White matter myelin loss and microstructural alterations underlying cognitive dysfunction and tremor in neuronal intranuclear inclusion disease
Year: 2026
Type: article
Abstract: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. While leukoencephalopathy is a hallmark of NIID, the specific involvement of white matter (WM) myelin, its coupling with microstructural fiber tract damage, and its contribution to clinical phenotypes remain poorly understood. This prospective study enrolled 10 patients with genetically and pathologically confirmed NIID and 10 age- and sex-matched healthy controls (HCs). In vivo myelin integrity was quantified using T1w/T2w ratio mapping, and WM microstructural integrity was assessed across 20 major tracts using multiple DTI-derived indices, including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Cognitive status was evaluated with the Montreal Cognitive Assessment (MoCA). Voxel-wise comparisons were conducted to map myelin deficits and identify compromised fiber tracts. Subsequently, correlation analyses were employed to investigate the interplay between myelin loss, tract-specific damage, and clinical manifestations (cognition and tremor). Compared with HCs, patients with NIID exhibited profound myelin depletion in the corpus callosum (CC) and periventricular white matter (PVWM), concomitant with significant microstructural impairment in the bilateral anterior thalamic radiation (ATR) and forceps minor. These myelin deficits in the CC and PVWM were intrinsically coupled with the disruption of the aforementioned fiber tracts (Bonferroni-corrected, p < 0.05). Furthermore, myelin loss in the CC and periventricular regions, alongside microstructural damage in the forceps minor, was significantly associated with cognitive decline ( p < 0.05). Subgroup analysis revealed that NIID patients with tremor manifested more severe myelin damage than those without tremor ( t = 3.148, p = 0.014). NIID is characterized by a distinctive pattern of myelin loss within the corpus callosum and periventricular regions, which is closely coupled with the disruption of key frontal-subcortical and commissural fiber tracts. These findings suggest that myelin impairment is a critical pathological substrate for cognitive dysfunction and phenotypic diversity in NIID, providing potential imaging biomarkers for clinical monitoring. Not applicable.
Source: BMC Medical Imaging
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W7225822565
FWCI:
Cites:
Cited by:
Related to: