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In patients with amyotrophic lateral sclerosis, age and forced vital
capacity progression rate predicted survival
Clinical Problem: A 60 year old male presents with an eleven month history of progressive
left leg weakness associated with upper and lower motor neuron signs and EMG/NCS criteria
for definite amyotrophic lateral sclerosis.
Clinical Question: Which patient characteristics and clinical signs predict improved survival in ALS?
Search Strategy:
Pubmed: “amyotrophic lateral sclerosis” (MeSH) and “prognosis” (text word), or “survival analysis” and “survival rate”
(both MeSH headings) in place of “prognosis”. Out of 340 articles, 16 articles in english, 1 in spanish, and 1 in
japanese, were relevant. Expert opinion revealed 2 additional articles. Five articles prospective population-based
studies focused on clinical patient characteristics (versus electrophysiology). The remaining studies were retrospective.
The selected article was chosen for its inclusion of important clinical variables and its strict utilization of the El
Escorial Diagnostic Criteria (EEDC) (Chiò et al.).
Clinical Bottom Lines:
1. 5 year overall survival for patients with definite or probable ALS was 24.7% (SE=3.1%). 3 year survival was
40.5% (SE=3.5%).
2.
Variables that predicted poorer survival were: functional vital capacity progression rate, rate of progression of
lower limb weakness, older age, rapid early bulbar progression and EEDC indicating definite ALS diagnosis.
3.
Gastric feeding tube placement and riluzole therapy were associated with longer survival. A randomized trial
would be required, however, to demonstrate the efficacy of these interventions.
The Evidence:
221 patients with ALS were identified prospectively from the practices of all neurologists in the Piemonte and Valle
d’Aosta region of northwestern Italy. Patients were assessed every 3 to 6 months. Clinical variables were outlined at
study outset and only patients meeting EEDC for definite or probable ALS were included in the survival analysis. Case
ascertainment details and demographics of this patient population were previously published and were consistent with
[1] [2] [3] [4]
other prospective studies (Appendix , , , ).
Data:
Outcome of ALS: Multivariate analysis (Adapted from Chio et al., 2002)
Variables
FVC % progression rate*
<3%
≥3%
PEG+
Yes
No
MRC, lower limbs, progression rate*
1.5
≥1.5
Age groups (y)
≤50
51-60
61-70
≥71
Hazard ratio
p Value
Reference
5.72
0.0001
reference
3.89
0.0004
reference
2.32
0.0011
reference
1.40
1.95
2.72
0.007
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Bulbar score progression rate**
<0.1
≥0.1
EEDC at diagnosis
Probable + possible + suspected
Definite
Riluzole therapy
Yes
No
reference
1.62
0.009
reference
1.55
0.01
reference
1.36
0.05
*Mean number of point lost per month in the 6 months after diagnosis.
**Included as time-dependent variable.
FVC=forced vital capacity; PEG=percutaneous endoscopic gastrostomy; MRC=Medical Research Council; EEDC=El
Escorial Diagnsotic Criteria
Comments:
1. The incidence of ALS in the population described in Chiò et al. is comparable to those in similar prospective
studies.
2.
Follow up was adequate.
3.
Outcome evaluations were not blinded.
4.
Although 95% confidence intervals were not calculated for the Hazard ratios, p values were provided.
5.
Increasing age and bulbar onset have previously been described as predictors of decreased survival (3,4,5).
6.
7.
Variables such as marital status and physical health were not included in this study, although they have been found
[5]
to be prognostic in other studies ( ).
Non-invasive ventilation was not significantly related to survival.
Reference:
Chiò et al. Early symptom progession rate is related to ALS outcome; a prospective population-based study. Neurology
2002;59:99-103.
Key Words: ALS, motor neuron disease, prognosis
Appraiser: Lawrence Korngut and the UWO Evidence Based Neurology Group
Date Appraised: February 2005
Copyright 2002-2005
Evidence Based Neurology Group
University of Western Ontario
Appendix:
Additional relevant articles
[1]
. Traynor et al. Incidence and prevalence of ALS in Ireland, 1995-1997: a population-based study. Neurology 1999;52:504-509.
[2]
. Scottish Motor Neuron Disease Research Group. The Scottish motor neuron disease register: a prospective study of adult onset
motor neuron disease in Scotland. Methodology, demography and clinical features of incident cases in 1989. J Neurol Neurosurg
Psychiatry 1992;55:536-541.
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[3]
. McGuire et al. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology
1996;47:571-573.
[4]
. Forbes et al. Unexpected decline in survival from amyotrophic lateral sclerosis/motor neuron disease. J Neurol Neursurg
Psychiatry 2004;75:1753-1755.
[5]
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. Del Aguila et al. Prognosis in amyotrophic lateral sclerosis; a population-based study. Neurology 2003;60:813-819.