Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease

Hong-Fei Tai; Tian-Tian Hua; Zai-Qiang Zhang; Yun-Yun Duan; Zhi-Zheng Zhuo; An Wang; Yi Zhou; Shao-Cheng Liu; Shan Lv

doi:10.3389/fnins.2022.1081383

Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease

Front Neurosci. 2022 Dec 7:16:1081383. doi: 10.3389/fnins.2022.1081383. eCollection 2022.

Authors

Hong-Fei Tai^{1

2}, Tian-Tian Hua^{3

4}, Zai-Qiang Zhang^{1

2}, Yun-Yun Duan^{3

4}, Zhi-Zheng Zhuo^{3

4}, An Wang^{1

2}, Yi Zhou^{1

2}, Shao-Cheng Liu^{1

2}, Shan Lv^{3

4}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² National Clinical Research Center for Neurological Diseases, Beijing, China.
³ Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Tiantan Image Research Center, National Clinical Research Center for Neurological Diseases, Beijing, China.

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.

Keywords: arterial spin labeling; cerebral blood flow; cortex; deep brain region; neuronal intranuclear inclusion disease.