The electrophysiology of axonal neuropathies: More than just evidence of axonal loss.

It is common belief that axonal neuropathies are characterized by simple axonal degeneration and loss and that the electrophysiological correlates are just reduced compound muscle action potential and sensory nerve action potential amplitudes with normal or slightly slow conduction velocity. However, axonal autoimmune neuropathies with involvement of the nodal region and axonal neuropathies due to energy restriction such as occurring in nerve ischemia, thiamine deficiency, critical illness, and mitochondrial disorders present conduction failure that can be either reversible with prompt recovery or progress to axonal degeneration with poor outcome. Moreover autoimmune axonal neuropathies due to nodal voltage gated sodium channels dysfunction/disruption may show slowing of conduction velocity, even in the demyelinating range, possibly due to prolongation of the depolarization time required to reach the threshold for action potential regeneration at subsequent nodes. These observations widen the spectrum of the electrophysiological features in some axonal neuropathies, should be taken into account to avoid misdiagnoses and for correct prognostication, and should stimulate the quest of timely targeted treatments that can eventually halt the progression from conduction failure to axonal degeneration.