science revisited

pathogenesis

Evidence for disease pathogenesis is derived from the animal model of GBS, named experimental allergic neuritis, which is caused by a combination of T-cell-mediated immunity to myelin proteins and antibodies to myelin glycolipids. Antibodies to peripheral nerve myelin were identified in the serum of AIDP patients, with a decline in titers corresponding to clinical improvement. Antibodies to myelin glycolipids are indicative of humoral autoimmunity in GBS variants. An autopsy study supporting humoral autoimmunity demonstrated an antibody-mediated complement deposition on the Schwann cell abaxonal plasmalemma but not on the myelin sheath, followed by vesicular paranodal myelin degeneration and retraction. Macrophages are then recruited to strip off the myelin lamellae. Bystander axon loss may occur with severe inflammation. The two early changes in AMAN are the lengthening of the node of Ranvier followed by the recruitment of macrophages to the nodal region. Nodal lengthening is reversible and results in impaired electrical impulse transmission due to the absence of sodium channels. Subsequently, complement activation results in macrophage recruitment. Macrophages distort paranodal axons and myelin sheaths, separate myelin from the axolemma, and induce condensation of axoplasm in a reversible fashion. Only a minority of motor axons undergo wallerian-like degeneration in severe cases, explaining the rapid recovery in some AMAN cases. Another proposed explanation is that axonal degeneration may involve the most distal nerve terminals. In seven fatal AMAN cases, immunoglobulin G and complement activation products were identified bound to the nodal axolemma of motor fibers. The suspected target autoantigen is likely GD1a because IgG antibodies to GD1a were present in 60% of AMAN cases and only 4% of AIDP cases. Molecular mimicry is suggested as the pathogenic mechanism of AMAN based on the strong association with C. jejuni infection. The lipopolysaccharide capsule of C. jejuni shares epitopes with GM1 and GD1a, resulting in cross-reacting antibodies. AMSAN shares many similarities with AMAN, although the attack in AMSAN is more severe or longer lasting, resulting in more intense and ultimately diffuse wallerian-like degeneration of sensory and motor axons. In addition to AMAN and AMSAN, molecular mimicry may also be the most plausible mechanism in the MFS because the overwhelming majority of cases has antibodies to GQ1b.

Antecedent Events

An antecedent infection is noted 2–4 weeks before the onset in three-quarters of GBS cases. Most are upper respiratory infections without any specific organism identified. Known viral precipitants are the Epstein–Barr virus (mononucleosis or hepatitis) and cytomegalovirus (CMV) in 6% of cases. CMV affects younger patients with severe disease and a higher likelihood of respiratory failure. In HIV, GBS occurs at the time of seroconversion or early in the disease. When suspected, it would be important to obtain an HIV viral load measure through the polymerase chain reaction, which is more sensitive than HIV antibodies. Bacterial infections are rarely associated with GBS and include Mycoplasma pneumoniae and Lyme disease.

C. jejuni enteritis is the most common identifiable antecedent infection and precedes GBS in approximately 33% of patients. As GBS develops about 9 days after the initial gastroenteritis, stool cultures for C. jejuni are often negative but serological evidence of recent infection remains. Although two million cases of C. jejuni infection occur each year in the USA, only about 1 per 1000 of these patients has the genetic susceptibility to develops GBS in association with specific HLA haplotypes. Other antecedent events that have been associated with GBS include immunizations, surgery, epidural anesthesia, and concurrent illnesses such as Hodgkin’s disease.

Electrophysiological Features

When GBS is suspected, electrophysiological studies are essential to confirm the diagnosis and exclude mimics. The differential includes other diseases associated with quadriparesis/paralysis such as myasthenic crisis, acute presentation of the idiopathic inflammatory myopathies, and the unusual motor neuron disease patient presenting with acute respiratory failure. Associated clinical features are often helpful in distinguishing these from GBS, e.g. extraocular muscle weakness, a cutaneous rash or upper motor neuron signs.