ABSTRACT
Background: Neuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients. Materials and methods: A total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted. Results: NIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p <0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p <0.005 uncorrected). Conclusion: NIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.
ABSTRACT
BACKGROUND: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. METHODS: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. RESULTS: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. CONCLUSION: Multimodal MRI could be used to monitor short-term brain changes in ALS patients.
