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

Ev Event Ex Exampl ple Bacterial Camplyobacter Jejuni** Mycoplasma Pneumonia Virus CMV EBV VZV Zika Virus COVID-19 Drugs Cyclosporine Pembrolizumab Vaccine Influenza Rabies 1976 Swine Flu Vaccine

■ Incidence of 1.65-1.75 per 100,000 ■ C. Jejuni represents 33% Cases ■ In 1976 H1N1 was spreading and President Ford wanted to immunize the Public ■ 450 cases following Swine Flu Vaccination of 45 million

About – Zika 2015

Endemic

• utbreaks 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 Axonal Neuropathy (AMSAN) GM1, GD1a Rapid Onset Motor and Sensory Deficits Poor Prognosis Acute Motor Axonal Neuropathy (AMAN) GM1, GD1a Rapid Onset Motor Deficits 6% cases America, 30-65% cases Asia Acute Inflammatory Demyelinating Polyneuropathy Unknown Classic GBS Presentation 60-80% cases America CSF presence of neurofascin, contactin-2 and NRCAM Pharyngeal-Cervical-Brachial Variant GT1a Muscular weakness localized 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, Ataxia Triad Affects women 2:1 Bickerstaff’s Brainstem Encephalitis GQ1b Altered Consciousness, Ophthalmoplegia, Hyperreflexia, Ataxia Differentiate from MFS via Drowsiness, Coma, Brain Fog,

• r Hyperreflexia

Polyneuritis Cranialis GQ1b Cranial Nerve Palsy absent limb weakness Often asymmetrical

GBS Spectrum – Pattern of Distribution

GBS Spectrum – AIDP vs AMAN and AMSAN

AID IDP

■ Most Common Subtype in America ■ Sensorimotor with often Autonomic and cranial nerve involvement ■ 50% will completely recover within 1 year ■ Relapse occurs in 3% ■ Mortality less than 5%

AMAN a and A AMSAN

§ Most Common Subtype in Asia, in younger patients § AMAN (Motor); AMSAN (Motor and Sensory) § Cranial Nerve and Autonomic dysfunction uncommon § More specific to C. Jejuni § Prognosis poor in AMSAN § 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

• Altered Consciousness, Bulbar Palsy

+ MFS

• GQ1b in 66% cases
• Cytoalbuminological Disassociation

less common

Polyneuriti tis Cr Cranialis

• Asymmetric Bulbar Palsy
• GQ1b in most cases
• Cytoalbuminological Disassociation

present

Diagnostics

■ History – Initial event, clinical manifestation 9 days post gastroenteritis ■ LP - Cytoalbumonologic Dissociation - CSF Protein elevated (>0.55g/L) by the 2nd 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

• nal
• 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

• re

De Description 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

References

■ Guillain-Barre syndrome. (2020, May 05). Retrieved September 17, 2020, from https://www.mayoclinic.org/diseases-conditions/guillain-barre-syndrome/symptoms- causes/syc-20362793 ■ Willison, H. J., Jacobs, B. C., & Doorn, P. A. (2016). Guillain-Barré syndrome. The Lancet, 388(10045), 717-727. doi:10.1016/s0140-6736(16)00339-1 ■ Falk, J. A., Cordova, F. C., Popescu, A., Tatarian, G., & Criner, G. J. (2006). Treatment of Guillain-Barré syndrome induced by cyclosporine in a lung transplant patient. The Journal

• f heart and lung transplantation : the official publication of the International Society for

Heart Transplantation, 25(1), 140–143. https://doi.org/10.1016/j.healun.2005.06.012 ■ Dimachkie, M. M., & Barohn, R. J. (2013). Guillain-Barré syndrome and

• variants. Neurologic clinics, 31(2), 491–510. https://doi.org/10.1016/j.ncl.2013.01.005

■ Han, C., Ma, J. A., Zhang, Y., Jiang, Y., Hu, C., & Wu, Y. (2020). Guillain-Barre syndrome induced by pembrolizumab and sunitinib: A case report. Molecular and clinical

• ncology, 13(1), 38–42. https://doi.org/10.3892/mco.2020.2042

■ Gordon, P. H., & Wilbourn, A. J. (2001). Early electrodiagnostic findings in Guillain-Barré

• syndrome. Archives of neurology, 58(6), 913–917.

https://doi.org/10.1001/archneur.58.6.913

■ Nguyen TP, Taylor RS. Guillain Barre Syndrome. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532254/ ■ Toscano, G., Palmerini, F., Ravaglia, S., Ruiz, L., Invernizzi, P., Cuzzoni, M. G., . . . Micieli,

• G. (2020). Guillain–Barré Syndrome Associated with SARS-CoV-2. New England Journal
• f Medicine, 382(26), 2574-2576. doi:10.1056/nejmc2009191

■ Walling, A. D., & Dickson, G. (2013). Guillain-Barré syndrome. American family physician, 87(3), 191–197 ■ Bromberg, M. (2018). Acute Inflammatory Demyelinating Polyradiculoneuropathy. In Peripheral Neuropathies: A Practical Approach (pp. 109-111). Cambridge: Cambridge University Press. doi:10.1017/9781316135815.019 ■ Ropper AH, Wijdicks EFM, Truax BT. In: Guillain-Barré Syndrome, Contemporary Neurology Series. Davis FA, editor. Vol. 34. Philadelphia, PA: 1991. Comp. ■ Ziganshin RH, Ivanova OM, Lomakin YA, et al. The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling

• f Physiological Fluids. Mol Cell Proteomics. 2016;15(7):2366-2378.

doi:10.1074/mcp.M115.056036 / ■ Styczynski, A. R., Malta, J. M. A. S., Krow-Lucal, E. R., Percio, J., Nóbrega, M. E., Vargas, A., Lanzieri, T. M., Leite, P. L., Staples, J. E., Fischer, M. X., Powers, A. M., Chang, G.-J. J., Burns, P. L., Borland, E. M., Ledermann, J. P., Mossel, E. C., Schonberger, L. B., Belay, E. B., Salinas, J. L., … Coelho, G. E. (2017). Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLOS Neglected Tropical Diseases, 11(8), e0005869. https://doi.org/10.1371/journal.pntd.0005869

■ Derksen, A., Ritter, C., Athar, P., Kieseier, B. C., Mancias, P., Hartung, H. P., Sheikh, K. A., & Lehmann, H. C. (2014). Sural sparing pattern discriminates Guillain-Barré syndrome from its mimics. Muscle & nerve, 50(5), 780–784. https://doi.org/10.1002/mus.24226 ■ https://30g7el1b4b1n28kgpr414nuu-wpengine.netdna-ssl.com/wp- content/uploads/2012/07/Yuki-PJA2012.pdf ■ Zare Mehrjardi, Mohammad & Carteaux, Guillaume & Poretti, Andrea & Sanei Taheri, Morteza & Bermúdez, Sonia & Heron, Werner & Hygino da Cruz, Luiz Celso. (2017). Neuroimaging findings of postnatally acquired Zika virus infection: a pictorial

• essay. Japanese Journal of Radiology. 35. 341−349. 10.1007/s11604-017-0641-z.

https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004- 282X2017000800600