AI Article Synopsis
- - The study focused on 1,330 Italian ALS patients to examine the clinical characteristics of those with an intermediate number of polyQ repeats, identifying 42 patients and 4 controls with ≥31 repeats, which was associated with a significant likelihood ratio of 10.4 compared to non-expansion cases.
- - Patients with ≥31 polyQ repeats exhibited distinct traits, including a greater tendency for spinal onset, shorter diagnostic delays, and faster progression of symptoms, along with higher instances of cognitive impairment and comorbid frontotemporal dementia.
- - The findings suggest that ALS patients with these genetic traits experience a more aggressive disease course and shorter survival, highlighting the potential for improved prognostic predictions and refined clinical trial designs in ALS research
Article Abstract
Objective: To detect the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) carrying an intermediate polyQ number of repeats in a large population-based series of Italian patients with ALS.
Methods: The study population includes 1330 patients with ALS identified through the Piemonte and Valle d'Aosta Register for ALS, diagnosed between 2007 and 2019 and not carrying and mutations. Controls were 1274 age, sex and geographically matched Italian subjects, identified through patients' general practitioners.
Results: We found 42 cases and 4 controls with≥31 polyQ repeats, corresponding to an estimated OR of 10.4 (95% CI 3.3 to 29.0). Patients with≥31 polyQ repeats (ATXN2+) compared with those without repeat expansion (ATXN2-) had more frequently a spinal onset (p=0.05), a shorter diagnostic delay (p=0.004), a faster rate of ALSFRS-R progression (p=0.004) and King's progression (p=0.004), and comorbid frontotemporal dementia (7 (28.0%) vs 121 (13.4%), p=0.037). ATXN2+ patients had a 1-year shorter survival (ATXN2+ patients 1.82 years, 95% CI 1.08 to 2.51; ATXN2- 2.84 years, 95% CI 1.67 to 5.58, p=0.0001). polyQ intermediate repeats was independently related to a worse outcome in Cox multivariable analysis (p=0.006).
Conclusions: In our population-based cohort, ATXN2+ patients with ALS have a distinctive phenotype, characterised by a more rapid disease course and a shorter survival. In addition, ATXN2+ patients have a more severe impairment of cognitive functions. These findings have relevant implications on clinical practice, including the possibility of refining the individual prognostic prediction and improving the design of ALS clinical trials, in particular as regards as those targeted explicitly to .
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606535 | PMC |
| http://dx.doi.org/10.1136/jnnp-2022-329376 | DOI Listing |
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