Amyotrophic lateral sclerosis: Can we predict the course of disease?

Adam Czaplinski, S. H. Appel

Research output: Contribution to journalArticle

Abstract

A variety of prognostic factors have been associated with survival and disease progression in amyotrophic lateral sclerosis (ALS). With knowledge of factors that affect prognosis, clinicians can best advise their patients about their future clinical course. Moreover, the evaluation of early prognostic variables and the understanding of "at first exam" factors related to outcome may impact on the selection of patient cohorts for clinical trails. This goal is highly desirable, since the appropriate stratification of eligible patients based on the described predictors could result in reduction of sample size and study duration. It is well known that factors like age, sex, site of symptom onset and diagnostic delay, if imbalanced among treatment groups, may have a larger effect on outcome in the clinical ALS trials than the treatment itself. Thus, matching patients for established demographic and clinical parameters is particularly important in planning clinical trials. However, the randomisation for too many variables in the entry criteria may cause a large increase in the number of patients needed to balance the trial. Based on our own data we describe here the value of prognostic factors related to outcome in patients with ALS and review the literature. The identification of younger age, limb site of onset and longer FS-FE delay as predictors of prolonged survival in an ALS clinic population is in agreement with the findings of several earlier studies that were based on smaller groups of patients. Moreover, given the well-known correlation between disease progression and survival, our finding that age at onset, time between first symptom and first examination, and site of symptom onset also act as significant and independent covariates of disease progression might be expected, although it remains at odds with certain previous reports. Younger age at the time of symptoms onset is clearly associated with slower disease progression. In addition, younger patients survive significantly longer even after adjustment for potentially confounding factors. Patients with limb symptoms at onset survived remarkably longer than bulbar-onset patients. Moreover, in patients exhibiting limb symptoms at onset a slower disease progression was observed. We hypothesise that bulbar-onset patients may have shortened survival and faster disease progression from earlier involvement of respiratory muscles, a higher rate of respiratory complications, malnutrition and dehydration. The delay between symptom onset and first examination (FS-FE time or disease duration at diagnosis) was a robust predictor of survival and disease progression in our studies as in others. This delay was negatively related to hazard, i.e. positively related to length of survival - in other words, the longer the delay, the longer the survival and the slower the disease progression. In our patient population patients whose first examination was longer than 12 months after first symptom survived longer compared with patients who were first examined within 12 months after the onset of symptoms. Furthermore, longer time between first symptom (FS) and first examination (FE) was associated with slower disease progression. These findings support the hypothesis that the time between first symptom and first clinical examination may be a measure of the initial rate of disease progression. The more rapidly a patient initially deteriorates, the shorter the delay before the first symptom and first examination. These results suggest that fast progressing patients tend to seek medical care earlier, whereas those with slower disease progression are referred later or adapt to first symptoms for a longer time before they visit a medical care facility. In addition, we describe the prognostic value of several "at first examination" clinical parameters - baseline value of functional rating scales such as ALSFRS and Appel score, initial progression rate and baseline value of the forced vital capacity (FVC) - all of which may have significant utility in patient management.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalSchweizer Archiv fur Neurologie und Psychiatrie
Volume157
Issue number7
DOIs
StatePublished - Oct 2006

Keywords

  • Amyotrophic lateral sclerosis
  • Disease progression
  • Outcome measurement
  • Survival

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Clinical Neurology
  • Psychiatry and Mental health

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