Prognostic Predictors in ALS
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork Presbyterian Hospital, Cornell Campus. Dr. Rubin reports no financial relationship to this field of study.
Synopsis: Faster progression of ALS is predicted by older age, presentation with bulbar signs, or presentation with distal limb muscle weakness.
Source: Czaplinski A, et al. Predictability of Disease Progression in Amyotrophic Lateral Sclerosis. Muscle Nerve. 2006;34:702-708.
Among 1034 patients seen between 1984-2004 and registered in the amyotrophic lateral sclerosis (ALS) database at Methodist Neurological Institute, Houston, 832 with definite or probable ALS had undergone at least 2 Appel ALS (AALS) evaluations and were included in this study, undertaken to define predictors of disease progression, which was defined as a 20-point change in the AALS score. AALS score measures muscle strength, and arm, leg, bulbar, and respiratory function, with scores ranging from 30 (normal) to 164 (maximal dysfunction). Data collected and evaluated encompassed clinical, laboratory, and electromyographic results from the initial visit, subsequent significant interventions including percutaneous endoscopic gastrostomy (PEG), noninvasive ventilation (NIV), and tracheostomy, and tri-monthly quantitative disease progression evaluations using the AALS score and forced vital capacity (FVC). Statistical analysis included Kaplan-Meier, log-rank, and Cox model 1 and 2 tests.
Men comprised 69.3% (n = 570) and women 30.7% (n = 253) of the 832 patients included in this study. Average age of onset was 53.3 years, with bulbar onset experienced in 16.4% (n = 135). Initial examination was delayed on average 15.9 months from symptom onset. 27.3 % (n = 225) and 12.4% (n = 102) of patients underwent, or were placed on PEG or NIV, respectively. 41.9% (n = 345) were prescribed riluzole 50 mg twice daily, in most instances at the initial evaluation. Median time to 20-point AALS disease progression was 9 months, and was observed in 70.8% (n = 583). Slower deterioration significantly correlated with age under 40 years, male gender, and limb as opposed to bulbar onset. No prognostic difference was appreciated between arm or leg onset in the limb-onset group, but patients with proximal limb involvement trended toward slower progression compared to those with distal limb involvement. AALS score less than 60 at initial evaluation, slower rate of progression between first symptom and first examination, and longer time between first symptom and first examination were all significantly associated with slower progression. The latter clinical features, as well as age and site of symptom onset, are all independent covariates of ALS progression.
Commentary
Effective therapy remains the pot-of-gold at the end of the rainbow in amyotrophic lateral sclerosis (ALS) research. Transgenic SOD G93A mice have recently been reported to demonstrate later disease onset when given erythropoietin, a known inhibitor of neurodegenerative processes, including those resulting from hypoxia, inflammation, excitotoxic injury, and oxidative stress (Grunfeld JF, et al. Exp Neurol. 2006, doi:10.1016/j.expneuol.2006.11. 002). Survival was not affected and, surprisingly, only females benefited, raising doubt as to whether this finding is real, considering that no pathophysiologic gender difference is known to exist in ALS. Translating this into a tangible benefit for humans seems unlikely. Further research into ALS therapeutics remains most welcome.
Faster progression of ALS is predicted by older age, presentation with bulbar signs, or presentation with distal limb muscle weakness.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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