Guillain-Barre’ Syndrome. Guillaine Barre Syndrome Guillain Barre Syndrome 1859 - Landry’s report on 10 patients with “ascending paralysis” 1916 - Guillain,

Guillain-Barre’ SyndromeGuillain-Barre’ Syndrome

Guillaine Barre SyndromeGuillaine Barre Syndrome

Guillain Barre SyndromeGuillain Barre Syndrome

1859 - Landry’s report on 10 patients with 1859 - Landry’s report on 10 patients with “ascending paralysis”“ascending paralysis”

1916 - Guillain, Barre, Strohl described two 1916 - Guillain, Barre, Strohl described two French soldiers with motor weakness, French soldiers with motor weakness, areflexia, and “albuminocytological areflexia, and “albuminocytological dissociation” in the CSFdissociation” in the CSF


EpidemiologyEpidemiology

1-3/100,000 - Europe, USA, Australia1-3/100,000 - Europe, USA, Australia

-occurs in any age group-occurs in any age group

-bimodal age distribution-bimodal age distribution

-increase incidence with age-increase incidence with age

-males > females-males > females

-seasonal variations-seasonal variations

-lower during pregnancy, increases after -lower during pregnancy, increases after deliverydelivery


Clinical FeaturesClinical Features

-antecedent event-antecedent event

respiratory infection 40%respiratory infection 40%

gastroenteritis 20%gastroenteritis 20%

-common manifestations-common manifestations

proximal limb weaknessproximal limb weakness

facial palsyfacial palsy

sensory symptoms 80%sensory symptoms 80%

pain 90%pain 90%

autonomic dysfunction autonomic dysfunction 66%66%


Clinical FeaturesClinical Features•Motor DysfunctionMotor Dysfunction

symmetrical limb symmetrical limb weaknessweakness

neck muscle weaknessneck muscle weakness

respiratory weaknessrespiratory weakness

CN III-VII, IX-XII palsiesCN III-VII, IX-XII palsies

areflexiaareflexia

wastingwasting

•Sensory dysfunctionSensory dysfunction

painpain

numbness, paresthesiasnumbness, paresthesias

loss of position sense, loss of position sense, vibration, touch, painvibration, touch, pain

ataxiaataxia

•Autonomic dysfunctionAutonomic dysfunction

sinus sinus tachycardia/bradycardiatachycardia/bradycardia

hypertension hypertension

postural hypotensionpostural hypotension

fluctuations, PR and BPfluctuations, PR and BP

tonic pupilstonic pupils

hypersalivationhypersalivation

anhidrosis or excess anhidrosis or excess sweatingsweating

urinary sphincter urinary sphincter disturbancedisturbance

constipationconstipation

gastric dysmotilitygastric dysmotility

abnormal vasomotor toneabnormal vasomotor tone

•OtherOther

papilloedemapapilloedema



-onset is acute or subacute-onset is acute or subacute

nadir nadir 12 days 12 days

improvementimprovement 28 days 28 days

recoveryrecovery 200 days200 days

-plateau phase -plateau phase reached 4 weeks from reached 4 weeks from onset onset in 98% of patients in 98% of patients

-plateau duration -plateau duration 12 days12 days


Antecedent EventsAntecedent Events

Campylobacter jejuniCampylobacter jejuni--most common pathogen most common pathogen

26-30% 26-30% USA and EuropeUSA and Europe

45% 45% JapanJapan

-AMAN and AMSAN more common-AMAN and AMSAN more common

-common preceding infection in Miller Fisher Syndrome-common preceding infection in Miller Fisher Syndrome

PathogenesisPathogenesis

””molecular mimicry”molecular mimicry”

GM1 ganglioside GM1 ganglioside



CytomegalovirusCytomegalovirus-second most common -second most common

5% 5% Japan Japan

11-13% 11-13% EuropeEurope

-more common in females and young age groups-more common in females and young age groups

-severe course, with respiratory difficulties-severe course, with respiratory difficulties

-reduced SNAPs are more common-reduced SNAPs are more common

PathogenesisPathogenesis

””molecular mimicry”molecular mimicry”

GM2 gangliosideGM2 ganglioside



Associated infectionsAssociated infections

Epstein Barr (10%) Epstein Barr (10%)

Mycoplasma pneumoniae Mycoplasma pneumoniae (5%)(5%)

HIVHIV

Lyme diseaseLyme disease

Possibly Associated infectionsPossibly Associated infections

hepatitis A, B, C, and Dhepatitis A, B, C, and D

typhoid typhoid

falciparum malariafalciparum malaria



Vaccines?Vaccines?

-influenza vaccine-influenza vaccine

-polio vaccination-polio vaccination

-measles-measles

-MMR-MMR

-hepatitis B-hepatitis B

presently no evidence for association with GBSpresently no evidence for association with GBS



-surgery-surgery

-epidural anesthesia-epidural anesthesia

-renal transplantation-renal transplantation

-bone marrow -bone marrow transplantationtransplantation

-SLE-SLE

-sarcoidosis-sarcoidosis

-lymphoma-lymphoma

-snake bite-snake bite

-some drugs-some drugs

Other anectodal associationsOther anectodal associations


Clinicopathological TypesClinicopathological Types

Acute Inflammatory Demyelinating PolyradiculopathyAcute Inflammatory Demyelinating Polyradiculopathy

most commonmost common

PathologyPathology

lymphocytic infiltration of peripheral nerveslymphocytic infiltration of peripheral nerves

macrophage mediated segmental demyelinationmacrophage mediated segmental demyelination

secondary axonal changesecondary axonal change

humoral and cellular immunity implicatedhumoral and cellular immunity implicated

ElectrophysiologyElectrophysiology

segmental deymyelinationsegmental deymyelination

Recovery with remyelinationRecovery with remyelination



Acute Motor Axonal NeuropathyAcute Motor Axonal Neuropathy

GBS in China (1991, 1992) GBS in China (1991, 1992)

55-65% pure motor axonal neuropathy55-65% pure motor axonal neuropathy

76% positive for 76% positive for C jejuniC jejuni

10-20% of sporadic cases10-20% of sporadic cases

PathologyPathology

anti-GM1, GD1a, GD1banti-GM1, GD1a, GD1b

Wallerian-like degeneration of motor axonsWallerian-like degeneration of motor axons

lengthening Nodes of Ranvierlengthening Nodes of Ranvier

distortion of paranodal myelindistortion of paranodal myelin

periaxonal macrophages periaxonal macrophages



Acute Motor Axonal NeuropathyAcute Motor Axonal Neuropathy


CMAP amplitudes reducedCMAP amplitudes reduced

tendon reflexes, preserved, exaggeratedtendon reflexes, preserved, exaggerated

Rapidly progressive weakness, respiratory failureRapidly progressive weakness, respiratory failure

Usually good recoveryUsually good recovery



Acute Motor Sensory Axonal NeuropathyAcute Motor Sensory Axonal Neuropathy

Feasby 1986 described 7 patientsFeasby 1986 described 7 patients

severe sensory motor dysfunctionsevere sensory motor dysfunction

marked wasting, poor recoverymarked wasting, poor recovery

PathologyPathology

Wallerian-like degeneration, motor sensory axonsWallerian-like degeneration, motor sensory axons

little demyelination, lymphocytic infiltrationlittle demyelination, lymphocytic infiltration

periaxonal macrophagesperiaxonal macrophages



Acute Motor Sensory Axonal NeuropathyAcute Motor Sensory Axonal Neuropathy


sensory and motor axonal dysfunctionsensory and motor axonal dysfunction

Fulminant diseaseFulminant disease

Slow incomplete recoverySlow incomplete recovery

Most severe form of immune mediated axonal damageMost severe form of immune mediated axonal damage



Miller Fisher SyndromeMiller Fisher Syndrome

Fisher 1956 described 3 patientsFisher 1956 described 3 patients

ataxia, areflexia, ophtalmoplegiaataxia, areflexia, ophtalmoplegia

5% of patients with GBS5% of patients with GBS

associated with associated with C jejuniC jejuni infection infection

PathologyPathology

anti-GQ1banti-GQ1b

demyelination CN III, VI, spinal ganglia, peripheral demyelination CN III, VI, spinal ganglia, peripheral nervesnerves


reduced/absent SNAPsreduced/absent SNAPs



Other VariantsOther Variants

pure sensorypure sensory

pure dysautonomicpure dysautonomic

pharyngeal-brachial-cervicalpharyngeal-brachial-cervical

parapareticparaparetic

10% of GBS10% of GBS


Electrophysiological FeaturesElectrophysiological FeaturesAIDPAIDP

reduced conduction velocityreduced conduction velocity

conduction block or temporal dispersionconduction block or temporal dispersion

prolonged terminal latencyprolonged terminal latency

absent or prolonged F-waveabsent or prolonged F-wave

AMANAMANabsent or reduced CMAPabsent or reduced CMAP

normal motor latency and NCVnormal motor latency and NCV

normal SNAPnormal SNAP

AMSANAMSANabsent or reduced SNAPabsent or reduced SNAP

absent or reduced CMAPabsent or reduced CMAP

normal motor latency and NCVnormal motor latency and NCV


Criteria for DiagnosisCriteria for Diagnosis

Required CriteriaRequired Criteria

progressive weakness > two limbsprogressive weakness > two limbs

areflexiaareflexia

progression < 4 weeksprogression < 4 weeks

other causes excludedother causes excluded

lead poisoning, vasculitis, botulism, porphyrialead poisoning, vasculitis, botulism, porphyria

Supportive CriteriaSupportive Criteria

mild sensory signsmild sensory signs

albuminocytological dissociationalbuminocytological dissociation

conduction blockconduction block


InvestigationsInvestigations

• cerebrospinal fluidcerebrospinal fluid• antiganglioside antibodiesantiganglioside antibodies• stool culture for C jejunistool culture for C jejuni• antibodies to C jejuni, cytomegalovirus, EBV, HSV, antibodies to C jejuni, cytomegalovirus, EBV, HSV,

HIV, M. pneumoniaeHIV, M. pneumoniae• biochemical screening: urea, electrolytes, liver biochemical screening: urea, electrolytes, liver

enzymesenzymes• full blood countfull blood count• ESRESR• autonomic function testsautonomic function tests• electrophysiologyelectrophysiology


TreatmentTreatment

Good intensive careGood intensive care

Respiratory support Respiratory support

Prophylaxis for dvtProphylaxis for dvt

RehabilitationRehabilitation


TreatmentTreatment

Plasma ExchangePlasma ExchangeBrettle 1978Brettle 1978

done within 2 weeksdone within 2 weeks

reduced period of hospital stay, duration of mechanical reduced period of hospital stay, duration of mechanical ventilation, time to reach ambulationventilation, time to reach ambulation

North American Trial 200-250 ml/kg body weight, 7-14 North American Trial 200-250 ml/kg body weight, 7-14 days days

French Cooperative GroupFrench Cooperative Group

2 exchanges for mild2 exchanges for mild

4 exchanges for moderate to severe4 exchanges for moderate to severe


TreatmentTreatment

Plasma ExchangePlasma Exchange

ComplicationsComplications

hypotensionhypotension

septicemiasepticemia

hypocalcemiahypocalcemia

abnormal clottingabnormal clotting


TreatmentTreatment

Intravenous ImmunoglobulinIntravenous Immunoglobulintx for immunologically mediated disorderstx for immunologically mediated disorders

anti-idiotypic suppression of autoantibodies anti-idiotypic suppression of autoantibodies

Kleyweg et al 1988Kleyweg et al 1988

given within 2 weeksgiven within 2 weeks

as effective as plasma exchangeas effective as plasma exchange

0.4 g/kg body weight for five days0.4 g/kg body weight for five days


TreatmentTreatment

ContraindicationsContraindications•selective IgA deficiencyselective IgA deficiency•Anaphylaxis with previous Anaphylaxis with previous IVIgIVIg

Relative contraindicationsRelative contraindications•severe congestive severe congestive cardiac failurecardiac failure•renal insufficiencyrenal insufficiency

Adverse EffectsAdverse Effects•malaise, myalgia, fever, chillsmalaise, myalgia, fever, chills•vasomotor symptoms, vasomotor symptoms, headacheheadache•nausea, vomitingnausea, vomiting•increase in liver enzymesincrease in liver enzymes•renal tubular necrosis, acute renal tubular necrosis, acute renal failurerenal failure•aseptic meningitisaseptic meningitis•hypercoagulable statehypercoagulable state•anaphylaxisanaphylaxis•rashesrashes•encephalopathyencephalopathy

Intravenous ImmunoglobulinIntravenous Immunoglobulin


Factors Associated with Poor OutcomeFactors Associated with Poor Outcome

EtiologyEtiology

previous GI infectionprevious GI infection

C jejuni infectionC jejuni infection

cytomegaloviruscytomegalovirus


older ageolder age

shorter latency to nadirshorter latency to nadir

longer time to clinical longer time to clinical improvementimprovement

need for mechanical need for mechanical ventilationventilation

greater disability and greater disability and disease severitydisease severity


absent or reduced absent or reduced CMAPCMAP

inexcitable nervesinexcitable nerves

Biochemical MarkersBiochemical Markers

Anti-GM1 antibodiesAnti-GM1 antibodies

Neurone specific Neurone specific enolase and S100benolase and S100b

proteins in CSFproteins in CSF

Documents

Guillain-Barre’ Syndrome. Guillaine Barre Syndrome Guillain Barre Syndrome 1859 - Landry’s report on 10 patients with “ascending paralysis” 1916 - Guillain,