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.

What does the ALSFRS-R really measure? A longitudinal and survival analysis of functional dimension subscores in amyotrophic lateral sclerosis

“…Slopes were calculated using the common convenience method for calculating ALSFRS-R slope=(48—ALSFRS-R/time from onset) based on the first ALSFRS-R for each person, as this methodology has been reported in prognostic models8 9 and can be calculated from a single score. This method was extended to produce convenience estimates for ALSFRS-R_bulb, ALSFRS-R_motor and ALSFRS-R_resp slopes.…”

A clinical tool for predicting survival in ALS

“…Further, most use a Cox's proportional hazards model; in a similar study of mortality in ALS,10 the use of such a model was examined and found to be ‘clearly inadequate’, as the effects of predictors including riluzole use were found to vary with time from diagnosis, violating the proportional hazards assumption. We know of only two explicit predictive models, of which one11 requires data which would not usually be available in the clinic, and the other12 omits important predictors.…”

Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis

“…Female sex, higher diagnostic certainty, lower score on the ALS Functional Rating Scale, and greater rate of disease progression after diagnosis may be associated with a worse prognosis, but the associations are less consistent (5)(6)(7)(8). More recently, rate of decline of ALS functional rating score before diagnosis and executive dysfunction have also been discussed as predictors of poor prognosis for ALS (9).…”