title: An autopsy case of frontotemporal lobar degeneration with the appearance of fused in sarcoma inclusions (basophilic inclusion body disease) clinically presenting corticobasal syndrome.
abstract: We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD-FUS), clinically presenting corticobasal syndrome (CBS). A 54-year-old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right-side dominant limb-kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left-dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb-kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA-binding protein-associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA-binding protein of 43 kDa (TDP-43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD-FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP-43 inclusions (FTLD-TDP), Pick's disease, Lewy body disease and CJD. However, FTLD-FUS (BIBD) has been rarely reported. Our case suggested further pathological heterogeneity in CBS than had previously been reported. It is necessary to consider FTLD-FUS (BIBD) as a background pathology for CBS in the future.
authors.affiliation: Departments of Neurology and Clinical Research Center, National Hospital Organization, Miyagi Hospital, Watari-gun, Miyagi.
authors.forename: Arifumi
authors.identifier: http://orcid.org/0000-0003-2464-2078
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology and Laboratory Medicine, National Hospital Organization, Sendai Medical Center.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Research, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Saitama, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Fukatsu
authors.affiliation: Departments of Neurology and Clinical Research Center, National Hospital Organization, Miyagi Hospital, Watari-gun, Miyagi.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Neurology, National Hospital Organization, Sendai Medical Center, Sendai.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Departments of Neurology and Clinical Research Center, National Hospital Organization, Miyagi Hospital, Watari-gun, Miyagi.
authors.forename: Kinya
authors.initials: K
authors.lastname: Hisanaga
mesh_terms: D001072:Apraxias / Q000473:pathology; D001284:Atrophy; D001344:Autopsy; D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000235:genetics / Q000523:psychology*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D018450:Disease Progression; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D005911:Gliosis / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012509:Sarcoma / Q000235:genetics / Q000473:pathology* / Q000523:psychology
keywords: TAF15; basophilic inclusion body disease; corticobasal syndrome; frontotemporal lobar degeneration; fused in sarcoma