Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model

Abstract

Netherlands ALS Foundation.

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis

“…The Cox proportional‐hazard regression analysis was performed via the backward method with a P ‐value threshold of 0.157, with the time to event being the time from blood sampling to death . Based on a recent study of prognostic factors in ALS , the following parameters were included as survival variables into the multivariate Cox regression: the tertiles of the serum levels of NfL, the disease progression rate stratified as slow, intermediate and fast, the number of regions with UMN and LMN degeneration, age at blood sampling, the FVC, gender, the diagnostic delay, the C9orf72 status, FTD status and the site of onset. The exclusion criteria for the Cox regression were a follow‐up shorter than a year (sampling between December 2016 and 2017) and, for the multivariate Cox regression, a time difference among the date of ALSFRS‐R, EMG and FVC with the date of blood sampling greater than 3 months.…”

“…The diagnosis of ALS was based on the Awaji and revised El Escorial criteria [3,5,10] (Table 1). Among those patients, 15 were C9orf72 mutation carriers and 15 were diagnosed with frontotemporal dementia (FTD). In addition, 11 patients were diagnosed with primary lateral sclerosis (PLS) and six patients were diagnosed with progressive muscular atrophy (PMA) ( Table 2).…”

Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs

“…In this context, a recent report in Journal Lancet concludes that classification of patients into very short, short, intermediate, long, or very long to reach an overall outcome (end of life or respiratory events) after symptom and onset helps the stratification of patients in RCTs and assists clinicians in obtaining an estimate of life expectancy for every patient with ALS in a personalized way, and thereby achieving ambitious precision ALS goals. 61…”

Survival prediction models in motor neuron disease

“…DT MRI measures were crucial to improve prognostic accuracy when only ALS patients were considered. Compared with the large number of studies assessing the diagnostic value of advanced structural MRI [18]. To our knowledge, this is the first study that aimed to develop a similar When the whole MND cohort was considered, the main clinical predictor of survival was a PUMN or PLMN presentation, which, together with diagnostic delay, yielded an AUC of 0.79 for survival prediction at 4 years.…”

“…This approach allows a categorical classification into a priori defined survival classes, but does not estimate the expected survival time at a single‐patient level. A recent large multicenter study developed a multivariable Royston–Parmar survival model using clinical and cognitive features in ALS patients, allowing the data‐driven identification of survival groups, showing good reproducibility across cohorts . To our knowledge, this is the first study that aimed to develop a similar prognostic model by the combination of multimodal neuroimaging with clinical and cognitive features.…”