Clinical and multimodal imaging features of adult-onset neuronal intranuclear inclusion disease.

Objectives: This study aimed to analyze the clinical and multimodal imaging manifestations of adult-onset neuronal intranuclear inclusion disease (NIID) patients and to investigate NIID-specific neuroimaging biomarkers.

Methods: Forty patients were retrospectively enrolled from the Qilu Hospital of Shandong University. We analyzed the clinical and imaging characteristics of 40 adult-onset NIID patients and investigated the correlation between these characteristics and genetic markers and neuropsychological scores. We further explored NIID-specific alterations using multimodal imaging indices, including diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and brain age estimation. In addition, we summarized the dynamic evolution pattern of NIID by examining the changes in diffusion weighted imaging (DWI) signals over time.

Results: The NIID patients' ages ranged from 31 to 77 years. Cognitive impairment was the most common symptom (30/40, 75.0%), while some patients (18/40, 45.0%) initially presented with episodic symptoms such as headache (10/40, 25.0%). Patients with cognitive impairment symptoms had more cerebral white matter damage (χ2 = 11.475, P = 0.009). The most prevalent imaging manifestation was a high signal on DWI in the corticomedullary junction area, which was observed in 80.0% (32/40) of patients. In addition, the DWI dynamic evolution patterns could be classified into four main patterns. Diffusion tensor imaging (DTI) revealed extensive thinning of cerebral white matter fibers. The estimated brain age surpassed the patient's chronological age, signifying advanced brain aging in NIID patients.

Conclusions: The clinical manifestations of NIID exhibit significant variability, usually leading to misdiagnosis. Our results provided new imaging perspectives for accurately diagnosing and exploring this disease's neuropathological mechanisms.