Definition
GBS is a clinically defined syndrome with several underlying pathologies. It affects 1–4 per 100 000 per year, men slightly more often than women. Diagnostic criteria¹ include progressive weakness of two or more limbs reaching a maximum within four weeks, reduced or absent tendon reflexes in the weak limbs, and exclusion of alternative causes (box 1).² Some cases may be so mild that medical attention is never sought. Most cases are caused by acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but some are caused by acute motor axonal neuropathy (AMAN) or acute motor and sensory axonal neuropathy (AMSAN).³ Primary axonal GBS is thought to be caused by an autoimmune attack on axonal antigens, and is common in Asia, but is responsible for less than 5% of GBS cases in Europe and North America. Reflexes are sometimes preserved in AMAN. Rarer variants of GBS are the pharyngo-cervico-brachial pattern, acute oropharyngeal palsy (not to be confused with diphtheria), involvement of the lower but not upper limbs, and a pure motor and a pure sensory form. Acute pandysautonomia and acute sensory neuronopathy may also be related.

Investigations
Cerebrospinal fluid examination is needed largely to exclude alternative diagnoses, such as infectious (for example, Borrelia or poliomyelitis) or lymphomatous polyradiculitis. The CSF protein is classically elevated as a result of albumin leakage from the blood, but may be normal within the first week. The CSF leucocyte count is usually normal but the diagnostic criteria allow up to 50 cells/µl. Pleocytosis is more likely in coexistent HIV infection.

GBS is preceded in two thirds of cases by an infection such as Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus or Mycoplasma pneumoniae.⁴ The infection is usually cleared before development of neurological symptoms. Identification of serum IgM antibodies to one of these agents demonstrates recent infection but is not clinically useful. Stool culture occasionally isolates C jejuni, but antibiotics probably do not influence outcome (level 4 evidence; box 2). The risk of developing GBS after C jejuni enteritis is less than 1 in 2500.

Serum antibodies to many peripheral nerve antigens have been found in GBS, but the majority of GBS patients have no identified autoantibodies so the pathogenesis of the disease is still debated. The antibodies that are found may also be present in other neurological diseases or occasional normal controls, and may be an epiphenomenon. Nevertheless, some antibodies do correlate with clinical subtypes of GBS (table 1).⁵ Their presence does not influence treatment.

Neurophysiology
Nerve conduction studies may help in diagnosis, classification and (to a limited extent) predicting prognosis. Neurophysiology helps to exclude alternative diagnoses such as myositis and myasthenia. Neurophysiological abnormalities are often very mild or occasionally normal in early GBS, and do not correlate well with clinical disability.⁶ The earliest consequence of acute demyelination is focal axonal conduction block, and it takes several days before slowing of conduction develops. Unfortunately for the purposes of diagnosis, conduction block is most common in the proximal nerve roots at sites that are awkward to test, at distal sites that mimic axonopathy, and at sites of compression, so it is often difficult or impossible to distinguish between axonal and demyelinating GBS in the early stages. Axonal degeneration may occur as a consequence of primary autoimmune attack on the axon or as a bystander phenomenon secondary to a primary attack on the myelin. It becomes evident after a few weeks as muscle wasting and electromyographic features of denervation, which signify a poor outcome. In the early stages, axonal neurophysiology may represent reversible axonal dysfunction rather than degeneration.

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