title: Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.
abstract: Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated 'dementia dominant group', followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated 'limb weakness group', followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|2 Department of Therapeutics for Intractable Neurological Disorders, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Jun
authors: J
authors: Sone
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.|3 Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Mie, Japan.
authors: Keiko
authors: K
authors: Mori
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Tomonori
authors: T
authors: Inagaki
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Ryu
authors: R
authors: Katsumata
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Shinnosuke
authors: S
authors: Takagi
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Satoshi
authors: S
authors: Yokoi
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Kunihiko
authors: K
authors: Araki
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Toshiyasu
authors: T
authors: Kato
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Tomohiko
authors: T
authors: Nakamura
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Haruki
authors: H
authors: Koike
authors: 4 Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Hiroshi
authors: H
authors: Takashima
authors: 4 Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Akihiro
authors: A
authors: Hashiguchi
authors: 5 Department of Neurology, Ibaraki Prefectural University of Health Sciences, Ami, Ibaraki, Japan.
authors: Yutaka
authors: Y
authors: Kohno
authors: 6 Department of Neurology, National Hospital Organization Kure Medical Centre, Kure, Hiroshima, Japan.
authors: Takashi
authors: T
authors: Kurashige
authors: 7 Department of Neurology, Ota Memorial Hospital, Fukuyama, Hiroshima, Japan.
authors: Masaru
authors: M
authors: Kuriyama
authors: 8 Department of Neurology, University of Yamanashi, Kofu, Yamanashi, Japan.
authors: Yoshihisa
authors: Y
authors: Takiyama
authors: 8 Department of Neurology, University of Yamanashi, Kofu, Yamanashi, Japan.
authors: Mai
authors: M
authors: Tsuchiya
authors: 9 Department of Neurology, Kosei Chuo General Hospital, Tokyo, Japan.
authors: Naoyuki
authors: N
authors: Kitagawa
authors: 10 Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
authors: Michi
authors: M
authors: Kawamoto
authors: 10 Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
authors: Hajime
authors: H
authors: Yoshimura
authors: 11 Department of Neurology, Tottori Prefectural Central Hospital, Tottori, Japan.
authors: Yutaka
authors: Y
authors: Suto
authors: 11 Department of Neurology, Tottori Prefectural Central Hospital, Tottori, Japan.
authors: Hiroyuki
authors: H
authors: Nakayasu
authors: 12 Department of Neurology, National Hospital Organization Utano Hospital, Kyoto, Japan.
authors: Naoko
authors: N
authors: Uehara
authors: 12 Department of Neurology, National Hospital Organization Utano Hospital, Kyoto, Japan.
authors: Hiroshi
authors: H
authors: Sugiyama
authors: 13 Department of Neurology, Kanto Central Hospital, Tokyo, Japan.
authors: Makoto
authors: M
authors: Takahashi
authors: 14 Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
authors: Norito
authors: N
authors: Kokubun
authors: 15 Department of Neurology, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan.
authors: Takuya
authors: T
authors: Konno
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Masahisa
authors: M
authors: Katsuno
authors: 16 Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
authors: Fumiaki
authors: F
authors: Tanaka
authors: 17 Department of Neuropathology, Institute for Medical Sciences of Aging, Aichi Medical University, Nagakute, Aichi, Japan.
authors: Yasushi
authors: Y
authors: Iwasaki
authors: 17 Department of Neuropathology, Institute for Medical Sciences of Aging, Aichi Medical University, Nagakute, Aichi, Japan.
authors: Mari
authors: M
authors: Yoshida
authors: 1 Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan sobueg@med.nagoya-u.ac.jp.|18 Brain and Mind Research Center, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors: Gen
authors: G
authors: Sobue
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D003704:Dementia / Q000209:etiology*; D005260:Female; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology*; D019636:Neurodegenerative Diseases / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D010375:Pedigree; D055815:Young Adult
keywords: dementia; diffusion-weighted image; intranuclear inclusion; leukoencephalopathy; skin biopsy