Predicting prognosis in amyotrophic lateral sclerosis: a simple algorithm

Abstract

The objective of the study was to develop and validate a practical prognostic index for patients with amyotrophic lateral scleroses (ALS) using information available at the first clinical consultation. We interrogated datasets generated from two population-based projects (based in the Republic of Ireland and Italy). The Irish patient cohort was divided into Training and Test sub-cohorts. Kaplan-Meier methods and Cox proportional hazards regression were used to identify significant predictors of prognoses in the Training set. Using a weighted grading system, a prognostic index was derived that separated three risk groups. The validity of index was tested in the Irish Test sub-cohort and externally confirmed in the Italian replication cohort. In the Training sub-cohort (n = 117), significant predictors of prognoses were site of disease onset (HR = 1.7, p = 0.012); ALSFRS-R slope prior to first evaluation (HR = 2.8, p < 0.0001), and executive dysfunction (HR = 2.11, p = 0.001). The risk group system generated using these results predicted median survival time in the Training set, the Test set (n = 87) and the Italian cohort (n = 122) with no overlap of the 95 % CI (p < 0.0001). In the validation cohorts, a high-risk classification was associated with a positive predictive value for poor prognosis of 73.3-85.7 % and a negative predictive value (NPV) for good prognosis of 93.3-100 %. Classification into the low-risk group was associated with an NPV for bad prognosis of 100 %. A simple algorithm using variables that can be gathered at first patient encounter, validated in an independent patient series, reliably predicts prognoses in ALS patients.

Fig. 1

This figure illustrates how to calculate of the ALS Prognostic Index for individual patients and how to allocate patients to the ALS risk groups

Fig. 2

Figure shows Kaplan–Meier plots for survival probabilities in the Irish test cohort (a) and Italian cohort (b). In all cases ALS patients were stratified by ALS prognostic risk group. Dashed line low-risk group, dotted line medium-risk group, and solid line high-risk group

Fig. 3

This figure illustrates proportion of patients in each cohort stratified by API risk group who a died within 25 months of symptom and b had a survival time of 50 months or more

Fig. 4

Figure shows Kaplan–Meier plots for survival probabilities in the Irish test cohort (a) and Italian cohort (b). In all cases ALS patients were stratified by ALSFRS-R slope only. Solid line ALSFRS-R slope of 1.0 points/month or more, dotted line ALSFRS-R slope 0.50–0.99 points/month, dashed line ALSFRS-R slope 0.25–0.49 points/month, dash and dot line ALSFRS-R slope <0.25 points/month