Definition: Guillain-Barre syndrome encompasses the spectrum of rapidly progressive demyelinating polyneuropathies of the peripheral nervous system; this group includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor-sensory axonal ne

Gillain-Barre Syndrome / Acute Inflammatory Demyelinating Polyneuropathy (AIDP)

Definition: Guillain-Barre syndrome (GBS) encompasses the spectrum of rapidly progressive demyelinating polyneuropathies of the peripheral nervous system; this group includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor-sensory axonal neuropathy, acute motor-axonal neuropathy, and the Miller-Fisher variant. In the majority of cases, the neuropathy is triggered by a preceding bacterial or viral illness.

Epidemiology: Can occur at any age, with a somewhat bimodal distribution in young adults and in the elderly. Occurs in approximately 2-3 per 100,000 people per year, with an estimated annual incidence of 8 per 100,000 people in persons over the age of 70.

Approximately 60-70% of patients with GBS report a preceding acute illness, typically a flu-like illness or gastrointestinal illness between 1-3 weeks prior to onset of neurologic symptoms. Campylobacter jejuni is the bacterial pathogen most frequently associated with GBS, while cytomegalovirus is the most common associated virus.

Pathogenesis: Though to result from an infectious trigger that initiates humoral and T-cell immune responses that result in lymphocytic infiltration of spinal and peripheral nerves; local macrophage recruitment results in damage to myelin, causing demyelination and nerve conduction block. In the axonal neuropathy variants of GBS, a primary autoimmune attack on nerve axons, possibly due to anti-ganglioside antibodies, causes axonal degeneration; patients with severe axonal loss generally have poorer overall recovery.

Clinical Characteristics & Diagnosis: Patients with AIDP (85-90% of cases of GBS) usually present with paresthesias beginning in the distal upper and lower extremities, followed within days by leg weakness that gradually ascends over days. Sciatica or pain is also relatively common in the proximal extremities or lower back. Exam characteristically shows markedly decreased or absent reflexes, symmetric extremity weakness, ± facial weakness, but minimal sensory loss despite paresthesias. Eventually weakness can progress to pharyngeal, ocular, and respiratory muscle weakness requiring mechanical ventilation in more severe cases; autonomic dysfunction also may occur. CSF may show slight elevation in protein (>55 and <250mg/dL). PNCVs show slowing of conduction velocities, prolongation of distal and F-wave latencies, and conduction block. Severity of disease is highly variable and recovery may be dependent upon degree of secondary axonal degeneration.

Patients with acute motor-sensory axonal neuropathy (AMSAN) generally have more fulminant onset of generalized paralysis (within 2-4 days of symptom onset) with greater severity, often requiring mechanical ventilation. PNCVs show markedly reduced or absent evoked responses to distal maximal motor and sensory nerve stimulation. Patients often develop significant muscle atrophy and recovery is generally poor.

Patients with acute motor-axonal neuropathy (AMAN) have rapidly ascending paralysis with reduced or absent distally evoked motor-compound potentials but normal nerve conduction velocities and action potentials in sensory nerves.

Miller-Fisher syndrome (MFS) is characterized by ophthalmoplegia, ataxia, and areflexia. IgG antibodies to GQ_1b ganglioside are seen in 96% of such patients.

Management and Course: Patients with GBS should be admitted under close observation, since progression to respiratory fatigue/failure may be quite rapid. 33% of patients eventually require ventilatory support and ICU-level care. Serial forced vital capacity (FVC) and negative inspiratory force (NIF) measurements should be made in patients who develop evidence of respiratory/airway compromise; an FVC <15mL/kg, NIF <30cmH₂0, or weakening cough are signs of impending respiratory failure. Complications of GBS include but are not limited to respiratory failure, dysphagia/aspiration, airway compromise, thromboembolic disease, infection, nutritional deficiency, dehydration, autonomic dysfunction, pain, and depression. Patients need to be closely monitored for disease progression and requirement of further supportive measures.

In addition to supportive care, GBS can be treated with immunomodulatory therapy:

Plasmapheresis has clearly been shown to improve outcomes and shorten disease time frame in 3 large, randomized, multicenter trials. Severe GBS patients treated with plasma exchange could be weaned from ventilatory support sooner, improved strength faster, and reached ambulation earlier than controls; in one study, 71% of treated patients recovered full motor strength, as opposed to 52% of controls. The use of fresh frozen plasma has not been shown to be superior to exchange with saline/albumin in these trials. The usual regimen consists of 1.5-2 plasma volumes per procedure on alternating days for 1-2 weeks (total of ~5 exchanges). Due to associated risks and high cost, plasmapheresis is primarily reserved for more severe cases of GBS presenting within the first 2 weeks of onset.

IVIG has become the mainstay of therapy due to ease of application and low treatment risk. In head-to-head trials with plasma exchange, IVIG performed as well as plasma exchange in terms of functional disability at 4 weeks. Hypothesized mode of action is competitive blockade of macrophage receptors and direct binding of autoantibodies. Usual dose is 0.4g/kg/day for 5 days, given in the first 2 weeks of the illness.

Corticosteroids have not been proven to show any significant benefit in patients with GBS, confirmed by a large, multicenter, double-blind, placebo-controlled trial (Lancet 1991;338:1142) and reconfirmed by the Cochrane Collaboration.

Disease progression varies in duration: 75% will reach nadir within 2 weeks while 94% reach nadir at 4 weeks. Resolution of paralysis can subsequently take weeks to months; physical therapy may be helpful. Overall recovery is generally good, with ~65% near-complete recovery with minimal deficits and ~15% with complete neurologic recovery; only 5-10% will have permanent disabling defects. Mortality is still 5-8%, largely due to avoidable complications of hospital stay.

D. Suh 3/29/01