Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia

208 

Abstract Submission 

Haoran Zhang¹, Qinxiu Cheng¹, Jinping Xu¹

¹Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong

Haoran Zhang  
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Shenzhen, Guangdong

Qinxiu Cheng  
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Shenzhen, Guangdong

Jinping Xu  
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Shenzhen, Guangdong

Idiopathic blepharospasm is a focal dystonia characterized by excessive blinking and eyelid spasms, potentially causing functional blindness (Defazio, Hallett et al. 2017). Patients with blepharospasm have a high risk and rapid symptom spread to other body regions, particularly the oromandibular area (Svetel, Marina et al. 2015). It is a multifactorial clinical syndrome, but the neuro-mechanisms specific and/or common to them were largely unexplored. The pathogenesis of idiopathic blepharospasm is a network model involving the combined action of multiple brain regions, with the thalamus responsible for receiving and distributing information among different brain areas (Hwang, Bertolero et al. 2017). In most previous studies, the potential useful information about distinct thalamic nuclei has been overlooked. They may be associated with different symptoms or disorders (Weeland, Vriend et al. 2022, Lee, Lee et al. 2023). We aimed to investigate: (1) thalamic atrophy in blepharospasm and blepharospasm-oromandibular dystonia; (2) associations between different thalamic nuclei and the clinical manifestation of blepharospasm and blepharospasm-oromandibular dystonia; (3) causal relationships among abnormal thalamic nuclei; and (4) whether these abnormal features can be used as biomarkers.

We recruited patients from movement disorder clinics who were diagnosed with adult onset blepharospasm or hemifacial spasm based on established criteria. T1-weighted MRI data using a 3T MRI scanner was collected from 56 patients with blepharospasm, 20 patients with blepharospasm-oromandibular dystonia, and 58 healthy controls. There were no significant differences in age or gender among the three groups. T1 images were processed using the standard segmentation pipeline in Freesurfer v7.1.1 with default settings. A statistical model was constructed using age, gender, and estimated intracranial volume as covariates to analyze differences in subcortical gray matter volume and 15 thalamic nuclei between the groups. Pearson correlation analysis was performed to examine the relationship between abnormal thalamic nucleus volume and disease course/JRS scores in patients with blepharospasm, and abnormal thalamic nucleus volume were used to train a support vector machine (SVM) classification model. Furthermore, a region-based Granger causality analysis (GCA) was conducted using the Brain Covariance Junction Toolkit (BCCT_V1.2, available at https://github.com/JLhos-fmri/NeuroimageTools) to explore the causal relationship between abnormal thalamic nuclei.

The lateral geniculate and pulvinar inferior nuclei in patients with blepharospasm, and ventral anterior and ventral lateral anterior nuclei in patients with blepharospasm-oromandibular dystonia were significantly decreased compared with healthy controls (Figure 1). These thalamic nuclear atrophy were negatively correlated with clinical severity and/or disease duration in these patients (Figure 2A). Using gray matter volume of the lateral geniculate, pulvinar inferior, ventral anterior and ventral lateral anterior nuclei as inputs, the SVM resulted accuracy = 0.89 and AUC=0.89 to distinguish blepharospasm from healthy controls, accuracy = 0.82 and AUC=0.86 to distinguish blepharospasm-oromandibular dystonia from healthy controls, as well as accuracy = 0.94 and AUC=0.96 to distinguish blepharospasm from blepharospasm-oromandibular dystonia (Figure 2B).

Taken together, these results suggested that the pulvinar inferior nuclear might be the focal origin in the thalamus of blepharospasm, extending to lateral geniculate nuclear atrophy, and subsequently extending to ventral lateral anterior nuclei causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provided potential targets for neuro-modulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ¹

Diffusion MRI ²

Movement Disorder