Upregulation of inward rectifying currents and Fabry disease neuropathy
N Geevasinga, M Tchan, D Sillence… - Journal of the …, 2012 - Wiley Online Library
N Geevasinga, M Tchan, D Sillence, S Vucic
Journal of the Peripheral Nervous System, 2012•Wiley Online LibraryPeripheral neuropathy and neuropathic pain are common clinical manifestations of Fabry
disease (FD). Although the mechanisms underlying the development of sensory neuropathy
remain to be fully elucidated, a chronic ischemic process was proposed. Consequently, this
study utilized axonal excitability techniques to gain further insights into the
pathophysiological mechanisms underlying the development of FD neuropathy. Median
motor and sensory axonal excitability studies were undertaken in 13 FD patients and results …
disease (FD). Although the mechanisms underlying the development of sensory neuropathy
remain to be fully elucidated, a chronic ischemic process was proposed. Consequently, this
study utilized axonal excitability techniques to gain further insights into the
pathophysiological mechanisms underlying the development of FD neuropathy. Median
motor and sensory axonal excitability studies were undertaken in 13 FD patients and results …
Abstract
Peripheral neuropathy and neuropathic pain are common clinical manifestations of Fabry disease (FD). Although the mechanisms underlying the development of sensory neuropathy remain to be fully elucidated, a chronic ischemic process was proposed. Consequently, this study utilized axonal excitability techniques to gain further insights into the pathophysiological mechanisms underlying the development of FD neuropathy. Median motor and sensory axonal excitability studies were undertaken in 13 FD patients and results were compared to 19 healthy subjects. A “fanning‐in” of threshold electrotonus, suggestive of membrane depolarization, was evident only in motor axons in FD patients. In contrast, the sensory axons exhibited a lower threshold in FD (p < 0.05) and a significantly increased hyperpolarizing current/threshold (I/V) gradient (FD 0.48 ± 0.03; controls, 0.31 ± 0.02, p < 0.001), which correlated with clinical scores of disease severity (Rho = 0.65, p < 0.05), neuropathy (Rho = 0.54, p < 0.05) and neuropathic pain (Rho = 0.56, p < 0.05). These findings indicate that upregulation of Ih, rather than ischemia, may underlie the sensory symptoms and possibly development of neuropathy in FD. Modulation of sensory Ih may prove therapeutically useful in Fabry disease.
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