Activity‐dependent hyperpolarization and conduction block in chronic inflammatory demyelinating polyneuropathy

Abstract

Voluntary activity produces activity-dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity-dependent conduction block paralleled the activity-dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%. Activity-dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites.

Fatigue and activity dependent changes in axonal excitability in amyotrophic lateral sclerosis

“…A stimulus, 20% greater than channel 1, was delivered on channel 2 and commenced following the period of voluntary contraction. This was done in order to ensure that the post-contraction maximal CMAP on channel 1 had remained truly maximal 23. On channel 3, a stimulus of 0.1 ms duration was delivered and its intensity fixed for the entire duration of the study to 70% of the precontraction maximal CMAP, in order to assess the effects of contraction induced excitability changes on CMAP amplitude.…”

“…Specifically, in peripheral nerves, voluntary contraction activates the axonal membrane Na + /K + pump,17 which attempts to return the resting membrane potential to baseline after contraction has ceased,18 – 21 resulting in activity dependent hyperpolarisation. The magnitude of activity dependent hyperpolarisation is determined by the impulse load22 and, in neurological diseases where the safety margin for impulse conduction has been reduced as occurs for instance in demyelinating neuropathy, may be sufficient to induce conduction failure 23 – 25. In an attempt to further delineate the mechanisms underlying fatigability and weakness in ALS, the present study measured activity dependent changes in axonal excitability induced by voluntary contraction.…”

Strength-duration properties and their voltage dependence as measures of a threshold conductance at the node of Ranvier of single motor axons

“…For example, the strength-duration properties of peripheral nerve axons have been measured in focal neuropathies 16 and generalized polyneuropathies. 10 They have been found to be abnormal in conditions with increased axonal excitability, such as hyperventilation, 17 nerve ischemia, 17 amyotrophic lateral sclerosis, 18,19 and neuromyotonia, 14 but not in cramp fasciculation syndrome (Kiernan, Hart, and Bostock, personal communication).…”

Role of Activity-Dependent Conduction Block in the Diagnosis of Primary Demyelinating Polyneuropathy

“…[1][2][3][4][5] This case illustrates that MVC for 10 seconds, which to our knowledge has not been previously reported, may be sufficient to screen for ADCB. [1][2][3][4][5] This case illustrates that MVC for 10 seconds, which to our knowledge has not been previously reported, may be sufficient to screen for ADCB.…”