An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia and Neuropathy.
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ABSTRACT:
SUBMITTER: Yamaguchi N
PROVIDER: S-EPMC6306544 | biostudies-other | 2018 Aug
REPOSITORIES: biostudies-other
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An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia and Neuropathy.
Yamaguchi Nanaka N Mano Tatsuo T Ohtomo Ryo R Ishiura Hiroyuki H Almansour M Asem MA Mori Harushi H Kanda Junko J Shirota Yuichiro Y Taira Kenichiro K Morikawa Teppei T Ikemura Masako M Yanagi Yasuo Y Murayama Shigeo S Shimizu Jun J Sakurai Yasuhisa Y Tsuji Shoji S Iwata Atsushi A
Internal medicine (Tokyo, Japan) 20180810 23
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with marked variety in its clinical manifestations. While characteristic neuroimaging and skin biopsy findings are important clues to the diagnosis, autopsy studies are still important for confirming the exact disease features. We herein report the case of a patient who received an antemortem diagnosis of familial NIID with dementia-dominant phenotype that was later confirmed by an autopsy. Our report is the first ...[more]
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Project description:Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Because of variable clinical manifestations, NIID was often misdiagnosed. According to published case reports, the common clinical manifestations of NIID include dementia, muscle weakness, autonomic impairment, sensory disturbance, rigidity, ataxia convulsions, etc. However, no cases of oromandibular dystonia were mentioned. Case Presentation: We describe a case of a 58-year-old woman presenting with mouth involuntary chewing initially. She started to show hand tremors, ataxia, and walking instability until 2 years later. Diffusion-weighted imaging showed high intensity signal along the corticomedullary junction. Fluid-attenuated inversion recovery imaging showed white matter hyperintensity. Electromyography (EMG) indicated peripheral nerve degeneration. Neuropsychological testing showed memory loss. Finally, skin biopsy and GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID. Conclusion: This case demonstrated that oromandibular dystonia could be the first symptom of NIID. This case report provides new characteristics of NIID and broadens its clinical spectrum.
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Project description:Neuronal intranuclear inclusion disease is a rare, neurodegenerative disorder with onset in childhood. We report a single case natural history over 10 years and present a review of juvenile parkinsonism and neuronal intranuclear inclusion disease. Our patient was initially seen at the University of Rochester at age 12 years after 4 years of progressive dysarthria, dysphagia, and clumsiness. His neurologic examination was notable for parkinsonism. He had excellent initial response to levodopa, but subsequently developed dopa-induced motor fluctuations, dyskinesias, psychosis, and dystonia. Later in the course, he developed multiple nonmotor symptoms and ultimately died from respiratory failure. Neuropathology demonstrated large eosinophilic nuclear inclusions and small ubiquitin-related modifier 1 (SUMO-1) immunoreactivity, confirming the diagnosis of neuronal intranuclear inclusion disease. This diagnosis should be considered in a patient presenting with juvenile parkinsonism. Clues to the diagnosis include early-onset dopa-induced dyskinesias, gastrointestinal dysfunction, and oculogyric crises.
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Project description:Optineurin (OPTN) is a multifunctional protein involved in cellular morphogenesis, vesicle trafficking, maintenance of the Golgi complex, and transcription activation through its interactions with the Rab8, myosin 6 (MYO6), huntingtin. Recently, OPTN immunoreactivity has been reported in intranuclear inclusions in patients with neuronal intranuclear inclusions disease (NIID). Other studies have shown that the RNA-binding protein, fused in sarcoma (FUS), is a component of intranuclear inclusions in NIID. We aimed to investigate the relationship between OPTN, its binding protein MYO6 and FUS in this study. In control subjects, OPTN (C-terminal) (OPTN-C) and MYO6 immunoreactivity was mainly demonstrated in the cytoplasm of neurons. In NIID patients, both neuronal intranuclear inclusions (NII) and glial intranuclear inclusions (GII) were immunopositive for MYO6 as well as OPTN-C. However, the intensity of OPTN-C immunostaining of the neuronal cytoplasm with and without NII was less than that of the control subjects. Double immunofluorescence staining for OPTN-C, ubiquitin (Ub), p62 and FUS revealed co-localization of these proteins within NII. Moreover, Ub positive inclusions were co-localized with MYO6. The percentage of co-localization of Ub with OPTN-C, FUS or MYO6 in NII was 100%, 52% and 92%, respectively. Ultrastructurally, the inclusions consisted of thin and thick filaments. Both filaments were immunopositive for Ub and OPTN-C. These findings suggest that OPTN plays a central role in the disease pathogenesis, and that OPTN may be a major component of NII.
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