ALSの病型―臨床と病理

Phenotypes in ALS―Clinical Features and Pathology

はじめに

　従来，孤発性筋萎縮性側索硬化症（amyotrophic lateral sclerosis：ALS）は，下位運動ニューロン障害のみを示す脊髄性進行性筋萎縮症，球麻痺症状のみを示す進行性球麻痺，上位運動ニューロン障害のみを示す原発性側索硬化症，およびそれらのすべてがみられる古典型ALSに分類されることが多かった。いずれの亜型で発病しても数年後にはすべての症状が出そろい，古典型ALSになることが多いとされてきた。しかし，近年，病変が運動系を超えて感覚系を含めた広範な部位に及ぶ多系統病変型，dementiaを伴うALS，両上肢近位部および肩甲帯に筋萎縮が限局するflail arm syndromeなど，種々の非典型的なALSが報告されるようになり，ALSはheterogeneousな疾患単位から成ることから，ALS syndromeと呼称されることもある。今回は，古典型ALSおよびそれ以外の，種々の亜型の臨床および病理について，特徴を概説したい。

Abstract

　Typical amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is not hard to diagnose, but when it comes to atypical forms of MND which account for about 20% in clinical setting, we may face some difficulties in differentiating clearly between atypical forms of ALS/MND and other non-ALS diseases, such as multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy and cervical spondylosis.　There is striking phenotypic variation in sporadic ALS/MND, i.e. flail arm syndrome (brachial amyotrophic diplegia), pseudopolyneuritic form, hemiplegic type, ALS/MND with markedly extended involvement beyond the motor system, MND with basophilic inclusion bodies, spinal progressive muscular atrophy, primary lateral sclerosis, progressive bulbar palsy and motor neuron disease with dementia.　These variations must be recognized when physicians are to tailor advice on disease progression, prognosis, drug therapy, and care to the needs of the individual.　Clinical trials of new therapeutic agents have been performed, on the assumption that patients with ALS/MND have the same underlying etiology, addressing the heterogeneous population of the patients under a single diagnostic category.　This can be detrimental to the well-being of the individual, because clinical heterogeneity may mask drug effects in clinical trials.　The attempt to categorize subgroups based on the clinical and pathological background within the spectrum of ALS/MND may be a critical step in facilitating clinical research in ALS/MND.　Definition of clinicopathologic syndromes in patients with ALS/MND is an important challenging task.　It will be necessary to accumulate motor neuron disease cases with phenotypic variation and analyze them clinically and pathologically to elucidate whether various kinds of subgroups of motor neuron diseases lie on the same spectrum of ALS.