Diffusion Spectrum Imaging Maps Early Axonal Loss and a Unique Progressive Signal in Neuronal Intranuclear Inclusion...

Area of Science:

• Neuroimaging
• Neuropathology
• Diffusion Spectrum Imaging

Background:

• Neuronal Intranuclear Inclusion Disease (NIID) is a rare neurodegenerative disorder with poorly understood white matter pathology.
• Current diagnostic methods may not fully capture the extent or early stages of NIID-related brain changes.

Purpose of the Study:

• To delineate specific in vivo white matter pathology in NIID using diffusion spectrum imaging (DSI).
• To establish the clinical relevance of identified white matter microstructural changes in NIID patients.

Main Methods:

• Diffusion spectrum imaging (DSI) was performed on 42 NIID patients and 38 matched controls.
• Microstructural integrity was assessed using quantitative anisotropy (QA), generalized fractional anisotropy (GFA), and isotropy (ISO) across 48 white matter tracts.
• Stringent statistical corrections were applied for group comparisons and clinical correlations.

Main Results:

• A tripartite signature of white matter pathology was identified in NIID.
• Universal QA reduction indicated pervasive axonal integrity loss, detectable even before radiological abnormalities.
• GFA reductions in specific fiber tracts correlated with cognitive and functional deficits.
• ISO decrease in brainstem-cerebellar pathways uniquely predicted disease duration.

Conclusions:

• DSI provides a framework to resolve distinct pathological processes in NIID.
• QA serves as a potential biomarker for early NIID detection.
• GFA and ISO changes correlate with symptom heterogeneity and disease progression, respectively.
• These findings advance the pathophysiological model and clinical assessment of NIID.