Progressive MS with inflammatory evidence) treated with Natalizumab (NTZ) on Hospital Federal da Lagoa (HFL). Methods: All patients included to this study live in Rio de Janeiro State and started NTZ treatment in HFL from July 2010 to October 2012. Variables analyzed included demographic and clinical characteristics; disability status [(EDSS) score] and annualized relapse rate (ARR); JC virus status. Results: 23 patients were included - 18 female; 68% white; mean time of age of disease onset 28,39 years ( 8,68) and mean time of disease duration 8,52 years ( 4,45); 18 RRMS and 5 SPMS. The JCV status was 70% positive. The mean EDSS score was 3.43 and mean ARR was 1.83 in the year prior to start treatment; the mean EDSS score was 3.34 and mean ARR was 0.04 after one year treatment. Median of 7 infusions (1 28). 1 patient discontinued treatment after his first infusion due to a toxic hepatitis. Conclusion: NTZ is indicated for treatment of active relapsingremitting MS. It has been available in Brazil since the second semester of 2011, gratuity offered by the Brazilian Ministry of Health, but it could be used before by health insurance paying or by private acquisition. This is a preliminary study. So far, the efficacy and safety data of relapsing MS patients treated with NTZ in HFL are confirming that is a well tolerate drug with a huge impact on the disease activity, mainly seen in the annualized relapse rate.
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A38 The relative frequency of neuromyelitis optica among multiple sclerosis in Brazilian patients from Rio de Janeiro state (Brazil) Regina Maria Papais-Alvarenga, Claudia Cristina Ferreira Vasconcelos, Solange Maria Gomes Camargo. Marcos Papais Alvarenga, Marina Papais-Alvarenga, Claudia Miranda Santos, iElizabeth Batista, Elizabeth Peixoto, Gutemberg Santos, Antnio Catarino, Katiane Marin, Erlane Fernandes, Bernardo Campos, Natalia Matheus, Melina Bernardes, Vanderson Carvalho Neto, Ulisses Linhares Institutions: Servio de Neurologia do Hospital da Lagoa (Minstrio da Sade) Programa de Ps graduao em neurologia (UNIRIO) Objective: to describe the spectrum of inflammatory idiopathic demyelinating diseases in a hospital series of fpatients from Rio de Janeiro state. Method: Were reviewed demographic, clinical , MRI and laboratorial data from medical records of 1278 patients [white 65%:Afro descendants 35%; men 24%:woman:76%] with IIDD assisted from 1995 to 2012 in Hospital da Lagoa, the main referral center for MS treatment in Rio de Janeiro state (Brazil). MS criteria (2005), and NMO criteria (2006) were applied. Results: 371 cases of NMO spectrum syndromes, 179 NMO (137 recurrent and 42 monophasic); 123 MTA (42 recurrent and 81 monophasic), 26 cases of optic spinal MS; 28 bilateral/ recurrent optic neuritis and 15 cases of ON or MTA with brainstem syndrome or encephalopathy and 807 MS cases (732 relapsing-remitting and 75 primary progressive) were found. The AQP4 antibody was positive in 36/55 NMOR, 1/15 BRON, 6/14 LETM and negative in 8 NMOM and 25 OS-MS tested. NMO patients differs from MS patients by race (> African descendants), morbidity and mortality. OS-MS patients were predominantly white and despite the recurrent involvement of optic nerve and spinal cord has a benign clinical course. Conclusion: The relative frequency of NMO among MS cases in a hospital series of a tropical region of Brazil with 40% of African descendants in the general population is 19,8%. This result is similar to Martinique (27%) and different from Hospital series from Firenze and Australia (1,2-1,5%) reinforcing the ethnic background influence in the spectrum of NMO worldwide.
A39 Demyelination is not always multiple sclerosis Ventura, N, Lopes, F Purpose: Although multiple sclerosis (MS) is the most known and studied demyelinating disease, demyelinating processes involving the CNS are related to a wide range of etiologies, including primary and secondary causes. This exhibit aims to illustrate the main secondary causes of demyelination processes, focusing in the MRI findings that help the differential diagnosis. Content Organization: Secondary demyelinating disorders: MRI findings Acute disseminated encephalomyelitis HIV encephalitis Progressive multifocal leucoencephalitis
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CreutzfeldtJakob encephalitis Osmotic demyelination Wernicke encephalopathy MarchiafavaBignami Posterior reversible encephalopathy syndrome Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) MS: key features for making the differencial.

Among MS patients, 79.1% did not present miscarriage, and in the control group, 81.4% did not present miscarriage.Among MS patients, 51.2% showed no complications in childbirth and in the control group, 55.8%. 68.3% of the MS patients desired vaginal childbirth, and in the control group, 52.3% had the same wish.The obstetrician not suggested the way of delivery in 7.0% of MS patients In the control group, the obstetrician suggested cesarean section for 46.3% and vaginal delivery for 18.6% of the cases. For 48.8% of the MS patients, cesarean section was indicated due to their MS, and for 23.3% of them, due to obstetric causes. In the control group, cesarean section was indicated for 46.5% due to obstetric causes. The delivery route most commonly used for patients with MS was cesarean section (79.1%), versus 61.6% in the control group. The second stage of labor was quick in 77.8% of the MS patients, versus 12.1% in the control group. 83.7% of the MS patients showed no complications in childbirth, versus 88.4% in the control group. Conclusion: In our series, it was observed that the second stage of labor did not present any kind of neuromuscular weakness, fatigue or exhaustion. Moreover, although the obstetricians suggestion was influenced by the disease, MS did not influence the delivery route.
Summary: Demyelinating processes can be caused by primary and secondary etiologies. The classic example of primary demyelination is MS. However, secondary processes represent an important group of demyelinating diseases, including infectious, hypoxic/ischemic and metabolic etiologies, among others. Since the imaging findings of both groups can be similar, radiologist should be aware of the special features that favor secondary causes.
A40 Determining factors in delivery route among Multiple Sclerosis patients Gisele Alexandre Loureno, Sandra Maria Garcia de Almeida, Fabola Rachid Malfetano, Isabella D Andrea Meira, Valria Coelho Santa Rita Pereira, Letcia Fzer, Simone Baptista, Yara Dadalti Fragoso, Soniza Vieira Alves-Leon Hospital Universitrio Clementino Fraga Filho (UFRJ), Programa de Psgraduao em Neurologia (UNIRIO) The influence of pregnancy on multiple sclerosis (MS) has been widely studied, but the delivery route among these patients has not been well characterized. Current studies show that the delivery route among patients with MS is subject to obstetric indications and depends on specific variables that may determine the cesarean option. Objective:To evaluate specific variables that determined the delivery route in a cohort of pregnant women with MS Methods: We conducteda case-control study. The patients were selected in accordance with the criteria of McDonald et al. (2001), such that those who became pregnant during or after the MS diagnosis were included. The control group consisted of healthy pregnant women, age-matched in the proportionsoftwo controls for each case. Interviews were conducted using a questionnaire, which asked about age, ethnicity, age at MS diagnosis, EDSS, EDSS during pregnancy, adverse events during pregnancy, miscarriages, desire for vaginal birth, obstetricianguidance on delivery route, cesarean section indication, secondstage of labor, delivery route andchildbirthcomplications. Results:We interviewed 115 women; 33 had multiple sclerosis and 82 were in the control group, with 129 pregnancies in total: 43 in the MS group and 86 in the control group. The mean age ofthe MS patients was 34.2 years and of the controls, 29.9 years.75.8% in the MS group were white and 70.7% in the control group. The mean age at MS diagnosis was 23.7 years.The mean EDSS of the patients with relapsing-remitting MS (RRMS) was 3.4 and it was 5.8 with secondary progressive MS (SPMS).The mean EDSS during pregnancy among RRMS patients was 0.35 and among SPMS, 0.8.
A41 - Oral presentation Disease modifying therapy withdrawal in relapsing-remitting multiple sclerosis: follow-up of 40 patients Retirada de terapia modificadora da doena em esclerose mltipla forma remitente-recorrente: seguimento de 40 pacientes Guilherme Sciascia do Olival1, Vitor Breseghello Cavenaghi2, Vitor Serafim2, Rodrigo Barbosa Thomaz1, Charles Peter Tilbery3 1MD, Neurologist of the Irmandade da Santa Casa de Misericrdia de So Paulo, So Paulo SP, Brazil; 2Medical Student of the Santa Casa de So Paulo, Faculty of Medical Sciences, So Paulo SP, Brazil; 3MD, PhD, Full Professor of the Santa Casa de So Paulo, Faculty of Medical Sciences, So Paulo SP, Brazil This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease modifying therapy (DMT) withdrawn. 40 patients that: made continuous use of one immunomodulator and remained free of disease for at least 5 years had their DMT withdrawal and were observed from 13 to 86 months. Out of the followed patients 4 (10%) presented new attacks. Besides these, 2 (5%) patients had new lesions in the magnetic resonance image that didnt correspond to clinical attacks. In spite of these results, the medication withdrawal is a hard decision to be taken, requires careful analysis and should not be treated as a synonym of suspending the treatment since these patients should be evaluated periodically and the immunomodulators have to be readily reintroduced if new attacks should arise. Nonetheless medication withdrawal is an option for a selected group of patients. A 42 - Oral presentation Prognostic Factors of Malignant Multiple Scleosis in a Cohort of Argentinean Patients Liliana Patrucco, Jimena Miguez, Vernica Fleitas, Juan Ignacio Rojas, Edgardo Cristiano Hospital Italiano de Buenos Aires, Argentina

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Malignant multiple sclerosis (MMS) has been ddefined as a clinical form that reaches a significant disability in the first five years of evolution. The objective was to analyze the variables associated with MMS in a sample of patients from Buenos Aires, Argentina. Methods: Patients with relapsing remitting MS with at least 3 annual visits and a follow-up of at least 5 years were included between January 1999- January 2012. MMS was considered in patients who reached an EDSS> 5.5 in to 5 years (National MS Society Advisory Committee on Clinical Trials of New Agents consensus). Demographic, clinical, electrophysiological and laboratory variables using multivariate analysis (significant p <0.05) were analyzed. Results: 105 patients were included. 29 (28%) met criteria for MMS. Follow up time in MMS was 9.3 1.7 years and 13.1 2.7 years for non MMS patients (p 0.02). All patients received immunomodulatory therapy. In multivariate analysis 1) older age at disease onset (37.1 1.2 years in MMS vs. 30.2 1.3, p <0.001, OR 1.72 95% CI 1.2-2.5), 2) incomplete recovery of first relapse (59% in MMS vs. 20%, p <0.001, OR 2.1 95% CI 1.5-3.1) and 3) EDSS 4 after the first relapse (24% in MMS vs. 3%, p0.002, OR 2.7 95% CI 2.3-5.5) were associated with MMS. Conclusion: age and severity at onset were associated with increased risk of MMS in this cohort of Argentinean MS patients.
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Conclusions: Clinical markers would assist in choosing initial therapy, monitoring response, detecting subclinical activity and predicting therapeutic failure. Both treatments induced DAF status in RRMS patients in the LT. Early treatment initiation could be an important predictor of DAF.
A43 Early Clinical Predictors of Sustained Disease-Activity-Free Status in Patients with Relapsing-Remitting Multiple Sclerosis Treated with Interferon Beta and Glatiramer Acetate Martnez A, Rojas G, Curbelo C, Vrech C, Steinberg J, Carr A. CABA, Argentina Background: The novel concept of sustained disease activity free (DAF) status could be a viable goal of therapy composed of 3 components used individually as endpoints of efficacy. The ultimate goal is to prevent the long-term (LT) accumulation of irreversible disability. Objective: To identify which clinical or MRI parameters obtained before/within the 1st yr of treatment are early predictors of DAF status in nave patients treated with IFN or GA. Design/Methods: DAF status defined as patient having no relapse, no 3-month sustained change in EDSS, and no new MRI lesions over a specified period. We assessed clinical predictors and the potential influence on the % of DAF patients in the LT. Categorical predictors: age, disease duration pre-treatment, n of relapses in the 1st yr. before treatment, basal EDSS, and treatment duration. Patient subgroups were stratified by baseline characteristics. Data analysis was performed with SPSS 14; Student-test; non-parametric tests Kruskall-Wallis for multiple groups; Wilcoxon signed rank test; ANOVA one way, linear regression between baseline variables and final EDSS. Results: Observational study of 245 nave RRMS who received IMDs over 10 yrs. DAF was observed in: IFN: 26/92 (28.3%) and GA: 40/108 (37%) ([OR] 0.67, 95% CI 0.361.21; p=0.18). After multivariate analysis, the only independent predictive factor for DAF status was <3 yrs. of disease duration pre-treatment (p=0.004), applicable to a subset of 30 patients (49%). When comparing both treatment groups, this finding was only pertinent on GA group (p=0.002).
A44 Early Initiation of Interferon Beta-1b After a First Clinical Event Suggestive of Multiple Sclerosis: Clinical Outcomes and Use of Disease-Modifying Therapy from the Benefit Extension Study Edan G.,1 Kappos L.,2 Montalbn X.,3 Polman C.,4 Freedman M.S.,5 Hartung H.P.,6 Miller D. H.,7 Barkhof F.,4 Lanius V.,8 Herrmann J.,9 Stemper B.,8 Pohl C.,8 Sandbrink R.*,8 Pleimes D.*10 *equally contributed 1CHU-Hpital Pontchaillou, Rennes, France; 2University Hospital Basel, Basel, Switzerland; 3Hospital Universitari Vall dHebron, Barcelona, Spain; 4VU Medical Center, Amsterdam, The Netherlands; 5Ottawa Hospital Research Institute, Ottowa, Canada; 6Heinrich-Heine Universitt, Dsseldorf, Germany; 7UCL Institute of Neurology, London, United Kingdom; 8Bayer HealthCare, Berlin, Germany; 9PAREXEL International, Berlin, Germany; 10Bayer HealthCare, Montville, US Objective: To evaluate the impact of early treatment with interferon beta-1b (Betaseron/Betaferon) in patients with a first event suggestive of MS. Methods: In the placebo-controlled phase, patients were randomized to interferon beta-1b 250 ug sc, eod or placebo for 2 years or until CDMS. Patients were then eligible for an openlabel single-arm follow-up study with interferon beta-1b, but were allowed to take other or no medication. Thereafter, an observational extension study enrolled any patient randomized and treated at least once in the placebo-controlled phase. Results: 284 of the initial 468 patients (60.7%; interferon beta1b: 176, placebo: 106) enrolled in the extension and were followed for a maximum of 8.7 years. Risk of developing CDMS was reduced by 32.2% (HR 0.678, 95% CI 0.5250.875; p=0.0029) and the annualized relapse rate was reduced (p=0.0012) in patients who received interferon beta-1b early. Disability remained stable over time, with a median EDSS of 1.5. Confirmed EDSS threshold of 3 points was reached by 58 patients (20.4%), 4 points by 20 patients (7.0%), and 6 points by 4 patients (1.4%). Of the patients originally randomized and treated, 441 (94.2%) received any DMT any time during the study period and 363 (77.6%) exclusively received interferon beta-1b, while only 31 (6.6%) received other DMTs that may be considered escalation therapies. Conclusions: This study provides further evidence supporting early initiation of interferon beta-1b in patients with a first event suggestive of MS. After 8 years, there was still a risk reduction of CDMS and relapse risk reduction in favor of early initiation of interferon beta-1b treatment. The majority of patients had stable EDSS scores over time with the minority of patients reaching an EDSS score of 3 on their last visit and infrequently needed to switch to escalating therapies up to 8 years.
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A45 Effect of Fish Oil on Cytokines, Oxidative Stress Markers and Progression Disability in Multiple Sclerosis Viridiana Ramirez Ramirez, Genaro Gabriel Ortiz, Miguel Angel Macias Islas, Erandis Torres Sanchez, Fermin Pacheco Moises, Alfredo Celis de la Rosa, Gustavo Orozco Avia University of Guadalajara, Health, University Center of Health Sciences, Pharmacology Department; Neurology Department in West National Medical Center of Mexican Institute of Social Security. Guadalajara, Jalisco, Mexico Objective: Assess the effect of Fish Oil supplementation on serum levels of TNF, IL-1, IL-6, Glutathione peroxidase (GPx), Lipid peroxidation (LPx) and Expanded Disability Status Scale (EDSS) in patients with Relapsing Remitting Multiple Sclerosis (R-R MS) treated with Interferon beta 1b (IFN-1b). Methods: We performed a double-blinded, placebo-controlled study that included patients (aged 18-50 years) with EDSS 5, one relapsing in the last year, treated with subcutaneous IFN-1b 250g each 48 hours. 50 Participants were randomly 1:1 ratio to receive orally Fish Oil 4g daily or placebo for up to 6 months. TNF, IL-1, IL-6, GPx, LPx were measured at 0, 3 and 6 months and EDSS at 0 and 6 months. Results: 23 of 25 (92%) patients of Fish Oil group and 21 of 25 (84%) patients of placebo group complete 6 months. The cytokines decreased mean significantly in the Fish Oil group TNF (30.83.1pg/ml vs 40.21.5pg/ml, p= <0.001), IL-1 (28.81.6 pg/ml vs 40.01.5pg/ml, p= <0.001), IL-6 (55837pg/ ml vs 71132 pg/ml, p= <0.001) after 6 months. There was no significant difference in GPx, LPx and EDSS. No new or unexpected adverse drug reactions were encountered in either of the groups during this study. Conclusions: Despite the effectiveness of Fish Oil on the reduction of serum levels of TNF, IL-1 and IL-6; oxidative markers and progression disability did not modify. A46 Effects of oral BG-12 (Dimethyl Fumarate) on Magnetic Resonance Imaging (Mri) Outcomes in RelapsingRemitting Multiple Sclerosis (Rrms): an Integrated Analysis of the Phase 3 Define and Confirm Studies Bar-Or, A.,1 Arnold, D.L.,1,2 Gold, R.,3 Fox, R. J.,4 MacManus, D. G.,5 Yousry, T.,5 Kurukulasuriya, N. C.,6 Zhang, R.,6 Viglietta, V.,6 Stephan, M.,6 Dawson, K. T.,6 Miller, D. H.5 1Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; 2NeuroRx Research, Montreal, QC, Canada; 3St Josef Hospital, Ruhr University, Bochum, Germany; 4Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA; 5University College London Institute of Neurology, NMR Research Unit, London, UK; 6Biogen Idec Inc., Weston, MA, USA Objective: To describe the neuroradiologic efficacy of BG-12 in a pre-specified integrated analysis of DEFINE and CONFIRM; the analysis was conducted to estimate treatment effect more precisely. Methods: RRMS patients were randomized to oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo in both studies. CONFIRM also included a glatiramer acetate reference comparator arm. MRI was performed in a subset of patients at

sites with validated MRI capability. The integrated analysis was pre-specified and conducted if baseline characteristics and treatment effects were consistent between studies. Results: The integrated MRI cohort comprised 347, 345, and 354 patients given placebo, BG-12 BID, and BG-12 TID, respectively. Over 2 years, BG-12 BID and TID significantly reduced the number of new/enlarging T2 hyperintense lesions vs placebo by 78% (lesion mean ratio 0.22; 95% confidence interval [CI] 0.17 0.28) and 73% (0.27; 0.210.34) (both p<0.0001) and new nonenhancing T1 hypointense lesions by 65% (0.35; 0.270.45) and 64% (0.36; 0.290.46), respectively (both p<0.0001). BG-12 BID and TID reduced gadolinium-enhancing lesion activity vs placebo by 83% (odds ratio 0.17; 95% CI 0.110.27) and 70% (0.30; 0.21 0.45), respectively (both p<0.0001) at 2 years. Conclusion: Treatment with BG-12 BID or TID resulted in significant reductions in MRI activity. Alongside robust clinical efficacy and an acceptable safety profile, the integrated analysis results suggest that BG-12 has the potential to become a valuable oral treatment option for patients with relapsing MS. A47 Encephalopathy in Neuromyelitis Optica Antonio Pereira Gomes Neto, Paulo Pereira Christo, Renata Brant de Souza Santa Casa de Belo Horizonte- Minas Gerais Objective: To report a case of atypical Installation and evolution in patient antibody antiaquaporina 4 positive. Methods: Case report. Results: FFS, female, 30years, Afrobrazilian, healthy until March 2011 when she had difficulty with gait imbalance and left dysmetria, being admitted to Santa Casa de Belo Horizonte. Performed lumbar puncture, rheumatologic tests and ophthalmologic examination were normal. Magnetic Resonance Imaging (MRI) of the brain revealed abnormal signal in the corpus callosum, parietal subcortical white matter . Received methylprednisolone pulse therapy (1g/day) by 07dias and was discharged with partial improvement. In April 2011 was readmitted with recurrent seizures. New MRI revealed thrombosis of cerebral sinuses Superior sagittal, transverse and sigmoid rights. In June 2011 had paresthesias in the lower limbs, urinary retention and paraparesis, reaching near impossibility to walk. Sensory level at T4. Thoracic Spine MRI revealed signal change between T3 and T9, central myelit without contrast enhancement . Subjected to pulse with progressive improvement . AQP 4 antibody (1:1280). Started Azathioprine without new relapses since. Conclusion: The phenotypic variability of cases of NMO requires us to think in this pathology, in front of atypical brain lesions suggestive of demyelination. Early diagnosis enables effective treatment, which reduces the failure and prevents recurrence of relapses. A48 Treatment Experience, Burden, and Unmet Needs (ENCOMS) in Multiple Sclerosis Study: The Costs of MS Patients in Argentina Ysrraelit Celica1, Caceres Fernando2, Villa Andrs Mara3, Melcon Mario4, Resk Maria Mercedes5, Rojas Juan Ignacio5,

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Kuperman Gaston5, Seifer Gustavo5, Machnicki Gerardo5, Cneo Jorge5 1FLENI, Buenos Aires; 2INEBA, Buenos Aires; 3Hospital Ramos Meja, Buenos Aires; 4Junn, Buenos Aires; 5Novartis Argentina Multiple sclerosis (MS) is a common neurological disease among young adults in Argentina. It is known that the cost of the disease is higher but no studies up to date have measured the cost imposed by MS on the Argentinean health system and society. Objectives: To estimate the direct costs of MS patients in Argentina focusing on disease severity. Methods: MS patients in Argentina (N=264) completed a questionnaire which captured information on demographics, disease characteristics, severity (Expanded Disability Status Scale [EDSS]), co morbidities, relapses as well as resource consumption and quality of life associated with MS. Patients were stratified according to disease severity using EDSS (group 1 with EDSS between 0 and 3; group 2 with EDSS >3 and <6; group 3 with EDSS >6) for the analysis. Direct costs included in the analysis were: inpatient care due to relapses, outpatient care due to relapses, inpatient care outside relapses, consultations, investigations, MS treatments, investments, professional care. Costs were obtained from public resources for 2011 and converted to USD. Results: 87,5 % of patients were RRMS, 10,6% SPMS and 1,5 % PPMS. 62% of patients have an EDSS score between 0 and 3; 22% and EDSS >3 and 6 and 14% and EDSS >6. Mean direct cost per year of patients with an EDSS between 0-3 was USD 69 747; for patients with EDSS > 3 and 6 was USD 70 586 and for patients with EDSS >6 was USD 44 871. The mean cost per patient per year increased with worsening disability up to EDSS of 6. In patients with EDSS >6 a decrease in direct cost was observed due to a reduction in the utilization of specific treatment for MS in this group of patients. Conclusions: This is the first study performed in Argentina that evaluated the cost of MS considering disease severity. This information provides important data for the economic analysis of the disease Argentina, where this kind of information is need. Currently is underway the inclusion of indirect cost in order to update their impact over disease MS costs in Argentina. A49 - Oral presentation Epidemiological Study on Multiple Sclerosis and Neuromyelitis Optica in Sul Fluminense Region in Rio de Janeiro State Brazil Ana Beatriz Calmon Nogueira da Gama Pereira, Fernanda Ferreira Chaves da Costa, Solange Camargo, Claudia Cristina Ferreira Vasconcelos, Marcos Papais Alvarenga, Claudio Manoel Brito4, Elder Sarmento4, Regina Maria Papais Alvarenga5. Postgraduate Master Program in Neurology , Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro RJ, Brazil; Severino Sombra University, Vassouras, RJ, Brazil; Neurology Department of Volta Redonda- RJ, Brazil; Neurology Department of Lagoa Hospital Rio de Janeiro RJ, Brazil; 4UNIFOA, University Center of Volta Redonda , RJ, Brazil; 5Postgraduate Master Program in Neurology, Federal University of the State of Rio de Janeiro (UNIRIO) Rio de Janeiro RJ, Brazil, Lagoa Hospital, Rio de Janeiro, Brazil.
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Objectives: Tracking cases of idiopathic inflamatory demyelinating disease in residents from Sul Fluminense region in Rio de Janeiro State located at latitude 22 31' 23" and longitude 44 06'15" with populational density of 1.000.000 inhabitants. Methodology: Clinical and demographic dates from alive residents from Sul Fluminense region in 2011 diagnosed with Multiple Sclerosis, Neuromyelitis Optica and other IIDD, were collected from Vassouras, Volta Redonda and Barra Mansa neurologists and from data base from the reference center to the MS treatment from Lagoa Hospital in Rio de Janeiro. Besides, they were examined from Cadastre of provision of high price medicines to treat MS by the Health Secretary of Vassouras. Results: Until 09/30/2012 there were identified 51 MS cases (37 women; 38 whites and 13 Afros) and 19 NMO spectrum disorders (16 womem; 11 whites and 8 Afros). Considerating these crude dates the MS prevalence is estimated to 5,1/100.000 and the NMO prevalence is 1,2/100.000. The NMO relative frequency (from which 50% are Afros) among the MS cases is 19%. Conclusion: Latin America presents the Multiple Sclerosis prevalence rates among 1.8 to 25 per 100.000 inhabitants. A study in 2002 estimated the MS prevalence of 5,0/100.000 in Rio de Janeiro and until that time there hasn`t been identified any case of MS in Vassouras. In this study we included 3 patients from Vassouras among 70 IIDD cases from the region. This significant increase of IIDD cases in Rio de Janeiro in the last decade is directly related to the organization of specialized attending nucleus, with the experts formation in clinical neuroimmunology and with MRI service introduction. At the end of the date collection in december 2012, the capture-recapture method will be applied to estimate the prevalence.
A50 Epidemiology of multiple sclerosis in the Island of Margarita, Venezuela Soto, A.1, Bracho, E.2, Ordaz, E.2, Gomez, S.2 and Gallardo, M.1 1Service of Neurology, Hospital Dr. Domingo Luciani, Caracas; 2Service of Neurology, Hospital Dr. Luis Ortega, Porlamar. Venezuela. asotor6822@gmail.com Objective: Determine the prevalence of multiple sclerosis (MS) In the Island of Margarita in Venezuela. Methods: A population-based transverse study was performed in Margarita Island in Venezuela from 2008 to 2009 with an estimated population of 436.944 (51.5% females and 49.5% males). All definite or probable MS cases, according to Poser and McDonalds criteria, were included in the study. The date of December 15th 2009 was established as the prevalence day by the authors. Clinical characterization and EDSS determination were also performed. Results: 23 cases with a diagnosis of MS were identified on the prevalence day, 6 male (24%) and 17 female (76%). F/M ratio: 3.1/1. Age: 39 years (Range: 2566 years), 65% had Relapsing Remitting MS, 17% had Secondary Progressive MS, Primary Progressive was observed in 5% and CIS was present in 13%. EDSS: 2.56 (Range: 1.06.5). Brain MRI was performed in 100% of cases (Abnormal: 100%). CSF Analysis was performed in 100% of cases (abnormal in 82%) (OCB or Intratecal Synthesis of IgG). 87% were on immunomodulator treatment and 13%
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did not receive treatment. Responders to treatment: 83% Nonresponders: 17%. Conclusions: The estimated crude prevalence was 6.9/100,000. The Island of Margarita could be considered as an area of low prevalence. This study constitutes the first epidemiological study on Multiple Sclerosis performed in Venezuela. We have not found significant clinical differences in the clinical characterization of these MS patients when compared to other studies performed in Latin America.

(RR) multiple sclerosis (MS) patients with increased disease activity. Methods: EBV infection was investigated in CSF from 20 subjects with relapsing-remitting MS by polymerase chain reaction (PCR) assays. MRI scans were performed, and cerebrospinal fluid samples were collected both during the diagnostic process. Results: Gadolinium-enhacing lesions on MRI observed in these patients correlated with intrathecal Ig M synthesis, but none of the MS patients tested positive for CSF EBV DNA. Conclusions: There was no evidence for EBV CNS infection in the sub group of RRMS patients with increased disease activity. Financial support: FAPESP
A51 Epstein-Barr virus and smoking habits in Brazilian patients with multiple sclerosis Celso LS Oliveira, Joseph BB Brooks, Sidney Gomes, Marcus VM Gonalves, Francisco TM Oliveira, Sonia BF Ribeiro, Heloisa H Ruocco, Ctia Silva, Fabio Siquineli, Yara D Fragoso Objective: To study the presence of anti-Epstein Barr virus antibodies in Brazilian patients with MS. Smoking habits of the patients were also registered, since both exposures (EBV and tobacco) might be interdependent risk factors for MS. Methods: IgG and IgM antibodies to EBV were measured in the blood of patients with MS. Patients were not undergoing relapses when blood was collected. Immunoenzymatic assay was used for the assessment. Smoking habits were obtained in the clinical consultation. Results: The group consisted of 201 patients (40 M and 161 F) with average age of 32.8 years. Disease duration was, on average, 6.7 4.4 years, while the average EDSS was 2.23 2.00. From the total group of patients, 98.5% were IgG positive for EBV (n=198) and none of them was IgM positive for EBV. Smoking (previous and present) was reported by 37 patients (18.4%). No association of smoking and EBV could be obtained in this sample of patients possibly due to small number of smokers and very high number of cases that were EBV positive. Conclusion: The near 100% positivity for IgG anti-EBV in Brazilian patients with MS is similar to that found in other countries. In fact, positivity is so high that some authors recommend caution in diagnosing MS in IgG anti-EBV negative patients. Association of risk factors in the development of MS in these patients could not be ascertained.
A53 Pediatric case of multiple sclerosis Isabella C. S. Defanti, Andr Pres*; Karoline Otranto**; Letcia Fzer***; Maria Lcia V. Pimentel****; Sergio A. P. Novis***** *Residente de Neurologia, **Ps graduando em Neurologia, *** Staff, ****Chefe de Clnica, ***** Chefe do Servio de Neurologia do HSCMRJ We describe a case of a 13 years old white girl who, in 2005, started with dizziness, vomiting and left optical neuritis. After a month she had axial ataxia and complained of worsening of her left visual acuity. Her EDSS was 3.5 At that time a MRI of the brain was made and there were multiple white matter lesions, without contrast enhancement showing already some black holes. She was treated with IV metilprednisolone in pulsetherapy and her improvement was not important. Five months later she had bladder retention and her MRIs did not show new or enhanced lesions. She continued to have many bouts in a short space of time, with many new MRI lesions. Her EDSS turned to be 5.5 and she did not havwe an improvement with metilprednisolone. At that time only glatirmer acetate were indicated to treat children with MS. She started with Copaxone on August 2006 but she continued to get worse and also complained of many side effects of the medication. Copaxone was changed to Rebif 22 after one year, which also did not controled her disease. Her brain MRI showed an increase in black holes and an accentuation of her cerebral giri. She was then medicated with Rebif 44 in October 2010, which made a difference in her disease evolution. She is now stable, EDSS of 1.0, with no new brain or vertebral MRI lesions. Paediatric MS brings to a worst incapacity after a longer period of time but in a younger age. Therefore, as in the adult, the diagnosis should be done as fast as possible, to initiate the proper treatment and to avoid major disabilities.
A52 Epstein-Barr vrus infection of the central nervous system and multiple sclerosis disease activity Carlos Otvio Brando, Brandao CO1, Denise Sayuri Tukada2, Tukada, DS2, Felipe von Glehn2, von Glehn F2, Alessandro S Farias2, Analeda F Longhini2, Adriel Dos Santos Moraes2, Juan Cabanillas2, Leonardo de Deus Silva3, Alfredo Damasceno3, Benito Pereira Damasceno3, Leonilda m b Santos1 1Departamento de Gentica, Evoluo e Bioagentes - Universidade Estadual de Campinas (UNICAMP); 2Departamento de Gentica, Evoluo e Bioagentes Universidade Estadual de Campinas; 3Departamento de Neurologia - Universidade Estadual de Campinas Objectives: To investigate Epstein-Barr virus (EBV) infection of the central nervous system (CNS) in relapsing-remitting
A54 - Oral presentation Resting-state functional Magnetic Resonance Imaging in the assessment of patients with neuromyelitis optica Rueda-Lopes, FC1, Miraldi, F2, Malfetano, F2, Meira, I2, Alves-Leon, S2, Domingues, R3, Bahia, PRV2, Gasparetto, EL1 1UFRJ/DASA; 2UFRJ; 3DASA

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Objective: Neuromyelitis optica (NMO) spectrum is an autoimune demyelinating disease usually related to optical neuritis and extensive myelitis, with occult diffuse white matter damage. Our objective was to investigate NMO patients using the restingstate functional magnetic resonance imaging (RS fMRI) compared to the controls, regarding the default-mode network (DMN) and the visual network, in order to evaluate the cortical adaptations in NMO. Methods: We studied 28 NMO spectrum patients (including myelitis, neuritis optica and/or both) [mean age 38 years (SD +/3,2, 18 female), and also 19 sex and age matched controls. All participants signed informed consent. MRI was performed in a 1.5 Tesla scanner, including 3D T1 weighted-images and RS fMRI was performed during rest. fMRI data was post-processed using MELODIC (FMRIBs Software Library), which was decomposed by independent component analysis (ICA) to identify the functional networks. A dual-regression approach was than carried out allowing comparisons of resting functional connectivity between both groups, using a p-value of 0.05. Results: Fourteen components were computed in the entire subject group by ICA. For the DMN, the precuneus region had significantly higher synchronization in NMO patients compared to healthy controls (p<0.05). In the visual network, there were increased synchronization values in the whole occipital cortex in NMO patients compared to controls (p<0.01). Conclusions: NMO patients have an increased synchronization during rest in the precuneus area of DMN as a form of compensation for the structural damage already described. Also, the higher synchronization values found in the occipital cortex in patients may be a form of compensation for the optical neuritis. A55 Evaluation of microstructural brain white matter damage in patients with neuromyelitis optica and multiple sclerosis C. Pires, F. Rueda, T. Doring, G. Gutfilen, N. Ventura, L. Fezer, S. Aves-Leon, E. Gasparetto Federal University of Rio de Janeiro (Rio de Janeiro, BR) Aim: To quantify and compare the microstructural white matter damage in patients with Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS) using diffusion tensor imaging (DTI) post-processed with tract-based spatial statistics (TBSS). Methods: 35 patients who fulfilled the diagnosis criteria for NMO and 35 patients with Relapsing-Remitting MS (RR-MS), age and sex matched (54 female and 16 male; mean age 41.6 years) were studied. Both groups underwent MR examinations at a 1.5T scanner, which included T1, FLAIR and DTI with 30 directions. Voxelwise statistical analysis of fractional anisotropy (FA) was performed with TBSS, and FA values were compared in the two groups. P <0.05 was considered statistically significant. Results: TBSS analysis revealed that NMO patients were found to have a lower FA compared to MS patients in many brain regions, including right and left superior longitudinal fascicule, splenium of corpus callosum, anterior and posterior left internal capsule, left anterior thalamic radiation, and right and left posterior corona radiata. The mean FA value of the voxels in NMO patients was 0.454 compared to 0.508 in the MS group (p< 0.05). Conclusions: Compared to patients with RRMS, NMO patients demonstrated more extensive brain white matter damage. This
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finding is in accordance to a poorer clinical prognosis observed in these patients, and highlights the possible role of not only Wallerian degeneration but also demyelination in NMO brain damage. A56 Experience of the ambulatory on Demyelinating Disorders of the Central Nervous System in Childhood at Fernandes Figueira/FIOCRUZ RJ T. Saad, A. Pena e Costa, E. Magalhes, C. Quero, AP. Barbosa, A. Meirelles, M. Calheiros, DeAzevedo L IFF-FIOCRUZ Neuropediatria Introduction: From challenges observed during the admission of two girls, one of 4 years old with a clinical picture mimicking meningitis and another of 8 with transverse myelitis in the ICU of IFF in 2008 concerning to the differential diagnosis and therapy, the specialized literature about Demyelinanting Disorders of the Central Nervous System in Childhood was revised, by comparing with the adulthood group. Since than new cases have arisen every year. This motivated the creation of the ambulatory of demyelinating disorders in childhood, to identify peculiarity of the clinical forms, and for early diagnosis. Although some similarities between adults and children, these demyelinating disorders during childhood presents a particular diagnosis. Objective: To describe a series of patients from 2 to 13 years old followed at the IFF, emphasizing some aspects and exchanging the expertise among clinicians from other reference centers in order to evaluate protocols and improve the treatment and the prognosis of these groups of illnesses in pediatrics. Methods: Descrpition and analysis of seven cases. Results: Until this moment our series has seven patients between the ages of two to thirteen years old at the first event. Two of them were characterized as ADEM, one as transverse myelitis (TM), and four of them as CIS, with lesions suggestive of multiple sclerosis and positive oligoclonal band in LCR. All four cases had outbreaks and new lesions at the MR characterizing dissemination in space and time, letting us to confirm MS diagnosis and to start highload betha interferon. The TM patient evolved with tumefative lesion and other TM outbreak greater than the first one, leading to optic neuromyelitis hypothesis, although without optic neuritis. She has been taking glatiramer for over a year. The first patient with ADEM became amaurotic whenever decreasing the steroids, leading the recurrent ADEM diagnosis. The lymphocytic panel and cytokines are analyzed from all patients in several evolutionary phases. Conclusion: The creation of a pediatric demyelinating disorders reference centre intends to increase the knowledge of these illnesses considered rare in the pediatric population and and the assessment of immunological profile to reach the best therapeutic approach. A57 - Oral presentation Frequency of Cognitive Changes in three Clinical Courses of Multiple Sclerosis: Relapsing/Remitting, Primary Progressive and Benign, using a Brief Neuropsychological Screening Battery Renata Alves Paes; Dora Neide Rodrigues; Cintia Villela Kirchmeyer; Aline Braz de Lima; Thais Conceio Monteiro;
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Gutemberg Cruz dos Santos; Claudia Cristina Ferreira Vasconcelos; Regina Maria Papais Alvarenga Universidade Federal do Estado do Rio de Janeiro - Hospital Universitrio Gaffre e Guinle-HUGG/UNIRIO-RJ Objective: To determine frequency rates of cognitive changes in RRMS, PPMS and BMS patients through the BNB. Methodology: A group-control design that included 91 MS patients, of both genders, ranging from 18 to 65 years, and different educational levels from (8 to 22 of education). The subjects were enrolled at the Neurology outpatient service of the teaching Hospital Gafre e Guinle from the Federal University of the state of Rio de Janeiro (HUGG/UNIRIO) and at the multiple Sclerosis unit of the neurology service of Hospital da Lagoa. All MS patients were diagnosed according to McDONALD criteria for definite MS (2001), by a neurologist. The control group with healthy subjects was paired to the MS group according to gender, age and educational level. All subjects in the sample, MS patients and healthy controls were submitted to a brief neuropsychological assessment. The brief neuropsychological battery comprised 4 tests: Rey Auditory Verbal Learning Test, Hooper Visual Organization Test, COWAT, Symbol Digit. Both Beck inventories, for anxiety (BAI) and depression (BDI) were also applied to the sample. Results: The final sample comprised 91 subjects (53 RRMS, 14 PPMS and 24 BMS) and 91 healthy controls. Frequency rates of cognitive dysfunction in the RRMS group was 13%; in PPMS, 50% and in BMS, 38%. The most impaired cognitive functions in the RRMS group were: attention span, information speed processing, followed by verbal fluency. In the PPMS group nearly all cognitive functions were impaired, on different levels. In BMS, attention span, information speed processing and long-term memory showed some degree of impairment. Average time subjects took to conclude BNB was significant to PPMS and BMS groups. Conclusions: BNB is sensitive to detect frequency of cognitive dysfunction in the 3 clinical forms of MS and it could discriminate the most impaired functions of each clinical form. PPMS patients showed more impairment than RRMS; whereas BMS presented more impairment than the RRMS patients. The brief neuropsychological battery was as efficient as its comprehensive version to detect cognitive decline in MS. Keywords: Cognition, Neuropsychological battery, Multiple sclerosis

higher risk. A natalizumab pharmacovigilance program has enabled risk stratification for MS patients included in treatment. Objective: We analyzed JC virus (JCV) test results and the initial results from an MS patient cohort who failed to respond to interferon beta (IFN-beta) and glatiramer acetate (GA) treatment. Results: This recent independent study on response and nonresponse to IFN-beta and GA in a cohort of MS patients, using the criteria of Rio et al, showed that the rate could range from 3.3% to 42.9%. Women accounted for 73%, and the median age was 36.14 years (minimum 18 and maximum 53 years 9.7). These patients were screened for natalizumab treatment. So far, 23 patients have undergone JCV testing and 52.2% were antibody-positive. Two of them had previous histories of immunosuppressive treatment. Out of the total of 132 infusions, the median EDSS at onset was 4.9 and the median EDSS after natalizumab treatment was 3.7. None of the patients presented new relapses or adverse events after treatment onset. Discussion: The high frequency of positive findings of JCV antibodies in the present study is similar to the results from other studies. These tests may contribute towards closer monitoring of progressive multifocal leukoencephalopathy (PML) risk, and have encouraged us to include patients, even if they are positive to JCV antibodies, who present high disease activity and fast evolution to greater severity of disability. The decrease in EDSS level of at least one point among these patients and the suppression of new relapses was remarkable. The patients who were JCV antibodypositive were monitored using clinical and MRI criteria.
A59 Gastrointestinal Tolerability Events in RelapsingRemitting Multiple Sclerosis (RRMS) Patients Treated with Oral Bg-12 (Dimethyl Fumarate) in Define and Confirm Bar-Or, A.,1 Selmaj, K.,2 Gold, R.,3 Fox, R. J.,4 Havrdova, E.,5 Kurukulasuriya, N. C.,6 Pace, A.,6 Novas, M.,6 Meltzer, L.,6 Hotermans, C.,6 Dawson, K. T.,6 Phillips, J. T.7 1Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; 2Medical University of Lodz, Lodz, Poland; 3St Josef Hospital, Ruhr University, Bochum, Germany; 4Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA; 5Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 6Biogen Idec Inc., Weston, MA, USA; 7Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA Objective: To characterize gastrointestinal (GI) adverse events (AEs) in RRMS patients treated with BG-12 twice daily (BID) in Phase 3 studies. Methods: Incidence, nature, severity and management of GI AEs (by manual review of indications of concomitant drugs and timing vs AEs) were summarized for patients treated with BG-12 240 mg BID vs placebo in DEFINE and CONFIRM, focusing on Months 03 (when GI AE incidence was highest). Results: 769 patients received BG-12 and 771 placebo, 70% and 65% completing 2 years of treatment, respectively; GI AEs were reported by 40% vs 31% patients overall, and 41% vs 34% who completed 2-year treatment, respectively (sensitivity analysis). The incidence of GI AEs was highest in Months 03 (27% BG-12
A58 Frequency of positivity in JCV testing in a cohort of MS patients and follow-up after natalizumab treatment Soniza Vieira Alves-Leon, Fabola Rachid Malfetano, Isabella D Andrea Meira, Valria Coelho Santa Rita Pereira, Letcia Fzer, Simone Batista, Gisele Alexandre Loureno, Sandra Maria Garcia de Almeida Clementino Fraga Filho Hospital - Federal University of Rio de Janeiro; Federal University of the State of Rio de Janeiro The criterion of responders versus non-responders to immuno modulatory treatment among multiple sclerosis (MS) patients has contributed towards switching to more efficacious treatments. However, drugs with greater efficacy have been associated with

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vs 17% placebo patients), most commonly (5% BG-12 patients) nausea, diarrhea, upper abdominal pain, abdominal pain or vomiting (9196% of events assessed as mild/moderate severity, 9396% resolved). In Months 03, 3% BG-12 vs <1% placebo patients discontinued treatment due to GI AEs, and 11% vs 4% had GI AEs that required symptomatic therapy, most commonly (>5 patients each) omeprazole, paracetamol, ranitidine, metoclopramide, domperidone or loperamide (efficacy not assessed). A60 -CSF enhances Foxp3+ T lymphocytes and modifies the proinflammatory response in Experimental Autoimmune Neuritis Fernando Pradella1,2, Adriel S. Moraes1,2, Mariana P. A. Santos1,2, Rosemeire F. O. DePaula1, Karina Y. Degaki3, Ana Leda F. Longhini1, Vania D. R. Silva1, Leonilda M. B. Santos2, Alessandro S. Farias1,2 1Neuroimmunomodulation Group. and 2Neuroimmunology Unit, Dep. Genetics, Evolution and Bioagents, University of Campinas, Campinas, SP, Brazil; 3Dep. Histology, University of Campinas, SP, Brazil Introduction and Objective: Guillain-Barr Syndrome is a human peripheral nervous system acute inflammatory disease. The disease may culminate in paresis of the whole patient body or even in its death. Experimental autoimmune neuritis (EAN), due to its wide range of similarities with GBS, the majority of scientific knowledge we have about this disorder was provided by studies in the animal model. The granulocyte-colony stumulating factor (G-CSF), has been reported to redeem an efficient role over T cells generation process. In the present study, we evaluated the effect of the treatment with G-CSF on the modulation of immune system of EAN model induced Lewis rats. Methods: EAN was induced by injection of P2 peptide in CFA. CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ T cells were quantified by flow cytometry; cytokines, transcription factors and BDNF by qPCR. Results: Short-term treatment with G-CSF significantly the severity of EAN. The protective effect of the treatment is accompanied by increasing number of CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ T cells. Moreover, The G-CSF treatment reduces the proinflammatory cytokines and transcription factor in the lymph nodes of treated animals. Interestingly, G-CSF treatment increases anti-inflammatory cytokines such as IL-10, TGFb as well as BDNF. Adoptive transfer of neuritogenic T lymphocytes cultured in the presence of this cytokine caused a less severe disease than control group. Conclusion: These results may be explained by the increase of Foxp3+ expression in CD4+ and CD8+ T lymphocytes after treatment. Moreover, the increased expression of BDNF suggests that the G-CSF acts simultaneously as anti-inflammatory and neuroprotective agent in the EAN model. Financial support: FAPESP, CNPq and CAPES. A61 Gender Related Differences in Atrophy and Lesion Load in Multiple Sclerosis Patients in Buenos Aires, Argentina JI Rojas1, L Patrrucco1, C Besada2, E Cristiano1
1MS Center, Hospital Italiano de Buenos Aires, Argentina;
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2Neuroradiology Center, Hospital Italiano de Buenos Aires, Argentina
Introduction and objective: Previous studies showed genderassociated clinical and MRI differences in multiple sclerosis (MS) evolution. However, only few studies were done with non conventional MRI techniques and no one was done in a South American MS population. The aim of this study was to investigate gender differences according to nonconventional MRI measures in patients with MS from Buenos Aires, Argentina. Methods: Relapsing-remitting MS patients (RRMS) with at least 6 years of follow up and an MRI at onset and at 6 years were included. Patients were assessed using nonconventional MRI measures: total brain volume (TBV), neocortical grey brain volume (GBV), white brain volume (WBV), lesion load (LL), % of brain volume change between onset and year 6 (% BVC) and regional brain volume change. Gender-related MRI differences were investigated using general linear model analysis. Results: 45 patients were included (25 female). Mean follow up time was 7.3 0.2 years. No differences in age, EDSS at onset, DMD treatment, TBV, GBV, WBV neither LL were found between gender at baseline. Six years later, males showed a decrease in TBV (p=0.002) and GBV (p=<0.001) and an increase in LL (p=0.02) and % BVC (p<0.001) vs. females. Female patients showed a decrease in the volume of frontal subcortical region. Conclusions: This is the first study showing differences in brain volume changes between gender in MS patients from South America. Future studies will confirm our initial findings. A62 Genetic variability in Peruvian patients with relapsing remitting multiple sclerosis, using STR markers DYS390, DYS391, DYS392 Y chromosome Cordova-Ruiz, M, Pectrims - Lima - Peru Objectives: To determine the allele and haplotype frequencies of STR markers DYS390, DYS391 and DYS392 in a group of Peruvian patients with relapsing remitting multiple sclerosis. Material and Methods: The group of patients with relapsing remitting multiple sclerosis, was comprised of 15 males (mean age 32.6 years, mean EDSS: 4.5) and 15 women (mean age 28.0 years, mean EDSS: 6.5). Patients came different regions of the country (considererndola a mixed sample). All patients were of mixed race. DNA was isolated from leukocytes with isoamyl Cloroformoalcohol. PCR amplicons were visualized obtained in 4% polyacrylamide gels, urea 7M, tris-borate-EDTA. We designed boxes haplotype frequencies (8 and 20 South American world). Was assessed with the statistical program HARLEQUIN and graphing of interpopulation genetic distances (UPGMA) with MEGA. Results: In the population sample (n = 30), presents DYS390 alleles 22 (0.049) 23 (0.39) 24 (0.440) 25 (0.101), DYS391 allele 10 (0.849) 11 (0.102) , 12 (0,048) 11 DYS392 alleles (0.049) 12 (0.249) 13 (0.399) 14 (0.299). The level of genetic diversity Allele frequencies for the three STR was: DYS390 +0,0548 = 0.6568; DYS391 +0,1244 = 0.2778 and 0.7201 DYS392 = +0,0506. A level of haplotype frequencies, we obtained a gene diversity index of 0.8841 +0,0538, taking 11 of 83 different haplotypes reported worldwide. Conclusions: We found significant differences (differentiation test) between the STR allele frequencies for DYS392 and published
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for the Amerindian population (general population genetic characteristics). The study population would differ from the other South American (general population genetic characteristics). The study population have more genetic similarity with Asian populations (general population genetic characteristics). It was not possible to compare our findings with other groups of patients with relapsing remitting multiple sclerosis from other Latin American countries of this continent, as we found no publications. A63 Geographical distribution of patients with multiple sclerosis treated with immunomodulator at public healthy system in Chile, 2008-2012 P. Agurto Merino.1, L. Acevedo Gonzlez1,R. Aracena Cont1, J. Nogales-Gaete1,2 Neurology Service, Barros Luco Hospital, Santiago, Chile; 2 Neurologys South Department, Universidad de Chile Introduction: The Center of National Reference of Multiple Sclerosis (Hospital Barros Luco, South Metropolitan Health Service, Santiago Chile) evaluates all beneficiary patients of the public health system of Chile, candidates to receive treatment with immunomodulators. All patients have theoretically equal access to this program. Objective: To describe the geographical distribution of patients beneficiaries of the public health Chilean system, in immunomodulator treatment. Methods: The rates of patients in immunomodulatory treatment beneficiaries of public health system, was calculated per 100,000 habitants. Results: At July 31-2012, there were 314 cases on treatment distributed from Arica to Magallanes, except Tarapac (Lat. 20S). 102(32.5%) cases were males and 212(67.5%) cases females. The national rate was 1,89 x 100.000 habs, with 0.96 of standard deviation. The higher rates were located in regions XI (lat. 45S) and XII (lat. 53S), followed by VIII (lat. 36S), IX (lat. 38S) V (lat. 33S) and Metropolitan (lat.33S). Surprisingly, the VIII region (uble Province, lat 36.4S) had a high rate (3.24). Conclusions: The national rate of 1, 89 is lower than the estimated prevalence of 14 x 100.000. This difference may be explained by the selection of patients that qualified for inmunomodulator treatment for this Program. We are amazed by the absence of cases derived from the I Region (lat. 20S), where count with neurologists and MRI; and the presence of a higher rate in Chilln. Although the patients distribution did not evidence a latitudinal gradient, there was a clear increase in rates of the regions below latitude 40 south. A64 Hemifacial Spasm as the First Clinical Manifestation of Multiple Sclerosis Arnoldo Soto1, Marisol Gallardo2 From Service of Neurology, Hospital Domingo Luciani, Caracas1; Service of Neurology, Centro Mdico Docente La Trinidad, Caracas, Venezuela2

Objetive: To describe a patient who was referred to our service with a diagnosis of RRMS with hemifacial spasm as the first clinical manifestation of the disease. Methods: We evaluated a patient with a diagnosis of RRMS Sclerosis who presented hemifacial spasm as the first clinical manifestation of the disease. Clinical history, physical examination and routine laboratory test were performed. Brain and cord MRI, CSF analysis and immunological test also were performed. Results: A 54 year-old woman developed hemifacial spasm followed two weeks later by weakness and parestesias of the upper left limb and lower limbs. Except for the hemifacial spasm the symptoms disappeared 4 months later. She received botulinum toxin as the only treatment for the hemifacial spasm. Six months later she presented gait difficulty, lower limb weakness, dizziness and urinary incontinence and a diagnosis of RRMS was made. The patient consulted our service in November 2008. Her physical examination showed paraparesia, deep sensory impairment in lower limbs and decreased sensation below the level T8-T9. Deep tendon reflexes were increased in lower limbs and left Babisnky Sing was observed. Mild gait ataxia was also observed. Brain MRI showed FLAIR and T2-weighted high signal lesions in periventricular areas and corpus callosum. A new Brain MRI test was performed demonstrated new FLAIR and T2-weighted high signal lesions in both cerebral hemispheres. Visual evoked potential was normal and CSF analysis was normal. The Immunological evaluation was normal. Conclusions: Movement disorders associated with multiple sclerosis occurs infrequently. They could be caused by demyelinating lesions in the basal ganglia. The case we are describing shows that hemifacial spasm could be the first clinical manifestation of Multiple Sclerosis. P.S: A video of this patient will be available. A65 High frequency of HLA allele DRB1*0301 among Brazilian NMO patients from Rio de Janeiro (Brazil) Hospital Federal da Lagoa, Alvarenga, M.P., Levya, L., Vasconcelos, C.F., Campanella, L., Cruz, G, Alves-Leon, Soniza, Papais-Alvarenga, R.M., Fernandez, O The aim of this study was to analyze the HLA class II alleles in an extensive series of NMO patients with relapsing clinical course from Rio de Janeiro (Brazil) to clarify the pattern of genetic predisposition or whether it is possible to determine different specific alleles of susceptibility or resistance. Method: DNA samples from 64 patients [64% Afro] with NMO (2006) from Rio de Janeiro (Brazil) were collected and sent to Research Laboratory of Carlos Haya Hospital in Malaga (Spain) to be genotyped. A case control study was done comparing the HLA class II alleles of NMO with 103 healthy controls from RJ [44% Afro] also genotyped in Malaga. The data entered was analyzed with SPSS. Allelic frequencies in patients and controls were calculated by direct counting, and the significance of the association was determined using the Chi-square test (p <0.05) and applying the Bonferroni correction (Pc) Results: Were identified 30 alleles for the HLA-DRB1 locus, 12 alleles for HLA-DQA1 locus and 16 alleles for the HLA-DQB1 locus and 34 haplotypes One haplotype and four HLA alleles showed higher frequencies in the NMO than in controls, DRB1*0301 [P

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= 0.042], DRB1*0102 [p= 0.011]; DRB1*1104 [P = 0.027] and DQA1*0105: [P = 0.008] but the statistical significance was lost after Bonferroni correction. None HLA class II allele of DR2 haplotype showed a significant association with the disease. Conclusion: NMO patients had a high frequency of HLA allele DRB1*0301 (39.9%). but this allele was detected in 24% of the controls and the statistical significance not resist to correction by total number of alleles. Previous studies on NMOsd also showed high frequency of the DRB1* 03 allele in Caucasian French (22%), Caribbean (26%), and Brazilian mulattos AQP4 + from Ribeiro Preto (25%). A66 Cognitive influence on walking of Multiple Sclerosis patients in the absence of clinical disability Leandro Alberto Calazans Nogueira; Luciano Teixeira dos Santos; Pollyane Galinari Sabino; Regina Maria Papais Alvarenga; Luiz Claudio Santos Thuler Objective: The purpose of this study was to analyse the cognitive influence on walking of Multiple Sclerosis (MS) patients in the absence of clinical disability. Methods: A case-control study was carried out with 12 subjects diagnosed with MS with no disability and 12 matched healthy controls, based primarily on gender and age, followed by an agreement between subject pairs in height, weight, and physical activity level. Twelve subjects diagnosed with MS (average age: 30.6 years, average height: 168 cm, average mass: 67.17 kg, gender: 9 females and 3 males, average IPAQ: 3221.75) and 12 healthy control subjects (average age: 33.2 years, average height: 169 cm, average mass: 68.17 kg, gender: 9 females and 3 males, average IPAQ: 3874.62) participated in this study. The subjects were referred for completion ten meters timed walk test, and 3D kinematic analysis. Participants were instructed to walk at comfortable speed, dual-task (arithmetic task) condition, and also the motor planning was measured by mental chronometry. Results: Scores of walking speed and cadence showed no statistically significant differences between the groups in three conditions. Dualtask condition showed an increase of double support duration in both groups. Motor imagery analysis showed statistically significant differences between real and imagined walking in MS patients. Conclusion: MS patients with no disability did not show any influence of divided attention on walking execution. However, motor planning was overestimated compared to real walking. A67 Identifying Pain In Multiple Sclerosis: Preliminary Results From A Study In A Tertiary Center Jos Vinicius M Silva , Joo Gabriel Dib, Vitor A. Kosac, Andre PC Matta, Osvaldo JM Nascimento Federal Fluminense University (UFF), Niteri, Brazil Introduction: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disease, which affects exclusively the central nervous system. Pain is not a usual initial manifestation (1% of cases). Nevertheless, as the disease progresses, episodes of pain become more and more frequent, with a prevalence
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of up to 80% of the affected population. Objectives: to evaluate the prevalence of algic symptoms in MS patients, and the different ways they evolve; describe the most frequent types of pain in the sample. Methodology: Cross-sectional, descriptive study of 100 consecutive MS patients patients from the Neuroimmunology service of the Antonio Pedro University Hospital (UFF), regardless the evolution, following revised McDonald criteria (2005). Pain will be characterized by semi-structured anamnesis, and classified as nociceptive (somatic or visceral), neuropathic or mixed. Cephalalgias will be studied separately. Pain intensity will be assessed with the 10-point visual scale. Exclusion criteria will be used: other known neurological diseases, peripheral neuropathy, cancer, chronic kidney disease, diabetes mellitus. Preliminary results: From the time this paper was written, fiftyone MS patients were evaluated. Females were majority (85%). Mean age was 47 years. Relapsing-remitting was the most common subtype (65%). Only one-fourth of patients had no complaints about pain. Nociceptive pain was the most prevalent (50%), of which lombalgia was the main complaint (50%), followed by headaches (45%) and trigeminal neuralgia (8%). Lhermittes Sign has been reported in 16 patients (31%). Conclusion: Data analysed until now are similar to the existing in the literature. The present study will follow in the next 6 months, when the final results should then be presented. A68 Idiopathic inflammatory demyelinating diseases of the CNS in Cuba Alina Gonzlez-Quevedo, MD, PhD*, Jos A. Cabrera Gmez, MD, PhD ** * Institute of Neurology and Neurosurgery, Havana, Cuba; ** MS Clinic of the International Center for Neurological Restoration, Havana, Cuba Objective: To describe the available information on the frequency of idiopathic inflammatory demyelinating diseases (IIDD) of the CNS in Cuba. Method: PubMed/ MEDLINE and the database of the Scientific Electronic Library Online (SciELO) were reviewed, as well as printed and electronical versions of journals available in libraries. Results: The epidemiological studies of MS which have been conducted in Cuba have shown a prevalence ranging from 10 to 25.5/100,000; although there are regions with higher frequencies (50/100,000), such as the municipality of Placetas in the province of Villa Clara. A nation-wide case ascertainment for NMO conducted in 2003 revealed a prevalence rate of 0.52 per 100,000 (95 % CI 0.390.67), and an estimated average annual incidence rate of 0.053 per 100,000 with no differences by ethnicity. Epidemiological studies for other diseases included in the spectrum of inflammatory idiopathic demyelinating diseases of the CNS were not available. Conclusions: The existing data suggest that among the IIDD of the CNS, MS is the most frequent in Cuba; but the use of the most recent diagnostic criteria for MS, NMO and ADEM and the design of national epidemiolgocial studies are required in order to establish the epidemiological profile of IIDD.
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A69 - Oral presentation Idiopathic Inflammatory Demyelinating Diseases: A Venezuelans Experience Dra. Ibis Soto Maracaibo University Hospital, VECTRIMS Group Objjective: To describe the spectrum of Idiopathic inflammatory demyelinating diseases (IIDDs) in Venezuela Material and Methods: We reviewed journal the idiopathic inflammatory demyelinating diseases records at the public hospitals, Maracaibo University Hospital, Caracas University Hospital and Childrens Hospital JM de los Rios, in 2011 period. These are referral centers for neurological diseases of the Western and central region of the country, which represent the most densely populated regions, Maracaibo with 3.000.000 citizens and Caracas(Metropolitan area) with 2.200.000 citizens and nearby towns. Results: 247 patients were quantified from of records from HUM, 129 and 118 records of patients from CUH and Children H JM Rios. The main decade of birth date 1970-1979(n= 85, with 34.4%) and the decade 2000-2009 (n=66 with 26.7%). Gender: women (n=165 with 66.80%) and men(n=82 with 33.19%). Ethnicity: White (n=17 el 6.88%),Afro-Americans.(n= 11, el 4.45%) mestizos (n=214 en 86.63%), Indians (n= 5, el 2.02%) The decade of the first outbreak was between 2000 and 2009(n =166, el 67.29%). The EDSS in the 2011 most significant was 0.0 at(n=68, with 27.53%), followed by 3.0 (n= 25 with 10.12%. Were ranked in demyelinating disease categories: 1. Rare and acute (n=2 with 0.8%), 2.ADEM (n= 57,with 23.00% ) , 3.CIS (n=10 with 4.04%) 4. EM (n= 92 with 37.24%), 5.NMO (n=92 with 20.64%) , 6. Other syndromes NMO (n= 35 with14.17%). It also made a specific diagnosis: Pseudotumoral form (n=2 with 0.80%); Marburg disease 0, Ballo disease 0; monophasic ADEM (n= 44 with17.81%); relapsing ADEM (n=14 with 5.66%), monofocal CIS + ON (n=4 with 1.61%); monofocal CIS+ brain stem syndrome (n= 2 with 0.80%); monofocal CIS + medullary syndrome(n= 2 with 0.80%); multifocal CIS (n=1 with 0.40%); RRMS (n= 79 with 31.98%); SPMS (n=12 with 4.85%); PPMS (n=3 with1.21%); monophasic course NMO(n=8 with 3.23%) ; relapsing NMO(n=43 with 17.40%); optic spinal MS 0; bilateral relapsing optic neuritis (n=6 with 2.42%) ; acute monofasic ATM (n=11 with 4.45% ); relapsing ATM(n= 6 with 2.42%); ATM +brain stem syndromes 0, ATM with encephalopathy 0, ON brainstem syndromes (n=10 with 4.04%); ON encephalopathy 0. These patient underwent diagnostic tests: magnetic resonance imaging (MRI) of the brain in (n=237 with 95.05%); Cervical and Dorsal RM (n=185 with 74.89%); CSF study in9n=186 with 75.30%); AQP4 Antibodies (n= 12, with 4.85%) were positive; negative (n=30 with 12.14%)ve and not done in (n=205 with 82.99%) not done. Conclusion: These studies show the high frequency of the NMO Complex compared with MS and the others IIDD and give an idea of the number of patients with this disease in a population in Venezuela. Indian people can suffer the disease to. A70 Immunologic markers Vs. Therapeutic handling of Multiple Sclerosis during childhood T. Saad, A. Penna e Costa, E. Magalhes, C. Quero, D. Santana, A. Bastos2, De Azevedo L 1Clnica Professor Pompeu, 2IFF-FIOCRUZ/Neuropediatria

Introduction: Multiple Sclerosis (MS) rarely occurs in Pediatrics. Nevertheless, the number of reports during childhood has increased due to the access to magnetic resonance imaging (MRI) and to further comprehension of physiopathology. Some differences are being observed in clinical presentation and evolutive course. Immunomodulatory treatment has been a challenge. Therefore, the search for immunologic markers may contribute to the selection of therapeutic strategy and assessment of efficacy. Objective: Case report of a child with Multiple Sclerosis since 20-month old, on Betainterferon for a year, with clinical, image (MRI), lymphocytic panel and cytokine level follow-up. Case Report: LBA, presented with gait ataxia on 20 months. Brain MRI presented nuclei terminals mielynation. On 25 months, head ataxia and right crural monoparesis. Demyelinating lesions in corona radiata and cerebellar peduncles. Asymptomatic after methylprednisolone. Extensive differential diagnoses was carried on. At 3 years old, relapsed with a new ataxia episode, and hearing loss. OCB was positive in CSF. Gait recovered after steroid pulsotherapy, maintaining hearing loss. Started Betainterferon1A 44 mcg 0,25 ml SC. B-Lymphocytes population raised, without image improvement, so Interferon dosage was decreased with better results. Besides high signal T2 cerebellar lesion maintained, therapeutic failure was not considered, once was clinically assymptomatic and therapeutic resources are exiguous for this age. Conclusion: MS admits a ranger rate of relapses, greater severity and most limiting sequelae in childhood relating to adults. The smaller the child, the greater the differential diagnosis. This may require long time follow up and search for immunological markers in order to support the clinical diagnosis, and also attempt to possibly enable an personalized therapeutic approach. A71 In vivo administration of TLR agonist reduces the severity of Experimental autoimmune encephalomyelitis. The role of plasmacytoid dendritic cells and B lymphocytes Mariana P. A. Santos1, Ana Leda F. Longhini1, Rosemeire O. de Paula1, Fernando Pradella1, Adriel S. Moraes1, Elaine C. Oliveira1, Felipe von Glehn1, Alessandro S. Farias1, Leonilda M.B. Santos1 1Neuroimmunology unit, Dept. Genetics, evolution and bioagents, Institute of Biology; University of Campinas Campinas- SP Brazil Introduction and Objective: The effect of in vivo administration of ODN-CpG was evaluated in the experimental autoimmune encephalomyelitis (EAE), an experimental model for studying multiple sclerosis. ODN-CpG is an agonist of the TLR 9, which is express in plasmacytoid dendritic cells and B lymphocytes. Methods: EAE was induced in C57Bl/6 mice by MOG3555 peptide in CFA. ODN-CpG was administrated in five consecutive doses (5-10 days after immunization). CD4+CD25+Foxp3+ T cells were quantified by flow cytometry and cytokines by qPCR. Results: The in vivo administration of ODN-CpG reduces significantly the severity of EAE, as well as the proliferative

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response of autoreactive T cells, which can be reversed by the depletion of plasmacytoid dendritic cells. The protective effect of the treatment is accompanied by increasing number of CD4+CD25+Foxp3+ T cells and expression IDO in the PDC. The administration of ODN- CpGsignificantly increase the expression of anti-inflammatory cytokines, such as IL-10 and TGFb, as well as the interferon both type I and II, with no significant changes in the IL-17 level. This treatment also stimulated de immunosuppressive effect of IL-10-producing B lymphocytes. The suppressive effect of both pDCs and B lymphocytes was confirmed by adoptive transfer of these cells, which resulted in significant reduction of severity of EAE. Conclusion: The data provide here suggest that in vivo administration of CpG, an agonist for TLR 9 activate the tolerogenic activity of plasmacytoid dendritic cells and B lymphocytes with a consequent reduction of the severity of EAE. Financial support: FAPESP, CNPq and CAPES A72 Infusion of Natalizumab in Multiple Sclerosis:Experiment realized at the Lagoa Hospital in Rio de Janeiro Carolino, F.S, M. Papais Alvarenga, Santos,G., Alvarenga, R.M.P4 Local: Universidade Federal DO ESTADO DO RIO DE Janeiro-UNIRIO Introduction: Natalizumab (NTZ) is the only monoclonal antibody released by FDA since 2004 to be used to treat relapsing remitting multiple sclerosis (RRMS),which was included in 2011 between the drugs dispensed by the Brazilian Health Ministry for the treatment of RRMS with treatment failure, inhibiting leukocyte migration through the hematoencephalic barrier. Efficiency demonstrated in the reduction of the disease activity and frequency of the outbreaks, is administered intravenously (IV) once every 28 days. Objective: Describe the occurrence of adverse events during the infusion of NTZ. Methodology: Retrospective study during 07/10/10 and 10/05/12, acquired in patients with RR and SP form in treatment with NTZ.Infusions were performed in the Hospital Federal da Lagoa (HFL) in monitored patients and with previous administration of promethazine, metocloropramina and omeprazol, all of them orally (protocol in that period). Results: From 23 patients,18 EMRR e 5 EMSP forms, 32% blacks and 68% white, aged between 16 and 47 years old; 18 are female. The number of infusions ranged between 1 up to 28. Infusion reaction occurred in 1 patient during the 12th infusion, after unfounded 33ml of solution; the patient reported feeling tightness in the throat and coughs, vital signs were kept stabilized. The procedure was to interrupt and administer hydrocortisone and diphenhydramine IV and than restart the infusion. Conclusion: The protocol of pre-medication in the HFL to IV. It appears that the infusion of NTZ is safe, when the observation of the standardization and systematization procedures is maintained. A73 Insulin resistance is associated with disability in multiple sclerosis patients Sayonara Rangel Oliveira, Ana Paula Kallaur, Andra Name Colado Simo, Helena Kaminami Morimoto, Damacio Ramn
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Kaimen-Maciel, Wilda Lice de Carvalho Jennings, Josiane Lopes, Edna Maria Vissoci Reiche State University of Londrina The aim of this study was to evaluate the inflammatory and metabolic parameters in multiple sclerosis (MS) patients, including the prevalence of insulin resistance (IR) and to verify the association between these markers and the clinical disability assessed by Extended Disability Status Scale (EDSS). The study enrolled 110 relapsingremitting MS (RR-MS) patients and 175 healthy individuals. The metabolic and inflammatory markers evaluated in the serum were lipid profile, insulin, glucose, high sensitivity C reactive protein (hsCRP) and inflammatory cytokines, such as tumor necrosis factor alpha (TNF-), interleukin-6 (IL-6), interleukin-17 (IL-17), and interferon-gamma (IFN-). IR was evaluated by homeostasis model assessment (HOMA-IR). All of the RR-MS patients were in the remission clinical phase and were not using corticosteroid. The patients presented higher serum levels of LDL-cholesterol (p=0.010), triglycerides (p=0.025), insulin (p<0.0001), IL-6 (p=0.002), IL-17 (p=0.037), IFN- (p=0.031), and a significant decrease of serum levels of HDL-cholesterol (p=0.020) than controls. There were no differences significant with regard to the serum hsCRP and TNF- levels. MS patients showed higher prevalence (40.0%) of IR and presented 2.48 times more chance for developing IR than controls. Furthermore, an association was observed between EDSS and serum levels of insulin (p=0.024) and HOMA-IR (p=0.030). MS patients with IR showed higher EDSS (p=0.031), hsCRP (p=0.005), IL-6 (p=0.028), and IL-17 (p=0.006) than MS patients without IR. The results suggest that IR can be correlated with progression of disease and should be monitored to prevention or to treat future cardiovascular comorbidities in these patients. Financial support: Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); State University of Londrina (PROPPG); and Bayer HealthCare. A74 - Oral presentation Inter- and intragenerational study of MS familial cases in a reference center in the city of Rio de Janeiro M. Bernardes, R. Papais-Alvarenga, F. Costa-Pereira, C.L. Anto-Paiva, M. Papais-Alvarenga, E. Batista2, C. Vasconcelos, S. Camargo2 1UNIRIO; 2Hospital da Lagoa Objective: To describe clinical and demographic characteristics of multiple sclerosis familial form in brazilian patients. Methods: A survey for familial forms was conducted in medical records of 810 MS patients, followed from 1995 to 2012, in Hospital da Lagoa (Rio de Janeiro) . Familial cases were classified into 3 groups: first-degree just first-degree relatives; multiplex different degrees relatives in a single family; second/third degree only second- or thirddegree kinship. We analyzed gender, race, clinical course, disease duration, age-of-onset and last evaluated EDSS (LEDSS), comparing groups and generations. Results: We found 54 familial cases: 29 first-degree (53,7%), 11 multiplex (20,4%) and 14 second/third-degree (25,9%), all concerning to collinear pairs (25 siblings/ 13 cousins), predecessors (04 parents/02 aunt/01uncle) and successors (05
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daughters/03 nieces). LEDSS was significantly lower in firstdegree versus multiplex (medians: 2,0 vs. 6,0, p = 0,032). In inter- and intragenerational analysis, LEDSS was significantly higher for predecessors compared to successors ( medians: 7,0 vs 1,5 , p = 0,002) and collinear (2,5 , p = 0,006). Predecessors disease duration was longer than successors (26,0 vs. 13,83 yr, p = 0,014), trending to overcome collinear (15,83 yr, p = 0,57). No differences were observed between the groups related to other variables. Conclusion: This study suggests MS familial forms in brazilian patients show different disability burdens regarding the degree of kinship considered, being more benign for first-degree collinear relatives. A75 - Oral presentation Demyelinating Disease: Prevalence of clinical presentation & demographic characteristics, Project Latam Dra. Adriana Carr, Curbelo Celeste, Martinez Alejandra, Steinberg Judith, Rojas Galeno Hospital Britnico de Buenos Aires, Argentina Introduction: Geographically MS describes three frequency zones. Prevalence studies provide our best information on the distribution of disease and a better understanding of MS in South America would help us to identify different disease pattern in our population. In Argentina, the capture-recapture assessment of MS risk in Buenos Aires demonstrated a rate of 18/100000 inhabitants. However other demyelinating disease should be considered within de distribution and risk of presentation. Objectives: To describe the frequency of consulting in a specialized centre; to analize clinical and demographic characteristics of the cohort, and to identify other epidemiological factors associated with all different forms of presentation. Methods: 124 patients were evaluated between JanuarySeptember 2012. Results: Transversal study. Clinical presentation: MS (106); NMO (3); CIS (8); RIS (5); ADEM(2). Age: 7y-70y; Female/81, Male/43; EDSS: 0-8.5; Conclusion: Generally, the risk of MS in African Americans is around half that of Caucasian Americans, and is extremely rare in Africans. Such differences in epidemiology who gets MS may yield clues to the genetic underpinnings of this disease. This report shows that the prevalence of the MS matches the racial characteristics of our populations, what is higher in Caucasian than in individuals of Asian, Mestizos or African origin. NMO was less frequency in our centre than other areas such some cities in Brazil. Further refinements will eventually allow powerful longitudinal studies to assess genetic and environmental interactions with implications for prediction of individual disease susceptibility and clinical course. A76 Interferon Beta and C-Phycocyanin: Molecular mechanisms associated to a new combined therapy for multiple sclerosis Pentn-Rol G1, Cervantes-Llanos M1, Lagumersindez-Denis N2, Llpiz Arzuaga A1, Falcn-Cama V1, Nazabal-Glvez M1, Cintado- Bentez1, Fernndez-Masso JR1, Cabrera-Gmez JA3, Pentn-Arias E1 1Center for Genetic Engineering and Biotechnology (CIGB). Ave 31 e/ 158 y 190, Cubanacan, Playa, Havana City PO Box 6162,

Havana 10600, Cuba; 2Center for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ava 23 e/ 214 y 222 PO Box 430, Havana, Cuba; 3International Center for Neurological Restoration (CIREN) Ave 25 No 15805, Havana, Cuba Email: giselle.penton@cigb.edu.cu; giselle.penton@
infomed.sld.cu
Beta IFN (IFN-b) was the first agent to show clinical efficacy for Multiple Sclerosis (MS) treatment. There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. In neurodegenerative diseases, neuronal and axonal loss is mediated by oxidative stress and excytotoxicity which constitute a final common toxic pathway. Objetives: To study the molecular mechanisms involved in the effect of a new combined therapy: IFN-b plus C-Phycocyanin (C-Pc) in MS. Methods: Peripheral blood mononuclear cells from MS patients were treated with IFN-b and C-Pc. Genes involved with regulatory T cell markers (CD25, Foxp3, IL-10 and TGF-B) were amplified and the CD4+CD25highFoxp3+ subset was measured by flow cytometry. Furthermore, the effect of C-Pc was tested in a monophasic EAE model in Lewis rats and chronic-progressive EAE model in C57BL6 mice. Finally, we compared the mRNA expression profile using Illumina bead-array platform in brain tissue of the EAE- mouse strain C57BL/6 Results: We demonstrated that IFN-b and C-Pc induced regulatory T cells in mononuclear cells from MS patients and in the EAE model, confirming the authenticity of the Tolerance Dominant paradigm in autoimmune diseases. On the other hand, ultra-structural analyses using Transmission Electron Microscopy demonstrated that C-Pc was able to remyelinate axons and the gene expression profile of Microarray studies identified common and specific processes modulated by C-Pc and IFN-b, suggesting the need of a combined MS therapy with two components targeting the main steps of the MS pathogenic mechanism, one related to immune dysfunction and the other directed towards neurodegenerative changes. Conclusion: Our results support a combination IFN-b/C-Pc as strong therapeutic candidate for the treatment of MS. A77 Unusual presentation of acute hemorrhagic leukoencephalitis: a case report Soto, I.1,2, Molina, O.1, Villalobos, V. 2,3, Mora de La Cruz, E. 1,2 and Castillo, M.C.4 1Hospital Universitario de Maracaibo, 2Hospital Clnico de Maracaibo, 3Hospital Militar de Maracaibo, 4Escuela de Medicina Universidad del Zulia. Venezuela. ibissoto@hotmail.
com
Objective: To report a clinical case of a patient diagnosed with acute hemorrhagic leukoencephalitis (AHLE) that initiates with a subarachnoid hemorrhage as clinical manifestation. Method: Clinical description of the case, descriptive analysis of the diagnostic approach and interpretation of laboratory findings, CT and MRI.

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Results: The initial clinical manifestation of the case was a generalized tonic-clonic seizure, associated with subarachnoid hemorrhage. A traumatic etiology or mycotic aneurysm rupture were both initially considered. Laboratory tests showed leukocytosis, maintained during the evolution: both CSF and PCR were negatives for HV, CMV and M. pneumoniae. During the course of the clinical evolution, neurological focalization symptoms and impaired consciousness state were observed. CT and brain MRI showed signs of subarachnoid and intraparenchymal hemorrhage in both hemispheres. The patient was treated with human immunoglobulin EV without favorable response. Conclusion: From the analysis of the clinical case and based on the differential diagnosis, the patient was diagnosed with AHLE, a rare inflammatory disease of the Central Nervous System, of unknown etiology, which is characterized by demyelination, multifocal hemorrhagic necrosis associated with seizures, neurological focalization, disorders of consciousness and coma. At present, the subarachnoid hemorrhage has not been reported as clinical presentation of the AHLE. The described case, and its diagnostic approach, represents an important contribution in the interdisciplinary clinical management of complex cases. A78 Juxtacortical Lesion Volume and Cognitive Performance in Early Onset Relapsing Remitting Multiple Sclerosis Patients L Patucco, JI Rojas, E Cristiano MS Center, Hospital Italiano de Buenos Aires, Argentina Objective: To investigate the relationship between juxtacortical lesion volume and cognitive performance in early onset relapsing remitting multiple sclerosis (RRMS) patients from Buenos Aires, Argentina. Methods: Patients from the MS Center of the Hospital Italiano de Buenos Aires, Argentina were selected. To be included, patients had to fulfill RRMS criteria (McDonald 2005 or Poser), had no more than 3 years from onset (first demyelinating symptom) and no history of cognitive impairment. Once included, brain MRI was performed and juxtacortical lesion volume in T2 and proton density sequences were analyzed. Cognitive performance was evaluated by Paced Auditory Serial Adition Test (PASAT). The relationship between juxtacortical lesion volume and PASAT score was examined using regression analyses. Results: 28 patients were included (64% female), mean age 29.8 3.6 years, mean time from disease onset 1.8 0.7 years. 26 (92%) were on immunomodulatory treatment. Mean juxtacortical lesion volume was 278 189 mm3. After adjusting for covariates, performance on PASAT was negatively correlated with juxtacortical lesion volume (r-0.73 p=0.001). Discussion: We found a strong negative correlation between juxtacortical lesion volume and cognitive performance in early onset RRMS. A79 Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism Brieva L1, Gonzalo H2, Moral E3, Mendive M4, Peralta S2, Guiu B2, Pamplona R2, Portero-Otin M2 1Neurology Department. Hospital Arnau de Vilanova. Lleida.
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Spain; 2Department of Experimental Medicine, PCiTALUniversitat de Lleida-IRBLLEIDA, Lleida, Spain; 3Neurology Department. Hospital Moises Brogi. Barcelona. Spain; 4Neurology Department. Hospital de Cruces. Bilbao. Spain Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. Methods: In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by massspectrometric measurements. Results: The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2 is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehydemediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketalmodified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor (PPAR). Conclusions: The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. A80 Melatonin and immunomodulatory drugs as treatment in autoimmune encephalomyelitis model applied to rats: clinical manifestations and histological changes in central nervous system Jos Alfonso Cruz-Ramos1, Genaro Gabriel Ortiz1, Miguel ngel Macas-Islas2, Fermin Pacheco-Moiss1, Elizabeth Hidalgo Velador1, Elizabeth Quiroz Lpez1, Franchesca RomeroSnchez1, Fernando Corts-Enrquez1 1Laboratorio de desarrollo, envejecimiento y enfermedades neurodegenerativas. Centro de Investigacin Biomdica de occidente (CIBO), IMSS. Guadalajara, Jalisco, Mxico; 2Departamento de Neurologa. Centro Mdico Nacional de Occidente, Unidad Mdica de Alta Especialidad (CMNOUMAE), IMSS. Guadalajara, Jalisco, Mxico. Objective -- Characterize a model of Experimental Autoimmune Encephalomyelitis (EAE) in rats, clinically and histologically. -- Evaluate the effect of melatonin (MEL) in rats with EAE. -- Compare the effect of interferon-1a (IFN -1a), glatiramer acetate (GA) and MEL in rats with EAE.
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available quantitative ELISA kits. OS markers were determined by spectrophotometric methods. Regulatory T cells markers were evaluated at the mRNA level and using flow cytometry. Multidimensional Scaling as a multivariate exploratory technique was used to find similarities or dissimilarities between molecular markers and clinical variables. Results: We found very low levels of TNF-alpha in NMO patients as well as low levels of IL-10 and a marked OS in both DD. Metalloproteinase 9 inhibitor (TIMP1) was identified to have predictive value over the degree of neurologic disability in NMO patients. Moreover, we demonstrated the induction of regulatory T cells as a mechanism of action for both type I IFNs. Conclusions: Our results provide early evidence of the neuroprotective role of TNF-alpha in NMO, is the first report of the study of OS molecular markers in NMO, found a clinicalmolecular correlation and evidenced elements involved in the mechanism of action of type I IFNs being the regulatory T cells induction a significant event in DD.
Figure 1. Score on EAE clinical scale. Methods: EAE was induced in male Sprague Dawley rats. Rats had free access to food and water. Rats were divided into 4 groups with n=6 for each treatment. Rats were monitored daily, EAE was scored on clinical scale 0 to 5, until 21 days after immunization; then rats were sacrificed for histological analysis. Results: Melatonin decreased the severity of encephalomyelitis and delayed the presentation of clinical signs; however, at day 21 the EAE clinical scale for the melatonin group matched the untreated group (see Figure 1). On histological data MEL was less effective than IFN -1a and GA. Conclusion: Melatonin influences the evolution of EAE reducing the severity. However, MEL therapy alone is less effective than IFN -1a or GA.
A82 Monitoring Algorithm for Patients with Multiple Sclerosis that Initiate Therapy with Immunomodulators Zalcman, J.1, Molina, O.1, Leon, R., Ravelo, M.E.1, Soto, I.1 and Soto, A.1 1On behalf of the Venezuelan Committee for Treatment and Research in Multiple Sclerosis - VECTRIMS. Venezuela. jyzalcmanp@hotmail.com Objective: To present and propose an algorithm for clinical following and therapeutic decisions of those patients with Multiple Sclerosis (MS) that initiate therapy with immunomodulators; in order to align and standardize those parameters and criteria taken into account for a clinical approach or a particular treatment decision. Method: Assessment of those clinical approaches on the monitoring of patients with MS under immunomodulator therapy, practiced in specialized centers for the diagnosis and treatment of MS in Venezuela. The methods were compared with those guidelines reported and described internationally. Results: The algorithm that was generated set out steps, clinical evaluations and paraclinical parameters for monitoring patients at baseline, three months and one year under therapy with immunomodulators. The algorithm considers actions in the case of a relapse, torpid or unusual evolution. The possibility of differential diagnosis with other demyelinating diseases and the possibility of non-responders to the therapy with immunomodulators are also considered. Parameters such as, clinical changes, MRI findings in the previous year, relapses rate and EDSS increase, are included as part of the assessment if it is the case of a decision to switch to a second-line treatment option. Conclusion: An algorithm for the following of patients with Multiple Sclerosis that initiate therapy with immunomodulators, enables a consensus on clinical and imaging criteria, aligns parameters used as an evaluation strategy to validate favorable response to that particular first-line therapy and permits the possibility for a timely switch to a second-line therapy.
A81 - Oral presentation Molecular targets involved in pathogenesis and response to therapy of Demyelinating diseases Majel Cervantes-Llanos1, Jose Cabrera-Gmez2, Ruby AlonsoRamrez3, Gregorio Martnez-Snchez4, Carmen ValenzuelaSilva1, Ileana Lopategui-Cabezas5, Pedro Lpez-Saura1, Giselle Pentn-Rol1 1Center for Genetic Engineering and Biotechnology, La Habana, Cuba; 2International Center of Neurologic Restoration, La Habana, Cuba, 3Center of Molecular Immunology, La Habana, Cuba; 4Center for Research and Biological Evaluations, Institute of Pharmacy and Food Sciences, University of Havana, Cuba; 5Higher Institute of Medical Sciences Victoria de Girn. La Habana, Cuba. email: majel.cervantes@cigb.edu.cu Abstract: Multiple sclerosis (MS) and neuromielitis optica (NMO) are demyelinating diseases (DD) of the central nervous system. Immunopathogenic mechanisms of both DD involve cellular and humoral immune response. In MS prevails cellular, rather than humoral immune response as it is the case of NMO where the cellular component is scarcely studied. Objective: Our research refers to molecular parameters associated to the cellular immune response involved in the pathogenesis of both DD, also looked for molecular variables with predictive value of the clinical outcome in NMO and finally, the molecular events involved in the mechanism of action of type I IFNs in MS. Methods: Serum levels of cytokines, chemokines, metallo proteinases/inhibitors were measured using commercially

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A83 Month of birth does not seem to interfere with the prevalence of multiple sclerosis for South American patients at latitudes zero to 40 degrees Yra Dadalti Fragoso, Tarso Adoni, Fiorella Barbagelata Aguero, Sandra Maria Garcia de Almeida, Soniza Vieira Alves-Leon, Walter Oleschko Arruda, Joseph Bruno Bidin Brooks, Adriana Carra, Rinaldo Claudino, Elizabeth Regina Comini-Frota, Eber Castro Correa, Alfredo Damasceno, Benito Pereira Damasceno, Ethel Ciampi Daz, Darwin Vizcarra Escobar, Ana Patrcia Peres Fiore, Clelia Maria Ribeiro Franco, Maria Cristina Baptista Giacomo, Sidney Gomes, Marcus Vinicius Magno Gonalves, Anderson K. Grzesiuk, Jose Luiz Inojosa, Damacio Ramn Kaimen-Maciel, Katia Lin, Josiane Lopes, Gisele Alexandre Loureno, Alejandra Diana Martinez, Mario Oscar Melcon, Nvea de Macedo Oliveira Morales, Rogrio Rizo Morales, Marcos Moreira, Shirlene Vianna Moreira, Celso Luis da Silva Oliveira, Francisco Tomaz Menezes de Oliveira, Joo Batista Ribeiro, Sonia Beatriz Flix Ribeiro, Claudia Crcamo Rodrguez, Liliana Russo, Juliana Safanelli, Kirsty D Shearer, Fabio Siquineli. Objective: To assess the prevalence of MS in relation to patients month of birth, in order to observe any correlation with the latitude. Furthermore, disease progression was also considered in order to assess whether the place of birth had any relation with disease severity. Method: Data were collected from four South American countries (Argentina, Brazil, Chile and Peru). The control cases were males and females of similar ages, born at the same latitude levels. Two-way and one-way ANOVA, linear regression analysis, Pearsons correlation and Students t-test were used to analyze the results. Results: Analysis on data from 1,207 MS patients and 1,207 control subjects did not show any significant variation in MS prevalence in relation to month of birth, irrespectively of the latitude zones evaluated (zero to 10; 11 to 20; 21 to 30; and 31 to 40 degrees). No significant differences exist between month of birth and disease progression. Conclusion: The results from this study show that children born from pregnancies at higher latitudes in South America do not show higher incidence of MS later in life, as is the case with the seasonal pattern observed in the Northern hemisphere. Several other factors, including genetic profiles and infections, may play a more important role in the development and severity of MS in the countries assessed.
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Objective: To investigate the relationship of mood disorders with physical and mental fatigue in multiple sclerosis (MS) patients. Method: 119 MS patients were enrolled in this cross-sectional study. They were assessed using the Expanded Disability Status Scale (EDSS), fatigue severity scale (FSS) and Hospital Anxiety and Depression Scale (HADS), along with the patients`s selfreported feelings of physical and mental fatigue. The sample was categorized into two groups (with and without fatigue) for statistical analysis taking into consideration p-values 0.05. Result: Most of the sample were women (73.9%) with the relapsing-remitting clinical course (72.6%), median EDSS score of 3 (1.25-4) points, median age 42 (29.75-51) years, median length of time with the disease 67 (30-124) months, median fatigue 44 (28-53) points (FSS) and median HADS anxiety and HADS depression scores of 6 (4-10) and 5(2-8), respectively. Anxiety was observed in 44.5% of the subjects, depression in 29.4% and both disorders in 25.2%. Presence of fatigue was associated with anxiety (OR 8.33, 95%CI 2.33-29.75, P < 0.001) and depression (OR 13.6, 95%CI 1.76-105.03, P = 0.002). There were significant associations for physical fatigue (OR 6.13, 95%CI 1.96-19.16, P = 0.001) and mental fatigue (OR5.47, 95%CI 2.42-12.34, P < 0.001) with anxiety and for physical fatigue (OR 4.02, 95%CI 1.12-14.42, P < 0.024) and mental fatigue (OR8.23, 95%CI 2.9123.33, P < 0.001) with depression. Conclusion: Anxiety and depression symptoms are associated with the physical and mental fatigue types in MS patients.
A85 - Oral presentation Multicenter Study to Assess Cognitive and Neuropsychiatric Disorders in Multiple Sclerosis Patients from Latin America -RELACCEM Study: Longitudinal Analysis Fernando Caceres, Sandra Vanotti, Ralph H. Benedict2, RELACCEM workgroup INEBA Insitituto de Neurociencias Buenos Aires; Jacobs Neurological Institute, Buffalo, USA Objective: 1)To describe the study population during the first year of follow-up from the longitudinal phase (LP) 2) to compare the results between the cross-sectional (CP) and LP. Background: Cognitive and psychiatric manifestations of Multiple Sclerosis (MS) are being investigated in Latin American through Relaccem study. Design/Methods: RELACCEM is a cross-sectional and longitudinal multicenter study (14 centers Argentina, Chile, Colombia, Mexico, Uruguay and Venezuela). Present the data from the first stage of the longitudinal phase of 89 Relapsing-remitting MS. Outcome measures: Disease Parameters: EDSS, MSFC; Cognition: MSNQ, BRB-MS, BVMT; Psychiatric: NEOFFI, Beck Inventory (BDI) and Neuropsychiatric Inventory (NPI); Quality of life: Caregiver Burden of Zarit; MusiQol. Results: 66.3% female; EDSS 2.05 (1.44); MSFC z-0.04; 36.2% of patients were impaired in two or more cognitive domains and 34.3% presented neuropsychiatric disorders. During this first year 14 patients presented adverse events and 18 reported relapses. The findings of the longitudinal phase performed worse than the crosssectional phase in Zarit (LP: 32.53 SD11.03; CP: 30.86 SD0.93 p
A84 Mood Disorders and Fatigue among Multiple Sclerosis Patients Josiane Lopes, Edson Lopes Lavado, Ana Paula Kallaur, Sayonara Rangel de Oliveira, Larissa Muliterno Pelegrino, Wilda Lice Carvalho Jennings Pereira, Renato Marques de Andrade, Milton Csar Rodrigues Medeiros, Kleber Edson Kawagoe, Rafael Gustavo de Mello Couto, Rafael William de Souza, Edna Maria Viscossi Reiche, Damacio Ramn Kaimen-Maciel State University of Londrina, Londrina, Parana, Brazil
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0.036) and BDI (LP: 10.60 SD8.35; CP: 8.74 SD8.48 p 0.01). In EDSS and Analogical Fatigue of the LP the results were lower than the results of the CP, but they werent significative. No differences were found on cognitive and psychiatric impairment between groups. Conclusion: The percentage of cognitive and psychiatric impairment remained unchanged throughout both phases of the study. Depression and caregiver burden are the variables that showed the highest decline during the first year of follow-up, followed by physical disability and analogous fatigue. A86 Fatigue and maximal exercise capacity in rrms patients without motor dysfunction H. Alvarenga-Filho, S.R.S Carvalho, R. Dias, C. Vasconcelos, R. Papais-Alvarenga Fatigue in multiple sclerosis (MS) is assessed by subjective and objective methods. This study evaluated fatigue perception through validated scales and cardiopulmonary exercise test (CPET) to evaluate exercise maximal capacity. Objectives: To evaluate patients with recurrent remitting multiple sclerosis (RRMS) without motor dysfunction and controls by CPET; to describe the frequency of perceived subjective fatigue by fatigue severity scale (FSS) and modified fatigue impact scale (MFISfis); to correlate exercise test parameters to demographic, clinical and physical characteristics and fatigue scales. Methods: A case-control study was conducted at the Gaffre Guinle Hospital (RJ, Brazil). The study was conducted by a multidisciplinary team and consisted of interviews, clinical evaluation and neurological examination by FS / EDSS. Patients and healthy controls were matched by sex, age, BMI and physical activity level. Participants performed CPET. All participants answered the Borg scale, FSS, MFISfis. Results: The sample was 27 MS patients and 24 controls. Perception of fatigue was significantly higher in MS patients. At the CPET, patients achieved the criteria for a maximal test. The exercise test results, cardio respiratory and metabolic parameters in MS were comparable to healthy individuals. However, there was a significant statistical difference for heart rate (p=0.0001) and cardiac reserve (p=0,04). Weak correlations were observed between physical activity, oxygen consumption and workload. Conclusion: Subjective tests indicated a high frequency of perception of fatigue, especially in the physical dimension in RRMS patients, differing significantly from healthy controls. Reduced heart rate in RRMS suggesting autonomic dysfunction. A87 Multiple sclerosis in patients of ethnic Shipibo conibo in Peru As Latin America develops adequate epidemiological records, there is a higher incidence and prevalence of MS in mestizos and other ethnicities. Cordova-Ruiz, M1, Sinnet, M2 1Pectrims - Lima Peru; 2Cta Rc Fl Usa Objective: Very little has been studied in Amazonian ethnic groups, such as the Shipibo-conibo (they do not establish marital ties with people outside their ethnicity). We report twelve cases of MS (McDonald 2001) in this ethnic group.

Materials and Methods: Cases were collected: patients Shipiboconibo ethnicity, they was derived to Lima by doctors working in Peruvian cities near the geographical territory of that ethnicity. Epidemilgicas characteristics were established in they. Uptake cases, Period :2002-2010. Results: Case : 12 (female: 8). Average age: 27 years (women: 28.6, males: 23.8). Type of MS: RRMS: 100%. Affected system to debut: Motor only: 33.3% sensitive only: 16.6%, Motor and sensory: 33.3%, NMO: 8.3%, Other: 8.3%. Average of Number of recurrences, EDSS and Time disease at diagnosis: 3.3, 2.0 and 4.3 years. Conlusions: The MS in Latin American native ethnic groups, such as the Peruvian Shipibo-Coniba, has been little explored, but we are finding cases of MS. For the cases presented, we postulate that MS in these ethnic groups, possibly have their own characteristics. Further research is necessary. A88 Multiple Sclerosis in the city of Rio de Janeiro Maria Clinete Sampaio Lacativa, Rogerio Naylor, Marcelo Cagy, Soniza Vieira Alves Leon, Valeria Coelho Santa Rita Pereira, Claudia Vasconcelos, Marcos Papais Alvarenga, Solange Camargo, Elizabeth Batista, Regina Maria Papais Alvarenga Hospital Federal dos Servidores do Estado (HFSE), Hospital Universitario Clementino Fraga Filho (HUCFF), Hospital Federal da Lagoa (HFL) Objective: To establish the prevalence of multiple sclerosis in Rio de Janeiro city, in southeast region of Brazil, with an area km located at latitude 22 54 10 S 43 12 28 W, of 1,171 with a population of 6.323.037 inhabitants (2010) applying the capture recapture method. A previous study (2000) estimated the MS prevalence in RJ in 5/100.000. Method: The medical records were reviewed to identify MS patients living in Rio de Janeiro and alive in 2011 by the neurological team of three Public Federal Hospitals that are reference centers for MS treatment: Hospital Federal da Lagoa e Hospital Federal dos Servidores do Estado (Ministrio da Sade) e Hospital Universitrio Clementino Fraga Filho (Universidade Federal do Rio de Janeiro - UFRJ). Results: Until 09/30/2012 we identified 1026 patients with MS; with these crude data we estimated the MS prevalence in Rio de Janeiro city in 20 /100.000 inhabitants. Conclusion: This preliminary study demonstrates a four-fold increase in the number of patients diagnosed with multiple sclerosis in Rio de Janeiro in the last decade. This increase is certainly related to implementation of reference centres for the treatment of multiple sclerosis in these public hospitals, where high-cost drugs are provided by the Ministry of health. At the end of the study we will applied the capture-recapture method to analyze the MS prevalence. A89 Cerebrospinal fluid findings in a series of cases of Neuromyelitis Optica and Multiple Sclerosis: Primary Progressive and Relapsing Remitting forms Vanderson Carvalho Neri, Carlos Otvio Brando, Claudia Cristina Ferreira Vasconcelos, Marcos Papais Alvarenga,

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Solange Camargo, Elizabeth Batista, Regina Maria Papais Alvarenga Universidade Federal do Estado do Rio de Janeiro-UNIRIO, Neurolife Laboratrios Objectives: To describe the general characteristics of the CSF (cellular, immune and biochemical) in NMO and compare with Relapsing-Remitting Multiple Sclerosis (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). Methods: Studies were performed taking into account the results of examinations of 238 patients selected from the demyelinating diseases Center Hospital da Lagoa, Rio de Janeiro-Brazil in the period from January 2000 to December 2010. There was inclusion of evaluating patients served by Neurology Service, who presented NMO diagnostic confirmation and two MS forms, with additional CSF assessment. For this study were described the laboratory aspects of CSF during relapsings and recurrences or during disease progression, with later statistical comparison. Results: The examinations were evaluated for CSF 55 patients with diagnosis of recurrent NMO, with 135 RRMS and 48 with PPMS. The NMO noted pleocytosis 5 cells in 25,4% of the cases (min 1 max. 64 12,6). Plecocytosis 50 cells/mm3 in 2 cases (3,6%); OCB present in 35.2%, elevation of IgG Index in 28.8%; barrier dysfunction in 19% cases. In recurrence of NMO noted persistent elevation of total protein pleocytosis, but with reduction of OCB and elevated IgG index. There was no record of nervous system infections associated with this syndrome. In relation to the RRMS noted pleocytosis 5 cells/mm3 (min 1 max 69 8,5) in 35% of cases with keeping of lymphocytes and monocytes, positive OCB in 74% and IgG index elevation in 66%; barrier dysfunction in 8% of cases. In PPMS, pleocytosis 5 cells/mm3 appeared in 25% (min 1 max 69 10,3), OCB present in 72% and elevated IgG index in 61% of the samples; barrier dysfunction in 18% of cases, as described in figures. Two cases of RRMS (4%) presented positive serology (IgM) for varicella-zoster and 1 case for herpes simplex virus, next to episodes of recurrence. Conclusion: This study demonstrated the findings in CSF of NMO and two forms of MS. There is cellular and biochemical differences between acute and recurrence course of NMO. The prevalence of OCB and the elevation of IgG index was higher in the MS forms. The pleocytosis, barrier dysfunction and elevated protein was greater in the recurrence of NMO. It was demonstrated the intrathecal synthesis of antibodies against varicella-zoster virus in MS, documenting chronic inflammatory process in the CNS, a fact that was not observed in NMO. CSF is a useful resource to complement the diagnosis of NMO and important in the differentiation of MS forms.
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dos Servidores do Estado, Rio de Janeiro, Brazil; 4Institute for Neurological Research Dr Ral Carrea, FLENI, Argentina; 5Instituto de Neurociencias de Rosario, Argentina; 6Novartis Argentina S.A.; 7Novartis Pharmaceutical Corporation, NJ, USA; 8Novartis Pharma AG, Basel, Switzerland; 9Department of Neurology, University Hospital, University of Basel, Basel Switzerland Purpose: Present efficacy and safety outcomes in the LatinAmerican cohort of the phase 3 TRANSFORMS (oral once-daily fingolimod vs. interferon beta-1a i.m. [IFN]) study. Methods: In this 12-month (M), double-blind, double-dummy study, patients were randomized to fingolimod 1.25mg (n=29), fingolimod 0.5mg (n=34) or IFN (n=34). A post hoc analysis of patients from Argentina and Brazil was done at M12 for: annualized relapse rate (ARR), MRI (no. of T1 Gd+ and new/ enlarging T2 lesions), 3-M confirmed disability progression, adverse events (AEs) and serious AEs (SAEs). Results: 91/97 (94%) patients completed the study. AEs were the main reason for study drug discontinuation (4.1%). Compared to fingolimod 1.25mg/IFN groups, fingolimod 0.5mg group had fewer T1 Gd+ lesions and lower T2 lesion volume, longer disease duration and a higher EDSS at baseline. Lower ARR was observed for both fingolimod groups vs. IFN (1.25mg: 0.16; 0.5mg: 0.14, IFN: 0.30), a relative reduction of 46% for 1.25mg and 55% for 0.5mg vs. IFN. Probability of staying progression-free was 96% for both fingolimod groups vs. 86% for IFN. Lower mean no. of T1 Gd+ lesions (1.25mg: 0.04, 0.5mg: 0.34, IFN: 1.77) and new T2 lesions (1.25mg: 0.6, 0.5mg: 2.0, IFN: 4.8) were observed for fingolimod vs. IFN. Most patients experienced AEs (1.25mg: 100%, 0.5mg: 94%, IFN: 94%). More SAEs were reported for fingolimod 0.5mg (8.8%)a vs. fingolimod 1.25mg (3.4%) or IFN (5.9%). Conclusion: Despite small no. of patients and imbalance in baseline characteristics in this cohort, patients treated with fingolimod 1.25mg /0.5mg had reduced ARR, were more likely to stay progression free and had fewer T1 Gd+ and new T2 MRI lesions at M12. This subgroup analysis from TRANSFORMS adds to the evidence of superior efficacy of fingolimod vs. IFN and indicates a positive benefitrisk profile in the Latin-American cohort. A91 Multiple sclerosis: a reality as demyelinating disease in Pediatrics Hernandez, F. Rios, G. Calzadilla, L. Correia, F. Hospital Universitario de Maracaibo. Venezuela freda. hernandez@gmail.com Objective: To identify demyelinating diseases present in children from Pediatric Neurology Service of the Hospital Universitario de Maracaibo in Venezuela. Methods: Retrospective and descriptive study. The population consisted of 55 patients between 1 and 18 years of age with a diagnosis of demyelinating diseases during January 2007 to January 2011. The considered diseases were: acute disseminated encephalomyelitis (ADEM), optic neuritis (NO), transverse myelitis (TM), multiple sclerosis (MS) and/or Neuromyelitis optica (NMO). Clinical, radiological, electrophysiological and immunological data were collected and analyzed.
A90 Comparison of oral fingolimod with interferon beta-1a in treatment of relapsing-remitting multiple sclerosis: subgroup analysis of the Latin-American cohort in TRANSFORMS study Alvarenga R.M.P1, Cohen J.A2, Naylor R.M3, Correale J4, Luetic G5, Frider N6, Ritter S7, Tomic D8, Kappos L9 1Neurology Department, Federal University of Rio de Janeiro State (UNIRIO), Rio de Janeiro, Brazil; 2Neurological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA; 3Hospital
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Results: Out of 55 patients studied, 27 were male (49.0%) and 28 were female (51.0%); 25 of them (45.5%) presented their first clinical manifestation between 7 to 11 years of age. ADEM was the predominated presentation in 34 patients (61.8%), 55,9% of them were male and the average age was 7 3,6 years. In the case of NO, 10 patients showed the disease (18.1%) predominantly females with an average age of 11.0 2.4 years. MT were diagnosed in 6 patients (10.9%) no gender were associated, an average age of presentation of 9.8 1.1 years and with relevant clinical manifestation like Back Pain (100%) and sphincter disorders (83.3%). In the case of MS, 4 patients (7.3%) were diagnosed, 75% were females with average age of 13.7 1.5; motor deficit were present in all patients and cognitive impairment was present in 25% of the patients before the motor deficit manifestations. Finally, NMO was present in 1 patient (1.8%). Conclusion: ADEM was the most frequent demyelinating disease among the studied population. MS is a reality in the spectrum of possible diagnostics in Pediatric Neurology in Venezuela. A92 - Oral presentation Multiple Sclerosis: natural history and prognostic factors in Brazilian patients G. Santos, C. Ferreira Vasconcelos, S. M. G. Gomes Camargo, F. Hampshire Araujo, J. Calvet Kallembach, L.C. Santos Thuler, R. Papais Alvarenga UNIRIO (Rio de Janeiro, BR); Hospital Da Lagoa (Rio de Janeiro, BR); INCA (Rio de Janeiro, BR) Background: Previous studies on natural history (NH) have indicated that certain initial clinical factors may be predictive of disability accumulation in multiple sclerosis (MS). Despite the variety of studies carried out in the world population, those addressing population of low-prevalence areas are still rare. Objective: Assess the NH of MS patients with 10 years or more of disease duration in a low-prevalence area and then analyze which clinical and demographic factors may influence in their long-term evolution and its prognosis. Methods: Among 993 MS patients catalogued at a Brazilian reference centre, we were able to identify 95 primary progressive (PP) form and 714 relapsing remitting (RR) form. We reviewed the medical records of 67 PP patients, and found 45 with 10 years or more of disease duration. Among 200 with RR form revised, we found 97 with 10 or more years of the disease who had never been treated or began treatment after reach EDSS 6. We performed a survival study to reach EDSS 3 and 6, and logistic regression to examine the influence of demographic and initial clinical factors on accumulation of disability in both groups and total sample (TS). Results: Afro descendent reached EDSS 3 (p= 0,03) and 6 (0,009) earlier in TS and according to form (p=0,05 and 0,04 in RR and p = 0,04 and 0,02 in PP, respectively). PP patients reached EDSS 6 earlier than RR ones (p < 0,001). Recovery of the first relapse (p < 0,001) was the factor that conferred more risk for reaching EDSS 3, 6 and secondary progression earlier in the RR group, followed by the number of relapses at the first year of disease (p = 0,007). Conclusion: Our findings confirm the worst evolution in the PP form. Ethnicity was found to be a factor of bad prognosis is both clinical forms. Beside it, number of relapses in the first year of

the disease and no recovery of the initial symptom are relevant clinical characteristics in RR patients that have to be taken in account in therapeutic decision-making. A93 Neuromyelitis optica and antibody antiaquaporin 4: the experience of CAPPEM-BH Antonio Pereira Gomes Neto, Paulo Pereira Christo, Renata Brant de Souza Santa Casa de Belo Horizonte- Minas Gerais Objective: To report our experience of the Centre of Attention to Patients with Multiple Sclerosis in Belo Horizonte (CAPPEMBH) in Neuromyelitis optica antibody and antiaquaporina 4. Methods: Descriptive analysis of the result charts of 38 patients with NMO, followed as outpatients Demyelinating DiseaseCAPPEM-BH. Results: As initial clinical signs of NMO, we could observe: transverse myelitis in 10 patients, in 24 patients with optic neuritis, neuritis and myelitis in 3 patients concomitant manifestation of encephalopathy and 01 inaugurating the course of the disease. There was 01 death of urinary tract infection, complicated by sepsis, as the disease progressed. The longest progression time of the disease was 31 years and the shortest 1 year. All patients started treatment with azathioprine, except one patient who refused to use the medication. Out of the 38 patients, 36 (95%) were tested for IgG antibody-NMO, and in 21 (58%) of these the result was positive. Conclusion: In recent years, there has been, in our service, a significant increase in the number cases of NMO. After the description of NMO-IgG antibody, immunoglobulin gamma serum marker which is highly specific for NMO, diagnosis became safer. As the disease course NMO is often severe, antibody detection antibody aquaporin 4 allows the prognosis and treatment earlier, when positive. Our results are similar to results from other published series, confirming the sensitivity and specificity of the test. A94 Neuromyelitis optica after thymectomy in a young myasthenia gravis patient using cyclosporine Cludia Suemi Kamoi Kay, Rosana Herminia Scola, Paulo Jos Lorenzoni, Lineu Cesar Werneck Universidade Federal do Paran Introduction: Myasthenia gravis (MG) and neuromyelitis optica (NMO) are immune-mediated diseases which rarely occur in same patient, mainly after thymectomy. We report a MG patient who developed NMO after thymectomy, in use of cyclosporine, and discuss if the presence of NMO-IgG antibody may influence the appearance of NMO. Case Report: A 17 years old Caucasian woman presented with palpebral ptosis, diplopia, dysphonia, dysphagia and proximal weakness. Diagnosis of MG was confirmed and treatment with pyridostigmine, prednisone and azathioprine resulted in partial improvement of symptoms. No remission of the disease was observed after six years of treatment; therefore, cyclosporine was started and she was underwent thymectomy.

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At age 27, she developed itching sensation on right hand, followed by hypoesthesia in trunk, upper and lower limbs, associated to severe pain. Cervical magnetic resonance imaging demonstrated lesions extending from C2 to C6. She did not improve after treatment with intravenous methylprednisolone, so she was underwent spine surgery and histopathology confirmed myelitis. Six months after surgery, she had progressive improvement of symptoms, but she had a sudden reduction of visual acuity in right eye which received the diagnosis of optic neuritis. NMO-IgG serum antibody was negative, but she had been using cyclosporine for 4 years. Her actual EDSS score is 4.0. Discussion: NMO in MG patients after thymectomy usually occurs associated with abnormal increased of NMO-IgG serum. However, our patient is seronegative to NMO-IgG and the NMOIgG seronegative patients less frequently have signs of co-existing autoimmunity. We speculate whether cyclosporine could be sufficient to let undetectable serum levels of NMO-IgG antibodies. As the cyclosporine reduces mainly interleukin 2 but interleukin 4 and 6 are reported to be increased in NMO patients. A95 Neuromyelitis optica and Multiple Sclerosis: a view from DNA, RNA and protein profiles. Giselle Pentn- Rol1, Nazabal-Galvez M1, Camacho-Rodrguez Hanlet1, Pedroso-Santana S1, Fernndez de Cosso ME1, Cervantes- Llanos M1, Cintado- Bentez A1, Ale-Martnez M1, Villarreal-Barrios A1, Daz-Argudn T1, Bentez-Fuentes J1, Pavn-Fuentes N2, Grass D2, Cabrera-Gmez JA2 1Center for Genetic Engineering and Biotechnology (CIGB), Ave 31 e/ 158 y 190, Cubanacan, Playa, Havana City PO Box 6162, Havana 10600, Cuba; 2International Center for Neurological Restoration (CIREN) Ave 25 No 15805, Havana, Cuba. giselle. penton@cigb.edu.cu; giselle.penton@infomed.sld.cu Neuromyelitis optica (NMO) is an uncommon CNS demyelinating syndrome often mistaken for severe multiple sclerosis (MS). Despite reported differences, it remains likely that these conditions are part or the same spectrum of inflammatory demyelination in which the genetic background and immune factors define the pattern of disease. The association of HLA class II alleles has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Cuban population. Furthermore, the connection of RNA and protein expression of, pro-inflammatory and regulatory cytokines in both pathologies is crucial for understand and distinguish of the NMO and MS. Objectives: To identify the association between HLA susceptibility or /protection of haplotypes related to MS and NMO in Cuban population. To quantify pro-inflammatory and regulatory cytokines at the mRNA and protein levels. Methods: HLA susceptibility alleles from NMO and MS patients were determined by PCR using single specific primers. Additionally, total RNA from NMO, MS and controls was extracted with the RiboPureTM Blood, kit. The Real-timequantitative-PCR data analysis for the genes TNF-a, IFN-g, IL17, IL-6, IL-10, TGF-b and Foxp3 was performed with Capital Bio RT-Cycler. Serum protein levels of TNF-a, IL-17 and IL-10 were measured using R&D kits.
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Results: A down-regulation of TNF-a and IFN-g was observed in both pathologies suggesting a neuroprotective and autoimmune roles of these cytokines respectively. Moreover, Foxp3 and TGFbeta were more marked down-regulated in NMO compared to MS patients and controls indicative of a decrement of the regulatory T cells. Interesting, an up-regulation of IL-10 was detected in NMO patients suggesting an involvement of a humoral response Conclusion: In our study an important immunopathologic differences between MS, NMO and controls have been identified. Precise classification of these disorders may have relevant prognostic and treatment implications. A96 Neuromyelitis Optica frequency in a cohort of Multiple Sclerosis patients and other Central Nervous System Demyelinating Diseases Soniza Vieira Alves-Leon, Isabella DAndrea Meira, Fabola Rachid Malfetano, Letcia Fzer, Simone Batista, Valria Coelho Santa Rita Pereira Clementino Fraga Filho Hospital - Federal University of Rio de Janeiro; Federal University of the State of Rio de Janeiro Background: Neuromyelitis Optica (NMO) represents actually the unique demyelinating disease, which a biological marker was included as one of the diagnostic criteria, but clinical and neuroimaging criteria can also support this diagnosis. This definition has been contributed for identifying NMO patients among other demyelinating diseases as multiple sclerosis (MS). We conducted the analysis of NMO frequency in a cohort of MS patients according to McDonald et al, 2011 criteria, and to NMO according to Wingerchuk et al 2006 criteria. Results: A total of 407 patients with demyelinating disorders were analyzed. Three hundred twenty-five patients were diagnosed with MS and 82 with NMO. The prevalence of NMO was 20.2%, with a MS:NMO ratio of 4:1. Women were more affected with the female: male ratio of 3.8:1. Patients with NMO evolved more quickly to 6.5 in the expanded disability status scale (EDSS). Discussion: Bizzoco et al reported prevalence 1.5% of NMO with a ratio of 42.7% in relation to MS. Higher frequency of NMO among demyelinating diseases has been associated with Africandescendent origin. Seven percent of Japanese MS patients had NMO. In Rio de Janeiro City the great mix of patients with different ancestry may have contributed to our higher prevalence of NMO when compared to other countries. The ratio of women to men may differ according to disease course being more prevalence in patients with a relapsing course. Most reports suggest a ratio of 1.4 to 1.8. The NMO patients in this series have been presented a more severe disease and have been reached EDSS level 6.5 or higher in a shorter period of time than MS patients. Conclusion: Genetic factors related to ethnic background must be contributing to a higher incidence of NMO and worse prognosis compared to literature. A97 Frequency of anti-aqp4 antibody in patients with neuromyelitis optica and optic spinal multiple sclerosis Regina Maria Papais Alvarenga, Ulisses Cerqueira Linhares, Marcos Papais Alvarenga, Marina Papais Alvarenga,
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Claudia C.F. Vasconcelos, Cleonice Bento, Luiz Cludio Thuler Institution: Programa de Ps-Graduao em Neurologia da UNIRIO Objectives: To evaluate the positivity of the antibody antiaquaporin 4 (anti-AQP4) in patients from Rio de Janeiro (Brazil) with neuromyelitis optica clinical phenotype and compare demographic, clinical and laboratorial data between neuromyelitis optica (NMO) and optic spinal multiple sclerosis (OS-MS) groups. Mtodo: The anti-AQP4 antibody was tested by indirect immunofluorescence method (Lennon et al, 2004) in consecutive patients with neuro myelitis optica phenotype attended in Hospital da Lagoa (RJ) between 2009 to 2011. The patients were classified in defined NMO according Wingerchuk et al (2006) in monophasic (NMO-M) or recurrent (R-NMO). Patients who did not meet those criteria (2006) were classified as opticspinal multiple sclerosis (OS-MS). Demographic, clinical and laboratorial data were compared between NMO and OS-MS groups. Results: We analyzed 99 patients: 66 were NMO-R, 8 NMO-M and 25 MS-OS. In NMO-R group, 91% were women, 65.2% African-Brazilian, mean age at onset 29.56 13.03 years, median EDSS of 6.0 (2.0 to 10) in the last evaluation after median disease time of 8 years (2-35); the positivity of anti-AQP4 was 56.1%. In group NMO-M, 62.5% were women, 65.5% AfricanBrazilian, mean age at onset 46.71 19.77 years, median EDSS of 3.0 (2.0 to 6, 0) in the last evaluation after 7 years of median disease time (3-14); the positivity of anti-AQP4 was 0.0%. In MS-OS group 84% were women, 16% African-Brazilian, mean age at onset 29.45 8.12 years, median EDSS of 3.0 (1.0 to 6.5) in the last evaluation after a median disease duration of 8 years (3.0 to 27.0); the positivity of anti-AQP4 was 0 %. There was a statistically significant difference between NMO and OS-MS groups concerning to race, long term disability, extension of the MRI vertebral lesion and positivity of anti-AQP4. Conclusion: The majority of NMO patients were African Brazilians, had severe disability at last evaluation and were positivity to anti AQP4. On the contrary, OS-MS patients were mainly whites, had a benign course of disease with mild disability and all were anti AQP4 negative. NMO and OSMS in Brazilian population are different demyelinating inflammatory diseases although share the same clinical phenotype presentation. The worst outcome in NMO patients requires a differentiated approach.

Immunological alterations mediating myelin damage begin with immune system activation in the periphery, through recognition of certain myelin antigens. This activation determines: a) clonal expansion of autoreactive T cells, b) production of different cytokines, and c) expression of adhesion molecules facilitating passage across the blood-brain-barrier into the CNS. These cells are ultimately responsible for CNS tissue damage. Axonal damage is concurrently observed, as a result of two different processes: a) autoimmune reaction against axon components, and b) axonal alterations in Na+ and Ca++ exchange inducing apoptosis, followed by expression of molecules inhibiting axonal growth, thus limiting intrinsic repair mechanisms. However, some autoreactive mechanisms may be necessary for neuro-regeneration, making macrophages and microglial cells necessary to remove myelin debris. Likewise, activation of p75 receptors by TNF- and certain IgM antibodies promote remyelination. Similarly, autoreactive T cells can produce IL-1, which contribute to production of neurotrophic factors like IGF-1. In this context, it is clear that the final result of CNS damage or repair in MS patients will result from the balance between deleterious mechanisms and repair processes, both mediated by the immune system. A99 Neuromyelitis Optica: Searching for a cognitive pattern Sandra Vanotti, Barbara Eizaguirre, Evangelina V. Cores, Luciana Melamud, Andres Villa Hospital Ramos Meja- Unidad de Neuroinmunologa y Electrofisiologia Objective: 1) To determine the pattern of Cognitive disorders in NMO patients 2) To analyze the visual imagery ability. Background: As NMO is a relatively new disease, little is known about its cognitive impairment pattern, frequency and its relationship with clinical variables. Considering patients complaints, the search for a cognitive pattern is necessary. Design/Methods: Eighteen NMO patients were compared to 18 healthy controls. Mean age 36.39 (12.35); Female: 15; education 11.44 (2.95); EDSS: 4.31(2.59); disease evolution 7.87(4.50) years. Controls: age 36.56 (12.39), education 12.00 (3.62). Outcomes measures: 1) Brief Repeatable Neuropsychological Battery, including: Long Term Storage (LTS), Long Term Retrieval (LTR) and Consistent Long Term (CLT) and Delay Recall (DR SRT) of the Selective Reminding Test (SRT), Correct Response (CR) and Delay Recall (DR) of the 7/24 Visuospatial Test, PASAT and Verbal Fluency (VF); 2) Beck Depression Inventory II (BDI II); 3) Vividness of Visual Imagery Questionnaire (VVIQRV). Results: 44,4 (%) NMO patients had abnormal performance in two or more cognitive tests. Compared to controls was found significant impairment on VF (NMO: 21.36 SD15.12; Controls: 37.82 SD11.52; CLT (NMO: 29.6116.14; Controls: 41.00 SD15.02); DRSRT (NMO: 7.61 SD3.12; Controls: 9.72 SD2.02); DR7/24 (NMO: 28.07 SD4.43; Controls: 29.76 SD6.28); Evidence for the presence of depression: 13,9% mild, 5,6% moderate; 11,1% severe. No differences were found on VVIQRV between groups. Conclusions: Cognitive and neuropsychiatric domains decline in NMO patients.
A98 - Oral presentation Immunopathogenesis of MS Jorge Correale Multiple Sclerosis (MS) is a demyelinating and inflammatory disease that affects the Central Nervous System (CNS). Although its cause remains unknown, different lines of investigation support autoimmunity as the main putative mechanism. In addition to inflammatory mechanisms, an underlying neurodegenerative process is probably responsible for irreversible symptoms observed in some patients during the course of disease.

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A100 Neuromyelitis Optica: the need to understand patients Quality of Life Sandra Vanotti, Barbara Eizaguirre, Evangelina V. Cores, Luciana Melamud, Andres Villa Hospital Ramos Meja- Unidad de Neuroinmunologa y Electrofisiologia Objective: 1) To evaluate Quality of Life (Qol) in Neuromyelitis Optica (NMO) patients 2) To describe relationships among cognitive, depression and Qol measures. Background: The determination of Qol is crucial to understand the impact of this disease in our population. Neuropsychiatric variables and disability are mostly unknown. Design/Methods: Eighteen NMO patients were compared to 18 controls. Mean age 36.39 SD12.35; Female: 15; education 11.44 SD2.95; EDSS: 4.31 SD0.59; disease evolution 7.87 SD0.50 years. Controls: age 36.56 SD12.39, education 12.00 SD.62. Outcomes measures: 1) SF36 Qol of life; 2) Brief Repeatable Neuropsychological Battery, including: Long Term Storage (LTS), Long Term Retrieval (LTR) and Consistent Long Term (CLT) and Delay Recall (DR SRT) of the Selective Reminding Test (SRT), Correct Response (CR) and Delay Recall (DR) of the 7/24 Visuospatial Test, PASAT and Verbal Fluency (VF); 3) Beck Depression Inventory II (BDI II). Results: Qol measures yielded significant differences between NMO group and normal controls on physical functioning (p=.007), pain (p=.036) and general healthy (p=.005). 44,4 % NMO patients had abnormal performance in two or more cognitive tests. Compared to controls was found significant impairment on VF (NMO: 21.36 SD15.12; Controls: 37.82 SD11.52); CLT (NMO: 29.61 SD16.14; Controls: 41.00 SD15.02); DRSRT (NMO: 7.61 SD3.12; Controls: 9.72 SD2.02); DR7/24 (NMO: 28.07 SD4.43; Controls: 29.76 SD6.28); Evidence for the presence of depression: 13,9% mild, 5,6% moderate; 11,1% severe. Considering SF36 dimensions and cognitive domains was found statistically significant correlation between memory and energy/fatigue (p=.012) and visual memory and emotional well-being (p=.027). BDI II was statistically associated with energy/fatigue (p=.047) and social functioning (p=.043). Conclusions: NMO patients presented worse QoL level than general population.
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Nowadays there are three main risk factors that can be evaluated to stratify progressive multifocal leukoencephalopaty (PML) risk in multiple sclerosis (MS) patients undergoing Natalizumab treatment. Objective: The present study objective is to study several new predictive markers for Natalizumab-associated PML. Methods: prospective coorte of 98 MS patients being 38 undergoing Natalizumab therapy and 60 as control group using other therapies. It was performed a longitudinal DNA research in peripheral blood, plasma and urine using real time polymerase chain reaction of JC virus and BK virus monthly. After DNA amplification the JC virus regulatory region was sequenced in the search for mutations. Laboratorial data was analyzed along with clinical data. Results: 25 patients undergoing Natalizumab therapy and 44 control patients have made proper follow-up ; 5 patients undergoing Natalizumab therapy has received the drug for more than 2 years and 12 for less than 2 years. The excretion of poliomavirus (JC virus and BK virus) in at least 1 sample were 54% in Natalizumab group and 52% in the control group. None of the JC virus have shown mutations and have presented in the archetypal the regulatory region. None of our patients have developed PML. Discussion: New predictive markers for Natalizumab-associated PML are required specially in patients undergoing Natalizumab for over 2 years. We believe that continuous viral excretion, JC virus and BK virus coinfection, JC viral load and increase in JC viral load and the presence of archetype or rearranged variants in the regulatory region are determinant predictive markers for PML development. Conclusion: continuous follow-up is required in order to discover new predictive markers for Natalizumabassociated PML. A102 - Oral presentation NMO and NMO complex: frequency of NMO-IgG antibody positivity in a Rehabilitation Hospital in Brasilia Brasil MC Del Negro, PB Marinho, D Umaki Hospital Sarah Brasilia Introduction: Autoantibodies that target aquaporin-4 (NMOIgG) are highly specific for neuromyelitis optica (NMO) and contribute to the definition of a spectrum of diseases that includes optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM), monophasic or recurrent. A positive result for the NMO-IgG allows early definition of NMO leading to prompt initiation of NMO-appropriate treatment. Objectives: To determine the prevalence of NMO-IgG in patients diagnosed as NMO or NMO complex and to evaluate some relevant characteristics of these groups. Methods: Retrospective analysis of medical records and neuroimaging of patients diagnosed as NMO or NMO Complex who underwent serum NMO-IgG test, from November 2009 (first month of NMO-IgG test by ELISA on Sarah Braslia Hospital) to July 2012. Results: Among 71 patients (58 female: 13 male) with NMO or NMO complex, 41 (58%) yield a positive NMO-IgG and 30 (42%) were NMO-IgG negative. Thirty five patients (31 female: 4 male) were diagnosed as NMO (49%); 16 patients (11 female: 5 male) had recurrent LETM (23%); 18 patients (15 female: 3 male) had monophasic LETM (25%) and 2 patients (1 female: 1 male) had recurrent ON. Among NMO patients, 74% were NMOIgG positive; 86% had recurrent course; 54% had nonspecific
A 101 New predictive markers for Natalizumab-associated progressive multifocal leukoencephalopaty, preliminary results G.S. Olival1, L. H. S. Nali2, R. F. Simm3, R. B. Thomaz4, C. M. Romano5, L. Moraes3, T. S. Faria6, V. B. Cavenaghi4, V. Serafim4, S. Apostolos4, L.S. Sumita6, C. P. Tilbery4, J. V. Bermudez1, D. Callegaro3, A. C. Penalva de Oliveira1, C. Fink4 1Instituto de Infectologia Emilio Ribas (So Paulo - SP, BR); 2Instituto de Medicina Tropical- IMT (So Paulo - SP, BR); 3USP (So Paulo - SP, BR); 4Santa Casa de So Paulo (So Paulo - SP, BR); 5Instituto de Medicina Tropical- USP (So Paulo - SP, BR); 6Instituto de Medicina Tropical - USP (So Paulo - SP, BR)
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serum antibodies; 88% had longitudinally extensive myelitis; 49% had cervicodorsal lesions; 74% had central cord lesions; 63% had brain MRI lesions; 4 patients were children. NMO-IgG was positive in 56% of recurrent LETM and 33% of monophasic LETM. Patients with ON had NMO-IgG negative tests. Conclusion: The frequency of NMO-IgG was higher in NMO and recurrent LETM patients, reassuring the importance of the test in diagnostic research.

plasma by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), carbonyl protein, metabolites of nitric oxide (NOx), sulfhydryl groups of protein, uric acid, and total radicaltrapping antioxidant parameter (TRAP). The EDSS of RRMS patients ranged from 0.0 to 6.5 (median 3.0); 71 (78.0%) of them exhibited EDSS with low disability and 20 (22.0%) with high disability. MS patients showed higher plasma levels of lipid hydroperoxide (p<0.0001), carbonyl protein (p=0.0081), and lower plasma levels of NOx (p<0.0001), TRAP (p=0.0088), sulfhydryl groups (p=0.0003) than controls. Patients with high disability showed higher CL-LOOH than controls (p=0.0093). A positive correlation was observed between CL-LOOH and EDSS (r=0.3244, p=0.0026) and between carbonyl protein and EDSS (r=0.3012, p=0.0041). The CL-LOOH marker was associated with the EDSS of the RRMS patients (r=0.0461, p=0.0001). These results underscore that oxidative stress may have an important role in the physiopathology of the MS progression, even in patients with clinical remission and further studies are needed to evaluate the effects of antioxidant therapies associated with conventional treatments in MS patients. Financial support: Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); State University of Londrina (PROPPG); and Bayer HealthCare. A 105 Parkinsonism Secondary to Progressive Multiple Sclerosis Arnoldo Soto1, Marisol Gallardo2 1From Service of Neurology, Hospital Domingo Luciani, Caracas and 2Service of Neurology, Centro Mdico Docente La Trinidad, Caracas, Venezuela Objetive: Describe a patient with a diagnosis of Progressive Multiple Sclerosis (PPMS) who clinically presented signs of Parkinsonism. Methods: Physical examination, routine laboratory, brain magnetic resonance imaging (MRI), CSF analysis and immunological test were performed. Results: A 51 years old Venezuelan man who developed rigidity and tremor in upper and lower left limbs followed by gait difficulty, slowness and short steps. He reported progressive worsening of symptoms in the last 2 years. He was hypomimic, bradykinetic with moderate rigidity in upper and lower left limbs. He scored 45 at the UPDRS. Brain MRI showed multiple hyperintense Flair and T2-weighted images in periventricular areas, corpus callosum and subcortical white matter in both cerebral hemispheres. VEP was normal. CSF analysis showed oligoclonal bands. Immunological test was normal. Treatment with levodopa (600 mgrs) was given with no improvement of the symptoms. A methylprednisolone pulse was administered followed by methylprednisolone 1 gr (IV) monthly. Three months later the patient had a significant improvement of the symptoms with a UPDRSS score of 36. Conclusions: Only 10 cases of Parkinsonism Secondary to MS have been reported in the literature. Our patient presented with Parkinsonism in the context of clinically definitive PMS of approximately 3 year of evolution. The fact that the symptoms improved with corticosteroid treatment and no improved with the administration of levodopa supports MS as the cause of his symptoms. The relative involvement of basal ganglia and
A 103 Optic Neuritis Frequency In Patients With Multiple Sclerosis Eduardo Cukierman, Bernardo Campos Rodrigues, Regina Maria Papais Alvarenga Local study: Hospital Universitrio Gaffre e Guinle; Hospital Federal da Lagoa Introduction: Multiple sclerosis is the most common neurological disease in young patients in the northern hemisphere. International studies suggest that optic neuritis is the presenting symptom of multiple sclerosis in approximately 20% of patients. About 53% of patients show optic symptoms along the disease. In Brazil, multiple sclerosis is a disease of low prevalence and only has been described from the 90s. Objective: To report the frequency of optic neuritis in brazilian patients with multiple sclerosis. Methodology: This study was a retrospective chart review of patients with multiple sclerosis of the Hospital Federal da Lagoa, identifying the percentage of patients who had reports of optic neuritis along the disease. Results: of the 101 records analyzed, 45 (44.5%) have reported optic neuritis along the disease. Conclusion: The visual changes are quite common in multiple sclerosis, but there are few Brazilian studies devoted to exploring in more detail this event. Optic neuritis, when it occurs in healthy individuals, is an important warning sign and strengthens the need for knowledge of this disease by ophthalmologists for an early diagnosis and intervention. A 104 Oxidative stress in relapsing-remitting multiple sclerosis patients in clinical remission: association with expanded disability status scale Sayonara Rangel Oliveira, Ana Paula Kallaur, Andra Name Colado Simo, Damacio Ramon Kaimen-Maciel, Josiane Lopes, Wilda Lice de Carvalho Jennings, Carolina Panis, Renato Marques de Andrade, Larissa Muliterno Pelegrino, Edna Maria Vissoci Reiche State University of Londrina The aim of this study was to evaluate oxidative stress in relapsingremitting MS (RRMS) patients and to verify its correlation with disability. This study included 91 RRMS during clinical remission and using interferon beta 1a or 1b. They were clinically evaluated to disability using Expanded Disability Status Scale (EDSS) and separated into two groups: EDSS 3.5 (low disability) and > 3.5 (high disability). The control group was composed by 196 healthy individuals controlled by age, gender, ethnicity, smoking, and body mass index. The oxidative stress was evaluated in

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subthalamic nucleus by MS plaques may explain the presence of movement disorders as a manifestation of Multiple Sclerosis. A 106 Pediatric Multiple Sclerosis at a Reference Center in RIO DE JANEIRO. Epidemiologic Characteristics The authors: Simone Cotrim Cerqueira Pinto e Regina Maria Papais Alvarenga Study realized at Lagoa Hospital Rio de Janeiro RJ Brazil Objective: To describe the prevalence and main demographic aspects and clinical forms of Pediatric Multiple Sclerosis (MS) at a reference center from Hospital da Lagoa / Rio de Janeiro / Brazil. Methods: According to a tranversal descriptive study, medical data from to patients assisted from 2011 to september of 2012 were analyzed. Results: 261 patients had a diagnostic of MS. The prevalence of pediatric MS was 10,6% ( n=27 ). Most of this cases ( 92,59%) occourred in the adolescense. MS relapsing-remmiting form was the most prevalent ( 77,7%) followed by MS secundary progressive form (18,51%), and MS primary progressive form (3,7% - just one case ). Among the pediatric patients group, 40,74% were African Brazilian, while in adult population the prevalence of this racial group was 33,76%. In the adolescent group, female to male ratio was 2.12:1. Discussion: In our group, pediatric MS was more prevalent than most of the several large series reports of the literature (2.2 4.4%). Despite others centers references had already reported a similar percentage of pediatric MS patients (10%); in our study an expressive prevalence of african brazilian patients was considered an interesting data. This fact can partly be explained by the large miscegenation in Brazil, especially in Rio de Janeiro. Conclusion: Pediatric MS can be more prevalent than expected in Brazil and this disease affect also African Brazilian patients in a larger scale than whe suposed. More studies must be realized, whith wider cohorts to came to a more precise conclusion about the influence of race and demographical aspects in Pediatric Multiple Sclerosis. A 107 Performance of Patients with Multiple Sclerosis in D2 Test Heleine Norman Clemente; Claudia Cristina Ferreira Vasconcelos; Helcio Alvarenga Filho; Renata Alves Paes; Regina Maria Papais Alvarenga Neurology Dpto. - Hospital Universitrio Gaffre e GuinleHUGG/UNIRIO-BRASIL In multiple sclerosis (MS), demyelization can affect circuits related to cognitive functions causing deficits, mainly in speed of information process (SIP), in attention and memory. The cancellation and concentrated attention test d2, aims to evaluate such functions, and has been used in research. This instrument is independent of intelligence, because it is a task of discrimination of details. Its a quick test, easy application and implementation, and not influenced by fatigue. Objective: Apply the D2 test in patients with multiple sclerosis relapse remission (EMRR), and analyze the performance of the sample.
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Method: A cross-sectional study carried out at Hospital Universitrio Gaffre e Guinle UNIRIO-Brazil, with 50 patients with EMRR submitted between 2010/2012 the evaluation with the D2 test. The test consists of mark all letters d with two interleaved traces between 648 characters, with measured time. The gross result (RB) is the sum of all characters marked on each line; the total number of errors (TE) is the amount of faults; the net result (RL) is the product of (RB-TE); the percentage of errors (E); and (AO) is the difference between the more and the less marked. The data were compared to the manuals table and analyzed by the Statistical Program SPSS 13.0. Results: The sample was of 39 women and 11 men, with average age: 39.7 years, time of disease: 7.1 years and EDSS: 2.2. The average performance in each index was RB:375,28, RL:338,52, TE:29,40; E%:14,68 and AO:13,5. Levels considered normal for this age group are RB:455 and RL:422. Conclusion: We conclude that the performance of the sample was below normal levels for this age group. It was noted in the SIP, slowing, instability in attention and prejudice in precision. Therefore, the application of the test, provided important data on the cognitive deficits present in this sample.
A 108 Perimetrics and Fundoscopys Findings in Patients with Multiple Sclerosis Treated with Interferon Pecho Trigueros, Jenny; Cruz Cruz, ANA; Sanchez Roque , Elio. Hospital nacional alberto sabogal sologuren. Essalud. Callao, Peru. Objective: Episode of optic neuritis and multiple sclerosis makes debut of anatomical and functional lesions, which currently with the early use of interferon has been shown to reduce and delay outbreaks of disease progression. As wished to determine the clinical fundus and visual field of patients with multiple sclerosis (MS) treated with interferon beta-1 (IF-) for at least one continuous year Alberto Sabogal Hospital. Method: We reviewed the medical records and evaluated 12 patients (24 eyes), diagnosed with multiple sclerosis treated for one continuous year 1 interferon beta. Evaluations were made central and peripheral perimeter Perimeter HFA II 750, and indirect ophthalmoscopy and retinal camera Canon retinoangiografa CF1. Results: Of the total, 75% were women, 6 patients (50%) led the predominant age group of 31-40 years. The BCVA was greater-equal 1.0 in 9 eyes (37.5%). Reportedly, one or more episodes of optic neuritis (ON) before treatment with IF- in 10 cases (83.33%), compared to 0% after treatment of optic neuritis. 29.17% perimetry identified central visual field in the normal 30-2 60-4 peripheral test showed higher defect depth of 6dB. The fundoscopy identified 6 eyes (25%) with optic atrophy. Conclusions: Patients with MS presented mostly with subsequent episodes of ON sequels of it. It traces the study suggests peripheral visual field even normales.La central visual field affected population is representative of the economically active group so sustained treatment with IF-, minimizes the risk of ON and early entry into the activity.
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A 109 Personality and Multiple Sclerosis a preliminary study Aline Braz de Lima , Renata Alves Paes, Regina M. P. Alvarenga Objective: To describe personality factors of recently diagnosed Multiple Sclerosis (MS) patients, to correlate these factors with demographic (age and education level) and clinic variables (EDSS and length of disease). Methodology: 33 female patients recently diagnosed with relapsing-remitting Multiple Sclerosis (mean age: 36.96; mean educational level: 15.86; mean EDSS: 1.57; mean length of disease: 21.09 months) underwent psychological evaluation with the NEO-FFI personality scale. The Beck depression (BDI) and anxiety (BAI) scales were also used in this sample. Results: No significant symptomathology was identified for anxiety or depression. Anxiety was mild and there was no depression in this sample. As for the personality factors, 69.8% presented significant level of neuroticism; 57.6% extroversion; 48.5% openess to experience; 72.7% agreeableness and 78.8% conscienciosness. A high neuroticism (proneness to experience negative affect) has to do with: lack of coping skills; low self-esteem and self-efficacy, dependant behavior and stress susceptibility. Neuroticism (measured by NEO-FFI) is associated to MS symptom exacerbation in many longitudinal studies. Conclusion: Literature on the relationship between personality and MS is scarce and fragmented. There are no Brazilian studies on this subject. The patients personality might complicate the experience of living with a chronic and disabling neurological condition, such as MS. Individual factors might interfere with psychological adjustment. Depression or anxiety disorders might also come along as secondary conditions. To identify psychologically vulnerable patients through early psychological assessment can be useful and prophilatic to lower relapse rates, achieve better treatment adherence and quality of life. Keywords: personality, multiple sclerosis, NEO-FFI. A 110 Positive predictors of drug adherence in a sample of Mexican patients with Multiple Sclerosis Aguayo Arelis Adriana1,3, Macas Islas Miguel ngel1,2, Rabago Barajas Brenda Viridiana1,3 1University of Guadalajara. Department of Neurosciences; 2Mexican Social Security Institute. Western National Medical Center; 3University Enrique Daz de Len. Psychology Objective: To establish positive predictors for medication adherence in Mexican patients with MS. Methods: Forty-two patients diagnosed with relapsing-remitting MS treated with Glatiramer acetate. For inclusion criteria did not take into account gender or disability. Comprehensive assessments included: clinical history, questionnaires of personality, depression, caregiver burden and adherence, cognitive function was assessed using the Raos Battery, a drug administration log was delivered to the participants in order to complete. For data analysis a p-value <0.05 was considered significant. Results: A total of 27 women and 15 men, mean age 358.7, education mean13.75.3, first symptoms mean age 26.87.8, diagnosis age 29.4 8.2, age from first symptom to diagnosis 2.92.5, disease duration 5.54.6 years. EDSS 2.51.5.

Adherence of 62%, cognitive impairment 55%, depression 20%, caregiver burden 45%. Patients with predominance on neurotic characteristics 62%, responsibility 14%, extroversion 12%, openness 10% and kindness 2%.Variables and Average drug administration during five months. Singles 1348, married 1396 (p=0.036). Patients Switched 1357.7, not switched 1406.5 (p=0.026). Long-term memory retrieval, adherents 25.314.9, non adherents 34.914.9 (p=0.049). Thoghts of have been misdiagnosed 1357.5, thoghts of have been well diagnosed 1406.9 (p=0.043). Conclusions: Over half of the patients met criteria medication adherence. Personality, mood and caregiver burden are not related to adherence. Marital status, having a single treatment since the onset of illness, cognitive performance, and expectations of the patient about the diagnosis, are variables that can be related to adherence. A 111 Predictive Factors for Lower Walking Speed in Persons with Multiple Sclerosis Leandro Alberto Calazans Nogueira, Luciano Teixeira dos Santos, Pollyane Galinari Sabino, Regina Maria Papais Alvarenga, Luiz Claudio Santos Thuler UNIRIO Objective: The purpose of this study was to evaluate predictors for lower walking speed in PwMS. Methods: A cross-sectional survey was conducted. The study participants were 120 consecutive PwMS, who were able to walk, even with device assistance. Demographic and clinical data were collected. Walking speed was measured in 10-meter walk test. Possible predictive factors were assessed: disability, fatigue, visual functioning, balance confidence, physical activity level, walking impact, cognitive interference and motor planning. A forward linear multiple regression analysis examined predictors for lower speed. Results: Lower walking speed was observed in 85% of patients. Fatigue (41%), recurrent falls (30%) and balance problems were also presented, even with the mild disability (average EDSS=2.68) and the good level of physical activity showed in most of the sample. Dual-task procedure revealed 11.58% of walking speed reduction. Many participants (69.57%) imagined greater walking speed than motor execution (mean 28.42% greater). Physical activity level was the only characteristic that demonstrated no significant difference between groups (lower X normal walking speed). Many mobility measures were correlated with walking speed, however, disability, balance confidence, and motor planning were predictors for lower walking speed. Conclusions: Disability, balance confidence, and motor planning were predictors that may lower walking speed. A112 - Oral presentation Prevalence of pseudotumoral demyelinating lesions in an oncology reference center Yasmine C Torres1, Soniza V Alves-Leon1, Marco Antonio S D Lima2 1HUGG/UNI-RIO, 2INCA Objectives: Determine the prevalence of pseudotumoral demyelinating central nervous system (CNS) lesions in an

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Oncology center as well as their etiology in different age groups; identify the main clinical and radiological features of these lesions. Methods: This is a retrospective study performed at the National Institute of Cancer, Rio de Janeiro. We reviewed the medical charts of patients admitted to the Neurosurgery and Pediatrics services from 2007 to 2011, who were initially diagnosed with CNS tumors but received a final diagnosis of a pseudotumoral demyelinating disease. Results: 876 patients were admitted from 2007 to 2011 and 40 of these had a diagnosis of pseudotumoral CNS disease (4,5%). Eight patients (20%) had demyelinating lesions. The mean age at onset was 19.6 years (range 7-42 years). The male-female ratio was 1:1. Four patients had motor or sensory symptoms as the first manifestation of the disease; headache in two; visual symptoms and seizures in one each. Five patients had an acute onset of symptoms, while three presented with a history of progressive neurological manifestations. Lesions were present in brain in 62% and in the spinal cord in 38%. None of the patients had lesions in the brain and spinal cord simultaneously. Contrast enhancement was observed in lesions of 5 patients. Three patients underwent surgery (brain biopsy in two and lesionectomy in one). The mean time from onset of symptoms until the final diagnosis was 10.1 months (range 2-24 months). Final diagnoses were: ADEM in 3 patients, multiple sclerosis in 2, transverse myelitis in 1 and idiopathic inflammatory demyelinating disease in 1. Conclusion: Although uncommon, demyelinating diseases such as ADEM, multiple sclerosis and tranverse myelitis may have a clinical and radiological presentation similar to CNS tumors. Therapeutic modalities frequently employed in brain tumor patients (surgery, chemotherapy and radiotherapy) led to an improvement in the outcome in recent years but are associated with potential short and long-term adverse effects. The early recognition of pseudotumoral presentation of a demyelinating disease may result in the prompt institution of the correct treatment avoiding unnecessary medical procedures and neurological sequelae. A 113 Prevalence of Thyroid Dysfunction and Autoimmunity in Patients with NMO Maria de Fatima da Rocha da Costa, Regina Maria Papais Alvarenga UFRJ Objective: Neuromyelitis Optica (NMO) or Devics disease is an idiopathic, inflammatory and demyelinating disorder involving the central nervous system myelin preferentially affecting the optic nerves and the spinal cord. It was for many years, on its recurrent form, considered a clinical variant of the relapsing remitting multiple sclerosis. The autoimmune thyroid diseases are shown as the most prevalent autoimmune endocrine diseases among the general population. They are considered organ-specific diseases, determined by changes in the immune response, leading to loss of immunological selftolerance. Their main representatives, Graves disease and Hashimotos thyroiditis are often presented with opposing clinical events. Some authors report a possible association of NMO with autoimmune disorders, including the thyroid. This study aims to evaluate the prevalence of thyroid dysfunction and autoimmunity in patients with NMO.
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Measures: It is a transversal and descriptive study, in which are included 33 patients seen at a reference center for diagnosis and treatment of demyelinating diseases. Descriptive statistics were performed using the 2005 SPSS program (version 14.0). Categorical variables were presented in absolute and relative values and the quantitative variables as averages, standard deviations, median, minimum and maximum values. Results: The presence of thyroid dysfunction and autoimmunity were demonstrated in 3 and 2 patients respectively. Conclusions: In the studied series, it was possible to establish the prevalence of thyroid dysfunction in 9.1% and autoimmune thyroid disease in 6.1% of patients with NMO. A 114 Profile of the oral and pharyngeal phases of swallowing in patients with multiple sclerosis: preliminary analysis Aline Fernandes da Costa Ribeiro1, Dborah Santos Sales2, Mrcia Lyrio3, Regina Maria Papais Alvarenga4 Objective: The purpose of this study was to describe the profile of the oral and pharyngeal phases of swallowing in patients with multiple sclerosis. Methods: Cross-sectional study of fourteen consecutive patients with relapsing remitting, primary and secondary progressive MS [12 female , 2 male; 7 white, 7 african descendants; 6 RR, 5 PP and 3 SP forms of MS; median age 53,5 years, SD 11,43; median disease duration 12,43 SD 8,3; median EDSS 6,0 (2,59,0)], evaluated by a structural [Oral motor sensory evaluation adapted by Protocol for bedside clinical evaluation (Carrarade-Angelis, 2009)] and functional protocol for the assessment of swallowing disorders adapted by Dysphagia Risk Evaluation Protocol (Padovani et al, 2007), between 05/2012 and 09/2012 in the University Hospital Gaffre Guinle (Rio de Janeiro). Each patient was observed during swallow of 3, 5 and 10 ml paste and liquid boluses (water), both given by spoon, and solid food (half a bread). Results: Among the 14 MS patients, alteration of motricity were found in the following muscles: 5 (36%) in lips; 3 (21%) in tongue; 1 (7%) in the soft palate; 2 (14%) in the jaw and 13 (93%) in the larynx. The frequency of dysphagia was not significantly different between the RR, PP and SP forms of MS. Sensitivity disorders were found in tongue (14%, N=2), and soft palate (14%, N=2). Dysphagia for liquid was found in 36% (N=5) and for paste bolus in 50% (N=7) of the cases. The frequency of dysphagia for liquids was higher in the group of patients with severity of disability level as measured by EDSS scores equal to or higher than 6.0. Conclusion: These preliminary results emphasize the importance of the assessment and management of swallowing function in Brazilian MS patients, especially in those with high grade of disability level. A 115 Sleep Quality and Disease Progression among Multiple Sclerosis Patients Josiane Lopes, Edson Lopes Lavado, Ana Paula Kallaur, Sayonara Rangel de Oliveira, Tas Brussantin de Oliva, Wilda Lice Carvalho Jennings Pereira, Renato Marques de Andrade, Milton Csar Rodrigues Medeiros, Kleber Edson Kawagoe,
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Rafael Gustavo de Mello Couto, Rafael William de Souza, Edna Maria Viscossi Reiche, Damacio Ramn Kaimen-Maciel State University of Londrina, Londrina, Parana, Brazil Objective: To determine the association between sleep quality and the multiple sclerosis (MS) progression. Method: This was a cross-sectional study on a sample of 117 MS patients. To stage the degree of disability, the Expanded Disability Status Scale (EDSS) was used. The assessment of sleep quality was performed by Pittsburgh Sleep Quality Index (PSQUI) and Epworth Sleepiness Scale (Epworth). The sample was divided into two groups based on the EDSS score ( 3 points and > 3 points) with correlation values of PSQUI and Epworth taking the significance level to be 5%. Result: Most of the sample were women (75.2%), caucasians (83.7%, MS with relapsing-remitting clinical course (72.6%) with median EDSS 3 (1.25-4) points, aged 42 (29.75-51) years, length of time with the disease 67 (30-124) months, and Epworth and PSQUI 6 (3-10), respectively. Lower PSQUI scores were significantly associated with lower EDSS scores (P = 0.04). Regarding the level of sleepiness (Epworth) was also significantly associated with lower scores on the EDSS (P = 0.05). Conclusion: The best levels of sleep quality and the normal levels of sleepiness are associated with lower MS progression. A 116 Reactivation of disease activity in patients with multiple sclerosis after Natalizumab discontinuation: a case report in Venezuela Soto, I.1,2, Ferrer, O.1 Molina, O.1Mora, E1, Villalobos,V2 1Hospital Universitario de Maracaibo, 2Hospital Clnico de Maracaibo. Venezuela. ibissoto@hotmail.com Objectives: To describe a clinical case of a patient with severe signs of neurologic focalization, MRI based, following the treatment discontinuation of Natalizumab. Method: Analysis of the clinical evolution and MRI findings and its interpretation. Results: 52 years old patient, diagnosed with Relapse Remitting Multiple Sclerosis in treatment with Betaferon for 7 years, was switched to Natalizumab. Infusions were administrated for the first three months, and then treatment was discontinued. Three months after the last infusion, the patient showed language disorders, decreased muscle strength in left hemisphere, difficulty in walking and disorientation in space and time. Physical examination showed consciousness, mixed aphasia, left central facial paresis, left global hemiparesis. CSF study was performed, JC virus test negative and brain MRI showed multiple hypertensive T2 FLAIR lesions. Solumedrol 1 g daily for 5 days was indicated as treatment. Based on the progressive and favorable improvement, it was decided to continue with Solumedrol 1 g IV monthly for 3 months. Conclusion: Based on the findings described, the clinical approach and the final interpretation of the case, we suggest that the discontinuation of Natalizumab treatment exerted a physiological condition that activated the clinical manifestations of the disease. The introduction of new therapies in our country is very recent and there is little experience regarding the transition between the available therapies. The limited reports that expose

the appropriate management of the patient during the transition between Disease Modifying Therapies in patients with Multiple Sclerosis; the presentation and discussion of clinical experiences is necessary to help and improve the adequate management of such patients in a safe and effective manner. A 117 Recurrent myelitis and tumefactive supratentorial lesion in childhood: neuromyelitis optica (NMO)? S. dos Santos1, A. Penna e Costa1, E. Magalhes1, M. Calheiros1, A. Friedreich2, Bastos2, De Azevedo L, T. Saad1 1IFF-FIOCRUZ/Neuropediatria; 2Clnica Professor Pompeu Introduction: CNS demyelinating disorders in childhood have different clinical presentation and evolutive course. In relation to NMO, 90% of the children exhibit more relapses, greater severity of disease and most limiting residual morbidities than adults. Objective: To describe a child with two episodes of myelitis and a supratentorial tumefactive demyelinating lesion, discussing the clinical hypothesis of NMO in attempted to define the most adequate therapy. Method: Case report. Results: FCS, 9-year-old afro descendant female, admitted in 2008 with cervical burning pain and hiccups, evolving to flaccid tetrapasesis. No preceding history of infection or vaccination. Hiperproteinorrachia. MRI: high T2 signal in medullar gray matter from the medulla oblongata to C7. After pulsotherapy with methylprenisolone, physical examination and image returned to normal. In 2009, new relapse with left crural paresis and pyramidal signs. MRI showed a tumefactive lesion in the right frontoparietal region, with contrast enhancement and perilesional edema. After pulsotherapy, had maintained residual alteration in SSP and MRI. Admitted in 2010 showing gait ataxia and left arm tremor. MRI with extensive medullar gray matter demyelination and necrosis. Improvement after venous steroids and gradual titration. At the moment, using glatiramer acetate for 9 months without new relapses. Anti-aquaporin-4 antibodies and OCB in CSF were negative. Conclusion: The Wingerchucks 2006 NMO-criteria cannot be fulfilled due to absence of optical neuritis. However, extensive myelitis and single supratentorial tumefactive lesion are uncommon presentations of Multiple Sclerosis. In this way, the child was included into the NMO-spectrum being initiated imunomodulatory therapy with glatiramer acetate and not interferon. A 118 Unit Registration demyelinating diseases Fleitas Vernica, Florentn Sara, Jos Snchez, Margarita Paredes. Central Hospital of the Institute of Social Security, AsuncionParaguay Introduction: The unit of demyelinating diseases began his registration in September of 2010, inspired by the commitment to treat and manage patients with Multiple Sclerosis (MS) on all bearing in mind that this is the only insurance of the country that considers within its coverage medication for this pathology.

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Objective: Provide the demographic and clinical characteristics of patients with MS of the Unit. Material and method: We included patients who fulfill the criteria for Mc Donalds 2010 for MS, excluding cases dubious and false diagnoses. The data were taken from clinic records used for the patients in the unit, the data were loaded into a database and the images were archived in a CD format Results: The unit has now 143 patients with a diagnosis of MS, the majority of them come from urban area, these 101 (70.6 %) patients were female and 42 (29.4 %) male, taking into account the clinical form 128 (89.5 %) patients are MS variety relapsingremitting (EMRR) ,11 (7.6 %) secondary progressive MS (MSSP) and 4 (2.8 %) primary progressive MS (MSPP), the average age of patients is 33.6 years, all patients with variety RR are treated with interferons , patients with treated with mitoxantrone EMSP . The scale of disability (EDSS) for the MSRR goes from 1.5 to 4.0 , for the MSSP OF 6.0 -8.0 and the MSPP of 4.5 to 6.5 Conclusion: In this series of cases predominated the MSRR clinical form, was more common in females and the average age of patients is 33.6 years. A 119 Relapsing Remitting Multiple Sclerosis (RR-MS) in Chile. Clinical characterization of patients treated with immunomodulators, in the public system, 2008-2012 Nogales G., Jorge1, Aracena C., Rodrigo1, Daz Z., Vannia1, Merino A., Paula1, Z., Sergio1, Eloiza C., Claudio1, Acevedo G., Lorena1, Martnez E., Sfora1, Araya S., Casandra2, Labb R., Silvia1, Flores C., Jazmn3 1Servicio de Neurologa, Complejo Asistencial Barros Luco; 2Escuela de Fonoaudiologa de la Universidad Autnoma de Chile; 3Escuela de Fonoaudiologa de la Universidad Andrs Bello Introduction: Communicating local experience RR- MS patients is important. In Chile the public health system provides coverage immunomodulatory since 2008. Objective: To describe baseline clinical characteristics and outcome of patients with RR-MS immunomodulatory therapy evaluated in the Barros Luco Hospital. Method: We reviewed clinical records of 314 patients. Results: There were 212 women, mean age was 35.17 years (1263). The average development time was 67 months evaluation. 44.3% of patients living in the metropolitan area. We don`t observed latitudinal gradient in the presentation of cases. The average rate of outbreaks two years prior to the assessment was 1.74 (0-6). Mean baseline EDSS was 3.02 (0 -7.5). Most of the patients had at least 3 Karkoff -Tintore criteria in baseline MRI with average 4.38 (1-7). The main manifestations of debut were: sensory, motor and optic neuritis with 64, 56 and 52% respectively. 28.9% had some cognitive impairment. 177 cases (57.46%) had depression of some magnitude to be severe in 75 cases. 125 patients had significant fatigue at baseline. Note 22.5 and 25.6% of treatment failure during the first and second year respectively. Conclusion: Patients evaluated resemble those published in the literature regarding clinical presentation, symptomatic problems and response to treatment. We also note the absence of latitudinal gradient unlike the northern hemisphere.
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A 120 Relapsing remitting multiple sclerosis (RR-MS) in Chile. The six-minute walking test in the complex care patients Barros Luco (CABL) Nogales G., Jorge Servicio de Neurologa, Complejo Asistencial Barros Luco Martnez E., Sfora Servicio de Neurologa, Complejo Asistencial Barros Luco Aracena C., Rodrigo Servicio de Neurologa, Complejo Asistencial Barros Luco Daz Z., Vannia Servicio de Neurologa, Complejo Asistencial Barros Luco Agurto M., Paula Servicio de Neurologa, Complejo Asistencial Barros Luco Eloiza C., Claudio Servicio de Neurologa, Complejo Asistencial Barros Luco Acevedo G., Lorena Servicio de Neurologa, Complejo Asistencial Barros Luco Cepeda Z., Sergio Servicio de Neurologa, Complejo Asistencial Barros Luco Introduction: Six-minute walking test (TM6 `) is a tool for evaluating patients with RR-MS. Objective: To characterize the behavior of RR-MS patients in the TM6 `treated at the CABL and its relationship with other variables, before immunomodulatory therapy. Method: Standardized evaluation of 108 patients using `TM6, with analysis of distance traveled, speed and percentage of physical capacity as Enrigth and Sherryl equation. Scores correlated with Expanded Disability Status Scale (EDSS) and fatigue level according Krupp scale. Results: 66% were women. The average age was 39.7 years. The average disease was 6.3 years. The mean body mass index was 26. The average distance traveled in TM6 `was 378 meters with physical capacity percentage of 53%, speed 1.0 m / s and 5.1 scoring average fatigue. As we observed that patients EDSS between 0 and 2.5 average fatigue were 3.6, 442.1 meters averaging toured, with 67.9% of their physical capacity and speed 1.2 m / sec. The with EDSS between 3.0 and 4.0 showed fatigue score of 4.4, 374.9 meters averaging toured with percentage of 60.3% and speed 1.0 m / s. The with EDSS between 4.5 and 6.5 showed fatigue score of 5.4 meters averaging 221.2 toured with percentage of 37.1% of their physical capacity and speed 0.6 meters / second. Conclusion. The TM6 ìs useful in the overall evaluation of RRMS discriminate functional levels. Patients evaluated exhibited lower yields 75% of the physical capacity considered normal. There seems to be a relationship between performance in TM6 with EDSS level and degree of fatigue. A 121 Relapsing Remitting Multiple Sclerosis (RR-MS.) in Chile. Description of socioeconomic aspects and impact of the cost of drug therapy in complex patients Barros Luco (CABL) Aracena C., Rodrigo, Daz Z., Vannia, Nogales G., Jorge, Labb R., Silvia, Agurto M., Eloiza C., Claudio, Acevedo G., Lorena, Cepeda Z., Sergio, Martnez E., Sfora, Araya S., Casandra Servicio de Neurologa, Complejo Asistencial Barros Luco Introduction: Knowing the family contributes to the overall management of patients with RR-MS. Objetive: To describe socio-economic aspects and clinical RRMS carriers in controlled immunomodulatory therapy in Santiago de Chile CABL.
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Method: We reviewed medical records of 42 patients: marital status, number of members and monthly family income, education, score on the Expanded Disability Status Scale (EDSS), fatigue and depression level. Results: The average was 3.8 members per family (2-6). In 18 cases only one adult lived more in the family being the sole family support network. In 6 of them this support was ineffective. The average monthly household income was U.S. $ 633.5 (126 -2100), the average monthly cost of immunomodulators in Chile is $ 1365. In 24 patients there was a history of having higher education at least partially, in 15 secondary and primary partial in 3. The mean EDSS was 2.96 (1 to 6.5). The average fatigue Krupp questionnaire was 4.15 (1-7). There were 14 patients with severe depression assessed by questionnaire Hamilton. In patients with greater than 3.5 EDSS or severe depression observed a tendency for absence of stable partner (8, 11 and 9, 14 respectively). Conclusion: Several of our patients, in addition to physical disabilities and mental characteristics of MS-RR, have poor family support network that affects their quality of life. Due to this fact any copayment for access drugs becomes an added difficulty and insurmountable. A 122 Relapsing remitting multiples sclerosis (RR-MS) IN Chile. Evolution of dysphagia and dysarthria in 84 patients Araya S., Casandra1, Flores C., Jazmn2, Lara G., Fabiola2, Quezada J., Gastn2, Nogales G., Jorge3, Aracena C., Rodrigo3, Agurto M., Paula4, Eloiza C., Claudio4, Acevedo G., Lorena4, Cepeda Z., Sergio4, Daz Z., Vannia4, Martnez E., Sfora4, Labb R., Silvia4 1Escuela de Fonoaudiologa de la Universidad Autnoma de Chile; 2Escuela de Fonoaudiologa de la Universidad Andrs Bello; 3Servicio de Neurologa del Hospital Barros Luco, Departamento de Neurologa Sur de la Universidad de Chile; 4Servicio de Neurologa del Hospital Barros Luco Introduction: In the management of MS-RR, directed evaluation of swallowing and speech contribute to better monitoring. Objectives: Describe the evolution of deglutition and speech disorders in 84 patients with RR-MS. Method: Review clinical records of results in the clinical assessment of speech and swallowing and Swallowing severity scales of the ASHA Rating Scale and Intelligibility Rating Scale of J. Duffy, before and during immunomodulatory therapy. Results: In swallowing, the initial assessment shows that 20 patients (24%) had normal swallowing, 36 (43%) discrete alteration without dysphagia swallowing; 17 (20%) mild dysphagia and 11 (13%) moderate dysphagia. In evaluation at 12 months: 21 patients (25%) with normal swallowing, 39 (46%) with abnormal deglutition without dysphagia, 14 (17%) with mild dysphagia and 10 (12%) with moderate dysphagia. In speaking, the initial assessment shows normality in 27 patients (32%); slight alteration without dysarthria in 49 (58%), mild dysarthria in 6 (7%) and moderate in 2 (2%). The control shows that patients with normal speech are 17 (20%) those with the signs of alteration without dysarthria 57 (68%), with slight dysarthria 6 (7%) and with moderate dysarthria 4 (5%). Conclusions: The evolution of swallowing in patients tested is stable in both measurements diagnostic categories tend to stay. In

the speech evaluation, it is observed that the time can affect basic motor processes since the results of the second evaluation tend to have more changes than the baseline. A123 - Oral presentation Relative Frequency Of Neuromyelilis Optica in Patients with Idiophatic Inflammatory Demyelinating Diseases- A Case Study from Florianopolis and Joinville, Santa Catarina, Brazil Suzana Costa Nunes Machado, Adaucto Wanderley da Nbrega Junior, Marcus Vinicius Magno Gonalves Objective: Collect data from cases of patients with neuromyelitis optica (NMO) attended at Multiple Sclerosis center in Florianpolis and Joinville, Brazil, during 2011, and establish the relative frequency of NMO among patients with Idiophatic Inflammatory Demyelinating Diseases (IIDDs). Method: Consultation forms from 104 patients attended in 2011 in Florianopolis and 96 forms from patients attended in 2011 in Joinville.The MS diagnosis followed the criteria of MacDonald (2010) e for NMO follow criteria established by Wingerchuck (2006). Information about gender, ethnic group, diagnosis date and expanded disability status scale (EDSS) of the last follow up were recorded. Results: 100 cases of MS, 1 case of Acute Disseminated Encephalomyelitis (ADEM), 3 cases of NMO were recorded in Florianopolis center. Among the cases of NMO two were female and all were caucasian. The average age was 40 years old and the EDSS scores lied from 2.0 to 5.0. In Joinville 96 cases of IIDDs were analyzed of which 85 were cases of MS, 3 cases of Clinical Isolated Syndrome (CIS) and 8 cases of NMO. Among the cases of NMO 6 were female, 2 were male. Of these 6 were caucasian and 2 afro-descendent. The average age was 38 years old and EDSS scores lied between 1.0 to 5.5. Conclusion:The relative frequency of NMO among IIDDs diagnosis 2011 at Multiple Sclerosis Center in Florianopolis, Brazil was 2,88 and at Joinville was 8,33.
A124 Research of locus Xq22.3 as transcription source for endogenous retrovirus and its association with the multiple sclerosis etiology G. S. Olival1, R. B. Thomaz1, C. Tilbery1, T. S. Faria2, L. S. Nali2, A. C. Penalva de Oliveira3, J. S. Casseb3, J. V. Bermudez3, V. Cavenaghi1, L. Moraes3, C. Fink4, L. Sumita4, C. M. Romano4 1Santa Casa de So Paulo (So Paulo - SP, BR); 2Instituto de Medicina Tropical - USP (So Paulo - SP, BR); 3Instituto de Infectologia Emilio Ribas (So Paulo - SP, BR); 3USP (So Paulo - SP, BR); 4Instituto de Medicina Tropical (So Paulo - SP, BR) Introduction: Multiple Sclerosis (MS) etiology is still unknown. Endogenous retroviruses are fossils virus who constitutes 8% of the human genome, and the over expression of a family specifies known as Multiple Sclerosis Endogenous Retrovirus (MSRV) has been associated with the etiology of MS. The MSRV envelopes associated with multiple sclerosis are defined for transcripts that

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may originate from different chromosomes, the main source being the locus Xq22.3 in previous studies. Objective: The objective of this study was to verify if the HERV-W/Xq22.3 locus is associated with the etiology of MS. Methods: 1) conducted an automated search of the human genome promoter sequences transcription in 10 000 base pairs near the locus HERV-W / Xq22.3. 2) were sequenced and analyzed 1085 base pairs of HERV-W / Xq22.3 of 47 MS patients from different ethnic backgrounds and different clinical presentations and 14 healthy individuals. Results: We found several potential binding sites for cofactors in human genome that could serve as activators for MSRV/Xq22.3 transcription. On the other hand, we found that both patients with MS as healthy individuals the do have a stop codon in 39 position, preventing the expression of a complete protein. No additional amino acid substitution has been found in both groups. Conclusion: The results suggest that mutations in the locus Herv-W / Xq22.3 previously associated with transcripts of MSRV are not related to the MS etiology and must have been artificially generated. A 125 Self Awareness and Anosognosia in Multiple Sclerosis E.G.Reich, E.D.Arias, M.D.Kerszberg Centro De Neurociencias, Hospital Julio Mendez, Universidad De Buenos Aires Background: Anosognosia is an impaired ability to recognize the presence of deficit or disease and is sparse studied in MS. Objective: To asses the prevalence of anosognosia in Multiple Sclerosis (MS). Methods: 39 patients (27 females and 12 males) with diagnosis of definite MS, were studied. The mean age was 34.6 years and the clinical picture was RR in 24 cases, and SP in 14 patients. Mean time of evolution was 4.7 years and the mean EDSS was 3.0 .The education period was 8.4 years . All the patients were evaluated with neuropsychological standards. The specific scales to evaluate anosognosia were the Visual-Analogue Test for motor impairment (VATA-m) and the Mayo-Portland Adaptability Inventory (MPAI). The severity and stages were measured with the Bisiach Scale. Coincidences and discrepancies between caregivers and patients in activities of daily living (IADL) and correlation between MRI number, size, and localization of lesions was established. Results: We observed a highly prevalence of anosognosia (59%), with dissociation between the perception of this symptom comparing patients and caregivers. The grade of anosognosia was mainly 1 or 2 and the awareness of impairment was strongly linked to deficits in neurocognitive tasks and fine motor skills. Our findings correlated positively with EDSS, evolution time and lesions located in the right temporo-parietal subcortical areas. No relationship with other variables (age, sex, education, treatments) were observed. Conclusions: Anosognosia is a highly prevalent disorder in MS patients, suggesting a dysfunction in the mechanisms of self awareness, with implications in the ADL and with predictive value on poor functional outcome. Neuroimaging studies revealed more often localization of lesions in right parieto temporal hemispheric localization.
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A 126 Serum levels of vitamin D in Brazilian patients with multiple sclerosis Celso LS Oliveira, Joseph BB Brooks, Sidney Gomes, Marcus VM Gonalves, Francisco TM Oliveira, Sonia BF Ribeiro, Heloisa H Ruocco, Ctia Silva, Fabio Siquineli, Yara D Fragoso. Objective: To study levels of vitamin D in Brazilian patients with MS and to correlate these levels to disease progression (EDSS / disease duration). Methods: Serum levels of 25-OH and 1.25 dihydroxi vitamin D were assessed and correlated to disease progression in patients with MS. Results: The group consisted of 156 patients (39 M and 117 F) with average age of 45.6 years. Disease duration was, on average, 6.6 4.5 years, while the average EDSS was 2.13 2.04. All patients lived in subtropical areas with hot summers and mild winters. There were no dietary restrictions that could influence vitamin D levels. Average levels of 1.25-diOH were 26.8 17.6 pg/ml; range 5.3 to 98 pg/ml (n=40) [normal levels=16-60 pg/ml]. Levels of 25-OH were 45.5 12.2 ng/ ml; range 2.8 to 92 ng/ml (n=156) [normal levels=30-74 ng/ ml]. There was no significant correlation between disease progression and serum levels of 1.25-diOH and/or 25-OH vitamin D in these patients. Conclusion: Serum levels of vitamin D (25-OH and 1,25 diOH) were typically within the normal range and were not correlated to neurological disability. A 127 Clinically Isolated Syndrome: Study in Venezuelan Patients Soto, I.1, Molina, O.1, Armas, E.1, Leon, R.1, Zalcman, J.1, Ravelo, M.E.1, and Soto, A.1 1On behalf of the Venezuelan Committee for Treatment and Research in Multiple Sclerosis - VECTRIMS. Venezuela. ibissoto@hotmail.com Objective: To describe the clinical, epidemiological, diagnostic, and treatment approaches of Clinical Isolated Syndrome (CIS) in Venezuela. Methods: Retrospective analysis of clinical records from the Instituto Venezolano de los Seguros Sociales (IVSS)-Multiple Sclerosis National Program (PNEM) Database, of patients with CIS from 2001 to 2011. Results: In the evaluated period, 1908 patients were diagnosed with MS as per PNEM records; 4.1% had an initial diagnostic of CIS and 70% were women. Although from different regions of the country, 49.3% were located in Caracas (Metropolitan Area). The most frequent associated symptoms were Sensory (56.9%), Motor (53.5%), Optic Neuritis (17.7%), ocular movement disorders (18.9%), ataxia (11.3%) and bladder dysfunction (13.9%). Less frequent symptoms were fecal incontinence (5%), sexual dysfunction (2.2%), abnormal movement disorders (6.3%), seizures 3.1%, and cognitive disfunction5%. Diagnostic approaches included Magnetic Resonance Imaging (MRI) in Brain (100%), Cervical Spinal Cord (44.3%) and Dorsal Spinal cord (30.3%); Visual Evoked Potentials (EP) (72.1%), Brain Stems EP (22.7%), Somatosensory EP (22.7%), Cerebrospinal Fluid (CSF) Analysis (99.4%) and immunologic screening (100%). All patients were treated as follows: Interferon Beta 1a IM (40.3%),
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interferon Beta 1b (27.8%), Interferon Beta 1a SC (16.4%), and Glatiramer Acetate (6.3%). Conclusion: CIS was found in low proportion of those patients included in the PNEM; it occurs predominately in women between 21 and 40 years. Sensory symptoms were the most frequent, followed by motor dysfunction. Brain MRI was performed in 100% of patients. Patients came mainly from metropolitan area of Caracas. All patients were treated with First Line immunomodulatory therapy. This is the first report of CIS in Venezuelan patients. A 128 Brainstem symptoms as first attack in NMO Brazilian experience F. M. H. Jorge1, P. Melo1, S. Apostolos1, R. Simm1, C. Hobi1, L. Moraes1, M. Fazzito1, D. Sato2, M. Lana-Peixoto3, D. Callegaro1 1Hospital das Clnicas FMUSP; 2Tohoku University Graduate School of Medicine; 3Faculdade de Medicina da UFMG Background: Neuromyelitis optica (NMO), an inflammatory demyelinating disease of the central nervous system, that usually causes severe optic neuritis and myelitis attacks. However neurological symptoms may occur due to the involvement of brain structures outside of the optic nerve or spinal cord. Brainstem symptoms can also ensue as a result of an extension of a cervical spinal cord lesion or as a brainstem restricted lesion. Previous reports demonstrate that brainstem symptoms (particularly incoercible nauseas, vomiting and hiccups) are associated with NMO. First-attack of brainstem symptoms in NMO patients has diagnostic and therapeutically implications in clinical practice. Objective: The aim of the present study is report the prevalence of brainstem symptoms without an extension of longitudinally extensive transverse myelitis as first attack of NMO in a Brazilian cohort. Methods: Retrospective data of 40 patients with NMO fulfilling Wingerchuks criteria were analyzed in Hospital das Clnicas of So Paulo. All have answered a questionnaire about the initial symptoms of the disease. Results: The sample consists of 40 NMO patients, female preponderance (87%), mean age at onset was 37 (range 9-66), and median EDSS score at last visit: 5.0 (range 1- 8). NMO IgG Status was positive in 27 out of 30 pacients who were tested (90%). There where brainstem symptoms as first attack in 5 of 40 (12,5%), being 80% female, 40% caucasian, 40% afro-brazilian and 0% native brazilian. Conclusion: In our sample brainstem symptoms triggered the clinical picture of NMO disease in 12,5% of patients. The authors suggest that brainstem symptoms may be regard as an index event of NMO disease, which implies early diagnosis and therapeutical approach. A 129 Subcutaneous interferon beta-1a in paediatric patients with multiple sclerosis: regional outcomes in an international retrospective study (REPLAY) Tenembaum, S.,1 Krupp, L. B.,2 Pohl, D.,3 Ghezzi, A.,4 Boyko, A.,5 Meinel, M.,6 Moraga, M. S.,6 McIIroy, C.,7 Lehr, L.,6

Banwell, B.;8 on behalf of the REPLAY Study Group 1Hospital de Pediatra S.A.M.I.C. Prof Juan P Garrahan, Buenos Aires, Argentina; 2Lourie Center for Pediatric MS, New York, USA;3 Pediatric Multiple Sclerosis Clinic, Childrens Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada; 4Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Gallarate, Italy; 5Russian State Medical University, Moscow, Russia; 6Merck Serono S.A., Geneva, Switzerland; 7Merck Serono Ltd, Feltham, UK; 8Pediatric Multiple Sclerosis Clinic, The Hospital for Sick Children, University of Toronto, Ontario, Canada Objective: The REPLAY study showed that adult doses of subcutaneous interferon beta-1a (scIFN-1a, 44 and 22 mcg 3x weekly) were well tolerated and associated with reduced annualized attack rate (AAR) in paediatric patients with multiple sclerosis. Post hoc analyses explored regional differences in treatment (Tx) practice and outcomes. Methods: Study of patients who had received 1 dose of scIFN1a for demyelinating events (DME) when aged <18 years, using retrospective data from medical records. Outcomes included prespecified medical events (PSMEs) and medically confirmed clinical attacks. Patient characteristics, Txs and outcomes were compared in the USA and rest of world (RoW). Results: Data from 307 patients were analysed: USA n=139; RoW n=168. For USA vs RoW, mean baseline body mass index: 26 vs 21 kg/m2; median time from 1st DME to 1st disease-modifying drug (DMD): 0.7 vs 1.1 years; patients who had received 1 other DMD prior to scIFN-1a: 33.8% vs 13.7%; initial scIFN-1a dose 44 mcg: 88.9% vs 24.3%; median time on Tx: 1.07 vs 1.73 years; proportion of patients receiving scIFN-1a at study end: 58.3% vs 75.6%; proportion of patients who switched Tx: 28.8% vs 13.1%. 54.7% of patients had 1 PSME after scIFN-1a initiation (USA 52.5%; RoW 56.5%); minor regional differences in PSMEs were seen. AAR was similar in USA and RoW prior to scIFN-1a (1.71 vs 1.84) and decreased after starting scIFN-1a, with a greater decrease in RoW vs USA: AAR (USA vs RoW): during scIFN1a Tx 0.75 vs 0.37, from scIFN-1a initiation to study end 0.83 vs 0.39. Median time from scIFN-1a initiation to 1st attack: 14.2 (USA) vs 27.2 months (RoW). Conclusion: Across all regions, scIFN-1a was well tolerated and associated with reduced AAR. Observed regional differences may be explained by differing access to healthcare, disease severity and/or other factors between the USA and RoW. A130 - Oral presentation Fatigue and disability Helcio Alvarenga Filho Institution: Universidade Federal do Estado do Rio de Janeiro (UNIRIO) Motor dysfunction and fatigue are the two most common and debilitating impairment associated with Multiple Sclerosis. Pyramidal syndrome occurs in 63-100% of patients irrespective of the clinical form of the disease or ethnicity. Fatigue is reported by 53%-92% of patients and is often described as the most disabling MS symptom, worse than the pain or physical disability, limiting routine daily activities and reducing the quality of life. The origin of central fatigue in MS is unknown. Fatigue has been related to

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motor dysfunction, high levels of pro inflammatory cytokines and changes in brain activation. Most of the knowledge about subjective experience of fatigue in MS patients came from the studies applying two self questionnaires: The Fatigue severity scale (1989) and the Modified fatigue impact fatigue with three domains: physical, cognitive and social presented (1994). The perception of fatigue measured by the FSS or the MFIS and subscales has been related to higher disability measured by EDSS in some studies but not in others. Objective tests have been applied to measure motor fatigue by the decline in motor function during physical activity. A reduction in walking speed over a distance of 500 meters and in the Six-Minute Walk Test (6MWT) has been showed in patients with MS and it was attributed to motor fatigue. A limitation of all those studies is that all MS patients evaluated had some degree of disability with EDSS scores ranging to 1,5 to 6,5. We will present in LACTRIMS the results of studies developed in the post graduate program in neurology (UNIRIO) applying subjective and objective tests in MS patients with relapsing remitting course and progressive primary disease and different scores of disability. It was possible to demonstrate that although there is a correlation between fatigue and motor dysfunction, fatigue also occurs in patients without disability, reinforcing the central theory. A 131 Survival Outcomes and Cause of Death from the 21-Year Long-Term Follow-Up Study Reder A.T.1, Goodin D.2, Ebers G.3, Cutter G.4, Rametta M.5, Kremenchutzky M.6, Oger J.7, Langdon D.8, Beckmann K.9 1Department of Neurology, University of Chicago, Chicago, IL, United States; 2Department of Neurology, University of California, San Francisco, CA, United States; 3Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom; 4Department of Biostatistics, UAB School of Public Health, Birmingham, AL, United States; 5Bayer HealthCare, Wayne, NJ, United States; 6London Health Sciences Centre, London, ON, Canada; 7Neuroimmunology Laboratories and Multiple Sclerosis Clinic UBC, Vancouver, BC, Canada; 8Department of Psychology, Royal Holloway, University of London, Surrey, United Kingdom; 9Bayer HealthCare, Berlin, Germany Few studies have investigated the long-term effects of disease modifying therapies (DMTs) on clinical outcomes, mortality, and cause of death in patients with multiple sclerosis (MS). Objective: To evaluate the effect of IFN-1b (Betaseron/ Betaferon) on long-term clinical outcomes and COD in patients who participated in the pivotal IFN-1b trial conducted between 1988 and 1993, 21 years after the start of randomized treatment. Methods: Originally, 372 patients were randomized to receive IFN-1b 50 g (n=125), IFN-1b 250 g (n=124), or placebo (n=123) eod. Patients remained on randomized treatment during the trial for a median of 3.8 years (maximum 5.1 years), before licensed treatment became available. Clinical status of alive patients was assessed with a questionnaire, including a validated phone-based Expanded Disability Status Scale (EDSS). Among patients who died, the cause of death and MS relationship was
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determined by an adjudication committee masked to treatment assignment. Results: Original randomization to IFN-1b 250 g showed 46.8% reduction in the risk of death over the 21-year long-term follow-up (21-Y LTF) period compared with placebo (log-rank, p=0.0173). Clinical outcomes at 21-Y LTF were similar across the treatment arms. The categorical cause of death has been determined for 82.7% of deceased patients. 78.3% of deaths were MS-related. Conclusion: With near-complete patient ascertainment (98.4%), an initial randomized control trial design, and the longest period of follow-up for a treatment-exposed MS population, these data provide insight into both the effects of IFN-1b on survival/mortality and long-term clinical outcomes. The difference in mortality between placebo and active treatment appears to be MS-related. Also, COD due to pulmonary infections was more frequent in placebo compared with active treatment. A 132 SWI phase values of the whole gray and white matter in patients with multiple sclerosis and neuromyelitis optica: a comparative study with controls Vanessa G A Itagiba1, Fernanda C Rueda-Lopes1, Emerson L Gasparetto1, Thomas M Doring1, Romeu C Domingues2, Paulo RV Bahia1 1UFRJ- Universidade Federal do Rio de Janeiro e CDPI Clnica de Diagnstico por Imagem (DASA); 2CDPI - Clnica de Diagnstico por Imagem (DASA); UFRJ- Universidade Federal do Rio de Janeiro Purpose: To analyze the phase change on susceptibilityweighted imaging (SWI)-filtered phase images in the whole gray matter (GM) and white matter (WM) of multiple sclerosis (MS) and neuromyelitis optica (NMO) patients compared to healthy controls (HC). First, we sought to create a reliable, reproducible and highly-automated framework for structurespecific analysis of SWI-filtered phase images. Second we aim to apply this technique to groups of MS and NMO patients and HC in order to analyze the phase change in the whole GM and WM. Material and Methods: 16 relapsing-remitting multiple sclerosis patients, 9 NMO patients and 24 HC were imaged on a 1.5T scanner. A post processing method was used to create single automated generated masks for the whole GM and WM. Radian values (RV) were determined for the whole GM and WM of MS and NMO patients and HC. Results: A significant difference (p= 0,0182) was detected between the RV of the GM of MS patients and HC. No difference was detected when comparing the RV of the WM of MS patients and HC (p = 0,1416). There was also no difference of the RV of the GM (p = 0,6966) and WM (p = 0,9282) when comparing NMO patients and HC, neither when comparing NMO and MS patients GM (p=0,5352) and WM (p= 0,5222). Conclusions: We were able to assess the whole GM and WM of MS and NMO patients and we found a significant difference between the RV of the GM in MS patients compared to HC. The possibility of having a single mask including the whole GM and WM would improve the iron overload detection.
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Clinical Relevance statement: This post processing method is fast, easy to execute and provides a wider range of information of the whole brains phase changes what would improve the iron overload detection. A 133 Symptoms of Oropharyngeal Dysphagia in Multiple Sclerosis: prevalence and clinical findings in a Brazilian population DS Sales, A Fernandes, M Lyrio, CCF Vasconcelos, LC Thuler, RMP Alvarenga Ps Graduao em Neurologia - Universidade Federal do Estado do Rio de Janeiro, Brazil; Hospital da Lagoa Objective: The purpose of this study was to determine the prevalence of swallowing symptoms in MS patients applying DYMUS. Methods: A hundred consecutive patients with relapsing remitting, primary and secondary progressive MS [69 female, 31 males; 42 white, 52 African descendants; mean age 41,67 years; SD 13,14, mean disease duration 9,25; SD 8,06, mean EDSS 3,5(0-9)], were screened by the DYMUS Questionnaire for the assessment of dysphagia in MS, between 08/2009 and 01/2010 in the Hospital of Lagoa (Rio de Janeiro). The DYMUS is a self-reported questionnaire composed by 10 questions that can be subdivided in two subscales: dysphagia for solids and liquids. All the answers are dichotomous, coded as 1 or 0, depending on the presence or the absence of the event. At onset all patients answer a question do you have swallowing problems? Irrespective of their response, DYMUS were administered. Dysphagia is defined by, at least, one abnormal response. Results: Among the 100 MS patients, 58 (58%) were classified as having dysphagia. For the 85 patients who claimed not to have swallowing problems at the time of the interview, DYMUS was abnormal in 43 cases (43%). A close relationship with dysphagia was found in the patients with neurological impairment in brainstem FS (mean 0,93; SD 1,25, p=0,003) and pyramidal FS (mean 2,22; SD 1,49, p=0,037). The patients with 3 score on Brainstem functional system showed a risk of developing dysphagia nearly eight times greater as compared with patients without severe in brainstem FS. Dysphagic patients also had a higher mean age (mean 44,2; SD 11,74, p=0,017). The frequency of dysphagia was not significantly different between the RR, PP and SP forms of MS. The multiple logistic regression analysis show that the severe impairment in the brainstem (OR= 8, 54; 95% CI1, 05-69, 57; P value 0,023) and cerebellar functional systems (OR=10, 70; 95% CI 1, 33-85, 86; P value 0, 01) were found to be closely related to the risk of Dysphagia. No statistically significant relationship was found between ethnicity and presence of Dysphagia. Conclusion: Dysphagic symptoms are also frequent in Brazilian patients with MS, and its frequency could increase with age, degree of disability, pyramidal and brainstem dysfunction. Further studies are required to correlate these results with instrumental evaluation of swallowing. A 134 The cervical spinal cord in neuromyelitis optica patients: A comparative study with multiple sclerosis using diffusion tensor imaging Fernanda Miraldi Clemente Pessa, Fernanda Cristina Rueda Lopes, Joo Victor Altamiro Costa, Soniza Vieira Alves-Leon,

Romeu Crtes Domingues, Emerson Leandro Gasparetto Federal University Of Rio De Janeiro; Radiology And Neurology Departments Of Hospital Universitrio Clementino Fraga Filho Introduction: This study aims to evaluate in vivo the integrity of the normal-appearing spinal cord in patients with neuromyelitis optica (NMO), using diffusion tensor MR imaging, comparing to controls and patients with multiple sclerosis (MS). Materials and methods: We studied 8 patients with NMO and 17 without any neurologic disorder. Also, 32 MS patients were selected. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were calculated within regions of interest at C2 and C7 levels in the four columns of the spinal cord. Results: At C2, the FA value was decreased in NMO patients compared to MS and controls in the anterior column. Also in this column, RD value showed increase in NMO compared to MS and to controls. The FA value of the posterior column was decreased in NMO in comparison to controls. At C7, AD value was higher in NMO than in MS in the right column. At the same column, MD values were increased in NMO compared to MS and to controls. Conclusions: There is extensive NASC damage in NMO patients, including peripheral areas of the cervical spinal cord, affecting the white matter, mainly caused by demyelination. This suggests a new spinal cord lesion pattern in NMO in comparison to MS. A135 - Oral presentation The epidemiology of Idiopathic Inflammatory Demyelinating Diseases in Department of Neurology at Santa Casa of Belo Horizonte-Brazil Antonio Pereira Gomes Neto, Paulo Pereira Christo, Renata Brant de Souza Santa Casa de Belo Horizonte- Minas Gerais Alpha Background Idiopathic inflammatory demyelinating disease(DDII) of the central nervous system compose a wide range of differential diagnoses, among them, Multiple Sclerosis(MS). It is studied in our city Belo Horizonte, located in Southeastern of Brazil where the MS crude prevalence was estimated in 18/100.000 inhabitants (2002). It is part of this group the neuromyelitis optica(NMO) which pathology that stood out in recent years, after the recognition antibody antiquaporin 4. Objective: Alpha To evidence the spectrum of IIDD in patients living in Minas Gerais, at southeastern Brazil, located at coordinates 19 55 15 S 043 56 16 O. Methods: Patients were seen in the neurology service at Santa Casa of Belo Horizonte (CAPPEM- Centro de Ateno aos Pacientes Portadores de Esclerose Multipla), in the year 2011. Evaluated epidemiological, clinical, radiological and laboratory aspects. The diagnostic criteria for MS (2005), NMO (2006) and other IIDD syndromes were applied. Results: 265 patients were consecutively seen at CAPPEM in the year 2011. Among them, 178 patients, which 143 cases of MS and 35 NMO, were selected for the study: 56,2% from Belo Horizonte and 43,8% from other cities. Women were more affected (79,2%) compared to men (20,8%)

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Regarding ethnicity, the dates were white (64,6%), mestizo (17,9%), African descendent (17,4%). The mean age at onset was 31,4 years. After 6,1 time of disease the EDSS was 2,65. Specifically about the multiple sclerosis, there were patients 126 RRMS, 8 SPMS, 9 PPMS. And 35 NMO were found. All cases were studied with spine and brain MRI besides CSF performed in 98% patients. IgG-NMO antibody were carried out in 98% cases of NMO among them 58% cases was positive. 2% of patients underwent visual evoked potencial. Conclusion: Our study showed that the prevalence of DDII in Santa Casa of Belo Horizonte in the year 2011 were 4 cases of MS to each 1 case of NMO.
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A 137 The profile of JCV in Brazilian patients with multiple sclerosis using natalizumab Yara Dadalti Fragoso, Maria Fernanda Mendes, Walter Oleschko Arruda, Livia Brito Bezerra de Albuquerque, Jefferson Becker, Joseph Bruno Bidin Brooks, Margarete de Jesus Carvalho, Elizabeth Regina Comini-Frota, Maria Lucia Brito Ferreira, Paulo Diniz da Gama, Sergio Georgeto, Sidney Gomes, Marcus Vinicius Magno Gonalves, Damascio Ramon Kaimen-Maciel, Josiane Lopes, Rogrio Rizo Morales, Andre Muniz, Celso Luis Silva Oliveira, Francisco Tomaz Menezes Oliveira, Heloisa Helena Ruocco, Fabiana Safanelli, Pedro Rippel Salgado, Massaco Satomi Objective: To assess the profile of JC virus in serum from MS patients undergoing natalizumab treatment in Brazil. Method: Data were collected from neurologists and health care providers involved in natalizumab infusions. All patients were already receiving natalizumab. These data are part of the independent task force on pharmacovigilance of natalizumab in Brazil. Results: The total number of patients undergoing treatment with natalizumab was 115 (79 F, 36 M), average age 40 years 11.8; attending 15 neurology units specializing in MS in eight Brazilian states. JCV+ was detected in 38 patients, JCV was negative in 44 patients and 33 patients still await the result. Twenty-nine (25%) patients had previously received immunosuppressive drugs. From this group, 10 were JCV-, 10 were JCV+ and 9 have no results on JCV yet. No cases of progressive multifocal leukoencephalopathy were observed in this population of patients. Patients in these reference MS units were closely monitored. Conclusion: The prevalence of JCV+ in Brazil is similar to that of other countries. Brazilian neurologists are well aware of the risks for patients who are JCV+ and have used immunosuppressive drugs in the past but, in agreement with the patient, are using natalizumab when there is therapeutic failure of immunomodulatory drugs.
A 136 The long term clinical course of relapsing-remitting MS: prognosis factors in Brazilian population Claudia Cristina Ferreira Vasconcelos1, Gutemberg Augusto Cruz Dos Santos1, Luiz Claudio Santos Thuler2, Solange Maria Das Graas Dos Santos Camargo3, Regina Maria Papais Alvarenga4 1Universidade Federal Do Estado Do Rio De Janeiro; 2Instituto Nacional Do Cancer/Uniersidade Federal Do Estado Do Rio De Janeiro; 3Hospital Da Lagoa; 4Universidade Federal Do Estado Do Rio De Janeiro/Hospital Da Lagoa Background: Studies on the clinical course of multiple sclerosis have indicated that certain initial clinical factors are predictive of disease progression. In Latin American, which have environmental and genetic factors that differ from areas of high prevalence, lack long term studies on the progressive course and disabling characteristics of the disease. Objective: to analyse the disability outcomes and the long-term evolution to progressive phase of the relapsing-remitting multiple sclerosis (RRMS) and its prognosis factors in Brazilian mixed population. Methods: the medical records of 623 MS patients assisted from 1995 to 2011 in Hospital da Lagoa, a Reference Center for MS treatment in the city of Rio de Janeiro were reviewed to select patients with relapsing remitting clinical course at onset who had the disease for ten or more years. A survival study and logistic regression was performed to examine the influence of demographic and initial clinical factors on development of permanent disability (using the Expanded Disability Status Scale - EDSS 3, 6 and 8) and disease progression. Results: Among 553 RRMS patients, 179 were selected for the study (79% female and 21% male; 75% Caucasian and 25% Afro descendent). In more than half of the patients the age at onset was lower than 30 years. The median of the time to reach EDSS 3 (118/179) and 6 (62/179) was, respectively 12 and 15 years. The African ancestry patients had higher risk to reach EDSS 3 (p=0.04) and a trend to reach EDSS6 (p=0.07). After Cox logistic regression Ancestry, age at onset of disease and the number of relapses in the first year after diagnosis were factors that conferred more risk for permanent disability and secondary progression. Conclusions:A greater understanding of the influence of ancestry on prognosis stimulate pharmacogenomics research and may clarify the poorly understood neurodegenerative progression of MS.
A 138 The profile of natalizumab adverse events in patients with multiple sclerosis Yra Dadalti Fragoso, Soniza Vieira Alves-Leon, Walter Oleschko Arruda, Margatere de Jesus Carvalho, Elizabeth Regina Comini-Frota, ber Castro Corra, Maria Lucia Brito Ferreira, Paulo Diniz da Gama, Sidney Gomes, Marcus Vinicius Magno Gonalves, Ramon Damasio Kaimen-Maciel, Maria Fernanda Mendes, Rogerio Rizo Morales, Andre Muniz, Pedro Rippel Salgado, Heloisa Helena Ruocco, Joseph Bruno Bidin Brooks, Letcia Fzer, Sergio Georgetto, Josiane Lopes, Fabola Rachid Malfetano, Isabella DAndrea Meira, Celso Luis Silva Oliveira, Francisco Tomaz Meneses de Oliveira, Fabiana Safanelli, Massaco Satomi. Objective: To assess the prevalence and the profile of adverse events (AEs) of natalizumab in patients with multiple sclerosis (MS). Method: Data collection from neurologists attending to patients with MS at specialized units in Brazil.
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Results: Data from 103 patients attending the infusion centers of 16 MS units in nine Brazilian states were included in the study. The total number of infusions was 1042. Seventy-nine patients (76.7%) did not present any AE. Twenty-four patients (23.3%) presented only mild AEs. The most frequent event was skin reaction during and immediately after the infusion in five cases (6%). This reaction was characterized by general redness and/or pruritus and most doctors resorted to dexamethasone or prednisone to relieve these symptoms. Another mild side effect was headache during or immediately after the infusion, affecting six patients (5.8%). Generalized pain and/or muscle spasms, nausea, vomiting, hiccups, dizziness, high blood pressure, asthenia, fatigue, worsen of spasticity, respiratory infection, urinary infection, visual blurring, low fever and paresthesia were much less frequently reported and were typical of the two days following the infusion. There were three major AEs, including two deaths. These three occurrences, although not necessarily being drug-related, must be taken into consideration. Conclusion: The profile of AEs for natalizumab shows that 97% of patients have none or only mild AEs. However, still due to safety worries, the use of this medication should be restricted to MS units under the care of specialized neurologists.

A140 - Oral presentation The spectrum of the idiopathic inflammatory demyelinating deseases of the Central Nervous System in the patients from Rio de Janeiro (Brazil) R. Papais Alvarenga, C. Vasconcelos, E. Batista, G. Santos, L. Campanella, M.P. Alvarenga, M. Papais Alvarenga, S. Camargo, V. Neri. Hospital Federal da Lagoa and NeuroRio Clinic Objective: To describe the IIDD spectrum in patients from Rio de Janeiro (RJ) assisted in Hospital Federal da Lagoa (HFL) and NeuroRio Clinic. Methods: descriptive cross-sectional study with prevalent cases. Six neurologists with specialized training in neuroimmunology reviewed the medical records of all IIDD patients consecutively assisted in 2011 in two neurological centers specialized in the treatment for MS located in RJ: a public hospital HFL and a private clinic NeuroRio. It was only included in the study city residents and those who fulfilled the current diagnostic criteria of MS [2010], NMO [2006], NMO Complex Spectrum [2007] and others IIDD, based on clinical data with laboratory support (MRI, CSF and Anti-Aquaporin 4). Results: 412 IIDD cases were selected [HFL 311; NeuroRio - 101]; 77.9% women and 22.1% men, 67,7% White and 32,3% AfricanBrazilian, and classified in 6 groups: pseudo tumor form (0,2%), ADEM (1,7%), CIS (2,9%), MS [2010] (76.2%), Neuromyelitis Optica [2006] and limited syndromes [2007] (18,9%). NMO is significantly different from MS regarding race (greater frequency among African-Brazilians) and long term disability (worse EDSS). Conclusion: Recent studies conducted in populations with different ethnicities estimated the relative frequency of NMO among MS cases between 1,2-1,5% (Italy and Australia) and 27% (Antilles). The high frequency of NMO/MS cases in RJ - 10,31%, a tropical city, of hot weather, with 40% of african-brazilians in general population, reinforces race influence in IIDDS distribution throughout the world. A141 - Oral presentation The spectrum of Idiopathic Inflammatory Demyelinating Diseases in Mato Grosso-Brazil AK Grzesiuk, BV Gomes, BR Gumieiro, BM Lllis, HH Siqueira Background: Idiopathic inflammatory demyelinating diseases (IIDD) of CNS comprise a heterogeneous group of disorders with demographic and clinical aspects that vary widely. Multiple sclerosis (MS) is the most studied DDII in our city, Cuiab, located in the midwest region of Brazil, where the MS crude prevalence was estimated in 4.4/100.000 inhabitants (2007). Patients with neuromyelitis optica (NMO) and limited NMO syndromes, however, have been diagnosticated here at the last years and have differentiated of MS by the newly diagnostic criteria. Objective: To describe the spectrum of IIDD in patients living in Mato Grosso, at mid-western region of Brazil, located at coordinates 15 35 S and 56 06 O. Methods: Demographic, clinical and laboratorial data from medical records of all DDII patients attended consecutively in the year 2011 in two neurological units in the city of Cuiaba, capital of Mato Grosso [1.outpatient private neurology clinic, 2. CRIDAC a public out patients neurology clinic and 3. HGU a public
A 139 The relationship between fatigue and gait in patients with Multiple Sclerosis Pollyane Galinari Sabino, Leandro Alberto Calazans Nogueira, Maria Regina Papais Alvarenga UNIRIO Objective: To analyze the relationship between fatigue and gait in patients with Multiple Sclerosis (MS) with different degrees of disability. Methods: We conducted an observational analytic study in patients diagnosed with MS. The selected subjects underwent a clinical neurological evaluation to define the level of disability (EDSS <6.5) and were instructed 1) to perform a trial of 10 meters of walking at normal speed selected by the subject and 2) to complete the questionnaire validated and adapted Modified Fatigue Impact Scale (MFIS-BR). All subjects that agreed to participate signed the consent form. The study was approved by the Ethics and Research Committee of HUGG (Gaffre Guinle University Hospital). Associations among fatigue, gait and level of disability were verified by Spearman correlation. Mann-Whitney test was used to compare groups with and without fatigue, considering statistical significance as p<0.05. Results: We evaluated 119 patients (32 men and 87 women) with a mean age (38 years), weight (68 kg), height (1.66 m), EDSS (3.0), MFIS-BR (33), gait speed (0.95 m/s) and stride length (1.10 m). We found correlations between MFIS-BR and EDSS (r = 0.47, p <0.01), MFIS-BR and gait speed (r = - 0.46, p <0.01) and MFIS-BR and stride length (r = 0.47, p <0.01). Groups with no fatigue and fatigue were not statistically different for age, weight and height, but were statistically difference for EDSS, MFIS-BR, walking speed and stride length. Conclusion: Fatigue is correlated with the level of disability and clinical characteristics of gait in patients with MS.

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universitary hospital] were reviewed. The diagnostic criteria for MS (2005), NMO (2006) and other IIDD syndromes were applied. Results: 70 patients living in Mato Grosso state were selected for the study: 65.7% from Cuiab and 34.3% from 16 different cities. The majority were female and white [women - 85.7%, men - 14.3%; distribution by ethnicity - white (67.4%), mestizo (27.14%), African descendent (5.71%)]. The mean age at onset was 31.7 12.45 years. After mean of 7.9 years of disease the EDSS in sample was 3.87 2.29. Sixty patients were classified as MS (35 RRMS, 21 SPMS, 04 PPMS) and 10 as NMO complex syndromes (8 NMO and 2 TM). Spine and brain MRI were performed in 100% of cases and CSF study, in 88.57% of the cases. Evoked Potentials were carried out in 05 patients and IgGNOM antibody in 05 cases of NMO, those two cases was positive. Conclusion: Out data showed that the relative frequency of definite NMO among MS plus NMO cases (8/68) is 11,76% what means that in the mid region of Brazil, a hot tropical area with a high mixed population for each seven MS cases of MS, one NMO case is found. Mestizos and afro descendants represent 32.8% of all DDII cases. A limitation of this study is the low number of ADEM and other acute limited syndromes probably because these patients are assisted in emergency rooms by general medical doctors. A142 - Oral presentation The spectrum of inflammatory and demyelinating disease of the central nervous system treated in a Rehabilitation Hospital in Brasilia-DF/Brazil Patricia Beatriz Christino Marinho1, Maria Cristina Del Negro Barroso Freitas1, Diogenes Umaki1 1Hospital Sarah Objectives: To study the profile of patients with DDII domiciled at Brasilia and surroundings met in 2011 at Sarah Brasilia Hospital Methods: Retrospective study of medical records. Results: 124 patients from Brasilia and surroundings were found. There was a mean age of 44 years, ranging from 21 to 78 years; 78.2% of subjects were female and 21.8% male; 51.6% of subjects were Caucasians, 25.8% mixed race, 4% afrodescendents, 0.8% Asian and 17.8% were not classified. The mean disease duration was 8 years, ranging from 0 to 38 years. The mean EDSS was 4, ranging from 0 to 9. Nearly 71% of patients were diagnosed as multiple sclerosis; 15.8% had NMO; 8.9% had other SNMO; 4.1% had CIS and 0.8% had ADEM. Analysis: There was a predominance of females and Caucasians. The most prevalent disease was multiple sclerosis, followed by NMO. The mean disease duration was 8 years, with a mean EDSS of 4.0. Conclusion: The profile of patients with DDII coming from Brasilia and surroundings resembles that of other epidemiological studies in Brazil. The greater degree of disability and longer disease progression in the group studied are probably related to the main activities of Sarah Hospital, which focuses on neurorehabilitation. A 143 The Sustained Disease Activity Free Status as Measure of Therapeutic Response & the Long Term Impact of Immunomodulatory Treatment Carr A; Rojas G; Martnez A; Curbelo C; Vrech C; Steimberg J.
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Background: IFN and GA provide similar levels of efficacy in RRMS patients and they have not been demonstrated to induce disease remission. The sustained disease activity free (DAF) status is a novel concept and viable goal of therapy based on clinical and radiological measures. Objective: To examine the effects of IFN and GA on DAF status. Design/Methods: DAF status was defined as no activity on clinical measures: absence of Gd+-enhancing L, new/enlarging T2 L, confirmed relapse and 3-month confirmed disability progression. All patients were matched according to baseline and treatment exposure. We assessed the impact of IMDs on the % of DAF patients. Data analysis performed with SPSS14; Student-test; non-parametric tests Kruskall-Wallis for multiple groups; Wilcoxon signed rank test; ANOVA one way, linear regression between baseline variables/ final EDSS, Kaplan Meir analysis. Results: Observational study of 245 nave patients who received IMDs over 10 yrs. IFN: 41/117 (35%) and GA 46/128 (35.9 were free of clinical disease activity ([OR] 0.96; p=0.8). 73/94 (77.7%) and 86/105 (81.9%) patients receiving IFN and GA respectively, were free of radiological disease activity ([OR] 0.76; p=0.45). Freedom from combined activity was observed in IFN:26/92 (28.3%) and GA 40/108 (37%) ([OR] 0.67; p=0.18). Although no differences were found between group treatments, subgroups analysis at different times of exposure demonstrated a greater proportion of patients free from clinical disease activity among those on >=5 years of GA therapy ([OR] 0.32, p<0.016). Other analysis considering the worst-case scenario was done. Conclusions: Findings from this subset analysis indicate that both IFN and GA induced DAF status in patients with RRMS sustained in the LT. DAF status could be an important measure of therapeutic response in MS, yet applicable to IMDs currently in use. A 144 Tract based spatial statistics (TBSS) in the evaluation of patients with neuromyelitis optica. Rueda-Lopes, FC1, Doring, T1, Martins, C2, Cabral, FC2, Malfetano, F2, Pereira VC2, Alves-Leon, S2, Gasparetto, EL2 1UFRJ/DASA; 2UFRJ Objective: To test the hypothesis that white matter damage in neuromyelitis optica (NMO) is more extensive than previously described and likely includes involvement of normal-appearing white matter not only related to wallerian degeneration but are also caused by demyelination using diffusion tensor imaging (DTI). Materials and Methods: Seventeen patients with NMO (mean age, 45 years; 14 women) were compared with 17 sex- and agematched control subjects. All subjects gave written informed consent. In addition to conventional magnetic resonance imaging sequences, DTI was performed along 30 noncollinear directions by using a 1.5-T imager. For tract-based spatial statistics (TBSS) analysis, the white matter skeleton was created, with a threshold of P less than .05 to enable the identification of abnormalities in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Partial correlation was applied to identify whether the number of clinical relapses and disease duration were correlated with all TBSS parameters.
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Results: TBSS showed multiple areas with significant FA decrease in patients with NMO, mainly located in the corona radiata, uncinate fasciculus, corpus callosum, optic radiation, internal and external capsules, and cerebral peduncles. The mean FA, RD, and AD in the abnormal voxels located on the corpus callosum for patients and controls were, respectively: 0.69 / 0.75, 0.39 / 0.33 x10-3mm2/sec, and 1.53 / 1.57 x10-3 mm2/sec (P<0.001). There was a highly significant inverse correlation between FA and RD (r=-0.976, P<0.0001). Conclusion: The use of TBSS allowed the identification of extensive white matter damage in patients with NMO. Multiple white matter tracts were involved, including the pyramidal tract, optic radiation, and corpus callosum, likely related to both demyelination and wallerian degeneration. A 145 Treatment Experience, Burden, and Unmet Needs (ENCOMS) in Multiple Sclerosis Study: the Costs of MS Patients in Argentina Gaston Kuperman Multiple sclerosis (MS) is a common neurological disease among young adults in Argentina. It is known that the cost of the disease is higher but no studies up to date have measured the cost imposed by MS on the Argentinean health system and society. Objectives: To estimate the direct costs of MS patients in Argentina focusing on disease severity. Methods: MS patients in Argentina (N=264) completed a questionnaire which captured information on demographics, disease characteristics, severity (Expanded Disability Status Scale [EDSS]), co morbidities, relapses as well as resource consumption and quality of life associated with MS. Patients were stratified according to disease severity using EDSS (group 1 with EDSS between 0 and 3; group 2 with EDSS >3 and <6; group 3 with EDSS >6) for the analysis. Direct costs included in the analysis were: inpatient care due to relapses, outpatient care due to relapses, inpatient care outside relapses, consultations, investigations, MS treatments, investments, professional care. Costs were obtained from public resources for 2011 and converted to USD. Results: 87,5 % of patients were RRMS, 10,6% SPMS and 1,5 % PPMS. 62% of patients have an EDSS score between 0 and 3; 22% and EDSS >3 and 6 and 14% and EDSS >6. Mean direct cost per year of patients with an EDSS between 0-3 was USD 69 747; for patients with EDSS > 3 and 6 was USD 70 586 and for patients with EDSS >6 was USD 44 871. The mean cost per patient per year increased with worsening disability up to EDSS of 6. In patients with EDSS >6 a decrease in direct cost was observed due to a reduction in the utilization of specific treatment for MS in this group of patients. Conclusions: This is the first study performed in Argentina that evaluated the cost of MS considering disease severity. This information provides important data for the economic analysis of the disease Argentina, where this kind of information is need. Currently is underway the inclusion of indirect cost in order to update their impact over disease MS costs in Argentina. A 146 Treatment Failure In Multiple Sclerosis: Vectrims Criteria Molina, O.1, Armas, E.1, Soto, A.1, Leon, R.1, Zalcman, J.1, Ravelo, M.E.1, and Soto, I.1 1On behalf of the Venezuelan Committee for Treatment and

Research in Multiple Sclerosis VECTRIMS, Venezuela.
omairamolina14@gmail.com
Objective: To describe the criteria for treatment failure in patients with Relapse Remitting Multiple Sclerosis, as an aligned and unified consensus, presented by the Venezuelan Committee for Treatment and Research in Multiple Sclerosis (VECTRIMS) from the Venezuelan Society of Neurology. Method: An evaluation and discussion of clinical cases, taking into account the criteria handled in different Multiple Sclerosis Reference Centers in Venezuela and compared with those reported, as guidelines, in the literature. Results: We established and aligned criteria of treatment failure, enabling to exhibit and present a proposal based on the experience in Venezuela, which was based on clinical findings (Expanded Disability Status Scale EDSS - increment), relapse rates, disease activity based on MRI and the exacerbated or rapid disease progression. Conclusions: Establishing criteria for treatment failure in Multiple Sclerosis is very controversial; VECTRIMS, in a team work initiative, achieves a consensus, unification and alignment on the criteria for its use in Venezuela. A 147 Treatment of Disease Devic with Plasmapheresis and Corticoid S. Gomes, F. T. M. Oliveira, J. H. F. Rosalino Hosp. B. Portuguesa Introduction: Neuromyelitis optica and the disease entity with characteristic inflammation of the central nervous system demyelinating character, which affects the spinal cord or nerve optical and reserved prognosis. Metodo.relato case Result: Femina patient, 35-year framework of acute visual loss in the left eye, accompanied by intense back pain for several days, and complaints of sensory loss at the level of c6-c7, quadriplegia predomnio of crural and urinary retention. Fundus with the pallor intense papilla optica. NMR of skull normal, NMR cervical cord thickening and hyper following cervical.liquor discrete alterations of protein ... raised the diagnosis of NMO and early pulse therapy with corticosteroids and non aprentando clinica.proposto response to plasmapheresis seven sessions and alternated with corticiode and favorable clinical response with contrle esfinctrianos ee gallows muscular.resultado aquaporina04 with the presence of antibody. Conclusion: The treatment of the disease and devic done initially with corticosteroids and long-term immunosuppressive drugs but before frames with clinical response to corticosteroid little indication of the plasmapheresis associated or not with corticosteroids and a therapeutic option. A 148 Tumor necrosis factor beta (TNF-b) NcoI genetic polymorphism is associated with multiple sclerosis independently of HLA-DRB1* Ana Paula Kallaur, Sayonara Rangel Oliveira, Andra Name Colado Simo, Elaine Regina Delicato de Almeida, Helena

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Kaminami Morimoto; Damcio Ramon Kaimen-Maciel, Josiane Lopes, Wildea Lice de Carvalho Jennings Pereira, Renato Marques Andrade, Daniele Frizon Alfieri, Edna Maria Vissoci Reiche. State University of Londrina Variations in genes coding for human leukocyte antigen (HLA), tumor necrosis factor (TNF) a, and TNF-b genes may play a role in multiple sclerosis (MS) susceptibility. This study investigated the association between TNF- NcoI genetic polymorphism with the susceptibility for MS, clinical progression, disease activity, and HLA-DRB1*. Genomic DNA was extracted from peripheral blood cells of 220 MS patients and 278 controls. A 782 base-pair fragment of the TNF- gene was amplified using PCR and the products were subjected to NcoI restriction digestion, and analyzed using RFLP. The HLA-DRB1* polymorphism was determined by PCR-SSOP. Serum TNF- level was determined using enzyme linkedimmunosorbent assay. The frequency of TNFB2/B2 genotype differed from TNFB1/B2 and TNFB1/B1 genotypes in MS patients and controls (p=0.0449, OR: 1.490 [IC: 1.0232.170] and p=0.0225, OR: 2.058 [IC: 1.0993.855], respectively). The TNFB2 allelic frequency differed between MS patients and controls (p=0.0089, OR: 1.427 [1.0931.863]). The association between HLA-DRB1*01, 03, 04, 07, 08, 11, 13, and 15 and TNF- NcoI alleles was not observed (p>0.05). TNF- NcoI polymorphism was not associated with the clinical characteristics evaluated (p>0.05). However, a tendency toward higher disease activity among the TNFB2/B2 carriers was observed (p=0.0722). Controls carrying TNFB2/B2 genotype presented higher values of TNF- than MS patients carrying TNFB2/B2 genotype (p=0.0287). Controls carrying TNFB1/ B2+TNFB1/B1 showed a trend towards higher TNF- levels than MS patients carrying TNFB1/B2+TNFB1/B1 (p=0.0750). The results suggested that TNF- NcoI polymorphism may influence TNF- levels, contribute for MS susceptibility independently of HLA-DRB1*, and could be used as a genetic biomarker for MS susceptibility in the Brazilian population. A 149 Using Maca (Lepidium meyenii Walp) in improving fatigue of patients with relapsing remitting multiple sclerosis Cordova-Ruiz, M1, Sinnett, M2 1Pectrims - Lima Peru, 2Cta Rc Fl Usa Objective: To establish the effect of maca (Lepidium meyenii Walp) on improving fatigue in patients with multiple sclerosis. Materials and Methods: Experimental, prospective, comparative study. The sample consisted of 20 patients with relapsing remitting multiple sclerosis (EDSS 0 1), who underwent physical activity to measure maximal oxygen consumption (VMO2) baseline, then were given for 90 days 1000 mg / day of concentrate Maca Powder presentation. Subsequently, they were returned to physical activity, determining maximum oxygen consumption (in ml / kg x min) and performance, telling a followup period of 30 days. Each assessment was conducted dosage of SGOT, SGPT and serum creatinine. Results: At baseline, we found that the average speed obtained in the endless belt was 15.46 km / h and the mean was 52.32 VMO2. In conducting the evaluation after 90 days of consumption of maca was found that
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the average speed was increased to 16.89 km / h for the mean was 7.75 VMO2. It showed an increase in physical performance of athletes on average 10.31%. In all cases, the values of GOT, GPT and serum creatinine remained in the normal range and no adverse reactions. Conclusion: The product is a maca energy activity allowing improved fatigue patients with relapsing remitting multiple sclerosis at a dosage of 1000 mg / day for a period of 90 days administration.
A150 - Oral presentation Use of Rituximab in Devics Disease, two years follow up. Mexican Experience Jose de Jesus Flores Rivera*, Lucinda Aguirre Cruz**, Leticia Salinas Vsquez*, Yamel Claudia Rito Garcia*, Teresa Corona Vzquez* *Neurodegenerative Diseases Clinical Laboratory, National Institute of Neurology and Neurosurgery. Mexico City; **Neuroimmunoendocrinology Laboratory, National Institute of Neurology and Neurosurgery, Mexico City Introduction: Devics disease (DD) is an inflammatory autoimmune demyelinating disease of the central nervous system, characterized by the presence of an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS. Is more common in meddle age women, affecting spinal cord and/or optical nerve in monophasic or relapsing. The disability in these patients is severe and the treatment selection prevents relapsing. Objective: To evaluate the efficacy and safety of Rituximab therapy in Devics Disease Mexican patients. Methods: We carried out a longitudinal study among patients with DD, who were attending at the Demyelinating Disorders Clinic at National Institute for Neurology and Neurosurgery (NINN) in Mexico City from January 2007 to June 2011. We recorded clinic and demographic variables in patients who follow the next schedule treatment of Rituximab (RTX): 1.5g IV as initial dose and after that 500mg each six months as follows. We used annualized relapse rates and Expanded Disability Status Scale (EDSS) to measure the effectiveness before and after the administration of treatment. Also we recorded the adverse effects during infusion and after. Results: We studied 13 patients, which 92% (12) were women, and 8% (1) men, with an average age of 33.3 (SD+-13.8) years old; at a median follow-up after finished treatment was 24 mouths (12-24); 3 subjects needed an extra doses of RTX (500mg) because one had relapsing and two lymphocytes CD19 count elevated. The median annualized pre treatment relapse rate was 1.0 (+-0.8) and the post treatment rate was 0.1 (+-0.3; p <0.05, Wilcoxon signed-rank test). The median EDSS score was 4.8 (+-3.3) at the start of treatment and 2 (+-3.3; p <0.05, Wilcoxon signed-rank test), at last follow-up. Rash occurred in 3 subjects during administration and one patient abandoned the treatment due to pregnancy 9 mouth after the first doses. No adverse effects were record in the newborn. No patient suspended treatment due to adverse effects. Conclusion: The use of RTX in patients with DD relapsing is effective in reducing disability and the number of relapses at 24 months follow up. Disclosure: None of the authors has conflict of interest.
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A 151 Validity and Reliability of Brazilian version of the Multiple Sclerosis Walking Scale (MSWS-12) Leandro Alberto Calazans Nogueira, Luciano Teixeira dos Santos, Pollyane Galinari Sabino, Regina Maria Papais Alvarenga, Luiz Claudio Santos Thuler UNIRIO Objective: The aim of the present study was to demonstrate the validity and reliability of the Multiple Sclerosis Walking Scale-12 (MSWS-12) in the Brazilian population. Methods: It was consecutively included 120 Multiple Sclerosis patients. The subjects underwent a standardized bedside neurologic examination by a neurologist to define the disability level by Expanded Disability Status Scale (EDSS), then completed MSWS-12, which is a 12-item self-report measurement of the impact of MS on walking, and Short Form Health Survey (SF-36) questionnaires, and also performed the 10 meters timed walk test. Results: The most affected item on patient`s perceived impact was the ability to run. After dichotomizing (EDSS < 4.5 vs. EDSS 4.5), it was observed significant differences patient`s perceived walking impact. Criterion validity was established by correlating MSWS-12 and EDSS (r=0.78), physical function domain of SF-36 questionnaire (r=-0.90) and walking speed (r=-0.70). Reliability results revealed high values of internal consistency (Cronbach alpha=0.96) and test-retest (ICC=0.88). Conclusion: The Brazilian version of the MSWS-12 is valid and reliable instrument of mobility assessment. A 152 Value of Aquaporin-4 Antibody NMO-Igg at the Diagnosis of CIS, MS and NMO Spectrum in Pernambuco, Brazil Maria Lcia B Ferreira, Maria ris M Machado, lvaro Jos Porto Moreira, Lvia Brito Bezerra de Albuquerque Centro Estadual de Referncia para Ateno aos Pacientes Portadores de Doenas Desmielinizantes (CRAPPDD)/Hospital da Restaurao, Recife, Pernambuco, Brazil Objective: To describe a State Reference experience of NMO-IgG value in a cohort of patients for the differentiation of neuromyelitis optica spectrum at clinical early symptoms. Methods: A cohort study was performed at the State Reference Center for Attention to Patients with Demyelinating Diseases, Recife, PE, Brazil, including 856 patients of both gender, aging from 2 to 79 years old (35.813,4), followed from 1996 to 2012, regarded as having MS, CIS or NMO spectrum. The diagnosis of neuromyelitis optica was performed by the 2006 Wingerchuk criteria associated to abnormal visual evoked potential. NMO-IgG test was determined by Lennon et al. method. The research was approved by Ethics Committee. Results: Among 856 patients, 532 (62.1%) were diagnosed as MS; 195 (22.8%) as CIS, and 89 (10.4%) fulfilled criteria for NMO spectrum. NMO-IgG test was performed in 22 (4.1%) MS patients who had relapses with motor, optic neuritis or brainstem cerebellar symptoms; in 32 (16.4%) CIS patients with optic neuritis or myelitis symptoms or refractivity to corticosteroids treatment, and in 89 (100.0%) patients, with NMO spectrum diagnosis. All NMO-IgG tests were negative for patients with MS and CIS. Among patients diagnosed as NMO spectrum, 44.9% had positive NMO-IgG and 55.1% were negative and considered as possible NMO.

Conclusion: NMO-IgG determination was crucial for differentiating NMO from CIS and MS, when there were similarities of relapsing clinical symptoms, showing that it must be restricted to cases in which initial diagnosis is not clear, because its value as a routine test is low in MS and CIS. Even in NMO spectrum, it must be interpreted cautiously because it considers 2006 Wingerchuk criteria as gold standard, and this seems questionable. The presentation of clinical, imaging and visual evoked potential abnormalities may occur before or after NMO-IgG positivity, so negativity of this biological marker indicates NMO spectrum. A 153 Visual Evoked Potentials measure and correlation with disability progression (EDSS) in RelapsingRemitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS) Piccolo, A.C. - Andrade, H.M.T - Brucki, S.M.D - Rocha, M.S.G Hospital Santa Marcelina So Paulo-SP Objective: To correlate the VEP abnormalities and EP score (EPS) to Expanded Disability Status Scale (EDSS) of patients with RelapsingRemitting (RRMS) and Secondary Progressive (SPMS) Multiple Sclerosis (MS). Methods: Seventy-five MS patients were included: 57 patients with RRMS and 18 SPMS. Statistical analyses examined correlations between EDSS and EPS. Results: Mean age was 37.5 years and EDSS ranged between 0-8.5 (median 2). Disease duration ranged 1-18 years (mean = 4.7). Mean diagnostic time in RRMS was 3.5 years and 7.1 years in SPMS. In RRMS, mean 29-MDA VEP latencies and amplitudes were 101.5 ms and 5.6 mA. Mean 14-MDA VEP latencies and amplitudes were 111.6 ms and 5.78 mA. In the SPMS, mean 29MDA VEP latencies and amplitudes were 131.8 ms and 4.1 mA. Mean 14-MDA VEP latencies and amplitudes in SPMS were 127 ms and 2.8 mA. The 29-MDA latencies were significantly larger in SPMS (p = 0,004), and 29 and 14-MDA amplitudes were significantly smaller in this group (p = 0,002 and p = 0,001). The rate of 14-MDA amplitudes equal to zero was significantly larger in SPMS (p = 0.007). Mean EPS on 29 MDA was significantly different between groups (RRMS - mean = 0.63, mean EPS in SPMS = 1.7, p = 0.0001). Mean EPS 14 MDA was significantly higher in SPMS (mean = 1.9) than in RRMS (mean = 0.7), (p = 0.0001). There was a positive correlation between EPS and EDSS (r = 0.52 - p = 0.000) and a negative correlation between EPS and visual acuity (r = 0.47 p = 0.002). There were not correlations between EPS and annualized relapse rate, age and disease duration. Multiple regression analyses evidenced significantly association between EDSS and EPS, with an increase of 0,30 points at EP score for each added point in EDSS (p = 0.001). Conclusion: EDSS and EP score were positively correlated. The study results corroborate the positive predictive value of VEP for future disability in MS patients. A 154 Vitamin D3-induced IDO+ Tolerogenic DCs Reduces the Severity of Experimental Autoimmune Encephalomyelitis Alessandro S. Farias*, Gabriela S. Spagnol*, Fernando Pradella*, Mariana P. A. Santos*, Adriel S. Moraes*, Elaine C. Oliveira*, Ana Leda F. Longhini*, Rosemeire F. O. de Paula* and

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Leonilda M. B. Santos* *Neuroimmunology Unit and Neuroimmunomodulation Group, Dept. of Genetics, Evolution and Bioagents, University of Campinas (UNICAMP) Campinas, SP, Brazil. Introduction and Objective: A growing body of evidence supports the hypothesis that vitamin D is an important environmental factor in the etiology of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS). However, the mechanisms that drive these beneficial effects are still poorly understood. Methods: EAE was induced by injection of MBP in CFA. CD4+CD25+Foxp3+ T cells were quantified by flow cytometry; cytokines, by qPCR. Bone marrow-derivated DCs were generated by GM-CSF alone or GM-CSF plus 400ng/ml of Vitamin D3 cultured for 12 days. Results: The present study provides evidence that the in vivo administration of vitamin D3, as well as the adoptive transfer of vitamin D3-induced IDO+ immature/tolerogenic dendritic cells leads to a significant increase in the percentage of CD4+CD25+Foxp3+ regulatory T cells in the lymph nodes in a rat model of MS, experimental autoimmune encephalomyelitis (EAE). Concomitant with the increase in this cell population, there is a significant decrease in the number of auto-reactive T cells in the central nervous system. Bone marrow-derived DCs cultivated in the presence of vitamin D3 present a tolerogenic profile with high IL-10, TNFa and IDO expression and decreased MHC-II and CD80 expression. The adoptive transfer of IDO+ DCs induces a significant increase in the percentage of CD4+CD25+Foxp3+ T cells in the lymph nodes, comparable with vitamin D3 treatment. Conclusion: These mechanisms contribute actively to the generation of a microenvironment in the lymph nodes that suppresses the activation of encephalitogenic T cells, resulting in downregulation of the inflammatory response in the central nervous system. A 155 Walking distances comparison between 1-minute intervals of 6-minutes walk test in multiple sclerosis patients C. T. Guerreiro1, D. G. Brum2, A. A. Barreira1 1Universidade de So Paulo - USP (Ribeiro Preto, So Paulo, BR); 2Universidade Estadual Paulista - UNESP (Botucatu, So Paulo, BR) Background: The aim of this study was to estimate the performances during the 1-minute intervals of 6-minutes walk test (6MWT) and compare them with the performance in 6 minutes. Methods: Fifty MS ambulant patients according to the McDonald criteria, including patients needing walking devices, were evaluated. The patients were asked to walk safely as fast as possible in a linear marked distance of 20 meters round trip and using their usual devices. The distances walked during the six intervals of 1 minute (T1, T2, T3, T4, T5, and T6) and the total distances were registered. Demographic data and functional capacity assessed by Expanded Disability Status Scale (EDSS) were obtained. All analyses were performed using the SPSS Statistics (SPSS Inc., Chicago, IL, USA) with level of significance set at p < 0.05. Results: The average of the distances walked during the six intervals of 1 minute were: T1 = 49.10 0.60 m (6-98), T2 =
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49.48 0.59 m (6-102), T3 = 45.97 0.59 m (8-93), T4 = 45.71 0.59 m (6-87), T5 = 46.28 0.61 m (6-97), and T6 = 43.07 0.58 m (8-93). The total distances were: T1 = 49.10 0.60 m (6-98), T2 = 97.52 0.92 m (12-200), T3 = 136.28 1.64 m (19-293), T4 = 188.23 1.94 m (24-380), T5 = 225.39 2.92 m (32-477), and T6 = 288 3.2 m (38-570). The results of T1, T2 and T3 explained 98.4% (R2 = 0.98%, p < 0.001), 98.9% (R2 = 0.98%, p < 0.001), 99.5% (R2 = 0.99%, p < 0.001) in T6 respectively. Conclusion: The analyzed data has showed that the performance of the patients in T1 allowed us to estimate the performance at T6.
A 156 - Oral presentation Epidemiological and clinical characterization of 100 patients with multiple sclerosis of Goias Marcos Alexandre Diniz Carneiro Denise Sisterolli Diniz Multiple sclerosis (MS) is an autoimmune disease, degenerative and demyelinating, occurring predominantly in young women. Differences in population exist and a regional characterization is important for the understanding of genetic and environmental factors surrounding the disease. Material and Methods: It reviewed the medical records of 100 patients seen at CRIEM (Reference Center for Research and Treatment of Multiple Sclerosis and similar diseases), at Hospital das Clinicas (HC) in Federal University of Gois (UFG)- Gois. All patients were seen in the year 2011 and / or 2012. Demographic data: gender, age at diagnosis and color were determined. The color was defined as: white, African descent, American Indian and Asian. The diagnoses classified as: MS, acute demyelinating multifocal encephalopathy (ADEM), clinical isolated syndrome (CIS) and neuromyelitis optica (NMO). The clinical forms of MS, classified into: relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (EMPS), primary progressive multiple sclerosis (PPMS) and rare forms: Balo, Marbug and etc.. Functional disability was determined by assessing functional systems and march, punctuated by EDSS. The initial presentations divided into: sensory-motor (SM), brainstem (BS), motor (M), spinal cord, cerebellum and multifocal. All study patients underwent magnetic resonance imaging (MRI). Study of cerebrospinal fluid (CSF), which, when was done, had a dosagem of immunoglobulin G (IgG) and oligoclonal bands (BO) by immunoelectrophoresis. Only patients with NMO-IgG antibody (NMO-IgG) positive were included in the study. Results of the total of 100 records reviewed, 82% were female, 58% white and 42% African descent. The mean age at diagnosis was 34.52 years, ranging from 9 to 59 years. Mean EDSS was 2.89 (range 1 to 7). The diagnosis of MS present in 82%, 13% in CIS and NMO in 5%, with RRMS had a frequency of 75.61%, 19.52% in EMPS, PPMS at 3.66% and 1.21 in Balo %. The clinical presentations were divided into: SM - 28%, BS - 27% NO - 14% Cord - 14% Multifocal - 9%, M-7 and Cerebellar% - 1%. Exams of BO in CSF were performed in 58% of patients and present in 53% of the cases. Determination of IgG in 53% of cases and was increased in 61%. Conclusion: The population studied showed a pattern very similar to other populations described in other regions of Brazil.
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A157 - Oral presentation Genetics Studies in Latinamerica Tereza Corona The first Multiple Sclerosis (MS) studies made in Latinamerica (LA), reported prevalence rates that are lower than those seen in Europe countries, because the latter are considered endemic zones of the diseases. During the last two decades, an increase in MS prevalence in several LA countries has been reported. Analysis of these studies, however, shows that the prevalence of the disease matches the racial characteristics of regional populations, that is, it higher in people with Caucasian ancestry than in individuals of Asian or African origin. Mestizos, Caucasians of European origin, and Afro-Americans are the most affected groups by MS in LA. An interesting fact is the lack of MS observed in unmixed (pure) Amerindians with ancestral Asian genes. Within the human leukocyte antigens (HLA) class II region, the main risk alleles associated with MS in Caucasians are HLA_DRB1*1501 and HLA DQB1*0602. Genetics studies in Mestizos, who are considered the main racial group en LA show that this alleles influence susceptibility to MS. Genetic studies of HLA class II molecules in LA indicate that Mestizos have similar distribution of haplotypes than European populations with high MS risk. It is possible that LA native Amerindians are protected against MS by their mongoloid genes, as has been observed in Canadian aboriginals and Japanese. Compared with the genetic susceptibility to MS in Caucasian populations, MS in LA is characterized by rare familial cases in different generations; these observations support the hypothesis that a recent rise in genetic or environment factors may be related to the development of MS. A158 - Oral presentation Idiopathic Inflammatory Demyelinating Diseases in Uruguay Carlos Oehninger, Ricardo Buz, Juan C Alcntara, Adriana Gmez-An, Marcela Arbildi, Fabiana Martnez Instituto de Neurologa, Seccin Enfermedades Desmielinizantes, Facultad de Medicina, Montevideo, Uruguay Objective: Description of IIDDs, limited syndromes and MS variants diagnosed in SEDIN during 2011 and 2012. 2010 McDonald revised diagnostic criteria and 2006 Wingerchuk NMO criteria were applied. All IIDD patients studied were Caucasian aged 18-48, mostly females. They were studied with brain and spinal cord magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) immunochemical analysis, Visual and Auditory Evoked potentials (EP), and serum Anti-aquaporin-4 IgG (AQP4 IgG).Results In 2012 the prevalence of MS cases is similar to that of 1997 (70% of IIDDs). 13 patients had clinically isolated demyelinating syndromes (CIS) of which 7 were unilateral Optic Neuritis (ON); 5 were brainstem and cerebellar ON; and 1 acute transverse myelitis (ATM). Some patients were initially considered IIDD after MRI but were finally diagnosed as other diseases. 5 patients had tumefactive or pseudotumoral RRMS with a focal neurological syndrome at onset. 2 cases were Bal disease and 5 were acute disseminated encephalomyelitis. 7 NMO cases had seropositive AQP4-IgG. 8 other patients had seropositive AQP4-IgG of which 3 had recurrent and

longitudinally extensive ATM and no ON; 2 had single-phase ATM, and 3 had ON with atypical MS brain MRI lesions. Conclusions: Prevalence of IIDD has continued to increase in recent years being the total prevalence in 2012 close to 30/100,000, mostly females. The CIS and atypical cases were rare in Uruguay but are currently accurately diagnosed, although there are MS border-line clinical forms of difficult diagnosis. This upward trend is not only explained by updated neurological expertise or easier access to diagnostic. Further investigation may help explain these findings. A159 - Oral presentation Stem cell therapy in multiple sclerosis Oscar Fernndez, MD, PhD, Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Avda. Carlos Haya s/n, 29010 Malaga, Spain. Multiple sclerosis (MS) is a disease that affects persons genetically susceptible, over which acts some environmental unknown factor, of possible infectious origin, causing an altered immune response, directed against myelin antigens of the central nervous system, giving rise to an inflammatory, demyelinating and neurodegenerative disease. MS can be treated, initially, with immunomodulators, which reduce around 30% of disease activity. Many cases do not respond to this first line therapy and, therapy escalates to a second line comprised by immunosuppressants with greater efficacy, reducing around 60-70% of MS clinical activity. Some MS cases are really aggressive and can be treated with bone marrow transplantation, but this exceptional therapy is associated with 1-2% mortality. In spite of all these mentioned therapies, there are patients in whom all therapies fail and clinical and magnetic resonance (MR) activity are maintained. This could happen due to the fact that all these drugs have mainly an anti-inflammatory profile, being efficacious in the relapsing-remitting phase (RRMS), and losing its effect as patients enter the more degenerative secondaryprogressive phase (SPMS). Spontaneous remyelination does occur in MS, but it is limited, and decreases with disease progression. The failure of remyelination can be due to a failure of recruiting or migration of endogenous oligodendrocyte precursors (OPCs), failure of OPC differentiation to remyelinating oligodendrocytes or to the existence of a deregulated signaling environment. Stem cell can be obtained from embryos, fetal or adult tissues. Cell from embryos or fetal tissues have, on one hand, ethical problems, and on the other hand its use can originate problems of oncogenesis. Due to these problems it has been preferred to initiate this kind of therapy in humans using autologous mesenchimal stem cells (MSC), which can be found in adult tissues (fat, skin, bone marrow, etc.). These cells are capable to grow, differentiate and repair. Also these cells have regulatory functions in the different organs, and can migrate to other places to develop their regulatory and regenerative activities. The differentiation of these cells is guided by the micro and macro environment of the organ were they pertain. Experimental studies performed in all models of Experimental Autoimmune Encephalomyelitis, using either animal or human MSC have been positive, showing that the treatment with MSC is able to produce remyelination and even neurogenesis. Both

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in mice and humans, it has been possible to demonstrate the occurrence of transdifferentiation of MSC into cells expressing oligodendrocyte and neuronal markers. Those cells can produce remyelination when administered by intravenous, intrathecal or local routes. At present, there are 24 clinical trials in MS, 2 in Spain (Malaga-Seville and Barcelona). The treatment of MS with stem cell must be considered, by now, as a treatment exclusively experimental, being necessary to wait for the conclusions derived of the ongoing studies to be able to give recommendations respect to its use in the therapy of this disease. A 160 Systematic Review of Multiple sclerosis in Latin America Cristiano E1, Rojas JI1 Romano M2, Frider N3, Machnicki, G4, Calegaro D5, Corona T6, Flores J6, Gracia F7, Macias-Islas M8, Giunta DH9 , Correale J10*. 1,9Hospital Italiano de Buenos Aires,Argentina; 2CEMIC, Buenos Aires Argentina; 3Novartis Latinoamerica & Canada; 5Hospital das Clinicas, Sao Paulo, Brazil; 6National Instiute of Neurology and Neurosurgery, Mexico; 7Santo Toms Hospital, Panam; 8Guadalajara University, Mexico; 10FLENI, Buenos Aires, Argentina Background: Incidence and prevalence of multiple sclerosis (MS) varies from region to region as demonstrated through extensive studies performed mainly in developed countries. Nonetheless, scant data are available in Latin America and the Caribbean (LAC). Methods: We conducted a systematic review of published articles and grey literature, including information from Ministries of Health, from January 1990 to May 2011. Results: After full-text review, twenty-two studies of 930 citations met the inclusion criteria. As we found great heterogeneity among studies, a meta-analysis was not performed. Incidence data were only found in three studies (from French West Indies, Argentina, and Panama) and ranged from 0.3 to 1.9 annual cases per 100,000 person-year. Prevalence was reported in ten studies (from Argentina, Brazil, Colombia, Ecuador, French West Indies Panam and Per) and ranged from 0.83 to 21.5 cases per 100,000 inhabitants. Relapsingremitting MS was the most prevalent subtype reported (48% to 91% of the series). Conclusion: This study represents the first systematic review of MS burden in LAC and provides important information on epidemiological features of MS in the region. Future research embracing other outcomes will expand the knowledge and contribute to a better management of the disease in the region. This study was partially supported by an unrestricted educational grant from Novartis. A 161 Long-term safety and efficacy of ocrelizumab in patients with relapsing-remitting multiple sclerosis: Week 144 results of a Phase II, randomised, multicentre trial L Kappos1, A Bar-Or2, A Sauter3, D Leppert3, D Li4, D Masterman3, F Barkhof5, J Tinbergen3, P O?Connor6, PA Calabresi7, SL Hauser8
1University
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Hospital, Basel, Switzerland; 2McGill University, Montreal, Canada; 3 F. Hoffmann- La Roche Ltd, Basel, Switzerland; 4University of British Columbia, Vancouver, Canada; 5VU Medical Center, Amsterdam, The Netherlands; 6University of Toronto, Toronto, Canada; 7Johns Hopkins University, Baltimore, MD, USA; 8University of California San Francisco, San Francisco, CA, USA Objective: Ocrelizumab (OCR), a humanised mAb targeting CD20 on B cells, reduced Gd+ lesions (primary endpoint) by 89% and annualised relapse rate (ARR) by 73% vs placebo at week (wk) 24 in a Phase II RRMS trial. Wk 144 data are reported here. Methods: At baseline, 220 RRMS patients (pts) were randomised 1:1:1:1 to intravenous OCR (days 1, 15) for a total dose of 600 mg (A); OCR 2000 mg (B); placebo (C); or open-label weekly intramuscular IFNbeta-1a 30 g (D). At wks 24, 48 and 72 all pts received OCR: treatment groups A, C and D received 600 mg per cycle; group B received 1000 mg at wk 24 and 48, and switched to 600 mg at wk 72. The study consisted of a 96-wk treatment period and a minimum of 48 wks follow-up (24-wk safety follow-up [SFU]), variable B cell monitoring period (BMP; ending with B cell repletion) and 24-wk observation period after B cell repletion (OSP). Results: Across treatment groups 8691% of initially randomised pts entered SFU after the 96-wk treatment phase, including pts who had withdrawn from treatment. Subsequently, 7382% of patients completed to wk 120 and 6778% completed to wk 144. Safety: Overall, there was no imbalance in the rates of adverse events (AEs) or serious AEs (SAEs) across all treatment groups over 144 wks. Two patients died after the 24-wk SFU (14 and 19 mo after last OCR administration; both were B cell repleted and event reported as not related to OCR). No new serious and no opportunistic infections were reported since last OCR administration. At the end of the B cell monitoring/observation period (Week 144), infection rates were 6.5% and 11.1% with the OCR 600 mg and 1000 mg regimens, respectively. Most infections were respiratory and urinary tract infections. Efficacy: During BMP/OSP, ARR remained at similar low levels as during the treatment period (0.040.28 across treatment groups), with no indication of increase or rebound. Conclusions: OCR was generally well tolerated with no imbalances in SAEs or infections and no reports of opportunistic infections over 144 wks. The magnitude of ARR reductions observed following OCR treatment up to wk 72 was maintained over 144 wks even after B cell repletion. a Data presented in this abstract and poster have been updated from those presented in the original abstract.
A 162 Risk of infections and malignancies after treatment with antiCD20 monoclonal antibodies: Ocrelizumab and rituximab in rheumatoid arthritis and multiple sclerosis L Kappos1, D Leppert 2, J Tinbergen2, M Gerber2, SL Hauser3 1University Hospital Basel (Basel, Switzerland); 2F. HoffmannLa Roche Ltd (Basel, Switzerland); La Roche Ltd (Basel, Switzerland); 3University of California San Francisco (San Francisco, USA)
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Background: Ocrelizumab (OCR) and rituximab (RTX) are CD20-targeting, B cell-depleting monoclonal antibodies. Safety data from their use in multiple sclerosis (MS) and rheumatoid arthritis (RA) may inform about expected risks in MS studies.

factors. a Some of the data presented in this abstract and poster have been updated from those presented in the original abstract.
was no increased risk of malignancies with RTX (allexposure RTX: 0.99/100 PTY [95% CI: 0.791.23] vs 1.05/100 PTY [95% CI: 1.011.09] in adult RA pts). Risk of PML with RTX was very rare with 6 confirmed cases in >188 000 RA pts (clinical cut-off date: 23 July 2012). OCR RA: In a pooled safety analysis of the double-blind, placebo-controlled phases of all pivotal OCR Phase III studies, SIE rates were comparable between low-dose (200 mg 2 or 400 mg 1) OCR and PBO. High-dose OCR (500 mg 2) was associated with higher SIE rates vs PBO, mainly due to Asia/Pacific data, where both dose groups had increased SIE rates. OIs were more frequent with OCR irrespective of dose vs PBO (9 vs 1 event). SIE and OI resolved with appropriate therapy. No PML was reported. The rate of malignancies was comparable between OCR dose groups and PBO and stable throughout the observation period. RTX relapsing-remitting MS (RRMS): SIE rates were similar for RTX (2.9%) and PBO (5.7%) in the Phase II HERMES study; no PML was reported. RTX PPMS: an imbalance in the rate of serious infections was observed in the OLYMPUS study (RTX 4.5% [13 patients experiencing 18 SIEs] vs <1% PBO); 9 out of 13 patients with SIE were aged above 55. OCR RRMS: Incidence of infections (serious and non-serious) was similar across both doses of OCR and PBO (SIEs: 0% and 1.9% during Week 024, respectively) and did not increase over time with continued OCR; no PML or other OIs were reported.
Conclusions: Treatment with anti-CD20 antibodies is not associated with an increased risk for malignancies. Incidences of SIEs and OIs with RTX and OCR treatment were generally low. No PML has been reported with OCR. These data inform the anticipated safety of OCR in ongoing Phase III MS trials where a lower risk of SIEs and/or OIs may be expected owing to diseaseinherent (co-medication) and trial design-inherent (region)
Methods: Data from all available OCR (RA, n=2820; MS, n=220), RTX studies (RA n=3914; MS, n=569) and post-approval data (RTX RA only; exposure n>188 000) were reviewed for rates of infection and serious infection (SI), including progressive multifocal leukoencephalopathy (PML), and incidence of malignancies. Results RTX RA: In the long-term safety extension of the Phase III studies (n=3194; 9.5 y follow-up), adverse event (AE) and serious AE (SAE) rates for RTX were comparable vs pooled placebo (PBO) arms from those studies. Serious infection event (SIE) rates for RTX were comparable vs PBO (all-exposure RTX: 3.94/100 patient-treated years (PTY) [95% CI: 3.60 4.31] vs PBO: 3.79/100 PTY [95% CI: 2.805.13]), and stable over time and multiple treatment courses up to 9.5 y. Serious opportunistic infections (OIs) were rare (all-exposure RTX, 0.06 events/100 PTY; PBO, 0.09 events/100 PTY). There
A 163 Speed of information processing in multiple sclerosis and depression Macas Islas Miguel ngel1,2, Aguayo Arelis Adriana1,3, Rabago Barajas Brenda Viridiana1,3 Institution: 1University of Guadalajara, Department of Neurosciences, 2Mexican Social Security Institute, Western National Medical Center, 3University Enrique Daz de Len. Psychology Objective: To analyze the relationship between speed of information processing and the presence and severity of depression in MS. Methods: ninety-six patients with MS. For inclusion criteria did not take into account age, gender, medical treatment, clinical type and EDSS. The assessments included: clinical history, Becks DepressionInventory, speed of information processing measured using the Paced Auditory Serial Addition Test (PASAT), verbal fluency (VF) and symbol digit test (SDT). For data analysis A p value <0.05 wasconsidered significant. Results: A total of 76 women and 20 men. Average age 33.810.8, education mean 13.43.4, disease duration 5.54,EDSS 2.91.8. Eighty-one patients with relapsing remitting MS (RRMS), 13 secondary progressive and primary progressive 2. 22.9% with mild depression and 22.9% severe. Significant differences were found between patients with no depression and with depression in PASAT (p =0.003), VF (p=0.004) and SDT (p=0.0001). Patients with no depression and with mild depression SDT (p=0.002). Patients with no depression and with severe depression PASAT 3 (p=0.002), PASAT 2 (p=0.006), VF (p=0.001) and SDT(p=0.002). RRMS patients with no depression and with mild depression TDS (p=0.018). Patients with no depression and with severe depression PASAT 3 (p=0.016), PASAT 2 (p=0.040), FV (p=0.027) and TDS(p=0.004). Conclusions: The results indicate that patients with depression have lower cognitive performance in comparison to patients with no depression. A 164 Oral presentation Genetics aspects of MS in Brazil Soniza Vieira Alves-Leon Institution: Post-graduation Program, Federal University of Rio de Janeiro State (UNIRIO), Hospital Universitrio Clementino Fraga Filho, Federal University of Rio de Janeiro (UFRJ) Multiple Sclerosis (MS) is a polygenic and multifatorial disease and belongs to a group of common disorders characterized by low disease risk heritability and multifaceted gene-environment interactions (Hafler et al, 2007; McElroy JP & Oksenberg JR, 2008). The susceptible MHC haplotypes have been identified and variation in MHC genes on chromosome 6p21.3, specifically the HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for MS. Studies based on single nucleotide polymorphisms have implicate genes outside the HLA region (Hafler et al, 2007). MS outcome has been associated to the HLA-DRB1*1501

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alleles (DeLuca et al, 2007; Barcellos et al, 2006) while others shows that DRB1 variation and both MS susceptibility and phenotypic expression have demonstrated conflicting results (Sospedra et al, 2006). In Brazil, we have found an ethinicitydependent association of HLA class II (DRB1*1501) alleles (Alves-Leon et al, 2007, Carvalho et al, 2006, Caballero et al, 1999). African-descendent presents DQB1*0602 association but White patients presents DR2 association (Papais Alvarenga et al., 2001) in Rio de janeiro City (RJC). In So Paulo City the association study of DRB1 region showed that Africandescendent presents DRB1*1501 association (Brum et al.) but we can not know about DR2 association because the other regions were not studied. Recently we evaluate the relationship between HLA class II (polymorphisms of HLA-DQA1, HLADRB1 and HLA-DQB1 loci) and CIITA polymorphisms -168A/G (rs3087456; promoter region variant) and +1614 G/C (rs4774*C; G500A; exon 12) in a Brazilian sample from RJC and we confirm the relative risk (RR) associated with the HLADRB1*15:01 allele (3.11, p value = 0.004); regarding the HLADQB1*06:02 allele it was 2.54 (OR = 2.86; Mantel Haenszel corrected p value = 0.03). These findings not only indicate that +1614G/C in exon 12 of CIITA gene, in conjunction with the HLA-DRB1*15:01+ allele increases the susceptibility to MS in this Brazilian sample but also reinforce the multifactorial and polygenic trait of the disease. These points suggest the importance of different genetic backgrounds associated to MS and probably to disease morbidity (Alves-Leon et al., 2008) and, perhaps, therapeutic response.
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Financial support: FAPESP, CNPq and CAPES (Nanobiotech, 2008). A 166 Oral Presentation Fatigue and functional MRI Fernanda Tovar Moll and Fernanda Erthal Institution: Instituto DOr de ensino e pesquisa, LABS, UNIRIO The origin of fatigue in unknown. Studies using Functional MRI (fMRI) showed that MS patients, performing simple voluntary movements with the thumb of one hand, had greater extent of activation of motor areas both ipsilateral and contralateral when compared with healthy controls. The highest cortical activation was correlated with greater number of demyelinating lesions. Rocca et all hypothesized that functional cortical reorganization would be an adaptive mechanism needed to maintain functional capacity in a brain-injured, recruiting more areas for the same function. We will present in LACTRIMS the results of a study to analyze the association of the pattern of cortical activation by fMRI during a motor command of finger tapping with fatigue identified by the fatigue severity scale (FSS 28) in MS patients from Rio de Janeiro, without disability. Ali patients were trained with the specific motor task (finger tapping) before the acquisition of images and patients were evaluated using fMRI. The activation maps of individual units were calculated on basis of statistical parameters analyzed voxel to voxel. In the processing of the images were quantified lesion volumes on T1, T2 lesions and after the administration of contrast (gadolinium). The software used for statistical analysis was the FSL and the images processed by the tool functional FEAT. The patients were classified in two groups according the FSS, with similar demographic and clinical features. Fatigue was not correlated with lesion volume on T1 and T2 and the number of enhanced lesion. The MS patients, regardless of fatigue, presented a pattern of activation of contralateral sensorimotor cortex, motor area ipsilateral and the cerebellum contralateral. FSS scores however were correlated with a significant increase of activation of the sensorimotor cortex bilaterally (most evident in the cerebral hemisphere ipsilateral to the movement ) and the insula contralateral. Those results bring new evidences for the role of the functional cortical reorganization that occurs in consequence of the MS white matter brain-injuries on fatigue, demonstrating the recruitment of more areas for the same function, regardless the absence of clinical motor dysfunction.
A 165 Suppressive effect of IL-27 on encephalitogenic Th 17 cells induced by multi-walled carbon nanotubes reduce the severity of Autoimmune Experimental Encephalomyelitis Adriel dos Santos Moraes, Alessandro S Farias, Alfredo Peterlevitz, Daniela Camilo, Elaine C. Oliveira, Felipe von Glehn, Fernando Pradella, Helder Ceragioli, Leonilda M.B. Santos, Mariana P. A. Santos, Rosemeire F. O. Paula, Vitor Baranauskas, Walkyria Volpini, Institutions: UNICAMP - FATEC Objective: To investigate the effect of MWCNT internalized by antigen presentation cells (APCs) in the presentation of MBP to encephalitogenic T lymphocytes. Methods: Expansion of encephalitogenic T lymphocytes in cell culture; the expression of mRNA cytokines such as IL-17 and IL-27 was evaluated by RT-PCR real time. Encephalitogenic T cells were co-cultured in presence of APC and APC + MWCNT following the adoptive transfer to nave Lewis rats. Results: Encephalitogenic CD4 T lymphocytes lines do not express IL-17, after incubation with APCs containing MWCNT. The expression of IL-17 returns when the cells were cultured in the presence of IL-27 neutralizing antibody. Adoptive transfer of the encephalitogenic cells devoid of Th17 caused a less severe EAE in normal Lewis rats. Conclusion: These results suggest that the internalization with MWCNT by APC induce increased production of IL-27 that suppresses the Th 17 lymphocytes differentiation. These mechanisms result in a less severe EAE.
A167 Oral Presentation The Spectrum of Demyelinating Inflammatory Idiopathic Disease: experience of Santa Casa da Misericrdia in Rio de Janeiro Maria Lcia Vellutini Pimentel, Letcia Fzer, Srgio Augusto Pereira Novis Institution: Santa Casa da Misericrdia do Rio de Janeiro Santa Casa da Misericordia of Rio de Janeiro is a General Hospital where the Ambulatory of Idiophatic Inflammatory Demyelinating Diseases at the Neurology Department was created only in 2003. There are patients coming from the city of Rio de Janeiro and sur-
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rounders. We reviewed 64 patients that had been attended in the year of 2011. There are 48 females and 16 males. Most of them (43) are Caucasians (67%) although Brazil is characterized by a population of 50% of non-Caucasian people. We found the diagnosis of multiple sclerosis in 51.6% among them and 11% of neuromyelitis optica; opticalspinal multiple sclerosis (OSMS) was seen in 25%, the pseudotumoral presentation of multiple sclerosis and ADEM were seen in 1.5% each, the secondary progressive form represented 4.7% as did mielytis (1/3 monophasic myelitis and 2/3 recurrent acute myelitis). Time of disease varied from less than one year to 41 years. The EDSS was not directly related to the duration of the disease; there were patients with a longer time course with a smaller EDSS than some patients who had the disease for a shorter period of time. Among the NMO patients there was a NMO female patient with 10 years of disease with an EDSS of 3.0, stable. All patients had a brain MRI done, 27% did not have a cervical MRI and 26.6% could not do a lumbar puncture.

In our genetic studies, compared with healthy controls, NMO/ NMO spectrum disorder (NMOSD) patients showed a significantly lower frequency of DRB1*0901 and significantly higher frequencies of DRB1*1602 and DPB1*0501, which conferred susceptibility to anti-AQP4 antibody-positive NMO/NMOSD, but not antibody-negative NMO/NMOSD. DRB1*0901 was a common protective allele, irrespective of the presence or absence of anti-AQP4 antibody. These results suggest that HLADRB1*1602 and DPB1*0501 alleles are risk factors only for antiAQP4 antibody-positive NMO/NMOSD, but not for anti-AQP4 antibody-negative NMO/NMOSD. We immunohistochemically examined actively demyelinating lesions infiltrated with numerous CD68+ macrophages from autopsied cases with Balos concentric sclerosis (BCS), MS, or NMO for astrocyte and oligodendrocyte/myelin markers. In autopsied NMO cases, preferential AQP4 loss is seen in some acute lesions, while in other acute lesions active demyelination without AQP4 loss can be found, suggesting heterogeneity of pathology in acute NMO lesions. Extensive AQP4 loss can be observed in autopsied cases with BCS and a fraction of MS cases, suggesting that AQP4 loss is not specific for NMO. Despite the presence of numerous GFAP- and MLC1-positive astrocytes, there were marked decreases in the levels of connexin (Cx)43, Cx32, and Cx47 in BCS lesions. At the leading edges, Cx43 and AQP4 were mostly absent, despite the positive immunoreactivity for GFAP, MLC1, Cx32, Cx47, MOG, MAG, and OSP. None of the six BCS patients was positive for anti-Cx or anti-AQP4 antibodies. BCS is thus characterized by extensive loss of Cxs and AQP4, with no autoantibodies against Cxs and AQP4. Similar extensive loss of Cxs and AQP4 without immunoglobulin or complement deposition was observed in acute lesions from MS and NMO cases. Autoantibody-independent astrocytopathy may contribute to demyelination via disruption of astrocyteoligodendrocyte/myelin interactions in BCS, MS, and NMO. Furthermore, we observed distal oligodendrogliopathy characterized by preferential loss of MAG with preservation of other myelin proteins not only in BCS and MS lesions, but also in NMO lesions, suggesting the occurrence of distal oligodendrogliopathy in these conditions. Therefore, coexistence of Cx/AQP4 astrocytopathy and distal oligodendrogliopathy seems to be a cardinal feature of extensive demyelinating lesions. In conclusion, these observations suggest that a simple dichotomy of MS produced by myelin-specific T cells and NMO caused by anti-AQP4 antibody is an over-simplification. It is suggested that Th17/Th1 cells and autoantibodies targeting various CNS antigens act in concert to produce a spectrum of demyelinating disorders, including MS, BCS and NMO.
A168 Oral Presentation Immunological and pathological features of neuromyelitis optica. Jun-ichi Kira Institution: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) selectively affecting the optic nerves and spinal cord. In this condition, longitudinally extensive spinal cord lesions (LESCLs) extending over three or more vertebral segments are regarded as characteristic. The nosological position of NMO has long been a matter of debate. However, the discovery of an IgG specific for NMO, initially designated NMOIgG but now known to be anti-aquaporin-4 (AQP4) antibody, suggested that NMO is a distinct disease entity with a fundamentally different etiology from multiple sclerosis (MS). However, NMO is heterogeneous. Clinically, it shows a monophasic or relapsing-remitting course. Immunologically, there are anti-aquaporin-4 (AQP4) antibody-positive and -negative cases; even pathologically, some cases show AQP4 loss while others show no AQP4 loss. The results of recent studies using experimental models indicate that anti-AQP4 antibody alone cannot induce severe inflammatory changes in the CNS, unless myelin antigen-specific T cells are co-transferred. Thus, the pathogenic roles of anti-AQP4 antibody in NMO still remain to be elucidated. We studied immunological, genetic and pathological features of NMO cases. In cerebrospinal fluid, the levels of Th17 cytokines (IL17) and Th1 cytokines (IFN-), as well as those of downstream proinflammatory cytokines such as IL-8, G-CSF, TNF- and IL-6, are all markedly elevated at relapse in NMO patients, irrespective of the presence or absence of anti-AQP4 antibody. Peripheral blood T-cell lines established from NMO patients showed inter- and intra-molecular epitope spreading with major myelin protein antigens, suggesting that NMO patients are sensitized by myelin antigens in vivo. These findings suggest that Th17/Th1 cells are likely to play an important role in initiating CNS inflammation in NMO.
A169- Oral Presentation The Th17 cell biology in multiple sclerosis and neuromyelitis optica Cleonice Alves de Melo Bento Institution: Universidade Estadual do Rio de Janeiro Following activation, CD4+ T cells differentiate into different lineages of helper T (Th) cells that are characterized by distinct developmental regulation and biological functions. Human Th17

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cells have recently been identified as a new lineage of effector T cells induced by IL-1- and IL-23-secreting dendritic cells. Different from traditional Th1 and Th2 subsets, Th17 are characterized as preferential producers of interleukin-17 (IL-17), IL-21, and IL-22 cytokines. Although their effector cytokines mediate host defensive mechanisms to various infections, especially extracellular bacteria infections, they are involved in the pathogenesis of many autoimmune diseases, such as multiple sclerosis (MS) and neuromyelitis opitica (NMO). MS and NMO are debilitating diseases of the central nervous system (CNS) in which CD4+ T lymphocytes play an important role in the pathogenesis by mediating the demyelination of neuronal axons via secretion of Th17-related cytokines resulting in the clinical manifestations. Nevertheless, recent results obtained from our group have indicated some immunological differences in T-cell cytokine profile in MS and NMO patients. While higher production of IL-17 was
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detected by in vitro activated CD4+ T cell from MS patients, these cells released elevated levels of IL-21 and IL-6 in NMO patients. This strong tendency to produce IL-21 and IL-6 cytokines in NMO-derived CD4+ T cells was associated with higher IL-23 and IL-6 production by lipopolysaccharide (LPS)-activated monocytes. Interestingly, the release of IL-21 and IL-6 by activated CD4+ T cells was directly correlated to neurological disability and more resistant to in vitro glucocorticoid inhibition. The excessive activity of the Th17 cells is, normally, associated with function damage of regulatory T cells (Trges) compartment, such as lower production of anti-inflammatory cytokines (IL-10 and TGF-). Therefore, although important questions have remained unanswered, the our current knowledge of Th17 cells biology and their relationship with disturbances in regulatory T cells networks can provide powerful therapeutic tools aiming to modify the disease course of MS and NMO.
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Torres, D.S Pasteur Hospital

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2Neuroradiology Center, Hospital Italiano de Buenos Aires, Argentina

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