GuillainBarre Syndrome

Minnie M. Chavez, M.D. June 30, 2011

GRAND ROUNDS

Leo Claire Dianne Kervin Variable Age/Sex 16/ M 14/F 12/F 2/M Preceding Respiratory RespiratoryRespiratoryRespiratory infection Yes Quad Yes Yes Yes riparesis Yes Bulbar Yes Yes Yes weakness Yes Cranial Yes Yes Yes neuropathy

Variable

Leo

Claire

Dianne

Kervin

Nerve conduction studies

AMAN AMAN Severe motor Day 30: denervation due to severe motor severe axonal denervation dysfunction and RUE/RLE demyelinating process

AMSAN AMAN Day 7: Day 6: severe severe motor sensorimotor denervation both denervation all upper & lower limbs; motor levels tested. denervation was Sensory due to severe Potential were demyelinating relatively spared and axonal dysfunction

Objectives
1.To present an atypical case of post - Rubeola GBS 2. 3.To discuss the approach to diagnosis, differentials, immuno pathogenesis, clinical course and complications in the context of a multi-disciplinary management

General data
16 years old Male Right handed Filipino Roman Catholic Cagayan De Oro April 25, 2011

CHIEF COMPLAINT
Difficulty of breathing

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

11 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

10 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

7 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

6 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

5 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

4 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

3 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

2 days

HISTORY OF PRESENT ILLNESS

fever cough rash pains numbness weakness dyspnea

Day of Admission

Family History

70

56

34

32

29

19

BIRTH AND MATERNAL History

Born to a 40 year old, G5P5 (5005) Non-smoker, non-alcoholic beverage drinker mother Regular prenatal check-ups to a private obstetrician No maternal illness No intake of abortifacient nor exposure to radiation Full term Normal spontaneous delivery Hospital in Cagayan De Oro assisted by an obstetrician No fetomaternal complications

NUTRITIONAL History
Patient was breastfed for few days followed by milk formula Regular diet consists of fried fish, eggs and bread in breakfast, soup, rice and fish at lunch, and rice, fish and meat at dinner No food preference

IMMUNIZATION History
BCG DPT-OPV x 3 doses Hepatitis B x 3 doses Measles MMR at 5 and 10 years old HiB Varicella vaccines

GROWTH AND DEVELOPMENTAL History

Recalled developmental milestones were achieved at appropriate ages

headsss
H Patient is closer to his mother. At home, he participates in household chores like washing the dishes and preparing meals E Presently, he is a 2nd year college student taking up Industrial Engineering in De La Salle University- Taft Avenue with three failed grades, however he claimed that his favorite subject is Science

A He enjoys playing soccer and other outdoor physical activities like mountain climbing D He has no predilection to drugs nor to dieting S At present, he has no relationship with the opposite sex but admitted having a relationship in the past that lasted for 2 years S He has no suicidal ideation S He attends mass on Sundays

headsss

PAST MEDICAL History

Diagnosed with Bronchial asthma No previous head trauma No previous hospitalizations No allergies to food or drugs

PHYSICAL EXAMINATION
Weak looking, bed-borne, and in respiratory distress Vital Signs: BP 130/70 CR 160 bpm RR 41 bpm T 36.8 C Weight : 62.5 kg Height : 172. 7 cm BMI : 21 kg/m2 HC : 50 cm Warm to touch with generalized brawny desquamation and hyperpigmentation

PHYSICAL EXAMINATION
Anicteric sclerae, hyperemic conjunctivae, no nasal discharge, no tonsillopharyngeal congestion, no cervical lymphadenopathies Symmetrical chest expansion, decreased breath sounds on the right with subcostal retractions and crackles on bilateral lung fields Adynamic precordium, apex beat at 5th left intercostal space mid-clavicular line, tachycardic, no murmurs Flat abdomen, normoactive bowel sounds, soft, nontender, no hepatosplenomegaly Tight sphincteric tone Pulses full and equal, no cyanosis nor edema

NEUROLOGICAL EXAMINATION
He is oriented to person, place and time .He has intact remote and recent memory. No agraphia, apraxia, dyscalculia, no left to right disorientation Cranial Nerves: I: intact II: Visual acuity 20/20, OU (Jaegers) ; no visual field cuts Fundoscopy: (+) ROR, clear media, AV ratio 2:3, distinct disc margin, no retinal hemorrhages II,III: pupils 2-3 mm equally reactive to light and accomodation III, IV, VI: Extra ocular muscles full and equal V: good temporalis and masseter tone; V1-V3 intact VII: unable to raise eyebrows and wrinkle forehead, unable to completely close both eyelids, unable to smile, unable to puff air into the cheeks VIII: gross hearing intact IX, X: weak gag reflex, bilateral; dysphagia with pooling of saliva (+) hoarse voice with dysphonia XI: turns head to both sides against resistance; good shoulder shrug XII: tongue midline on protrusion

Motor Exam: A. Strength

Manual Muscle Testing (MMT) Arm elevation Arm adduction downward Arm adduction across the chest Arm abduction Elbow flexion Elbow extension Wrist Flexion Wrist Extension

NEUROLOGICAL EXAMINATION
Right 3/5 3/5 3/5 3/5 3/5 3/5 3/5 3/5 Left 3/5 3/5 3/5 3/5 3/5 3/5 3/5 3/5 3/5 Manual Muscle Testing (MMT) Finger Abduction Finger adduction Finger extension Finger flexion Hip flexion Thigh abduction Thigh adduction Hip extension Knee extension Knee flexion Foot dorsiflexion Foot inversion Foot eversion Plantar flexion Toe flexion Toe extension Right Left 3/5 3/5 3/5 3/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 3/5 3/5 3/5 3/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5 2/5

Scapula adduction 3/5

NEUROLOGICAL EXAMINATION
B. Tone symmetrically hypotonic in all extremities C. Absence of atrophy/Bulk D. No muscle tenderness/ pain on palpation E. No involuntary involvements Sensory: intact pain and temperature, position and vibration, light touch, 2-point discrimination Cerebellar: Because of the weakness patient was unable to do FTNT, tandem walking and other cerebellar function tests Deep Tendon Reflexes Biceps (C5, C6) Brachioradialis (C5, C6) Triceps (C6, C7, C8) Patellar (L2, L3, L4) Achilles Tendon (S1, L5) No extensor toe sign, no clonus Meningeals: no nuchal rigidity Right +1 +1 +1 0 0 Left +1 +1 +1 0 0

Salient Features
16 year old male, right handed Preceded by a 10 day history of a systemic viral illness Low back pains and paresthesias in the toes Acute ascending symmetric motor weakness Normal mental status Facial diplegia, hoarseness, decreased muscle strength, hypo/areflexia, no extensor toe sign

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Approach to Diagnosis

Is there a disease in the nervous system? Yes

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Levelize the Lesion

2+

Levelize the Lesion

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LocalizATION
Patient
Reflexes

Absent Absent Absent

Atrophy

Fasciculations

Tone

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Decreased Negative

Babinski

THE PERIPHERAL NERVE

Which part of the peripheral nervOUS SYSTEM?

PERIPHERAL NERvous system

Anterior horn cell Neuromuscular junction Muscle x q q Roots q Nerve x x

What is the etiology?

AUTOIMMUNE
Post-infectious

2+

Peripheral

nerve

disorders

CLASSIFICATION OF POLYNEUROPATHIES

DIFFERENT DISEASES WITH polyneuropathies

HYPOTHYROIDISM
Fatigue Delayed DTRs Slow movement and speech Cold intolerance Constipation and weight gain

ALCOHOLIC

NEUROPATHY

Distal to proximal involvement Slowly progressive (over months) abnormalities in sensory, motor, autonomic, and gait function
No history of chronic alcohol use with nutritional deficits

TOXIC

NEUROPATHY

Drug abuse and exposure to chemicals Distal > proximal Pains

METAL

NEUROPATHY

immunopathology

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IMMUNOPATHOGENESIS

TRIGGERS
Upper Respiratory Tract Infection
Cytomegalovirus Epstein-Barr Virus

50% 32%

Gastro-intestinal Tract Infection

Campylobacter jejuni

Vaccination, Malignancies, Bone marrow transplantation, surgeries

ImmunoPathogen

2+

MOLECULAR

MIMICRY
A process wherein exogenous antigens have structural appearance to selfantigens The host generates an immune response to the inciting factor (usually an infectious organism) that shares epitopes with hosts affected tissue

CELLULAR AND HUMORAL IMMUNITY

COMPLEMENT

SYSTEM

Working Impression
Acute post- Rubeola poly radiculoneuropathy (Guillain-Barre Syndrome) with impending respiratory failure

2+

HISTORICAL

BACKGROUND

Landry's ascending paralysis, French polio, acute idiopathic polyneuritis, or acute idiopathic polyradiculoneuritis French physician Jean Landry had described the condition in 1859 Named for Georges Guillain and Jean Alexandre Barre: increased level of protein with normal cell count in cerebrospinal fluid (1916)

DEFINITION
An acute, immune-mediated disorder of peripheral nerves, spinal roots, and cranial nerves, commonly presenting as a rapidly progressive, areflexive, relatively symmetric ascending weakness of the limb, truncal, respiratory, pharyngeal, and facial musculature, with variable sensory and autonomic dysfunction

Whats new in Guillain-Barr syndrome? J Pritchard; Dr Jane Pritchard, Neurology Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; jpritchard@doctors.org.uk

DIAGNOSTIC CRITERIA
Features required for diagnosis
Progressive weakness in both arms and legs Areflexia

Features strongly supporting diagnosis

Progression of symptoms over days, up to four weeks Relative symmetry of symptoms Mild sensory symptoms or signs Cranial nerve involvement, especially bilateral weakness of facial muscles Recovery beginning two to four weeks after progression ceases Autonomic dysfunction Absence of fever at onset High concentration of protein in cerebrospinal fluid, with fewer than 10 cells per cubic millimeter Typical electrodiagnostic features

Features excluding diagnosis

Diagnosis of botulism, myasthenia, poliomyelitis, or toxic neuropathy Abnormal porphyrin metabolism Recent diphtheria Purely sensory syndrome, without weakness

GLOBAL AND LOCAL Incidence

Annual incidence globally is 0.5 - 1.5 cases per 100,000 population per year < 18 years old. Youngest recorded patient: 2 years old, male predominance. Axonal type in Asians.

Source: Pediatric Guillain-Barre Syndrome Author: Sameer Chhibber, MD, FRCPC; Chief Editor: Amy Kao, MD

From the Philippine Pediatric Society Registry: 168 GBS patients have been reported from a total of 992, 341 cases
www.pps.org/ Registry.

From the Philippine Childrens Medical Center: 120 patients have been seen from 1995 to June 2011
Philippine Childrens Medical Center Medical Records Section

Clinical Manifestations

2+

Weakness Reduced or absent reflexes Sensory disturbance Pain Cranial nerve involvement Respiratory dysfunctions Dysautonomia

TWO Pathologic classificationS

SPECTRUM OF GBS 2010

AIDP Autonomic AMAN

PCB FD MFS BBE Sensory

AMSAN

JB Winter/ Journal of Immunology 231 (2011)

variants

ELECTRO PHYSIOLOGICAL CRITERIA

AIDP

AMSAN

AMAN

Classification of GBS syndrome and related disorders

Typical antiganglioside antibodies by pathology Acute inflammatory demyelinating Unknown polyradiculoneuropathy (AIDP) Acute motor and sensory axonal GM1,GM1b,GD1a neuropathy (AMSAN) Acute motor axonal neuropathy GM1,GM1b,GD1a, (AMAN) GaINac-GD1a Acute sensory axonal neuropathy GD1b Acute pandysautonomia Regional variants GQ1b,GT1a Fishers syndrome GT1a Oropharyngeal Overlap Fishers syndrome/ GBS overlap GQ1b,GMi, Gmib, GD1a, GaINac-GD1a syndrome

AIDP
Acute Inflammatory Demyelinating Polyneuropathy

Multifocal mononuclear cells infiltration throughout the peripheral nervous system in which the distribution of inflammation corresponds to the clinical deficit Macrophag s invade the e mye she lin aths and de nude the axons

FISHER S SYNDROME
Activation of antiGQ1b and anti-GT1a antibodies that target oculomotor and bulbar nerves

The pre synaptic ne rve te rminal axons and pe risynaptic Schwann ce are lls damaged

AmSan
Acute Motor Sensory Axonal Neuropathy

The pathology resembles that in AMAN, with the same pattern of macrophag invasion of e the pe rinodal space The dorsal, as well as the ventral, roots are affected There is the same paucity of lymphocytic inflammation consistent with an antibodymediated pathogenesis

Aman
Acute Motor Axonal Neuropathy

Macrophag s invade the e node of Ranvie s r, where they insert between the axon and the surrounding Schwann cell axolemma, leaving the myelin sheath intact Severe: axons are damaged in the ventral root, which may cause severe

Course in the ICU

ABG
pH pC02 p02 HC03 02 sat BE -0.5 CBC Hgb Hct WBC Seg Lym Mono Platelet 156 0.46 17.7 0.92 0.02 0.06 494 7.4 39 70 24.2

ADMISSION

Is the most common serious complication of Guillain-Barre syndrome Acute Respiratory Failure: 1.Alveolar-arterial oxygen gradient of 300mm Hg with an inspired oxygen fraction of 1.0 2.Arterial PC02 above 45mm Hg 3.Static inspiratory pressures below 30 cm H20 Mechanical failure of the thoracic bellows is the problem

Intubation criteria 1.Mechanical ventilator failure with reduced expiratory VC of 12-15 ml/kg 2.P02 below 70 mm Hg with inspired room air 3.Severe oropharyngeal paresis with difficulty clearing secretions or repeated coughing and aspiration after swallowing 4. Mortality rate was 3% for all patients who could not walk and zero for those who required mechanical ventilation directly as a result of GBS Complications of tracheostomy in GBS: 7-55%

investigations

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LUMBAR PUNCTURE AND CSF ANALYSIS

Before treatment because IVIG can cause aseptic meningitis WBC < 10 x 10 cells/ L Raised protein but normal in the first week

Whats new in Guillain-Barr syndrome? J Pritchard; Dr Jane Pritchard, Neurology Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; jpritchard@doctors.org.uk

IMMUNO THERAPY
The main modalities of therapy: Intravenous immune globulin Plasmapheresis

EVIDENCE FOR IMMUNOTHERAPY

Plasma Exchange
Strong evidence supports PE recommended in nonambulant patients within 4 weeks of onset of neuropathic symptoms (Level A*, Class II**)

IVIg
IVIG recommended in non ambulant patients within 2 weeks of onset of neuropathic symptoms (Level A, Class II)

Combined Treatments

Cortico steroids

Sequential treatment Steroids not with PE followed by recommended IVIG does not have in the treatment a greater effect than of GBS (Level either treatment A, Class I) given alone (Level A, Class I)

2003 Practice Parameter Quality Standards Subcommittee of the American Academy of Neurology

PLASMAPHERESIS

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PLASMAPHERESIS

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Course in the ICU

2nd 5th Hospital Day

weaning
Improvement in strength Serial Pulmonary function tests Tracheostomy

Villaure, Wilson. Guillain-Barr syndrome: Treatment and Prognosis Version 7. Knol. 2009 Feb 8. Available from: http://knol.google.com/k/wilson-villaure/guillain-barr-syndrome/1bbsle13m97c0/127.

The autonomic neuropathy involves both the sympathetic and parasympathetic systems Manifestations: alternating hypotension with hypertension, urinary retention, sweating abnormalities, and sinus tachycardia

Villaure, Wilson. Guillain-Barr syndrome: Treatment and Prognosis Version 7. Knol. 2009 Feb 8. Available from: http://knol.google.com/k/wilson-villaure/guillain-barr-syndrome/1bbsle13m97c0/127.

ACUTE

PHASE REHABILITATION

Orsini, M., de Freitas M., Presto, M. Guidelines for Neuromuscular Rehabilitation In Guillain-Barre Syndrome: What can we do ? Rev Neuroscience 2010; 18: 4: 572-580

Course in the ICU

Thyroid function tests
Free T3 Free T4 TSH < 0.05 (1.4-4.2) 2.135 (0.8-2 ng/dl) 0.208 uIU/ml (0.4-7 uIU/ml)

6th - 7th Hospital Day

TSH High

T4 Normal

T3 Normal

High Low Low Low

Low Normal

Low or normal Normal High or normal Low or normal

Interpretation Mild (subclinical) hypothyroidism Hypothyroidism

High or normal Low or normal

Mild (subclinical) hyperthyroidism Hyperthyroidism

Nonthyroidal illness; rare pituitary (secondary) hypothyroidism

Peeters RP, van der Geyten S, Wouters PJ, Darras et al Tissue thyroid hormone levels in critical illness. Journal of Clinical Endocrinology and Metabolism. 90: 6498-6507. 2005

Non thYRoidalillness SYNDROME

Peeters RP, van der Geyten S, Wouters PJ, Darras et al Tissue thyroid hormone levels in critical illness. Journal of Clinical Endocrinology and Metabolism. 90: 6498-6507. 2005

Course in the ICU

8th - 9th Hospital Day

SIADH

1/3rd of patients Rarely symptomatic In ventilated patients: 42% versus 19% Average occurrence: 10 days after intubation (range 1-23 days) Resolved after fluid restriction Downward osmotic resetting and enhanced renal sensitivity to ADH

Neurophysiology
NCV Amplitudes of sensory nerve action potentials ( SNAPs ) evoked on antidromic stimulation of the left median , left ulnar , left radial , right and left ( bilateral ) sural nerves were normal . Distal sensory latencies were normal . Sensory nerve conduction velocities ( NCVs ) were normal . No compound muscle action potentials ( CMAPs ) were evoked on proximal stimulation of right peroneal tibial nerve . Amplitude of the CMAPs evoked on stimulation of the left medial , left ulnar and bilateral peroneal nerves were severely reduced . Temporal dispersion was appreciated Motor latencies were generally prolonged Motor NCVs of the left median and left ulnar and right peroneal nerves were normal. Distal and proximal motor NCVs of the left peroneal nerve were normal and mildly slowed, respectively. Motor NCV of the left tibial nerve was mildly slowed

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Course in the ICU

Plasma Renin 132.5 pg/ml Supine: 1.1-20 pg/ml Upright: 1.8-60 pg/ml.

10th - 12th Hospital Day

PLASMA

RENIN

ELEVATED LIVER FUNCTION TESTS

ELEVATED LIVER FUNCTION TESTS

100 patients with Guillain-Barre syndrome On admission, 38% showed an increase SGPT ..10% had serologic evidence of recent cytomegalovirus infection. The remaining 28 patients were negative for other known causes of liver damage In the IVIg-treated group, 35% before to 69% shortly after treatment In the PE-treated group, 41% to 36% Conclusion:

GBS patients had mild liver function disturbances without obvious cause IVIg was associated with mild transient liver function disturbances through an unknown mechanism

Liver function disturbances in Guillain-Barre syndrome. A prospective longitudinal study in 100 patients P. G. Oomes, MD, F.G.A. van der Meche, MD, PhD and R. P. Kleyweg, MD, PhD

Course in the ICU

13th -16th Hospital Day

Course in the ICU

17th - 23rd Hospital Day

Course in the ICU

24th 26th

Hospital Day

Course in the ICU

27th- 30th Hospital Day

Treatment

SUMMARY

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SUPPORTIVE

CARE

prognosis
Mortality rates range from 2 to 13% Most common causes of deathAction Potential low mean Compound Muscle after GBS: respiratory (CMAP) - the most powerful predictor Amplitude failure cardiovascular and autonomic disturbances of poor recovery rate thrombo-embolisms

Guideline for Neuromuscular Rehabilitation in Guillain-Barr Syndrome: What can we do? Marco Orsini, Marcos RG de Freitas, Bruno Presto, Rev Neurocienc 2010;18(4):572-580 15% have mild illness, remain ambulatory, and

2+

recovery after few weeks 5-20% have fulminant course

recurrence
Monophasic 10% - early relapse in 1st week or two following treatment 3% - subsequent years CIDP

Whats new in Guillain-Barr syndrome? J Pritchard; Dr Jane Pritchard, Neurology Specialist Registrar, The National Hospital for Neurology and Neurosurgery, Queen Square, London; WC1N 3BG, UK; jpritchard@doctors.org.uk

Final Diagnosis
Post-Rubeola Guillain-Barre Syndrome with respiratory failure, resolved Secondary Hypertension Secondary Hypothyroidism Exposure Keratitis, OU

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Follow - up

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