99 years of Guillain-Barré syndrome: pathophysiological insights from neurophysiology.

To cite: Uncini A. Pract Neurol 2015;15:88–89. Wakerley and Yuki report the wide heterogeneity of the clinical spectrum of Guillain–Barré syndrome (GBS), highlighting atypical presentations and reviewing the differential diagnoses. The approach is practical and their intent is to facilitate early diagnosis and treatment without relying on laboratory and electrophysiological findings. It is nearly 100 years since the description of GBS, the recognition of its numerous variants and subtypes is just part of its continuously evolving and fascinating history. GBS has long been considered synonymous with acute inflammatory demyelinating polyradiculoneuropathy (AIDP); the characteristic electrophysiological correlates of demyelination were described from the 1960s. For years, the electrodiagnosis of GBS was considered relatively easy but with time it has become increasingly complicated. In the 1990s, GBS was recognised to include two primary axonal subtypes: acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN), both associated with antecedent Campylobacter jejuni infection and autoantibodies to gangliosides. AIDP, AMAN and AMSAN are difficult to distinguish on clinical grounds and there are different proposed criteria sets for electrodiagnosis. The criteria for AIDP differ both at the nerve level (where there are different cut-off limits for electrophysiological measurements) and at the patient level (where different numbers of abnormalities are required). The criteria for AMAN and AMSAN were proposed on the assumption that they were pathologically characterised by simple axonal degeneration and that this was electrophysiologically recognisable by the absence of demyelinating features and decreased amplitude of (or unrecordable) compound muscle action potentials (CMAPs) and sensory nerve action potentials. However, patients with AMAN and antibodies to GM1 or GD1a also have transient conduction block (‘reversible conduction failure’) and transient conduction slowing. This can mimic demyelination but without the development of abnormal temporal dispersion—the electrophysiological correlate of remyelination—on serial studies. Not identifying distal reversible conduction failure as the explanation for reduced distal CMAP amplitudes in a single test may lead to an erroneous diagnosis of axonal degeneration, with a correspondingly incorrect poor prognosis. However, failing to distinguish reversible conduction failure from demyelinating conduction block might wrongly classify patients with AMAN as having AIDP. This could explain the apparent association between AIDP and antiganglioside antibodies. Recent studies using serial recordings, which considered reversible conduction failure as expression of axonal pathology, found twice the number of axonal subtypes diagnosed at follow-up than were diagnosed on the first electrophysiological study. All patients who shifted from either AIDP or an equivocal diagnosis to the axonal group had antibodies to gangliosides. This recognition of reversible conduction failure also explains why recovery from axonal GBS with antiganglioside antibodies may be more prompt and complete than expected in an axonal degeneration process. Interestingly, in patients with AMSAN and in patients with the pharyngeal-cervical-brachial subtype of GBS and antiganglioside antibodies, there is reversible conduction failure in both motor and sensory fibres. There is also reversible conduction failure restricted to sensory fibres in patients EDITORIAL