神經退化與疼痛症候群之小纖維神經病變診斷與治療

Diagnosis and Treatment of Small Fiber Neuropathy in Syndromes of Neurodegeneration and Pain

周邊神經可以依據神經的直徑大小，分類為小纖維神經（small fiber，職司溫覺與疼痛）與大纖維神經（large fiber，負責本體感覺），當發生神經退化疾病時（稱為周邊神經病變），造成小纖維神經病變（small fiber neuropathy）與大纖維神經病變（large fiber neuropathy），各有不同的臨床表徵。小纖維神經病變的臨床表現，除了包括溫覺消失的負性症狀，更多的是神經異常興奮造成神經疼痛的正性症狀，臨床評估並需檢查症狀分佈。典型的周邊神經病變如糖尿病神經病變、化學藥物神經病變、神經末梢，如腳趾開始，逐步向近端足踝、小腿、手指延伸，這是典型以肢體末梢為主的分佈（length-dependent, distal predominance）。除了以肢體末梢為主的臨床表現，周邊神經病變也可以在個別神經的分佈範圍，如右側正中神經、左側尺神經的症狀，此稱非長度分布（non-length distribution）、或是非對稱性之多發型單一神經病變（mononeuropathy muleiplex）。對於小纖維神經病變，傳統的檢查只能依據病人主觀的症狀描述，缺少量化的評估，不像大纖維神經病變可以使用神經傳導檢查（nerve conduction studies）。從1990年代開始，科技的進步，逐漸發展出：（1）感覺神經功能量化檢查（quantitative sensory testing）作為心理物理（psychophysics）的評估；（2）皮膚切片定量表皮神經為基礎的病理檢查；（3）痛覺誘發電位（pain evoked potential）為依據的神經生理檢查，並逐步擴產到：（4）功能性磁振造影（functional magnetic resonance imaging, fMRI）的神經影像檢查，作全面性的整合評估檢測平台。現有對於小纖維神經病變的治療，是以神經病變痛的調控緩解症狀，包括：（1）抗癲癇藥物；（2）抗憂鬱藥物；（3）類嗎啡類藥物；（4）局部貼片。這些檢測可以提供以藥物為基礎的精準醫學治療。自1990年代、這30年來，雖然檢查、藥物開發有長足的進步，但仍然未臻完美，未來包括神經病理、生化、生理、藥理的研究，可以對於小纖維神經病變的精準治療提供基礎與契機。

Sensory nerves are classified into small-diameter nerve (small fiber for pain and thermal sensations) and large-diameter nerves (large fiber for proprioceptive and position sensations) with different functions and consequences if nerve degeneration (neuropathy) develops: small fiber neuropathy and large fiber neuropathy respectively. In addition to a loss of temperature sensations as negative symptoms, patients with small fiber neuropathy also had neuropathic pain as positive symptoms due to neuronal hyper-excitability. Typical small fiber neuropathy due to diabetes and chemotherapy etc, presents with either (1) length-dependent polyneuropathy, i.e. starting from feet and extending to legs and palms or (2) non-length-dependent mononeuropathy multiplex. In contrast to large neuropathy which is traditionally assessed with nerve conduction studies, objective and quantitative evaluations for small fiber neuropathy were lacking till 1990+. Over the last three decades, the advancement of technology enabled multi-disciplinary examinations to form a comprehensive platform for nerve degeneration and neuropathic pain in small fiber neuropathy, consisting of (1) skin biopsy for pathology of innervation, (2) quantitative sensory testing for psychophysical aspects, (2) pain evoked potential for neurophysiology, and (4) functional magnetic imaging (fMRI) for brain plasticity after peripheral nerve degeneration. Currently available therapies for neuropathic pain in small fiber neuropathy include anticonvulsants, antidepressants, opioid drugs, and patches of local anesthetic agents. So far, the treatments for neuropathic pain are not satisfactory. Further development of therapeutic strategies will rely on the incorporation of these examinations to investigate the unique characters of each patient for precision treatment.