University of Oulu

Korhonen, V. E., Remes, A. M., Helisalmi, S., Rauramaa, T., Sutela, A., Vanninen, R., … Leinonen, V. (2019). Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus. Dementia and Geriatric Cognitive Disorders, 47(1–2), 91–103. https://doi.org/10.1159/000497306

Prevalence of C9ORF72 expansion in a large series of patients with idiopathic normal-pressure hydrocephalus

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Author: Korhonen, Ville E.1; Remes, Anne M.2,3,4,5; Helisalmi, Seppo2;
Organizations: 1Department of Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
2Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland
3Medical Research Center, Oulu University Hospital, Oulu, Finland
4Department of Neurology, Kuopio University Hospital, Kuopio, Finland
5Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
6Institute of Clinical Medicine - Pathology, School of Medicine, University of Eastern Finland and Department of Pathology, Kuopio University Hospital, Kuopio, Finland
7Department of Radiology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
8A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
9Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2019092629904
Language: English
Published: Karger, 2019
Publish Date: 2020-05-01
Description:

Abstract

Background/Aims: The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH).

Methods: We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age > 65 years).

Results: While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52–67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers.

Conclusion: This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.

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Series: Dementia and geriatric cognitive disorders
ISSN: 1420-8008
ISSN-E: 1421-9824
ISSN-L: 1420-8008
Volume: 47
Pages: 91 - 103
DOI: 10.1159/000497306
OADOI: https://oadoi.org/10.1159/000497306
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
3124 Neurology and psychiatry
Subjects:
Funding: The study was supported by research grants from the Academy of Finland, the Kuopio University Hospital VTR Fund (5252614), Sigrid Juselius Foundation, the Finnish Medical Foundation, Olvi Foundation, Kuopio University Hospital Research Foundation, Emil Aaltonen Foundation, and the Finnish cultural foundation – North-Savo regional Fund.
Copyright information: © 2019 S. Karger AG, Basel. This is the peer-reviewed but unedited manuscript version of the following article: Korhonen, V. E., Remes, A. M., Helisalmi, S., Rauramaa, T., Sutela, A., Vanninen, R., … Leinonen, V. (2019). Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus. Dementia and Geriatric Cognitive Disorders, 47(1–2), 91–103. https://doi.org/10.1159/000497306. The final, published version is available at https://doi.org/10.1159/000497306.