Guillain-Barre Syndrome

Guillain-Barre SyndromeGuillain-Barre Syndrome

DR. INTEKHAB AHMADDR. INTEKHAB AHMAD

25 JAN 2010 25 JAN 2010

DefinitionDefinition

It is an acute inflammatory It is an acute inflammatory demyelinating polyneuropathydemyelinating polyneuropathy

leading to progressive muscle weakness & leading to progressive muscle weakness & areflexiaareflexia . .

Guillain Barre SyndromeGuillain Barre SyndromeCommonest cause of rapid-onset Commonest cause of rapid-onset

flaccid paralysis since polio declineflaccid paralysis since polio declineOccurs as an autoimmune response Occurs as an autoimmune response

following a GI or respiratory infectionfollowing a GI or respiratory infectionPotentially severely debilitating Potentially severely debilitating

disorder affecting 1-3 per 100,000disorder affecting 1-3 per 100,00010% die from associated complications10% die from associated complicationsA further 10% suffer from long term A further 10% suffer from long term

neurological sequelae and physical neurological sequelae and physical dependencedependence

HistoryHistory

Guillain, Barre and Strohl first Guillain, Barre and Strohl first described a disease affecting French described a disease affecting French soldiers ( motor weakness, areflexia soldiers ( motor weakness, areflexia and CSF abnormalities) in 1916and CSF abnormalities) in 1916

Descriptions date back to 1859 when Descriptions date back to 1859 when Landry described ascending paralysisLandry described ascending paralysis

Aetiology Aetiology

All ages affected with bimodal distribution All ages affected with bimodal distribution towards young adults and the elderlytowards young adults and the elderly

Slight male preponderanceSlight male preponderance Children less severely affectedChildren less severely affected Most commonly occurs within a month of Most commonly occurs within a month of

GI or resp upset.GI or resp upset. Commonest organism is campylobacterCommonest organism is campylobacter Others inc EBV, CMV, HIV, herpes & Others inc EBV, CMV, HIV, herpes &

mycoplasma mycoplasma

Have been reports of association Have been reports of association with vaccines, surgery, epidurals, with vaccines, surgery, epidurals, bone marrow and organ bone marrow and organ transplantation, SLE, lymphoma, transplantation, SLE, lymphoma, sarcoidosissarcoidosis

Pregnancy and OCP confer some Pregnancy and OCP confer some protectionprotection

Pathogenesis Pathogenesis

Immunologically mediated nerve injuryImmunologically mediated nerve injury Inflammatory cell infiltrates are seen in Inflammatory cell infiltrates are seen in

association with the demyelination, which is association with the demyelination, which is regarded as the primary pathological processregarded as the primary pathological process

Precise mechanism of sensitisation not knownPrecise mechanism of sensitisation not known Antibodies formed against nonself antigens Antibodies formed against nonself antigens

(inf agents,vacc) but misdirected to host (inf agents,vacc) but misdirected to host nerve tissue (neural target- gangliosides) due nerve tissue (neural target- gangliosides) due to molecular mimicry leading to to molecular mimicry leading to demyelinationdemyelination

Figure 1.Figure 1. Structural components of peripheral nerves. In the endoneurial Structural components of peripheral nerves. In the endoneurial compartment (En), a single Schwann cell envelops several unmyelinated axons, and compartment (En), a single Schwann cell envelops several unmyelinated axons, and another Schwann cell provides multiple wrappings of plasma membrane forming the another Schwann cell provides multiple wrappings of plasma membrane forming the myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by a single Schwann cell is called the internode, and internodes are separated by nodes a single Schwann cell is called the internode, and internodes are separated by nodes of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are bundled into a fascicle by the perineurium (Pe). The perineurium consists of several bundled into a fascicle by the perineurium (Pe). The perineurium consists of several layers of flattened perineurial cells connected by tight junctions and covered layers of flattened perineurial cells connected by tight junctions and covered internally and externally by a basal lamina. The layers of perineurial cells are internally and externally by a basal lamina. The layers of perineurial cells are separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled together by the epineurium (Ep) to form a nerve. The epineurium consists primarily together by the epineurium (Ep) to form a nerve. The epineurium consists primarily of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between fascicles is termed the fascicles is termed the interfascicular epineuriuminterfascicular epineurium, and that encompassing all of the , and that encompassing all of the fascicles is termed the fascicles is termed the epifascicular epineuriumepifascicular epineurium. Arterioles (A) and veins are oriented . Arterioles (A) and veins are oriented primarily longitudinally within the epineurium. primarily longitudinally within the epineurium.

Distributed throughout the nerve length Distributed throughout the nerve length but focused at nerve roots, spinal nerves but focused at nerve roots, spinal nerves and major plexusesand major plexuses

Macrophages actively strip myelin from Macrophages actively strip myelin from bodies of schwann cells and axonsbodies of schwann cells and axons

Underlying immune response is complexUnderlying immune response is complex Effectiveness of plasma exchange and IgG Effectiveness of plasma exchange and IgG

is thought to be blocking of demyelinating is thought to be blocking of demyelinating antibodiesantibodies

VARIANTSVARIANTS

Several distinct clinical pictures describedSeveral distinct clinical pictures describedAcute inflammatory demyelinating Acute inflammatory demyelinating

polyradiculopathy (AIDP)polyradiculopathy (AIDP)Acute motor axonal neuropathy (AMAN)Acute motor axonal neuropathy (AMAN)Acute motor sensory axonal neuropathy Acute motor sensory axonal neuropathy

(AMSAN)(AMSAN)Miller-Fisher syndrome ( ataxia, areflexia Miller-Fisher syndrome ( ataxia, areflexia

and opthalmoplegia ) which may be and opthalmoplegia ) which may be accompanied by limb weakness, ptosis accompanied by limb weakness, ptosis and facial and bulbar palsyand facial and bulbar palsy

Clinical presentationClinical presentation

Classical picture is that of ascending limb Classical picture is that of ascending limb weakness with areflexia, although a purely weakness with areflexia, although a purely sensory variant has been well documentedsensory variant has been well documented

Features of GBS includeFeatures of GBS include Progressive motor weakness, usually Progressive motor weakness, usually

ascending from the legsascending from the legs AreflexiaAreflexia Facial palsy and bulbar weaknessFacial palsy and bulbar weakness Sensory symptoms—mainly subjectiveSensory symptoms—mainly subjective Bladder/bowel—in severe casesBladder/bowel—in severe cases

Severe pain esp girdleSevere pain esp girdleResp muscle weaknessResp muscle weaknessAutonomic dysfunction( over or Autonomic dysfunction( over or

underactivity of the SNS or PSNS)underactivity of the SNS or PSNS)

Features required for diagnosisFeatures required for diagnosisdefined by national institute of neurological and defined by national institute of neurological and

communicative diseases and strokescommunicative diseases and strokes

Progressive muscle weakness of Progressive muscle weakness of more than one limbmore than one limb

Areflexia or marked hyporeflexiaAreflexia or marked hyporeflexiaCSF cell counts of no more than 10CSF cell counts of no more than 10Features highly suggestiveFeatures highly suggestiveFeatures required to rule out other Features required to rule out other

diagnosisdiagnosis

Doughtful diagnosisDoughtful diagnosis

Definite sensory levelDefinite sensory levelMarked, persistent asymmetry of Marked, persistent asymmetry of

motor weaknessmotor weaknessSevere & persistent bladder/bowel Severe & persistent bladder/bowel

dysfunctiondysfunctionCSF cell count > 50CSF cell count > 50

Monitoring Monitoring

CardiacCardiacBlood pressureBlood pressureVital capacity measured three times Vital capacity measured three times

a daya dayBulbar function monitored to prevent Bulbar function monitored to prevent

aspirationaspiration

Investigations Investigations

In over 90% patients CSF protein is raised In over 90% patients CSF protein is raised ( >0.4g/l) within a week of onset of ( >0.4g/l) within a week of onset of symptomssymptoms

Level does not correlate with clinical Level does not correlate with clinical findingsfindings

Nerve conduction studies demonstrate Nerve conduction studies demonstrate reduced conduction velocity reduced conduction velocity

Liver and renal function may be impairedLiver and renal function may be impaired Antiganglioside antibody should be Antiganglioside antibody should be

searched forsearched for

SIADH may occur in association with SIADH may occur in association with GBSGBS

Stool cultures for campylobacterStool cultures for campylobacterEcg’s for QT, T and ST abnormalitiesEcg’s for QT, T and ST abnormalitiesHead CT to exclude raised ICP and Head CT to exclude raised ICP and

other pathology prior to LPother pathology prior to LP

Treatment Treatment

Major challengeMajor challengeOutcome excellent if complications Outcome excellent if complications

treated or avoidedtreated or avoidedPrevented by meticulous attention to Prevented by meticulous attention to

detaildetail

Specific treatment-disease Specific treatment-disease modifying modalitiesmodifying modalities

Plasma exchangePlasma exchange Immunoglobin Immunoglobin Both should be used when patient Both should be used when patient

non-ambulatory or resp non-ambulatory or resp decompensation occursdecompensation occurs

Both have been examined in RCT and Both have been examined in RCT and no difference in efficacy no difference in efficacy demonstrated between themdemonstrated between them

Plasma exchangePlasma exchange 2 RCT showed reduction in ventilation 2 RCT showed reduction in ventilation

and reduced time to motor recoveryand reduced time to motor recovery Mortality was not alteredMortality was not altered Most effective within 7 days of onsetMost effective within 7 days of onset 3-5 exchanges of 1-2 plasma volumes 3-5 exchanges of 1-2 plasma volumes

each over 1-2 weekseach over 1-2 weeks Ffp more complications than albumin Ffp more complications than albumin CI include CVS instability, sepsis and CI include CVS instability, sepsis and

haemostatic problemshaemostatic problems Side effects are hypotension, Side effects are hypotension,

hypocalcaemia,coagulation hypocalcaemia,coagulation abnormalities and sepsisabnormalities and sepsis

IV ImmunoglobinIV Immunoglobin 0.4mg/kg daily for 5-6 days0.4mg/kg daily for 5-6 days Easier administration Easier administration Fewer side effectsFewer side effects Commence tx within 2 weeks of onset of Commence tx within 2 weeks of onset of

symptomssymptoms CI include IgA deficiency(anaphylaxis)CI include IgA deficiency(anaphylaxis) Renal function may deteriorateRenal function may deteriorate Severe congestive cardiac failure major Severe congestive cardiac failure major

contraindicationcontraindication RCT has suggested as effective as RCT has suggested as effective as

plasma exchangeplasma exchange

Steroids Steroids

No place in the treatment of GBSNo place in the treatment of GBSRCT have shown no advantageRCT have shown no advantage

CSF filtrationCSF filtration

Few case reportsFew case reportsWhen plasmapheresis and IgG have When plasmapheresis and IgG have

failedfailedLogistics difficult!Logistics difficult!

Supportive careSupportive care

Respiratory,Respiratory, 25% require ventilated25% require ventilatedPhysio and VC monitoring in the spont Physio and VC monitoring in the spont

breathing. If less than 15ml/kg or rising breathing. If less than 15ml/kg or rising pCO2, mechanical ventilation likelypCO2, mechanical ventilation likely

Monitoring of bulbar function for prevention Monitoring of bulbar function for prevention of aspirationof aspiration

Non-invasive ventilation often not useful as Non-invasive ventilation often not useful as does not eliminate the problem of not being does not eliminate the problem of not being able to clear secretions due to poor coughable to clear secretions due to poor cough

Early tracheostomy should be consideredEarly tracheostomy should be considered

Supportive careSupportive care

Cardiovascular Cardiovascular Full invasive monitoringFull invasive monitoringCare with induction of anaesthesia as Care with induction of anaesthesia as

leads to hypotension and arrhythmiasleads to hypotension and arrhythmiasCare with suxamethonium may lead to Care with suxamethonium may lead to

arrhythmiasarrhythmiasInstability may be worsened by other Instability may be worsened by other

drugsdrugsAutonomic instability commonAutonomic instability common

Supportive care Supportive care Nutrition, fluid and electrolytesNutrition, fluid and electrolytes Paralytic ileus commonParalytic ileus common Tpn may be requiredTpn may be required Energy and fluid requirements are Energy and fluid requirements are

reduced in these patientsreduced in these patients PhysiotherapyPhysiotherapy DVT prophylaxisDVT prophylaxis Sepsis survellienceSepsis survellience Psychological carePsychological care analgesiaanalgesia

Prognosis Prognosis Death in up to 25% of those who require Death in up to 25% of those who require

ICU has been reported often from ICU has been reported often from autonomic abnormalitiesautonomic abnormalities

Approx 16% patients suffer permanent Approx 16% patients suffer permanent disabilitydisability

Those who require ventilation, improve Those who require ventilation, improve after more than 3 weeks, not improved after more than 3 weeks, not improved within 1 month have greater risk of within 1 month have greater risk of poorer outcomepoorer outcome

Gradual improvement may occur over Gradual improvement may occur over 18months -2years18months -2years

Recurrence n 2-5% casesRecurrence n 2-5% cases

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