A total of 94 patients (51 men; mean survival from symptomatic onset 2.95 years (95% CI 2.54–3.35 years), mean survival from diagnosis 1.89 years, 95% CI 1.54–2.24 years) were identified of whom 13 (13.8%, 95% CI 7.9%–22.8%; 8 men) survived five years or more following disease onset (). The mean survival among LTS was 7.04 years (95% CI 6.14–7.94 years), and ranged from 5.11 to 9.35 years. The mean time from symptomatic onset to diagnosis for the entire population was 1.06 years (95% CI 0.86–1.26 years). LTS had a significantly longer mean time from symptomatic onset to diagnosis of 1.77 years (95% CI 0.95 to 2.58 years) as compared to non-LTS of 0.94 years (95% CI 0.75–1.13 years) (p=0.02). There were 6 patients who survived five years or longer from the time of diagnosis (6/94, 6.38%; 95% CI 2.38–13.38). All long term survivors identified in the study period have now died.
Survival function for all individuals with ALS in Olmsted County (1925–2004)
Bulbar symptoms were present in 30 percent of patients at onset (28 out of 92 patients with information about bulbar symptoms at onset; 95% CI 21.27–40.90%). Bulbar symptoms were less likely to be the initial presentation of LTS (2/13) as compared to non-LTS (26/79 = 33%), though this difference was deemed not to be statistically significant (p=0.34). Age at diagnosis, calendar year of disease onset, and sex did not influence the frequency of long term survival in ALS, as verified by logistic linear regression models. Six patients (6%) had a family history of ALS in a primary relative but no LTS had a known positive family history of ALS.
Presentation at the time of initial evaluation, among LTS, was lower motor neuron in 5, upper motor neuron in 1, and combined lower and upper motor neuron in 7. In 3 patients, the "flail limb" syndrome was the phenotypic presentation of ALS while in 2, bulbar palsy was the initial presentation (). El Escorial category at the time of first evaluation was available in the 81 patients who had an EMG. Patients were categorized as definite (0/13 LTS, 9/68 non-LTS), probable (7/13 LTS, 23/68 non-LTS), possible (0/13 LTS, 8/68 non-LTS), and suspected (1/13 LTS, 13/68 non-LTS). Some patients did not meet criteria for even the suspected category at first evaluation (5/13 LTS, 15/68 non-LTS). In some patients, precise information was unavailable to accurately ascribe an El Escorial category, retrospectively, for the time of first evaluation (0/13 LTS, 9/68 non-LTS).
Clinical features of long term survivors of amyotrophic lateral sclerosis in Olmsted County (1925–2004)
Comparisons based on a dichotomization of year of diagnosis to pre- and post-1964 suggested that neither the proportion of LTS (p=0.45) nor mean survival (p=0.26) varied over time. Dichotomization at the observed median year of diagnosis (1983) yielded similar results. Conclusions were also similar using other categorizations of year of diagnosis as well as using year of diagnosis as a continuous variable and adjusting for other potential confounders in a logistic regression model. In 13 patients, ALS was diagnosed before the advent of electromyography (EMG) and nerve conduction studies. There were no LTS in this group of early patients who did not undergo electrophysiologic evaluation.
An additional analysis was made in patients who presented with limb-only symptoms. Disease course was separated into (a) time from limb symptom onset to time of bulbar symptom onset and (b) time of bulbar symptom onset to death. The proportions of LTS and non-LTS who developed bulbar symptoms following limb onset were not significantly different. LTS had longer mean disease duration from both limb onset to bulbar onset and from bulbar onset to death as compared to non-LTS. Mean duration between limb onset and bulbar onset was 4.64 years in LTS (95% CI 2.93–6.35) compared to 1.33 years in non-LTS (95% CI 0.97–1.69) (p=0.04). Mean duration between bulbar onset and death was 2.28 years in LTS (95% CI 0.95–3.62) compared to 0.90 years in non-LTS (95% CI 0.70–1.10) (p=0.002).
No patient surviving five years or longer took riluzole, although four LTS were diagnosed after the drug became available. Overall, less than 10% of eligible patients took riluzole in Olmsted County. Similarly, no LTS had a tracheostomy placed.