Factors predicting survival in ALS: a multicenter Italian study

Abstract

The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

Decreased Levels of Foldase and Chaperone Proteins Are Associated with an Early-Onset Amyotrophic Lateral Sclerosis

“…Age is a known risk factor for ALS. The majority of ALS patients have disease onset between 55 and 75 years of age, however patients with an age of onset <55 years and >75 years do exist and represent, respectively, the 22% and the 16% of all patients, as recently reported in a large multicenter Italian study (Calvo et al, 2016). Several factors, both genetic and environmental/exogenous, have been reported to modify age of onset in patients and animal models of ALS.…”

What causes amyotrophic lateral sclerosis?

“…Most studies find that longer survival is associated with younger age at symptom onset, presentation with limb dysfunction rather than swallowing or speech disturbance, and specific forms of ALS such as symmetrical patterns (e.g. flail arm syndrome) or upper motor neuron predominant forms 50 . Conversely, cognitive impairment comprising executive dysfunction, rapid weight loss, and respiratory involvement at first examination, although not necessarily respiratory onset, predict a poor prognosis 51– 58 .…”

Association between premorbid body mass index and amyotrophic lateral sclerosis: causal inference through genetic approaches

“…Among extensive epidemiological researches of ALS, an interesting and surprising observation is that ALS patients often encounter a loss of weight or a decrease of body mass index (BMI) at the early phase of diagnosis with many possible explanations [1, 13, 14, 15, 16, 17, 18, 19, 20]. Indeed, substantial change of BMI in ALS patients has been identified as an independent prognostic factor and has been linked to disease progression [13, 21, 22, 23, 24, 25, 26, 27]. For example, it is observed that a rapid reduction of BMI in ALS patients at the initial disease stage is a strong indicator of faster disease progression and shorter survival time; in contrast, nutritional intervention for ALS patients to increase BMI can prolong the survival time and leads to a delay in disease progression [28, 29, 30].…”