Inês Alves, Marta Gromicho, Miguel Oliveira Santos, Susana Pinto, Mamede de Carvalho
{"title":"Assessing disease progression in ALS: prognostic subgroups and outliers.","authors":"Inês Alves, Marta Gromicho, Miguel Oliveira Santos, Susana Pinto, Mamede de Carvalho","doi":"10.1080/21678421.2024.2407412","DOIUrl":null,"url":null,"abstract":"<p><p><i>Background</i>: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. <i>Objectives</i>: This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS. <i>Methods</i>: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed. <i>Results</i>: ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients. <i>Discussion</i>: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyotrophic lateral sclerosis & frontotemporal degeneration","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21678421.2024.2407412","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. Objectives: This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS. Methods: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed. Results: ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients. Discussion: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.