Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID)

Abstract

Background Neuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort. Methods Patients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed. Results Thirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aβ42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a “kite-like” specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia. Conclusions Specific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.

Clinical features of neuronal intranuclear inclusion disease with seizures: a systematic literature review

“…The areas of epileptic lesions seen on EEG are consistent with the high-signal areas on DWI (20). EEG in Case 17 showed a low-amplitude fast wave starting from the left parietal lobe (C3) and gradually spreading to the bilateral cerebral hemispheres, with widespread spikes and sharp waves (6). T2WI showed diffuse white matter lesions in both frontal lobes, whereas DWI shows a high signal hyperintensities at the corticomedullary junction between the frontal and left parietal lobes (6).…”

“…Patients with NIID with seizures may develop secondary brain injury (29) leading to neurological dysfunction (6,27,30). After clinical symptoms gradually recover, brain tissue edema and layered necrosis can remain in the areas with the strongest epileptic discharge, delaying the recovery of brain function (6,(31)(32)(33).…”

“…Patients with NIID with seizures may develop secondary brain injury (29) leading to neurological dysfunction (6,27,30). After clinical symptoms gradually recover, brain tissue edema and layered necrosis can remain in the areas with the strongest epileptic discharge, delaying the recovery of brain function (6,(31)(32)(33). In the present review, Case 15 experienced significant deteriorations in cognitive function after experiencing behavioral changes and seizures within 1 month of onset (34).…”

“…This disease can also cause various types of seizures in infant, junior and adult patients (1,18,19). The area of epileptic lesions seen on electroencephalography (EEG) is consistent with the DWI hyperintensities (20), and areas with swelling and layered necrosis in the brain are also the areas with the strongest epileptic discharge (6). Thus, the cerebral cortex near the DWI hyperintense areas may be more active than other regions, which is likely related to the occurrence of seizures in these patients (21).…”

“…NIID can be divided into child, adolescent, and adult types based on the OPEN ACCESS EDITED BY age and course of onset. The adult type can be further divided into sporadic and familial types based on family genetics (5,6). The clinical manifestations of NIID are heterogeneous and involve the central, peripheral, and autonomic nervous systems (7)(8)(9)(10).…”