| 摘要: | 神經興奮度檢查為可以非侵入性方式檢測軸突膜屬性之電生理檢查技巧。其可測出之前只能透過侵入式檢查方能獲得的軸突屬性資料。本論文將使用神經興奮度檢查研究原發性修格蘭氏症候群之免疫性周邊神經病變，及笑氣濫用之毒性周邊神經病變。
本研究收案共40位原發性修格蘭氏症候群病患以研究該疾病之軸突異常。血清陽性原發性修格蘭氏症候群病患（n=28）之運動神經興奮度檢查發現其有較高的閾值(P<0.05)，較高的基本電位(P<0.01)，較高的最低電流／電壓斜率(P<0.01)及超極化電流／電壓斜率(P<0.05)，較長的相對不反應期(P<0.001)，外展的去極化閾值電緊張曲線(P<0.05)，及內縮的超極化閾值電緊張曲線(P<0.05)。血清陰性的病患(n=10)則無上述明顯之運動軸突異常，只出現了較高的最低電流／電壓斜率(P<0.05)。感覺神經興奮度檢查則發現有自體抗體的病患有較高的閾值(P<0.01)，較短的潛時差(P<0.01)，較長的相對不反應期(P<0.01)，較高的過低興奮度(P<0.05)。血清陰性的病患則亦無明顯之感覺軸突異常。溫熱定量感覺檢查顯示出血清陰性患者之感覺異常較血清陽性患者明顯。SSA及SSB抗體可能引起軸突蘭氏結，蘭氏結間區域，及小纖維神經功能性異常；而血清陰性修格蘭氏症候群之自體免疫抗體主要影響小纖維神經。總的來說，血清陽性及陰性修格蘭氏症候群周邊神經病變之病理機轉有所不同。
本研究另收案共18位笑氣濫用及維生素B12缺乏之病患以研究笑氣濫用引起之軸突異常。笑氣濫用病患(n=8)之運動之運動神經興奮度檢查發現其有較低的峰值反應(P=0.05)，較長的潛時差(P<0.01)，較高的過高興奮度(P<0.05)，外展的去極化閾值電緊張曲線(P<0.05)；而感覺神經興奮度檢查只發現較低的峰值反應(P<0.05)。維生素B12缺乏病患(n=6)之運動之運動神經興奮度檢查只發現內縮的過極化閾值電緊張曲線(P<0.01)；感覺神經興奮度檢查發現較低的峰值反應(P<0.05)，較高的過高興奮度(P<0.001)，較高的過低興奮度(P<0.05)，及外展的去極化閾值電緊張曲線(P<0.001)。與維生素B12缺乏相比，笑氣濫用病患有較明顯的運動過高興奮度變化及較不明顯的感覺過高興奮度變化，提示其周邊神經病變病理機轉可能與維生素B12缺乏不同。笑氣濫用導致之軸突異常可能不只與甲硫氨酸代謝阻斷相關，而亦可能與影響蘭氏節側區之毒性相關。
神經興奮度檢查的確能發掘原發性如修格蘭氏症候群之免疫性周邊神經病變，及如笑氣濫用之毒性周邊神經病變的軸突異常。此檢查釐清了這些疾病的神經病變機轉，並可望未來有機會疾病診斷工具之一。
The nerve excitability test is an electrophysiological technique that could noninvasively assess axonal membrane properties. It could obtain valuable axonal properties data that previously can only be acquired through invasive and laborious procedures. The present study would use the nerve excitability test to study immune-mediated peripheral neuropathy in primary Sjögren’s syndrome (pSS) and toxic peripheral neuropathy in Nitrous oxide (N2O) overuse.
A total of 40 pSS patients were enrolled to study the axonal abnormalities in pSS. Paired motor and sensory nerve excitability tests were performed. Motor nerve excitability test of the seropositive pSS group (n=28) revealed higher stimulus for 50% compound muscle action potential (CMAP) (P<0.05), increased rheobase (P<0.01), increased minimum I/V slope (P<0.01) and hyperpolarizing I/V slope (P<0.05), prolonged relative refractory period (RRP, P<0.001), reduced accommodation of Threshold electrotonus (TE) toward depolarizing current (P<0.05) and increased accommodation toward hyperpolarizing current (P<0.05). The seronegative pSS group (n=10) had much less pronounced motor axonal changes, showing only increased minimum I/V slope (P<0.05). Sensory nerve excitability test in the seropositive pSS group revealed higher stimulus for 50% sensory nerve action potential (SNAP) (P<0.01), reduced latency (P<0.01), prolonged RRP (P<0.01), and increased subexcitability (P<0.05). The seronegative pSS group shown no significant sensory axonal changes. Thermal QST showed more prominent abnormalities in the seronegative pSS group compared to the seropositive pSS group. Considering the nerve excitability test results in the present study, we speculated that Anti-SSA/Ro and anti-SSB/La autoantibodies might cause abnormalities in the axon’s nodal and internodal region and small nerve fibers; meanwhile, autoreactive antibodies in the seronegative pSS group mainly affects small nerve fibers. Thus, the underlying pathophysiology for peripheral neuropathy in the two types of pSS is different.
Eighteen patients with N2O overuse or vitamin B12 deficiency were also recruited to study the axonal abnormalities in N2O overuse by comparing the nerve excitability test results in the two groups. In the N2O overuse group (n = 8), the motor nerve excitability test showed a decrease in peak response (P=0.05), prolonged latency (P<0.01), prolonged superexcitability (P<0.05), and reduced accommodation to depolarizing current (P<0.05); the sensory nerve excitability test showed only reduced peak response (30.54±5.98 µV, P<0.05). Motor test in the vitamin B12 deficiency group (n = 6) showed only reduced accommodation to depolarizing current (P<0.01); the sensory test showed reduced peak response (P<0.05), increased superexcitability (P<0.001), increased subexcitability (P<0.05), and reduced accommodation to depolarizing current (P<0.001). Compared to the vitamin B12 deficiency group, the N2O overuse group showed prominent motor superexcitability changes and less pronounced sensory superexcitability changes, indicating a unique pathological process different from that of vitamin B12 deficiency. N2O overuse might cause axonal dysfunction by toxicity affecting the paranodal region in addition to its blockage of methionine metabolism.
In conclusion, the nerve excitability test was able to identify the axonal abnormalities in immune-mediated neuropathy such as pSS, and toxic peripheral neuropathy such as N2O. It provided valuable pathophysiological insights into the diseases and showed potential as a diagnostic tool in the future. |
