Guillain-Barré Syndrome:A Mechanistic Study

Casey BarkaCasey Barka

03/26/0103/26/01

History

�� First documented symptomsFirst documented symptomsin 1859 Jean Baptistein 1859 Jean BaptisteOctave Landry de ThezillatOctave Landry de Thezillat(1826-1865)(1826-1865)

�� Called it LandryCalled it Landry’’ssascending paralysisascending paralysis

�� Affects both sensory andAffects both sensory andmotor systems, but themotor systems, but themotor system is the mostmotor system is the mostvulnerablevulnerable

History Cont’

�� 1916 1916 –– Georges Guillain Georges Guillain(top), Jean Alexander Barr(top), Jean Alexander Barréé(bottom), and Andre Strohl(bottom), and Andre Strohl(not shown) documented(not shown) documenteddecreased peripheraldecreased peripheralreflexes and increased CSFreflexes and increased CSFproduction with normal cellproduction with normal cellcountcount

�� Called it Guillain-BarrCalled it Guillain-BarrééSyndromeSyndrome

What Is Guillain-Barré Syndrome (GBS)

�� An autoimmune demyelinating peripheralAn autoimmune demyelinating peripheralpolyneuropathypolyneuropathy

�� Also called acute idiopathic polyneuritisAlso called acute idiopathic polyneuritis�� Symmetric, rapidly progressive weakness whichSymmetric, rapidly progressive weakness which

eventually leads to total paralysis, including theeventually leads to total paralysis, including therespiratory and gastrointestinal systems (in severerespiratory and gastrointestinal systems (in severecases cases –– 20-30%) 20-30%)

�� Patients may develop CNS abnormalities, such asPatients may develop CNS abnormalities, such aspapilledema or extensor plantar responsespapilledema or extensor plantar responses

�� Annual incidence of 0.6-1.9 cases per 100,000Annual incidence of 0.6-1.9 cases per 100,000(about 0.001% of the population)(about 0.001% of the population)

Guillain-Barré Cont’

�� Most severe stages of disease reached within twoMost severe stages of disease reached within twoto four weeksto four weeks

�� 50% recover completely50% recover completely

�� 35% experience permanent neurological damage35% experience permanent neurological damage

�� 10% will relapse during recovery10% will relapse during recovery

�� 2-5% experience recurrence after full recovery2-5% experience recurrence after full recovery

�� Death occurs in 5-8% of cases due to sepsis orDeath occurs in 5-8% of cases due to sepsis orpulmonary embolipulmonary emboli

Guillain-Barré Cont’�� Often preceded by a viral/bacterial respiratory orOften preceded by a viral/bacterial respiratory or

gastrointestinal infection by 1-3 weeksgastrointestinal infection by 1-3 weeks�� Can also be associated with Campylobacter jejuniCan also be associated with Campylobacter jejuni

infection (most common), hepatitis, infectiousinfection (most common), hepatitis, infectiousmononucleosis, Mycoplasma pneumoniae,mononucleosis, Mycoplasma pneumoniae,cytomegalovirus, vaccination, surgery, lymphoma,cytomegalovirus, vaccination, surgery, lymphoma,pregnancy, HIV, or SLEpregnancy, HIV, or SLE

�� Lymphocytic infiltration of spinal roots andLymphocytic infiltration of spinal roots andperipheral nervesperipheral nerves

�� Macrophage-mediated demyelination andMacrophage-mediated demyelination andsecondary axonal degenerationsecondary axonal degeneration

Guillain-Barré Cont’

�� The first area of theThe first area of thenervous systemnervous systemappears to be at theappears to be at theNode of RanviNode of Ranviéérr

�� During recovery, thisDuring recovery, thisis also the area thatis also the area thatseems the remyelinateseems the remyelinatethe slowest, draggingthe slowest, draggingout the symptomsout the symptoms

Symptoms (listed in order of syndrome progression)

�� Numbness, tingling, and other sensations in distalNumbness, tingling, and other sensations in distalextremitiesextremities

�� Complete paralysis of limbsComplete paralysis of limbs

�� Paralysis of breathing musclesParalysis of breathing muscles

�� Paralysis of swallowing mechanismParalysis of swallowing mechanism

�� Blood pressure and heart rate are also affectedBlood pressure and heart rate are also affected

�� ��Characteristic of familial Characteristic of familial dysautonomia dysautonomia andandhypophosphataemiahypophosphataemia

Pathogenesis

�� Mechanism is unclear, but believed to beMechanism is unclear, but believed to beimmunologicimmunologic

�� In animals, caused by inoculation withIn animals, caused by inoculation withmyelin P-2 and GM antigens eliciting both amyelin P-2 and GM antigens eliciting both acell-mediated and humoral responsecell-mediated and humoral response

�� Immune response to infecting organismsImmune response to infecting organismscross-reacts with neural tissues leading tocross-reacts with neural tissues leading tothe symptoms of GBSthe symptoms of GBS

These are microscopic views of peripheral nervesshowing lymphocytic infiltration on the LEFT andfragmentation of myelin on the RIGHT.

Diagnosis

�� Diagnosis very difficult due to its variedDiagnosis very difficult due to its variedsymptomssymptoms

�� Spinal Tap to check for increasedSpinal Tap to check for increasedcytoalbumin dissociationcytoalbumin dissociation

�� Electromyogram (EMG) to test muscleElectromyogram (EMG) to test muscleactivity and nerve conductionactivity and nerve conduction

�� Nerve conduction Velocity Test (NVC) toNerve conduction Velocity Test (NVC) totest nerve impulse speedstest nerve impulse speeds

Treatment�� High-dosage immunoglobulin therapyHigh-dosage immunoglobulin therapy

(IV IgG)(IV IgG)�� Intravenous injection of the proteins that, in smallIntravenous injection of the proteins that, in small

quantities, the immune system uses naturally toquantities, the immune system uses naturally toattack invading organismsattack invading organisms

�� 0.4 g/kg daily for 5 days0.4 g/kg daily for 5 days�� Derived from a pool of thousands of normalDerived from a pool of thousands of normal

donors, but supply is limited at this timedonors, but supply is limited at this time�� Costly procedureCostly procedure�� Some renal impairment due to osmotic effect ofSome renal impairment due to osmotic effect of

sucrose in the solutionsucrose in the solution

Treatment Cont’

�� Therapeutic plasma exchange (TPE) (akaTherapeutic plasma exchange (TPE) (akaplasmapheresis)plasmapheresis)

�� Five 50 mL/kg exchanges over 8-13 daysFive 50 mL/kg exchanges over 8-13 days

�� Seems to reduce the severity and durationSeems to reduce the severity and duration

�� Appears to work better in children than adultsAppears to work better in children than adults

Treatment Cont’

�� OTC analgesics, Valium for muscle spasms, andOTC analgesics, Valium for muscle spasms, andGabapentin, a tricyclic antidepressant to treatGabapentin, a tricyclic antidepressant to treatlingering sensation problemslingering sensation problems

�� PhysiotherapyPhysiotherapy�� HydrotherapyHydrotherapy�� Note: Combination therapy does not appear toNote: Combination therapy does not appear to

provide an additional benefit to recoveryprovide an additional benefit to recovery�� Corticosteroids have not shown to be of anyCorticosteroids have not shown to be of any

benefit, exceptbenefit, except……

GBS Variations�Miller-Fisher Syndrome�� Acute disseminated encephalomyeloradiculopathyAcute disseminated encephalomyeloradiculopathy�� Very rareVery rare�� minimal motor weakness, gait ataxia, areflexia,minimal motor weakness, gait ataxia, areflexia,

and diplopia (ophthalmoparesis), facial sagging,and diplopia (ophthalmoparesis), facial sagging,and slurred speech (indicates all cranial nerves,and slurred speech (indicates all cranial nerves,esp. VII, but not I or II)esp. VII, but not I or II)

�� More sensory based with no known causeMore sensory based with no known cause�� Increased CSF proteinIncreased CSF protein�� Can be treated with corticosteroids such asCan be treated with corticosteroids such as

methyl-prednisolonemethyl-prednisolone

GBS Variations�CIDP�� Chronic Inflammatory DemyelinatingChronic Inflammatory Demyelinating

PolyradicalneuropathyPolyradicalneuropathy�� Attacks the epitopes contained in the axonalAttacks the epitopes contained in the axonal

membranemembrane�� Less common than GBSLess common than GBS�� Evolves more slowly Evolves more slowly –– months to years months to years�� Continuous periods of worsening andContinuous periods of worsening and

improvementimprovement�� Very depressing and debilitatingVery depressing and debilitating�� Similar treatment methodsSimilar treatment methods

GBS Variations�GBS Axonal Form

�� Nearly identical to demyelination exceptNearly identical to demyelination except ……

�� Attack directly to the axon itself in the formAttack directly to the axon itself in the formof an acute toxic peripheral polyneuropathyof an acute toxic peripheral polyneuropathy

�� Extremely debilitatingExtremely debilitating

�� Recovery rarely more than 40-50%Recovery rarely more than 40-50%

�� Very poor prognosisVery poor prognosis

Continuing Research

�� Find new treatments and refine existing onesFind new treatments and refine existing ones

�� Determine which immune cells are responsibleDetermine which immune cells are responsible

�� Figure out why GBS usually results from viral andFigure out why GBS usually results from viral andbacterial infections and their actions in thebacterial infections and their actions in theinappropriate immune responseinappropriate immune response

�� Come up with better preventative careCome up with better preventative care

Final Comments

�� Very devastating and potentially life-Very devastating and potentially life-threatening illnessthreatening illness

�� Significant advances in treatment have beenSignificant advances in treatment have beenmade that affect the disease course andmade that affect the disease course andoutcome.outcome.

�� Treatment requires a team approachTreatment requires a team approach

�� Personal experiencePersonal experience

References

�� Acute and chronic inflammatory demyelinatingAcute and chronic inflammatory demyelinatingpolyradiculoneuropathies. In Wynngaarden JB, Smith LH,polyradiculoneuropathies. In Wynngaarden JB, Smith LH,Bennet JC (eds): Cecil Textbook of Medicine, 20Bennet JC (eds): Cecil Textbook of Medicine, 20thth Edition. Edition.W. B. Saunders Company, 1996.W. B. Saunders Company, 1996.

�� Dematteis, J A, M.D. Guillain-Barre Syndrome: A TeamDematteis, J A, M.D. Guillain-Barre Syndrome: A TeamApproach to Diagnosis and Treatment. National Office ofApproach to Diagnosis and Treatment. National Office ofthe Muscular Dystrophy Association.the Muscular Dystrophy Association.http://www.mda.org.nz/intouch/GBSSYN2.htmlhttp://www.mda.org.nz/intouch/GBSSYN2.html

�� Guillain-BarrGuillain-Barréé Syndrome: Syndrome: http://www.idiom.com/-http://www.idiom.com/-~drjohn/gbs.html~drjohn/gbs.html

�� Guillain-BarrGuillain-Barréé Syndrome Foundation International Syndrome Foundation International –– Main MainPage. Page. http://www.webmast.com/gbs/http://www.webmast.com/gbs/

References

�� Guillain-BarrGuillain-Barréé Syndrome Support Group. Syndrome Support Group.http://www.gbs.org.uk/http://www.gbs.org.uk/

�� GBS.org webpage. GBS.org webpage. http://www.gbs.org/http://www.gbs.org/�� Guillan-Barre syndrome project. Guillan-Barre syndrome project. http://guillan-http://guillan-

barre.webpark.sk/history.htmbarre.webpark.sk/history.htm�� Guillian-Barre Syndrome. Harish Jasti, M.D.Guillian-Barre Syndrome. Harish Jasti, M.D. Case of theCase of the

Week. Week. http://genmed01.upmc.edu/GIM/MH/guil.htmlhttp://genmed01.upmc.edu/GIM/MH/guil.html�� Hahn, AF. Guillain-BarrHahn, AF. Guillain-Barréé Syndrome. The Lancet 1998; Syndrome. The Lancet 1998;

352: 635-641.352: 635-641.�� Healthcite Web Page. Healthcite Web Page. http://www.healthcite.com/Health-http://www.healthcite.com/Health-

review/p3847.htmlreview/p3847.html

References

�� Hughes, R. Guillain-BarrHughes, R. Guillain-Barréé Syndrome. London: Pringer- Syndrome. London: Pringer-Verlag, 1990.Verlag, 1990.

�� Mckhann GM: Clinical and therapeutic observations. Mckhann GM: Clinical and therapeutic observations. AnnAnnNeurolNeurol 27(suppl 1): S13, 1990. 27(suppl 1): S13, 1990.

�� National institute of Neurologic Disorders and Stroke.National institute of Neurologic Disorders and Stroke.http://www.ninds.nih.gov/http://www.ninds.nih.gov/

�� National Institutes of Health. National Institutes of Health. http://www.nih.gov/http://www.nih.gov/

�� Parry, G J. Guillain-BarrParry, G J. Guillain-Barréé Syndrome. New York: Syndrome. New York:Thierne Medical Publishers, 1993.Thierne Medical Publishers, 1993.

References

�� Plasma Exchange/Sandoglobulin Guillain-BarrPlasma Exchange/Sandoglobulin Guillain-Barréé Syndrome SyndromeTrial Group. Randomized trial of plasma exchange,Trial Group. Randomized trial of plasma exchange,intravenous immuneglobulin, and combined treatments inintravenous immuneglobulin, and combined treatments inGuillain-BarrGuillain-Barréé Syndrome. Lancet 1997; 349: 225-30. Syndrome. Lancet 1997; 349: 225-30.