Manifestations of axonal excitability in patients with neurofibromatosis type 1

• Main Authors: Ya-Wen Chiang, 江雅雯
• Other Authors: Ming-Jen Lee
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/29548252570863353091

碩士 === 國立臺灣大學 === 分子醫學研究所 === 102 === Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder, affecting approximately one in every 4000 individuals. Although the penetrance rate for NF1 is 100%, the clinical features are highly variable among families as well as intra-family. It has been estimated that 1.3~2.3% of NF1 patients has neuropathic symptoms, and neuropathic pain is one of the common complaints. Traditional nerve conduction test and electromyography which is usually unremarkable in NF1 patients, cannot provide information such as changes in membrane potentials and nerve excitability. This study employed the newly developed nerve excitability test (NET) to compare the parameters of nerve membrane potential and axonal excitability between NF1 and healthy individuals. In this study, we have recruited 75 NF1 patients and 70 healthy individuals as normal controls. Every subject is evaluated in 5 individual nerves: median motor and sensory nerve, ulnar motor and sensory nerve, and tibial motor nerve. The results of the NET can be divided into 5 main categories: (1) SR, stimulation-response curve; (2) Strength-duration curve; (3) Threshold electrotonus; (4) Current-voltage curve; and (5) Recovery cycle. In the stimulation-response curve test, NF1 subjects had higher rheobase and higher current in stimulus for 50% max response in the motor axons of median nerve and the sensory one in both median and ulnar nerves. The reason might be due to different density of the nerve fascicles and dysmyelation of some nerve areas in NF1 patients, which could cause inactivation of the fast K+ channels at the paranodal region. In the threshold electrotonus test, NF1 subjects had lower TEh (overshoot) in the sensory axons of the ulnar nerve. This indicates an increase in slow K+ current and keep the axonal membrane in a hyperpolarization state which possibly reasults from the dysfunction of the Na+/K+ pump in the conduction block region. In the current-voltage curve test, the NF1 subjects had significantly higher Hyperpolarization I/V slope in the motor axons of the median, ulnar and tibial nerves compared to that of the controls. This might due to the increase of the outward rectification of the K+ current causing a slow polarizating effect. Proliferation of schwannoma cells in NF1 will cause increasing of K+ outward current and result in a more obvious hyperpolarization than healthy subjects. In the Recovery cycle test, compared to controls, the latency of the sensory axons in NF1 patients is conspicuously short rendering the high frequency of neuropathic pain in NF1 patients. The refractoriness at 2.5ms showed a significant low threshold in the motor axons of the ulnar and sensory ones in the median nerves of the NF1 subjects, indicating that the threshold to generate a new action potential is reduced. Concerning the threshold in RRP (relative refractory periods), NF1 patients had a significant low threshold comparing to that of controls suggesting the reactivation of the nodal Na+ channel is faster in NF1 patients than in healthy subjects. The nerve excitability change in NF1 neuropathy has not yet being well studied. The results from our study provide more information about the changes of the electrophysiological parameters in NF1 which will facilitate our understanding of the neuropathic pain in NF1.