Guillain-Barre’ Syndrome

Guillain Barre Syndrome 1859 - Landry’s report on 10 patients with “ascending paralysis” 1916 - Guillain, Barre, Strohl described two French soldiers with motor weakness, areflexia, and “albuminocytological dissociation” in the CSF Guillaine Barre Syndrome

Guillaine Barre Syndrome Epidemiology 1-3/100,000 - Europe, USA, Australia -occurs in any age group -bimodal age distribution -increase incidence with age -males > females -seasonal variations -lower during pregnancy, increases after delivery Guillaine Barre Syndrome

Guillaine Barre Syndrome Clinical Features -antecedent event respiratory infection 40% gastroenteritis 20% -common manifestations proximal limb weakness facial palsy sensory symptoms 80% pain 90% autonomic dysfunction 66% Guillaine Barre Syndrome

Guillaine Barre Syndrome Clinical Features Motor Dysfunction symmetrical limb weakness neck muscle weakness respiratory weakness CN III-VII, IX-XII palsies areflexia wasting Sensory dysfunction pain numbness, paresthesias loss of position sense, vibration, touch, pain ataxia Autonomic dysfunction sinus tachycardia/bradycardia hypertension postural hypotension fluctuations, PR and BP tonic pupils hypersalivation anhidrosis or excess sweating urinary sphincter disturbance constipation gastric dysmotility abnormal vasomotor tone Other papilloedema Guillaine Barre Syndrome

Guillaine Barre Syndrome Clinical Features -onset is acute or subacute nadir 12 days improvement 28 days recovery 200 days -plateau phase reached 4 weeks from onset in 98% of patients -plateau duration 12 days Guillaine Barre Syndrome

Guillaine Barre Syndrome Antecedent Events Campylobacter jejuni -most common pathogen 26-30% USA and Europe 45% Japan -AMAN and AMSAN more common -common preceding infection in Miller Fisher Syndrome Pathogenesis ”molecular mimicry” GM1 ganglioside Guillaine Barre Syndrome

Guillaine Barre Syndrome Antecedent Events Cytomegalovirus -second most common 5% Japan 11-13% Europe -more common in females and young age groups -severe course, with respiratory difficulties -reduced SNAPs are more common Pathogenesis ”molecular mimicry” GM2 ganglioside Guillaine Barre Syndrome

Guillaine Barre Syndrome Antecedent Events Associated infections Epstein Barr (10%) Mycoplasma pneumoniae (5%) HIV Lyme disease Possibly Associated infections hepatitis A, B, C, and D typhoid falciparum malaria Guillaine Barre Syndrome

Guillaine Barre Syndrome Antecedent Events Vaccines? -influenza vaccine -polio vaccination -measles -MMR -hepatitis B presently no evidence for association with GBS Guillaine Barre Syndrome

Guillaine Barre Syndrome Antecedent Events Other anectodal associations -surgery -epidural anesthesia -renal transplantation -bone marrow transplantation -SLE -sarcoidosis -lymphoma -snake bite -some drugs Guillaine Barre Syndrome

Clinicopathological Types Acute Inflammatory Demyelinating Polyradiculopathy most common Pathology lymphocytic infiltration of peripheral nerves macrophage mediated segmental demyelination secondary axonal change humoral and cellular immunity implicated Electrophysiology segmental deymyelination Recovery with remyelination Guillaine Barre Syndrome

Clinicopathological Types Acute Motor Axonal Neuropathy GBS in China (1991, 1992) 55-65% pure motor axonal neuropathy 76% positive for C jejuni 10-20% of sporadic cases Pathology anti-GM1, GD1a, GD1b Wallerian-like degeneration of motor axons lengthening Nodes of Ranvier distortion of paranodal myelin periaxonal macrophages Guillaine Barre Syndrome

Clinicopathological Types Acute Motor Axonal Neuropathy Electrophysiology CMAP amplitudes reduced tendon reflexes, preserved, exaggerated Rapidly progressive weakness, respiratory failure Usually good recovery Guillaine Barre Syndrome

Clinicopathological Types Acute Motor Sensory Axonal Neuropathy Feasby 1986 described 7 patients severe sensory motor dysfunction marked wasting, poor recovery Pathology Wallerian-like degeneration, motor sensory axons little demyelination, lymphocytic infiltration periaxonal macrophages Guillaine Barre Syndrome

Clinicopathological Types Acute Motor Sensory Axonal Neuropathy Electrophysiology sensory and motor axonal dysfunction Fulminant disease Slow incomplete recovery Most severe form of immune mediated axonal damage Guillaine Barre Syndrome

Clinicopathological Types Miller Fisher Syndrome Fisher 1956 described 3 patients ataxia, areflexia, ophtalmoplegia 5% of patients with GBS associated with C jejuni infection Pathology anti-GQ1b demyelination CN III, VI, spinal ganglia, peripheral nerves Electrophysiology reduced/absent SNAPs Guillaine Barre Syndrome

Clinicopathological Types Other Variants pure sensory pure dysautonomic pharyngeal-brachial-cervical paraparetic 10% of GBS Guillaine Barre Syndrome

Electrophysiological Features AIDP reduced conduction velocity conduction block or temporal dispersion prolonged terminal latency absent or prolonged F-wave AMAN absent or reduced CMAP normal motor latency and NCV normal SNAP AMSAN absent or reduced SNAP Guillaine Barre Syndrome

Criteria for Diagnosis Required Criteria progressive weakness > two limbs areflexia progression < 4 weeks other causes excluded lead poisoning, vasculitis, botulism, porphyria Supportive Criteria mild sensory signs albuminocytological dissociation conduction block Guillaine Barre Syndrome

Guillaine Barre Syndrome Investigations cerebrospinal fluid antiganglioside antibodies stool culture for C jejuni antibodies to C jejuni, cytomegalovirus, EBV, HSV, HIV, M. pneumoniae biochemical screening: urea, electrolytes, liver enzymes full blood count ESR autonomic function tests electrophysiology Guillaine Barre Syndrome

Guillaine Barre Syndrome Treatment Good intensive care Respiratory support Prophylaxis for dvt Rehabilitation Guillaine Barre Syndrome

Guillaine Barre Syndrome Treatment Plasma Exchange Brettle 1978 done within 2 weeks reduced period of hospital stay, duration of mechanical ventilation, time to reach ambulation North American Trial 200-250 ml/kg body weight, 7-14 days French Cooperative Group 2 exchanges for mild 4 exchanges for moderate to severe Guillaine Barre Syndrome

Guillaine Barre Syndrome Treatment Plasma Exchange Complications hypotension septicemia hypocalcemia abnormal clotting Guillaine Barre Syndrome

Guillaine Barre Syndrome Treatment Intravenous Immunoglobulin tx for immunologically mediated disorders anti-idiotypic suppression of autoantibodies Kleyweg et al 1988 given within 2 weeks as effective as plasma exchange 0.4 g/kg body weight for five days Guillaine Barre Syndrome

Guillaine Barre Syndrome Treatment Intravenous Immunoglobulin Adverse Effects malaise, myalgia, fever, chills vasomotor symptoms, headache nausea, vomiting increase in liver enzymes renal tubular necrosis, acute renal failure aseptic meningitis hypercoagulable state anaphylaxis rashes encephalopathy Contraindications selective IgA deficiency Anaphylaxis with previous IVIg Relative contraindications severe congestive cardiac failure renal insufficiency Guillaine Barre Syndrome

Factors Associated with Poor Outcome Etiology previous GI infection C jejuni infection cytomegalovirus Clinical Features older age shorter latency to nadir longer time to clinical improvement need for mechanical ventilation greater disability and disease severity Electrophysiology absent or reduced CMAP inexcitable nerves Biochemical Markers Anti-GM1 antibodies Neurone specific enolase and S100b proteins in CSF Guillaine Barre Syndrome