Frequency-Dependent Conduction Block In Demyelinating Focal Neuropathies
It is the objective of this thesis to demonstrate conduction block across regions of focal demyelination by utilizing a conventional electrophysiological technique used frequently in the diagnosis of peripheral nerve disease. Specifically, patients with moderate to severe carpal tunnel syndrome (CTS), but, with no evidence of conduction block via conventional motor nerve conduction study techniques, were assessed in the initial studies of this thesis for evidence of frequency-dependent conduction block (FDB) by way of high-frequency nerve stimulation (HFNS) applied across the region of entrapment. The final studies examined whether FDB could be demonstrated along the median motor fibers in mild cases of CTS, despite the presence of normal motor nerve conduction studies and lastly, whether other focal entrapment or compressive neuropathies behaved similar to the results obtained from CTS patients. The application of HFNS (30-Hz, 20 stimuli) was successful in demonstrating FDB in the median motor fibers across the region of the carpal tunnel (CT), in moderate to severe CTS patients (experiment 1). FDB was shown to be rate dependent and was more demonstrable using higher stimulus frequencies in cases with greater prolonged distal motor latencies. Unlike previous studies, these results suggest that demyelination plays a role in the pathophysiology and focal conduction slowing in CTS patients and that FDB may be responsible for the grip weakness and fatigue often described by these patients, particularly in the absence of conduction block. FDB was successfully demonstrated again across the region of the CT, similar to experiment 1, but was also observed more distally across the distal margins of the palmar aponeurosis and motor terminal axon (experiment 2). These results suggest that demyelination may occur distal to the lesion in CTS, supporting previous morphological and histological observations. Further, this data also suggests that the safety margin for impulse transmission can be impaired distal to the presumed site of injury in CTS and that this region should be considered as a potential site of injury, particularly in patients who fail to respond to more proximal steroid injection or surgical treatment. Mild cases of CTS with complaints of hand weakness, but, with normal motor nerve conduction studies were then examined to determine if FDB could be demonstrated using physiological rates of HFNS (experiment 3). The results indeed demonstrated evidence of FDB (albeit mild) in patients with mild CTS that were significantly different than what was observed in controls, despite having similar conventional motor nerve conduction study results. This suggests that the FDB (also referred as activity-dependent block) may be partially responsible for the hand weakness or the difficulties with normal everyday tasks often described by patients with mild CTS. Further, this provides evidence that conventional motor nerve conduction studies, which use stimulation rates well below physiological rates of motor unit activation, fail at times to demonstrate the extent of the underlying pathophysiology affecting the motor fibers. Lastly, the relationship between focal entrapment neuropathies with respect to the degree of FDB was examined in patients with relatively acute ulnar neuropathy localized to the elbow (UNE) and compared to previous results obtained in CTS patients from experiments 1 and 2 (experiment 4). Surprisingly, the results failed to demonstrate FDB in the remaining ulnar motor fibers across the elbow, despite evidence of severe demyelination as demonstrated by the significant conduction slowing and conduction block observed through conventional motor nerve testing. This suggests that the margin of safety for ulnar nerve transmission is intact at physiological rates of 30-Hz in the remaining ulnar motor fibers, despite the evidence of significant conduction slowing, and that there may be a separate mechanism involved in acute focal UNE that differs from the more chronic entrapment of CTS.
frequency-dependent conduction block, activity-dependent conduction block, demyelination, high-frequency nerve stimulation, carpal tunnel syndrome, ulnar neuropathy, electrophysiology, nerve conduction studies, neurophysiology, peripheral nervous system, focal entrapment neuropathies
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