Clinicopathological features of adult-onset neuronal intranuclear inclusion disease
Top Cited Papers
Open Access
- 25 October 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 139 (12), 3170-3186
- https://doi.org/10.1093/brain/aww249
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.Keywords
This publication has 60 references indexed in Scilit:
- Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsyJournal of Neurology, Neurosurgery & Psychiatry, 2013
- White matter dementiaTherapeutic Advances in Neurological Disorders, 2012
- GFAP mutations, age at onset, and clinical subtypes in Alexander diseaseNeurology, 2011
- A Patient with Fragile X-Associated Tremor/Ataxia Syndrome Presenting with Executive Cognitive Deficits and Cerebral White Matter LesionsCase Reports in Neurology, 2011
- Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion diseaseNeurology, 2011
- Review of Alexander disease: Beyond the classical concept of leukodystrophyBrain & Development, 2009
- The Frontal Assessment Battery (FAB): normative values in an Italian population sampleNeurological Sciences, 2005
- Neuronal intranuclear hyaline inclusion disease with progressive cerebellar ataxiaPediatric Neurology, 1994
- Demyelinative Process Associated with Atypical Intranuclear Glial InclusionsUltrastructural Pathology, 1994
- A light and electron microscopy study of an unusual widespread nuclear inclusion body diseaseActa Neuropathologica, 1968