Introduction

Sleep-related hypermotor epilepsy (SHE), a rare type of focal epilepsy, is characterized by brief and hyperkinetic seizures, predominantly arising during sleep[1, 2]. The majority of SHE patients have normal routine MRI findings and uninformative interictal and ictal electroencephalogram (EEG). The diagnostic criteria of SHE was mainly based on clinical history and seizure semiology[1]. The surface-based morphometry (SBM) analysis has been widely used in epilepsy research to estimate cortical thickness and sulcal depth, characterize the amount of folding, and index brain surface complexity[3]. However, there are no studies using surface-based approaches to explore cortical microstructural variations in SHE, which could help further understand its neuropathophysiological mechanisms.

Methods

Participants
The study was authorized by the local ethical committee of our hospital. All participants provided written informed consent. 79 patients with sporadic SHE and 69 age- and gender-matched healthy controls (HCs) were prospectively enrolled.
Image acquisition and processing
T1­weighted images (T1WIs) were acquired with a Siemens 3.0T MRI scanner (Trio Tim, Erlangen, Germany), using an eight-channel head coil. T1WIs were acquired with a Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence. The scan parameters were as follows: repetition time/echo time (TR/TE) = 2250/2.6 ms, flip angle = 9°, slice thickness = 1 mm, matrix size = 256 × 256, field of view = 256 × 256 mm2, and acquisition time = 5.43 min. T1WIs were processed using an automated program in the Computational Anatomy Toolbox (CAT12) within SPM12, including two stages: voxel-based processing and surface-based processing[4].
Statistical analysis
The two-sample t-tests were used to between-group comparisons of cortical morphological indices by utilizing age and sex as covariates. Multiple comparisons were conducted by cluster-level family-wised error (FWE) method (p < 0.05).
The two-sample t-test and the Chi-squared test were performed to compare the demographic and clinical data using SPSS 23.0. Pearson or Spearman correlation test was used to assess the association between cortical structural parameters and clinical data.

Results

A total of 69 patients with SHE (mean age = 31.41±11.88 years; male : female = 45:24) and 69 HCs (mean age = 31.51±12.09 years; male : female = 35:34) were prospectively included in this study. Compared with HCs, patients with SHE exhibited significantly decreased cortical thickness in left inferior-parietal, fusiform and lingual, right superior-parietal, and bilateral lateral-occipital cortices (p = 0.00001-0.00004), and shallower sulcus depth in right precentral and postcentral gyri (p < 0.00001). However, no differential brain region was found in between-group comparisons of fractal dimension and gyrification (all P>0.05). Correlation analysis showed a negative correlation between the cortical thickness of left inferior-parietal region and SHE duration (r= -0.325, p=0.0064).

Discussion

In this study, we found a bilateral brain atrophy pattern, primarily distributed in the bilateral parietal and occipital, and left fusiform cortices. Previous voxel-based morphometry (VBM) study also reported reduced gray matter volume in the left fusiform and inferior-parietal regions in patients with SHE[5]. Structural MRI studies in temporal lobe epilepsy have demonstrated that cortical thinning potentially result from the seizure-induced damage[6, 7], even in the bilateral and extra-epileptogenic cortical regions[8]. These findings suggest that focal epilepsy may involve brain network dysfunction rather than just impacting epileptogenic zone.
The parietal lobe is known to participate in the posterior default-mode network, which is crucial for maintaining consciousness[9]. The microstructural abnormalities in parietal lobule provide a possible explanation for loss of consciousness suffered by SHE patients. The fusiform gyrus has been considered as a key structure for functionally-specialized computations of high-level vision such as face perception and object recognition[10]. The lateral-occipital region belongs to visual cortex. The visual areas of brain were often connected to motor regions for the sensory guidance of movement[11].
Patients with SHE showed decreased sulcus depth in the right precentral and postcentral gyri, which form part of the sensorimotor network (SMN) [12]. A resting-state functional MRI study reported that SHE patients showed higher local intrinsic activity in SMN regions[12]. Involvement of SMN is consistent with the clinical “hypermotor” semiology of SHE. Altered cortical folding could be a structural manifestation of neural network disturbance underlying the seizure. Past study found significantly higher functional connectivity of SMN and thalamus in SHE[13].
We found a negative correlation between epilepsy duration and cortical thickness of left inferior-parietal region. It is possible that the accumulation of microstructural changes or secondarily generalized seizures due to the long-standing nature of disease[14].

Conclusion

SHE-related alterations of cortical thickness and sulcus depth in some cerebral regions may provide a direction for further uncovering the neuropathological process and exploring potential neuro-biomarker of brain impairment in the future.

Acknowledgements

This study has received funding by the National Natural Science Foundation of China (Grant No. 82271961, 81621003), the National Key R&D Program of China (2022YFC2009900) and the Sichuan Provincial Foundation of Science and Technology (Grant No. 2019YFS0428).

References

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