GUILLAIN-BARR SYNDROME (GBS) By: Ryan Chetram, MS-3 Caribbean - PowerPoint PPT Presentation

GUILLAIN-BARRÉ SYNDROME (GBS) By: Ryan Chetram, MS-3 Caribbean Medical University SOM

About - History ■ Named after Guillain, Barre, and Strohl who first reported it in 1916 ■ GBS is a peripheral polyneuropathy usually following an inceptive event in 70% of cases ■ Was originally thought to be a demyelinating disease only ■ C. Miller Fisher described MFS in 1956; Edwin Bickerstaff described BBE in 1951 ■ In 1980 the first subtype was discovered called AMAN

About – Epidemiology ■ Incidence of 1.65-1.75 per Event Ev Ex Exampl ple 100,000 Bacterial Camplyobacter Jejuni** Mycoplasma Pneumonia ■ C. Jejuni represents 33% Cases Virus CMV EBV ■ In 1976 H1N1 was spreading and VZV President Ford wanted to immunize Zika Virus COVID-19 the Public Drugs Cyclosporine Pembrolizumab ■ 450 cases following Swine Flu Vaccine Influenza Vaccination of 45 million Rabies 1976 Swine Flu Vaccine

About – Zika 2015 Endemic outbreaks in Asia, South America, and the Caribbean due to Zika Virus 2/10,000 Incidence GBS

Presentation – Classic Appearance ■ Symptoms typically begin 1 week after immunological event ■ Classically presents with symmetrical ascending progressive muscular weakness as well as loss of Deep Tendon Reflexes beginning in the lower limbs ■ Diaphragmatic involvement can prove fatal causing respiratory distress (30%) – Expected with weakened neck and inability to count aloud to 20 ■ 50% patients have cranial nerve involvement ■ Autonomic involvement common – Diaphragm, Cardiac, GI, Bladder ■ Symptoms can vary depending on the numerous subtypes ■ Sural sparing in 50-67% patients

Presentation - Continued

Presentation - Timeline • Antibody development near 9 days after initial infection/event • Symptomatic Peak at 2-4 weeks • Recovery can last months

Pathogenesis ■ Molecular mimicry from prior immunological event generates ganglioside autoantibody formation ■ Up to 6 weeks after develop IgG autoantibodies targeting GM1, G1Qb, GD1a, and/or GT1a Axonal G Ganglioside T Type Fu Function GM1 Neurotropin Release (Paranodal) G1Qb Paranodal Region of Oculomotor Nerve GD1a Motor Neuronal Axon (Node of Ranvier) GT1a Neuronal Ganglioside

Pathogenesis – Axonal Molecules Sum Summary GM1, GD1a – Anterior Roots GQ1b, GT1a – Cervical Nerve Roots, CN IV & X GQ1b, GT1a – CN III, IV, VI, GD3, GD1c Muscle Spindle, Reticular Formation

Pathogenesis – Summary 1. Initial Immunological Event 2. Immune response 3. Antibody Development to Immunological Event 4. Molecular Mimicry results in self- reactice Antibodies towards Axons 5. GBS Neuropathy

Va Variant Related A Antibody Clinical M Manifestation Mo More Acute Motor and Sensory GM1, GD1a Rapid Onset Motor and Poor Prognosis Axonal Neuropathy (AMSAN) Sensory Deficits Acute Motor Axonal GM1, GD1a Rapid Onset Motor Deficits 6% cases America, Neuropathy (AMAN) 30-65% cases Asia Acute Inflammatory Unknown Classic GBS Presentation 60-80% cases America Demyelinating Polyneuropathy CSF presence of neurofascin, contactin-2 and NRCAM Pharyngeal-Cervical-Brachial GT1a Muscular weakness localized Variant to Pharynx, Arms, and Face Sensory GBS GD1b Acute onset symmetrical sensory deficits Paraparetic GD1b Acute Onset Lower Limb Weakness Miller-Fisher Syndrome GQ1b, GT1a Ophthalmoplegia, Areflexia, Affects women 2:1 Ataxia Triad Bickerstaff’s Brainstem GQ1b Altered Consciousness, Differentiate from MFS via Encephalitis Ophthalmoplegia, Drowsiness, Coma, Brain Fog, Hyperreflexia , Ataxia or Hyperreflexia Polyneuritis Cranialis GQ1b Cranial Nerve Palsy absent Often asymmetrical limb weakness

GBS Spectrum – Pattern of Distribution

GBS Spectrum – AIDP vs AMAN and AMSAN AID IDP AMAN a and A AMSAN ■ Most Common Subtype in America Most Common Subtype in Asia, in younger § ■ Sensorimotor with often Autonomic patients and cranial nerve involvement AMAN (Motor); AMSAN (Motor and Sensory) § Cranial Nerve and Autonomic dysfunction § ■ 50% will completely recover within 1 uncommon year More specific to C. Jejuni § ■ Relapse occurs in 3% Prognosis poor in AMSAN § ■ Mortality less than 5% GD1a AMAN specific, GM1 AMSAN specific §

GBS Spectrum – Miller Fisher Syndrome ■ Specific Antibodies – GQ1b, GT1a ■ Class triad – Ophthalmoplegia, Areflexia and Ataxia Va Variants Bickersta taff B Brainstem E Encephaliti tis Polyneuriti tis Cr Cranialis • Altered Consciousness, Bulbar Palsy • Asymmetric Bulbar Palsy + MFS • GQ1b in most cases • GQ1b in 66% cases • Cytoalbuminological Disassociation • Cytoalbuminological Disassociation present less common

Diagnostics ■ History – Initial event, clinical manifestation 9 days post gastroenteritis LP - Cytoalbumonologic Dissociation - CSF Protein elevated (>0.55g/L) by the 2 nd week ■ in 88% of cases ■ EMG – Decrease CMAP and Nerve Conduction Velocity ■ MRI Spine – Enhanced anterior nerve roots ■ Ultrasound – Enlarged spinal and peripheral nerves ■ Blood Work – Thyroid Panel, B12, Folate, HBA1C, ESR, Rapid Protein Reagent

Diagnostics – Presentation Criteria Rule In In • Progressive Extremity Weakness • Areflexia in Extremities • Later stage autonomic dysfunction • Later state Cranial Nerve dysfunction Rule O Out • CSF – Increased cell count >50 cells/microliter • Respiratory failure without ataxia • Fever at onset of symptoms • Gradual symptom progression past 4 weeks

Diagnostics – Motor Nerve Conduction Ax Axon onal • Both patients have GBS • Right Median Nerve CMAP • Amplitudes drop with to lowest point near 2 week mark • Recovery usually begins from 1 month point but can be a long wait

Diagnostics – Motor Nerve Conduction Ne Nerve Co Conducti tion Velocity ( (m/s) Median (45-70) Sensory (49-64) Motor Ulnar (48-74) Sensory 49+ Motor Peroneal 44+ Motor Tibial 41+ Motor Sural 46-64 m/s

Diagnostics - MRI • Pointing towards Cauda Equina • Surface thickening and contrast enhancement • Enhancement of anterior horn nerve roots

Diagnostics - Ultrasound

Diagnostics - Ultrasound A. *Median Nerve Forearm, 7mmD. D. *Median Nerve Forearm, 65mm •

Prognosis ■ Recovery typically begins at 28 days of disease ■ 80% cases completely resolve within 200 days ■ Relapse rate 5% within first 8 weeks ■ Mortality ranges between 5- 7%

Prognosis – Predictive Factors Key F Factors • Bulbar Symptoms • Neck weakness and Inability to count to 20 • Reduced PFT’s • Rapid Progression of Symptoms • Motor and Sensory Affected • Age of contraction

Prognosis – GBS Disability Scale [Hughes et al] Sc Scor ore De Description 0 Healthy State 1 Minor Symptoms with Running Capability 2 Able to walk >10m without assistance but unable to run 3** Able to walk 10m with assistance 4 Bedridden or Chairbound 5 Requiring assisted ventilation for portion of the day 6 Deceased

Prognosis– AIDP vs AMAN Ti Time unti til re recovery by by 1 Hu Hughe ghes Gra Grade

Management and Treatment ■ Gold Standard: IVIG 2g/kg over 2-5 days ■ Plasmaphoresis 4-6 sessions on alternate days – Risk hypotension in patients with autonomic dysfunction ■ Monitor autonomic function with supportive care – Ventilator use indicated at FVC<15cc/kg or NIF<60cmH20 – Catheter implementation with difficult urination – Laxative administration with constipation ■ Physical Therapy

Differential Diagnosis • MS – CNS disorder • CIDP – More indolent, peak weakness arrives longer than 8 weeks on average • Diabetes – Sensory>Motor, Chronic Manifestation • Radiculopathy – Acute, Localized, MRI visualization • Myasthenic Gravis/Lambert Eaton – Serology, Symptoms vary with usage • Wernicke’s Encephalopathy– Thiamine produced effective relief • Multifocal Motor Neuropathy – Motor Symptoms Only, Patchy Neuronal Involvement,

GBS and COVID-19