The frontotemporal syndrome of ALS is associated with poor survival.
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 < 0.001) in a multivariate model. Patients with an FS had a shorter survival after NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV.
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.a.govaarts@amc.uva.nl.
Rosanne
http://orcid.org/0000-0002-4550-3977
R
Govaarts
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Emma
E
Beeldman
Center for Home Mechanical Ventilation, University Medical Center Utrecht, Utrecht, The Netherlands.
Mike J
MJ
Kampelmacher
Neuroimaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Marie-Jose
MJ
van Tol
Department of Neurology, Brain Center Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Leonard H
LH
van den Berg
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anneke J
AJ
van der Kooi
Department of Home Mechanical Ventilation/Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Peter J
PJ
Wijkstra
Department of Intensive Care/Center for Home Mechanical Ventilation, University Medical Center, Erasmus MC, Rotterdam, The Netherlands.
Marianne
M
Zijnen-Suyker
Department of Respiratory Medicine/Center of Home Mechanical Ventilation Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Nicolle A M
NA
Cobben
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Medical Psychology, University of Amsterdam, Amsterdam, The Netherlands.
Ben A
BA
Schmand
Clinical Research Unit, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Rob J
RJ
de Haan
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Marianne
M
de Visser
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Neurology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
Joost
J
Raaphorst
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics; D000073885:C9orf72 Protein; D003072:Cognition Disorders / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D063087:Noninvasive Ventilation / Q000379:methods; D011506:Proteins / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D018911:Trinucleotide Repeats / Q000235:genetics
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
Amyotrophic lateral sclerosis; Behavioral changes; Cognitive impairment; Frontotemporal syndrome; Non-invasive ventilation; Survival
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