Demyelinating neuropathies

Abstract

Clinical neurophysiology plays a critical role in the diagnosis, classification, and prognosis of demyelinating neuropathies. Abnormalities include slowed nerve conduction velocities, prolonged distal latencies, prolonged or absent H reflexes and F-wave latencies, conduction block, and varying degrees of denervation. However, the degree of conduction slowing documented using standard neurophysiological investigation does not correlate well with clinical disability, and even when patients have fully recovered, conduction velocity may remain permanently slow. Separately, the abnormalities of nerve excitability that underlie conduction slowing, block and ectopic impulse activity are not adequately explored by routine nerve conduction studies. Acute demyelination lowers the safety margin for impulse conduction, such that axons can become sensitive to shifts in membrane potential, even when those shifts occur through normal physiological mechanisms. In critically conducting axons, impulse conduction can be impaired by the effects of heating and activity and probably by any mechanism that produces a significant shift in membrane potential, whether depolarizing or hyperpolarizing. The important message is that critically conducting axons are delicately poised. Conduction may block if membrane potential is too far from threshold (i.e., the axon is hyperpolarized) or if the Na+ current becomes inadequate (because of heating or because of a limitation on the number of functioning Na+ channels). Significant changes in activity or significant shifts in membrane potential, whether depolarizing or hyperpolarizing, may be sufficient to produce a transient worsening of symptoms.