The frontotemporal syndrome of ALS is associated with poor survival

• Published in: Journal of neurology 2016-12, Vol.263 (12), p.2476-2483
• Main Authors: Govaarts, Rosanne, Beeldman, Emma, Kampelmacher, Mike J., van Tol, Marie-Jose, van den Berg, Leonard H., van der Kooi, Anneke J., Wijkstra, Peter J., Zijnen-Suyker, Marianne, Cobben, Nicolle A. M., Schmand, Ben A., de Haan, Rob J., de Visser, Marianne, Raaphorst, Joost
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - complications; Amyotrophic Lateral Sclerosis - genetics; C9orf72 Protein; Cognition Disorders - etiology; Cognitive ability; Cohort Studies; Dementia; Disease; Female; Frontotemporal Dementia - complications; Frontotemporal Dementia - genetics; Frontotemporal Dementia - mortality; Frontotemporal Dementia - therapy; Humans; Male; Medicine; Medicine & Public Health; Mental Disorders - etiology; Middle Aged; Neurology; Neuropsychological Tests; Neuroradiology; Neurosciences; Noninvasive Ventilation - methods; Original Communication; Patients; Proteins - genetics; Psychiatric Status Rating Scales; Surveys and Questionnaires; Survival Analysis; Trinucleotide Repeats - genetics; Ventilators
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-016-8290-1

Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as >22 points on the ALS-Frontotemporal-Dementia-Questionnaire or ≥3 points on ≥2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on ≥2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53–5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44–3.65, p