運動神經元疾病的臨床表現、診斷與致病原因

Clinical Manifestation, Diagnosis and Etiologies of Motor Neuron Diseases

肌萎縮性側索硬化症（ALS）是一種運動中樞、皮質脊髓束、腦幹與脊髓的運動神經元退化死亡造成漸行性肌肉麻痺無力的疾病。發生率在西方國家是每10 萬人口中，每年會有1.47 至2.7 個新病例產生，而盛行率是每10 萬人口有2 至7 人。平均發病年齡50 至60 歲，男性罹患此病的機會是女性的1.3 至1.5倍，大多數患者屬於散發性ALS，10％的患者具有體染色體家族遺傳。症狀早期常以單側上肢或下肢的近端或遠端肌肉無力與萎縮為主要表現，逐漸病人因無力萎縮的肢體與增強性的肌肉張力造成了手的動作變得遲鈍笨拙與下肢行走困難。約有二成的病人會以說話與吞嚥困難等症狀為起始表現。3 至5 年內病人最終將因嚴重的全身無力導致呼吸困難而死亡。ALS 的診斷端賴臨床的病史、神經理學檢查、肌電圖異常與核磁共振攝影檢查排除頸椎壓迫所引起的症狀。ALS 的病理變化主要是大腦皮質、腦幹運動核和脊髓前角的運動神經元的退化和死亡，引起所支配的肌纖維去神經化的萎縮。ALS 的運動神經元常見有細胞質包涵體，由神經細纖維所組成的Bunina body 包涵體，是ALS 特有的變化。致病原因不明，遺傳因素、重金屬中毒、SOD1 基因突變、激活的microglia 細胞、病毒的侵犯、生長激素的缺乏與過度的興奮毒性是可能的危險因子。ALS 的治療包括症狀支持、緩和與多科合作療法，riluzole 是目前證實唯一可以提高患者存活率的藥物。

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neuron in the motor cortex, corticospinal tracts, brainstem and spinal cord. The incidence is 1.47 to 2.7 per 100,000/year and prevalence is 2 to 7 per 100,000 persons in Western countries. The mean age of onset for sporadic ALS is about 50-60 years. Overall, there is a slight male prevalence (M:F ratio 1.3-1.5:1). Most ALS cases are sporadic but 10% of cases are familial. Patients with typical ALS present symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Twenty percent of ALS patients present bulbar onset showing dysarthria and dysphagia. Paralysis is progressive and leads to death due to respiratory failure within 3-5 years for ALS cases. The diagnosis is based on clinical history, neurological examination, electromyography and exclusion of ALS-mimics (e.g. cervical spondylotic myelopathy) by appropriate investigations. The pathologic hallmarks comprise motor neuron degeneration and death with gliosis replacing lost neurons. Cortical motor cells disappear leading to retrograde axonal loss and gliosis in the corticospinal tract. The spinal cord becomes atrophic. The affected muscles show denervation atrophy. Intracellular inclusions in degenerating neurons and glia are frequent neuropathological findings of ALS. Bunina bodies are unique to ALS and consist of neurofilament aggregates. The etiology of ALS is unknown. A number of potential mechanisms have been proposed including genetic factors, toxins, SOD1-mediated toxicity, microglial activation, viral infections, growth factor deficiency and excitotoxicity. The management of ALS is supportive, palliative, and multidisciplinary. Riluzole is the only drug that has been shown to extend survival.