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

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Abstract

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.

Introduction

Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurodegenerative diseases affecting upper and lower motor neurons preferentially, and shows progressive muscle wasting of the limb, bulbar and respiratory musculatures. Almost half of ALS patients expire within three years of onset, primarily due to respiratory failure [1], [2], [3], [4], [5], [6]. Approximately 5–10% of ALS patients show a familial trait, while more than 90% of the patients are sporadic, and the causal mechanism of the motor neuron degeneration is largely unknown. Although many clinical trials of potential therapeutic agents for the treatment of sporadic ALS have been performed [7], effective therapeutics against motor neuron degeneration in ALS except for riluzole [8], [9] have not been developed. The clinical features of ALS have been established for the most part. However, many aspects of symptomatic manifestations such as the influence of age at onset on clinical features, the frequency of rare symptoms and many other symptomatic details have not been well characterized, particularly based on a nationwide scale sample. In Japan, the proportion of the ALS patients with TPPV is relatively higher than in other countries [10], [11]. Rare symptoms such as ophthalmoplegia are more frequently seen in those who receive TPPV to prolong survival [12], [13], so the clinical profile of ALS patients in Japan might have unique features. Data concerning the clinical features are important to establish an early diagnosis, treatment plan, and prognostic estimation, as well as to design clinical trials.

The aim of this study was to profile the detailed clinical features of sporadic ALS on large-scale samples in Japan.

Section snippets

Research design and methods

A nationwide registration of patients with intractable diseases including ALS has been conducted by the Ministry of Health, Labor and Welfare of Japan since 1974. When a patient is diagnosed as having ALS, the patient can apply for registration in this system, and receive financial support from the state for medical expenses incurred for the treatment of ALS, independent of the disease severity. In 2003, a data collection system was developed for research use of this registration system.

Clinical features of sporadic ALS patients

The mean age at onset was 65.4 ± 10.7 years, the male to female ratio was 1.37:1, and the mean duration from disease onset to registration was 1.5 ± 1.4 years. The initial symptom was dysarthria in 36.3%, dysphagia in 21.1%, weakness of neck in 7.1%, respiratory disturbance in 6.3%, weakness of the upper extremities in 48.1%, weakness of lower extremities in 34.1%, when allowing overlapping descriptions (Table 1). When we analyzed these demographic clinical features between male and female patient

Discussion

The results of the present study demonstrate the characteristic clinical profiles of Japanese sporadic ALS patients. A very high rate of Japanese ALS patients (29.3%) were under TPPV compared to patients in North America or Europe [10], [11], [17], [18] which are 2.1–5.4%, respectively. The frequency of patients showing rare symptoms such as ophthalmoplegia increased with disease progression, particularly under long-standing TPPV.

A striking observation in the present study is that the age at

Acknowledgements

This work was supported by Health and Labor Sciences Research grants for research on measures for intractable diseases and comprehensive research on Aging and Health by the Ministry of Health, Labor and Welfare, Japan.

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