Guillain-Barre Syndrome

Nerve Roots (acute polyradiculopathies) Guillain-Barre Syndrome Lyme disease Sarcoidosis HIV Other viruses (CMV, VZV, West Nile) Cauda Equina Syndrome Plexus lesions (brachial plexitis, lumbosacral plexopathy)

Epidemiology Most common cause of acute flaccid paralysis in Western countries Overall incidence 1-2/100,000; up to 8.6/100,000 in elderly population All age groups can be affected, however more common in elderly Bimodal peak, small peak in young adults and larger peak in elderly; rare in infancy

75% have an antecedent ‘event’ 1-4 weeks before onset of weakness: respiratory (68%), GI (22%), resp and GI (10%), surgery (2%), vaccination or pregnancy The best documented antecedents included infection with C.jejuni, EBV, CMV, HSV, and Mycoplasma. C. jejuni is often associated with more severe axonal cases and most likely sensitizes the immune system to shared antigens.

Clinical Course Initial paresthesias in fingers/toes followed by weakness Weakness rapidly worsens, sensory loss usually minimal Usually symmetric, though can be asymmetric initially Classically distal weakness ascending up legs and arms, but proximal weakness not uncommon at onset

Cranial nerve involvement (unilateral or bifacial weakness 50%, oculomotor paralysis 5%, charachteristic in Miller Fischer Syndrome 66% reach nadir in 2 weeks, 92% in 3 weeks; by definition must peak at 4 weeks Brief plateau phase then improvement and gradual resolution over weeks to months

Complications Respiratory weakness/failure (20-30% will need intubation at some point during admission) Autonomic dysfunction in up to 65% including: arrythmias, hypotension or hypertension, labile fluctuating BP, Ileus, urinary retention Pain in up to 85%: typically back pain, radiculopathic and musculoskeletal, the straight leg raise test will be positive

Papilledema (secondary to high CSF protein) Compression neuropathies (particularly ulnar and peroneal) DVT/PE SIADH (26%) Acute Renal Injury (secondary to IVIG TX) Hypercalcemia (secondary to immobility) Hepatocelluar dysfunction (30% early on, as high as 60% later in course

Mortality/Morbidity 85% of patients will achieve a full and functional recovery within 6-12 months, maximal recovery at 18 months 7-15% of patients will have permanent neurological sequelae including bilateral foot drop, intrinsic hand muscle wasting, sensory ataxia, dysesthesia Despite intensive care, 3-8% of patients die

Required criteria for ‘typical’ GBS Required Features Progressive weakness in both arms and legs Areflexia (or hyporeflexia)

Features supportive of Diagnosis Progression of symptoms over days to 4 weeks Relative symmetric Mild sensory signs or symptoms CN involvement, especially bilateral facial weakness Recovery begins 2-4 weeks after progression ceases Absence of fever at onset Typical CSF and EMG/NCS features

Pathophysiology GBS is believed to result from autoimmune humoral- and cell-mediated responses to a recent infection or any of a long list of medical problems. Antibodies formed against ganglioside-like epitopes in the lipopolysaccharide (LPS) layer of some infectious agents have been shown in both necropsy and animal models to cross-react with the ganglioside surface molecules of peripheral nerves.

Symptoms generally coincide pathologically with various patterns of lymphocytic infiltration and macrophage-mediated demyelination, depending on the subtype in question. In a subset of patients, GBS is associated primarily with myelin-sparing axonal damage resulting from a direct cellular immune attack on the axon itself.

Types/Variants Acute Inflammatory Demylinating Polyradiculoneuropathy (AIDP) Acute Motor-Sensory Axonal Neuropathy (AMSAN) Acute Motor Axonal Neuropathy (AMAN) Miller Fisher Variant Pharyngeal-Cervical-Brachial Variant Acute Pandysautonomia

Acute Inflammatory Demylinating Polyradiculoneuropathy (AIDP) Most common variant, 85% of cases Primarily Motor Generally preceded by bacterail or viral infection Lymphocytic infiltration and macrophage mediated demylination of periopheral nerves is present Symptoms generally resolve with remylination, max of 4 weeks of progression

Acute Motor-Sensory Axonal Neuropathy Motor and sensory involvement with severe course Respiratory and bulbar involvement Primary axonal degeneration Patients are typically adults with both motor and sensory dysfunction with marked muscle wasting and poor recovery

Acute Motor Axonal Neuropathy (AMAN) Motor only with early and severe respiratory involvement, primary axonal degeneration More prevalent amongst pediatric age groups Up to 75% positive for C. jejuni serology, often also anti-GM1, anti-GD1a positive Hypereflexia is significantly associated with the presence of anti-GM1 antibodies Characterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery.

Miller Fisher Variant Triad: opthalmoplegia, sensory ataxia, areflexia 5% of all cases 96% positive for anti-GQ1b (antiganglioside) antibodies Patients may also have mild limb weakness, ptosis, facial palsy, or bulbar palsy. The ataxia tends to be out of proportion to the degree of sensory loss. Recovery generally occurs within 1-3 months

Pharyngeal-Cervical-Brachial Variant Often associated with IgG anti-GT1a Presents with proximal descending weakness Must distinguish from botulism and diptheria

Acute Pandysautonomia Widespread sympathetic and parasympathetic failure Very rare Cardiovascular involvement is common, and dysrhythmias are a significant source of mortality in this form of disease Recovery is gradual and often incomplete

Workup Clinical Diagnosis Elevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm very presumptive Normal CSF protein does not rule out GBS as the level may remain normal in 10% of patients, and a rise in the CSF protein level may not be observed until 1-2 weeks after the onset of weakness

Imaging MRI is sensitive but nonspecific Spinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and is caused by disruption of the blood-nerve barrier Selective anterior nerve root enhancement appears to be strongly suggestive of GBS The cauda equine nerve roots are enhanced in 83% of patients

Nerve Conduction Studies A delay in F waves is present, implying nerve root demyelination Compound muscle action potential (CMAP) amplitude may be decreased Patients may evidence of conduction block or dispersion of responses at sites of natural nerve compression. The extent of decreased action potentials correlates with prognosis

Treatment Only plasmapheresis (the exchange of patients plasma for albumin) and intravenous serum globulin (IVIG) have proven effective Both therapies have been shown to shorten recovery time by as much 50% Combining plasma exchange and IVIG neither improved outcomes nor shortened the duration of illness Corticosteriods are ineffective as monotherapy

IVIG Randomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as pasmapheresis Dosed at 0.4 gram/kg/day IV for 5 Days Same dose in pediatrics May increase serum viscosity and tromboembolic events May increase frequency of migraines May cause aseptic meningitis

Sequela of IVIG Increased antiviral and antibacterial antibody titers for one month Six-fold increase in ESR lasting two to three weeks Apparent hyponatremia