Age at onset influences on wide-ranged clinical features of sporadic amyotrophic lateral sclerosis

Purpose: To profile the detailed clinical features of sporadic amyotrophic lateral sclerosis (ALS) on large-scale samples in Japan. Methods: We assessed the clinical features of sporadic ALS patients in Japan, based on the nationwide registration system of the Ministry of Health, Labor and Welfare of Japan. We described 3428 new cases registered cases between 2003 and 2006 to analyze initial symptoms and related clinical features, 4202 cases registered in the single year of 2005 to describe the cross-sectional overview of the ALS patients, and a total of 2128 cases with tracheostomy positive pressure ventilation (TPPV) from all of the registration data from 2003 to 2006 to describe the features of ALS patients with TPPV. Results: The patients with an older age at onset progressed more rapidly to the TPPV stage than those with a younger age at onset. The subpopulation of patients with long-standing TPPV showed ophthalmoplegia, while its appearance rate was less in the patients with an older age at onset than in those with a younger age at onset. Furthermore, age at onset strongly influenced the frequency of initial symptoms: dysarthria, dysphagia, neck weakness and respiratory disturbance were more frequent in patients with an older age at onset, while upper or lower limb weakness was observed more frequently in patients with a younger age at onset. In addition, those initial symptoms were still the most prominent at the follow-up stage, suggesting that the initial symptoms determine the major clinical features even in advanced illness. Conclusions: Our present study demonstrated that symptomatic features of ALS are strongly influenced by the age at onset by the large scale of samples.