CASE REPORT
Primary Neuroleptospirosis
A Case Report and Literature Review
Alfredo Chiappe-Gonzalez, MD,* Csar Ticona-Huaroto, MD,* Valerie Hoerster, MS,
Carlos Coral-Gonzales, MD, and Moiss Sihuincha-Maldonado, MD
Abstract: Leptospirosis is a highly prevalent, globally distributed zoono-
sis with an incidence 10 times higher in tropical regions, where the propor-
tion of new cases correlates with rainy seasons. Secondary effects to the
central nervous system in the immune phase of the illness typically mani-
fest as aseptic meningitis. However, neurologic sequelae can be diverse
and, although rare, other central and peripheral neurologic presentations
have been described including the Guillain-Barr syndrome. Neuroleptospirosis
as a primary disease manifestation is even more unusual. Below, we present
the case of a 27-year-old woman with a Guillain-Barrlike syndrome as
a primary manifestation of neuroleptospirosis as confirmed by positive
IgM serology test result in paired samples and microscopic agglutination
test reactive for Leptospira icterohaemorrhagiae in the convalescent phase.
The patient had a favorable clinical outcome after treatment with antibi-
otics, corticosteroids, ventilator support, and physical therapy.
Key Words: leptospirosis, primary neuroleptospirosis,
Guillain-Barr syndrome, aseptic meningitis
(Infect Dis Clin Pract 2017;00: 0000)
L eptospirosis is a zoonosis caused by mobile aerobic spirochetes
of the genus Leptospira, of which 21 species and more than
200 serovars have been identified. It is globally distributed and
highly prevalent, with an estimate of 873,000 cases and 48,600
deaths annually.1 The incidence is 10 times greater in tropical regions,
where the proportion of new cases correlates with rainy seasons.2
In Peru, leptospirosis is an endemic illness. In the rainforest,
the regions Loreto, Madre de Dios, and San Martn have the
greatest density of cases. In Loreto, the districts of Belen, Punchana,
San Juan Bautista, and Iquitos currently report the highest inci-
dence of disease.3
CASE REPORT
A 27-year-old woman, originally from Punchana (Peru), was
admitted to the emergency department at the Hospital de Apoyo
Iquitos (Apoyo de Iquitos Hospital) with a 2-week history of
progressive loss of visual acuity in the right eye, followed by ip-
silateral hemiparesis and subsequent lower-extremity weakness
that progressed to a flaccid paraplegia with urinary retention. On
the day of admission, her symptoms intensified; she developed
dyspnea from respiratory muscle weakness for which she sought
care. She had a medical history of vaginal delivery 10 weeks
ago and a urinary tract infection (UTI) 5 weeks previously. No re-
cent history of vaccination or flu-like illness. Vital signs showed
From the *Infectious Disease and Tropical Medicine Service, Hospital Nacional
Dos de Mayo; Universidad Nacional Mayor de San Marcos, Lima, Peru; UT
Southwestern Medical Center, Dallas, TX; and Infectious Disease and Tropical
Medicine Service, Hospital de Apoyo Csar Garayar Garca, Iquitos, Peru.
The authors have no funding or conflicts of interest to disclose.
Correspondence to: Alfredo Juan Chiappe-Gonzalez, MD, Av. Del Sur 237,
Dpto. 203. Distrito Santiago de Surco, Lima, Peru 33.
Email: alfredochiappe911@hotmail.com.
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 1056-9103
Infectious Diseases in Clinical Practice Volume 00, Number 00, Month 2017
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
fever, pallor, hypotension, tachypnea, and oxygen saturation of
94%. Clinical examination revealed bladder distention and an ab-
normal ventilatory pattern, with thoraco-abdominal dissociation.
Neurological findings were consistent with right optic nerve atro-
phy, anisocoria (RP 4 mm, LP 3 mm), deficient right pupillary
light response, and flaccid areflexic tetraparesis without marked
sensory deficits. Blood tests revealed leukocytosis, leukocyturia,
and moderately raised alanine transaminase level. No electrolyte
disturbance or impaired renal function was detected. Brain com-
puted tomography was normal (Table 1).
Given the suspicion of Guillain-Barr syndrome (GBS), the
patient was transferred to the intensive care unit for mechanical
ventilation. Although treatment with intravenous immunoglobulin
was planned, it was not administered due to lack of resources.
During her intensive care unit stay, alternating episodes of fever
and hypothermia were observed; therefore empiric antibiotic treat-
ment (ceftriaxone 2 g/d) for suspected UTI was continued along
with the implementation of corticosteroids (dexamethasone
8 mg intravenous 3 times a day) (Fig. 1). Neurological function
slowly improved, allowing removal of ventilatory support after
4 days. After initial negative serology for Leptospira in the first
week of disease, positive results for Leptospira IgM were subse-
quently received, for which she completed 14 days of ceftriaxone.
In the convalescent phase, both a positive serology and a re-
active microscopic agglutination test with 1/400 dilution titer for
Leptospira icterohaemorrhagiae confirmed the spirochetal infec-
tion (Table 2). She was discharged after 30 days of hospitalization,
after remission of the febrile episodes, and partial recovery of
the motor function. At 1 year follow-up, motor function has
further improved.
DISCUSSION
Neurological compromise during Leptospira infection is not
infrequent; however, due to the diversity of neurological syn-
dromes and the large number of asymptomatic infections, there
is a low rate in case recognition. Neurological manifestations oc-
cur in 10% to 21% as reported by Gancheva et al,4 who observed
children and adolescents are often the most affected. The com-
promise in the central nervous system (CNS) can be present in
the immune phase of the disease, which occurs after the first
week. In 50% to 85%, it manifests as aseptic meningitis,5 but
also other CNS and peripheral nervous system (PNS) neurologi-
cal presentations have been described including facial palsies,
GBS, myeloradiculopathies, myelopathies, encephalitis, menin-
goencephalitis, intracranial hemorrhage, involuntary movements,
dysautonomias, cerebellar disorders, mononeuritis, polyneuritis,
polyradiculoneuritis, and polymyositis.
Although primary neuroleptospirosis is extremely unusual,
aseptic meningitis is also the predominant presentation.6
The involvement of cerebrospinal fluid with the cerebral tis-
sue occurs 48 hours after bacterial inoculation, affecting the ner-
vous system in a biphasic pattern. In the leptospiremic phase,
the bacteria can contaminate the CSF without significant cytologic
www.infectdis.com 1
Chiappe-Gonzalez et al Infectious Diseases in Clinical Practice Volume 00, Number 00, Month 2017

TABLE 1. Auxiliary Examinations Requested in the HAI

Hemoglobin 11.2 g/dL Total protein 6.13 g/dL Sodium 138 mEq/L
Hematocrit 32.7% Albumin 2.54 g/dL Potassium 4.14 mEq/L
MCV 74 fl Globulin 3.59 g/dL Chloride 102 mEq/L
MCH 25.3 pg Total bilirubin 0.42 mg% Calcium 8.8 mg/dL
Leucocytes 15,550 Direct bilirubin 0.20 mg% Lumbar puncture
Granulocytes 14,320 Indirect bilirubin 0.22 mg% Glucose 54 mg/dL
Lymphocytes 108 AST 55 U/L Protein 67 mg/dL
Platelet 322,000 ALT 213 U/L G index (csf/ser) 0.6
Glucose 113 mg/dL Arterial gasometry
BUN 24 mg/dL pH 7.47 Chest x-ray Normal
Creatinine 0.8 mg/dL PCO2 29.9 mEq/L Brain CT Normal
CRP 11.2 mg/L HCO3 21.6 mEq/L
LDH 468 U/L PO2 81 mm Hg
Urine test PO2/FiO2 385.7 mm Hg
Leucocytes >100 x/c O2 Sat 96.8%
Erythrocytes 810 x/c G (A-a) 32.4 mm Hg
Epithelial cells Absent FiO2 21%
HAI indicates Hospital Apoyo Iquitos; MCV, mean corpuscular volume; BUN, blood urea nitrogen; CRP, c-reactive protein; LDH, lactate dehydroge-
nase; AST, aspartate transaminase; ALT, alanine transaminase; HCO3, bicarbonate; O2 Sat, oxygen saturation; G (A-a), alveolar-arterial gradient; FiO2, frac-
tion of inspired oxygen; CSF, cerebrospinal fluid; G index (csf/ser), glucose index between CSF and serum glucose; CT, computed tomography.

or biochemical changes; meningeal irritation is unusual. In the
immune phase, we find meningitis signs, cerebrospinal fluid
with proteinorrachia, mononuclear pleocytosis, and normal glu-
cose; antibodies are detectable, but bacteria are no longer isolable.6,7
The mechanism of neurological compromise has not been
elucidated. Postulates include direct effects of the bacteria or an
immunologic reaction. In a patient, Lepur et al describe the menin-
goencephalitic and PNS compromise after a Leptospira infection
with detectable anti-GD1a and anti-GM1 antiganglioside antibod-
ies, which explain the polyneuritis. However, they do not explain
the diffuse CNS compromise, highlighting the agent's potential
ability to simultaneously induce multiple pathogenic mechanisms.8
Our patient was admitted with a febrile neurological syn-
drome suspicious of GBS with a concurrent UTI, but the neuro-
logical examination detected a CNS and PNS compromise. Such
compromise has been described as a primary manifestation of
neuroleptospirosis by Panicker et al,6 who reported diagnoses
of myelopathy, myeloradiculopathy, and GBS representing the
42.5% of all their cases. Other reports similar to ours exist, with
diagnoses of transverse myelitis, paraplegia, axonal motor neurop-
athy, or GBS-like syndromes as the primary presentation. In these
reports, patients are predominantly male, older than the age of
40 years,with high fever, muscular deficits, and renal and/or he-
patic compromise with or without hyperbilirubinemia. Sensory in-
volvement is minimal.911
The patient's optic nerve atrophy could correspond to sequalae
of a lesion produced by neuritis or an anterior ischemic stroke, both
of which have been described in ocular leptospirosis. More fre-
quently, neuritis, retinal periphlebitis, and panuveitis are reported.12
It is also interesting to mention the positive Rose Bengal test, which
could be explained as a cross-reaction to antibodies against many
other agents; this particular cross-reactivity has also been reported
in livestock vaccinated against Leptospira.13
The patient had a favorable outcome with the established
therapy. Reports describe a complete clinical recovery 6 to
8 weeks after neurological presentation. Poor prognostic indica-
tors described include altered consciousness, proteinorrachia,
and seizure.5,7
The workup focused on looking for infectious and autoim-
mune diseases associated with GBS. Serology for cytomega-
lovirus, Epstein-Barr virus, and toxoplasma showed previous
exposure. Dengue and chikungunya virus workup ruled out recent
infection that would justify the clinical picture. Acute retroviral in-
fection was ruled out with a negative human immunodeficiency

FIGURE 1. Temperature curve during hospitalization.

2 www.infectdis.com 2017 Wolters Kluwer Health, Inc. All rights reserved.

Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Infectious Diseases in Clinical Practice Volume 00, Number 00, Month 2017 Primary Neuroleptospirosis

TABLE 2. Infectious and Autoimmune Research (Hospital Apoyo Iquitos)

HIV Nonreactive Leptospira IgM (paired samples) Positive

VDRL Nonreactive Leptospira MAT + icterohaemorrhagiae
CMV IgG 107.2 (+) Brucella set
CMV IgM 0.29 () Bengal Rose test Positive
Toxoplasma IgG 439.7 (+) 2-Mercaptoethanol Negative
Toxoplasma IgM 0.24 () Agglutination in tube Negative
EBNA IgG 13 (+) Blocking antibodies Negative
EBNA IgM 3.3 () Prozone phenomenon Negative
Dengue IgM Negative Urine culture Negative
Dengue NS1 Negative Blood culture (2) Negative
CHIKV IgM Negative AFB sputum Negative
CHIKV IgG Negative ANA Negative
Malaria research (4) Negative c-ANCA and p-ANCA Negative
HIV indicates human immunodeficiency virus; VDRL, venereal disease research laboratory; IgG, immunoglobulin G; IgM, immunoglobulin M; CMV,
citomegalovirus; EBNA, Ebstein-Barr nuclear antigen; NS1, nonstructural protein 1; CHIKV, chikungunya virus; MAT, microagglutination test; AFB, acid
fast bacilli; ANA, antinuclear antibodies; c-ANCA, cytoplasmic antineutrophil cytoplasmic antibodies; p-ANCA, perinuclear antineutrophil cytoplasmic
antibodies.

virus ELISA test result after the detection window period, as
well as neurosyphilis with a negative serum venereal disease re-
search laboratory. Screening results for autoimmune diseases were
also negative.
Neuroleptospirosis should therefore always be considered in
the differential diagnosis of a patient coming from an endemic
area who presents with fever associated with various forms of
acute neurological compromise.
To conclude this case report, it is important to keep in mind
the following:
Leptospirosis can present as a primary neurological syndrome.
The clinical patterns of the nervous system manifestations
due to Leptospira infection are diverse and include Guillain-
Barrlike syndromes.
The presence of fever with neurological compromise should
suggest the diagnosis and justifies the empiric treatment of
neuroleptospirosis in highly endemic areas.
It is extremely important to treat neuroleptospirosis with both
antibiotics and corticosteroids due to the direct and indirect
(immunologic) damage of the bacteria.
REFERENCES
1. Abela-Ridder B, Bertherat E, Durski K. Global burden of human
leptospirosis and cross-sectoral interventions for its prevention and
control. In Prince Mahidol Award Conference 2013. Bangkok, Thailand:
Prince Mahidol Award Conference. Available at: http://www.
pmaconference.mahidol.ac.th/dmdocuments/2013-PMAC-Poster-P9-
Bernadette%20Abela-Ridder.pdf; 2013.
2. Blanco RM, Romero EC. Fifteen years of human leptospirosis in So
Paulo. Brazil J Epidemiol Res. 2016;2(1):5661.
3. Vargas E. Situacin de la leptospirosis en el Per, aos 20132014
(a la SE 19). Bol Epidemiol (Lima). 2014;23(19):382385. Available at:
http://www.dge.gob.pe/portal/docs/vigilancia/boletines/2014/19.pdf.
4. Gancheva GI, Kostadinova MA, Kostadinova PI. Involvement of
central nervous system in leptospirosis. J Biomed Clin Res.
2009;2(2):109114.
5. Berman SJ, Tsai CC, Holmes K, et al. Sporadic anicteric leptospirosis in
South Vietnam. A study in 150 patients. Ann Intern Med. 1973;79(2):
167173.
6. Panicker JN, Mammachan R, Jayakumar RV. Primary neuroleptospirosis.
Postgrad Med J. 2001;77(911):589590.
7. Bharucha NE, Bharucha EP, Bhabha SK. Infections of nervous system.
In: Bradley WG, Daroft RB, Fenchel GM, et al, eds. Neurology in
Clinical Practice. Boston, MA: Butterworth-Heinemann; 1996:
12141215.
8. Lepur D, Himbele J, Klinar I, et al. Anti-ganglioside antibodies-mediated
leptospiral meningomyeloencephalopolyneuritis. Scand J Infect Dis.
2007;39(5):472475.
9. Mumford C, Dudley N, Terry H. Leptospirosis presenting as a flaccid
paraplegia. Postgrad Med J. 1990;66(773):218220.
10. Kavitha S, Shastry BA. Leptospirosis with transverse myelitis.
J Assoc Physicians India. 2005;53:159160.
11. Silva AP, Burg LB, Locatelli JF, et al. Leptospirosis presenting as ascending
progressive leg weakness and complicating with acute pancreatitis.
Braz J Infect Dis. 2011;15(5):493497.
12. Rathinam SR. Ocular manifestations of leptospirosis. J Postgrad Med.
2005;51(3):189194.
13. Naves JH, Rezende LM, Ramos GC, et al. Interference in diagnostic tests
for brucellosis in cattle recently vaccinated against leptospirosis.
J Vet Diagn Invest. 2012;24(2):283287.

2017 Wolters Kluwer Health, Inc. All rights reserved. www.infectdis.com 3

Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.