本邦における筋萎縮性側索硬化症の病勢経過―厚生省特定疾患神経変性疾患調査研究班調査より

The natural course and prognostic factors of amyotrophic lateral sclerosis in Japan

　本邦における，代表的な神経内科医療機関における1985年以降10年間の，筋萎縮性側索硬化症による死亡例について，経過と予後因子の解析を行った。発症年齢は58.8±10.8歳と，以前の調査に比べ高齢化の傾向が認められた。全経過は40.6±33.1カ月であった。気管切開や人工呼吸器装着を行った群は，全経過49.1±37.2カ月であったが，行わなかった群は35.8±31.1カ月と明らかに短かった。一方，Cox回帰による予後因子の解析では，臨床型，発症年齢，医療機関受診までの期間，人工呼吸器装着などの医療行為の有無が，予後を決定する因子として抽出された。球型，高齢発症，発症から1年未満の医療機関受診，医療行為を受けないものの生存率が低いことが示された。

　Amyotrophic lateral sclerosis is a slowly, steadily progressive disease with poor prognosis. Recently, the prognosis of this disease has changed with progress in medical care including artificial ventilation, nutrition and a newly developed drug which is expected slowing the disease progress. Clarification of natural course of ALS patients under standard medical care at present is important for judgment of efficacy of interventions including new drugs and establishment of various socio-economical supports for patients and families.

　A working group in the research committee of CNS degenerative diseases, the Ministry of Health and Welfare of Japan, made a study on 612 ALS patients who died between 1985 and 1994 in hospitals where qualified neurologists worked with complete coverage of medical costs by medical insurance and governmental supports for the in-tractable diseases. Time courses of various factors were examined with Kaplan-Meier life-table method and extractions of factors contributing to time courses were made with Cox proportional hazards model.

　The mean age of onset for all patients was 58.8±10.8 years（common type 58.2±10.6, bulbar type 62.9±10.8 and pseudo-polyneuritic（lower limb onset）type 55.3±10.4）. The duration of disease was 40.6±33.1months（common type 42.2±34.6, bulbar type 32.3±27.2 and pseudo-polyneuriric type 46.3±30.5）. The mean age of onset was older and the duration of the disease was shorter significantly for the bulbar type than the other types. With tracheostomy and usage of respirator, the duration of the disease was significantly prolonged. The patients who were older with age at onset had a shorter duration of disease until death compared with the younger onset group. As for the periods from the disease onset to the various end points which included abolishment of upper limb function, inability to walk, anarthria, and start of artificial nutrition, tracheostomy, start of artificial ventilation, the bulbar type had a significantly shorter periods to anathria and to artificial nutrition than the other types. The pseudo-polyneuritic type had significantly longer periods to tracheostomy and to artificial respiration compared with the other types. There were 4 significant prognostic factors extracted from the Cox methods. They were the clinical type, age of onset, duration from onset to first medical examination, and duration from onset to tracheostomy or artificial respiration. The common type and the bulbar type had higher hazard ratio to the pseudo-polyneuritic type（1.18 times and 1.53 times respectively）. The age of onset was an important factor in amyotrophic lateral sclerosis：the hazard ratio of patients who developed the disease at the age more then 70 years was 3.96 times higher than those whose ages of onset were less than 40 years. The hazard ratio for the patients who visited a doctor for the first examination in less than one year from recognizing a symptom was 1.90 times higher than those who visited a doctor after more than one year. Without tracheostomy and an artificial respiration, the hazard ratio was 1.77 times higher than those received respiration assistance.

（Received：August 29, 2003）