Clinical and genetic characteristics associated with ALS diagnostic timeline: a population-based study
Ton Fang1, Peter Pacut1, Yuyao Sun2, Jeff Gao1, Brooke McNeilly1, Shravan Sivakumar1, Eduardo Inacio Nascimento Andrade1, Abigail Bose1, Bianca Trombetta1, Mehdi Ghasemi1
1Department of Neurology, University of Massachusetts Chan Medical School, 2Department of Neurology, University of Massachusetts Chan Medical School; Department of Neurology, University of Kentucky
Objective:
We studied the impact of clinical and genetic risk factors on the diagnostic timeline of ALS.
Background:
Amyotrophic lateral sclerosis (ALS) has a mean survival of 3 to 5 years, but despite this diagnosis can take 10 to 16 months, leading to delays to treatment.
Design/Methods:
Baseline characteristics, family history, gene testing, onset location, time from symptom onset to diagnosis and first doctor visit to suspected ALS was collected. We used multiple regression to assess for interaction of these factors on ALS diagnostic timeline. Sharpio Wilks test was used to test for normality and non-normally distributed groups were tested using Wilcoxon rank sum or non-parametric Kruskal-Wallis test and normalized groups using two sample t-test and analysis of variance (ANOVA). We analysed a subgroup of patients with genetic testing and compared positive/negative tests, sporadic/familial and ALS-related genes to time for diagnosis.
Results:
We analyzed 448 patients diagnosed with ALS at University of Massachusetts Medical Center between January 2007 and December 2021. Median time to ALS diagnosis was 12 months and remained unchanged from 2007 to 2021 (p=0.20). Diagnosis was delayed in patients with sporadic compared with familial ALS (mean months [standard deviation, SD], 16.5 [13.5] and 11.2 [8.5], p<0.001); and cognitive onset (41 [21.26]) was slower to diagnose compared to bulbar (11.9 [8.2]), limb (15.9 [13.2]), respiratory (19.7 [13.9]) and ALS with from multiple onset locations (20.77 [15.71], p<0.001). 134 patients had gene testing and 32 tested positive (23.8%). Gene testing (p=0.23), a positive genetic test (p=0.16), different ALS genes (p=0.25) and sporadic (p=0.92) or familial (p=0.85) ALS testing genetically positive did not change speed to diagnosis.
Conclusions:
Time for ALS diagnosis remained unchanged from 2007 to 2021, bulbar, limb onset and familial ALS made for faster diagnosis. Genetic testing did not affect diagnostic speed but future improvements to ALS screening may improve diagnostic delay.