Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus
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CitationKorhonen, VE. Remes, AM. Helisalmi, S. Rauramaa, T. Sutela, A. Vanninen, R. Suhonen, NM. Haapasalo, A. Hiltunen, M. Jääskeläinen, JE. Soininen, H. Koivisto, AM. 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. 10.1159/000497306.
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.