TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features. (1st June 2021)

• Record Type: Journal Article
• Authors: Samanci, Bedia; Bilgiç, Başar; Gelişin, Özlem; Tepgeç, Fatih; Guven, Gamze; Tüfekçioğlu, Zeynep; Alaylıoğlu, Merve; Hanagasi, Hasmet A.; Gürvit, Hakan; Guerreiro, Rita; Hardy, John; Emre, Murat
• Is Part Of: European journal of neurology. Volume 28:Number 8(2021)
• Page Start: 2603
• Page End: 2613
• Publication Date: 2021-06-01
• Subjects: behavioral variant of frontotemporal dementia -- genetic analysis -- Nasu–Hakola disease -- neuroimaging -- TREM2; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.14908
• Languages: English
• ISSNs: 1351-5101

Abstract

Abstract: Background and purpose: Nasu–Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early‐onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. Method: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. Results: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. Conclusion: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling. Abstract : Nasu–Hakola disease is typically characterized by bone cysts and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia and other early‐onset dementias. Patients in our series presented with neurological symptoms, and only two of 14 patients had bone cysts. A combination of white matter changes, enlarged ventricles, atrophy of caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests Nasu–Hakola disease in patients with frontotemporal dementia syndrome. This result broadens the clinical spectrum associated with TREM2 mutations, which should be considered in patients with early‐onset dementia with leukoencephalopathy and atrophy even in the absence of symptomatic skeletal symptoms.