Abstract Details

Title Naturally-Occurring Prognostic Subgroups within the ALS Population: A Data-Led Approach

Topic Anterior Horn

Presentation(s) P07 - (-)

Poster/Presentation
Number 078

Objective

Background BACKGROUND: ALS is a neurodegenerative disorder characterized by a highly variable rate of motor progression. Identification of reliable prognostic predictors would facilitate appropriate timing of medical interventions and effective patient stratification in clinical trials.

Design/Methods DESIGN/METHODS: A population-based, case-control longitudinal study design was used.The motor and cognitive aspects of the disease were prospectively documented in a large population-based sample of ALS patients. Neuropsychological performance of ALS patients was compared to age, sex, and education matched healthy controls. Cluster analysis was applied to the motor data (survival time and prospectively estimated rates of motor progression) to identify prognostic subgroups. This was followed by an investigation of the characteristics and predictors of these subgroups.

Results RESULTS: Cluster analysis of 88 patients with no evidence of C9orf72 repeat expansion suggested the presence of three prognostic subgroups, with the following median survival times: (1) 15 month (95%CI 11.6-18.4); (2) 20 months (95%CI 17.4-22.6); and (3) 60 months (95%CI 27.5-92.5, p<0.0001). Characteristics of the subgroup with the worst prognosis were faster bulbar and respiratory progression compared to the other two subgroups (p<0.0001), significant cognitive impairment compared to healthy controls at baseline, and rapid cognitive decline with time. Reliable predictors of the prognostic subgroups included gender (p=0.013), executive dysfunction (p=0.005), the recently proposed King's College Staging System (p=0.04). Using these three parameters, the positive predictive value for the subgroup with the poorest prognosis was 69.6% and the negative predictive value was 80.0%.

Conclusions CONCLUSIONS: Interrogation of a data-set generated using a deeply phenotyped ALS patient cohort suggests the presence of three prognostic subgroups within the C9orf72 negative population. Clinical and neuropsychological data gathered at the first evaluation of ALS patients may reliably predict poor prognosis.

Authors/Disclosures
Marwa Elamin, MD, PhD (University College Hospital Galway) PRESENTER	Dr. Elamin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche .
Peter Bede, MD, PhD (Academic Unit of Neurology)	Dr. Bede has nothing to disclose.
Susan C. Byrne, MD	No disclosure on file
Niall Pender, PhD	No disclosure on file
Orla Hardiman, MD, DSc, FRCPI, MRIA, FAAN (Trinity Biomedical Sciences Institute)	Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.
Seward B. Rutkove, MD, FAAN	Dr. Rutkove has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Myolex, Inc. Dr. Rutkove has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neuorlogy . The institution of Dr. Rutkove has received research support from NIH. The institution of Dr. Rutkove has received research support from NASA. The institution of Dr. Rutkove has received research support from Blavatnik Family Foundation. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received intellectual property interests from a discovery or technology relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received publishing royalties from a publication relating to health care. Dr. Rutkove has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with NIH.

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