ALSFRS-R score and its ratio: A useful predictor for ALS-progression

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. To determine predictors of survival, we studied different parameters in our ALS Database including 479 patients. The effects of individual prognostic factors of survival were studied using Kaplan–Meier life table. The prognostic value of each factor of interest was expressed in terms of a hazard ratio. Survival from symptom-onset ranged from 4 months up to 11.9 years. Gender had no effect on survival in our cohort. However, age, site of onset, forced vital capacity, symptom duration and ALSFRS-R score at the first visit were independent prognostic factors in our population (log-rank p < 0.01). The ratio of ALSFRS-R score between first symptom and first examination, during whole disease or within 100 days, correlates with survival time.

We conclude that the ratio of ALSFRS-R score within 100 days is a useful parameter for clinical trials and daily clinical work in a tertiary ALS-clinic.

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of upper and lower motor neurons with a progressive limbic or bulbar muscular weakness and wasting. The median survival from first symptom in ALS ranges from 2 to 4 years [1], but the survival of individual ALS-patients has a wide variety and is considered difficult to predict in individual cases [2]. Moreover, this variety of survival and in particular, long-term survival impairs the results of clinical trials. Therefore, predictors of survival are subjects of great interest. Covariates of survival are age of onset, site of onset, respiratory function and time from symptom onset to diagnosis [3], [4], [5], [6], [7], [8], [9], [10]. Gender has also been reported to be a predictor in some studies [5], [11]. Recently, the ALSFRS-R (Amyotrophic lateral sclerosis functional rating scale revised) score and its progression rate have been debated as survival predictors [7], [12]. The ALSFRS-R is a well-established and widely distributed score for the functional status of patients with ALS. It is based on 12 items, each of which is rated on a 0–4 point scale. The rate of total functional disability thus ranges from 0 (maximum disability) to 48 (normal) points. In addition to survival, it has been a further outcome measure [4], [13], [14], [15], [16]. The Appel Score is another clinical scoring system for ALS-patients [17] and its progression rate has also been used as a potential prognostic factor in ALS [1], [18]. Factors which can predict progression and survival in ALS are important for designing new trials and correcting inaccuracies. To assess potential predictors of survival we studied different parameters in our ALS Database, including age, gender, site of onset, forced vital capacity (FVC), symptom duration and the ALSFRS-R and its changes over time.