Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update

Abstract

Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment.

Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm

“…Moreover, the difference in dFC strength between the right PMC and ipsilateral cerebellar lobule VIII remains in patients with BSP compared to those with HFS, indicating that such alterations may be attributed to specific pathophysiological processes of dystonic origin but not to excessive involuntary movements. This is consistent with previous resting-state fMRI studies showing altered FC in widespread brain areas, including the cerebellum, basal ganglia, and primary/secondary sensorimotor areas in patients with BSP [43].…”

“…Voxel‐based resting‐state FC analyses of cerebellar subregions revealed that cerebellar lobule VIII mainly displayed correlations with the sensorimotor network and thalamus [44]. It has been shown that the role of the cortico‐ponto‐cerebello‐thalamo‐cortical circuit is essential for coordination of eyelid movements and the blink reflex, as demonstrated on fMRI [43]. Furthermore, cerebellar connectivity reduction would definitely result in a loss of inhibition in the sensorimotor cortices and cause further excessive involuntary movement [45].…”

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases

“…In addition to the many original reports of OMD summarized, there have also been several reviews and commentaries focusing on OMD ( 4 , 5 , 15 , 54 ). Though these reviews focus on different aspects of OMD, they also describe a picture consistent with our report relating to age of onset, female predominance, and delayed diagnosis due to poor recognition of the varied phenotypes of OMD.…”

“…Most experts agree that the varied phenotypes of OMD represent a clinical syndrome arising from multiple factors. A combination of genetic and environmental factors are thought to combine to reach a threshold for manifestation of clinical symptoms ( 54 ). Early symptoms of disease are varied and may be subtle, which is believed to contribute to delayed diagnosis may result in a higher actual prevalence than previously reported ( 4 ).…”

Patient selection and injection techniques for botulinum neurotoxin in oromandibular dystonia

“…Amongst the different classes of oral medications, clonazepam and anticholinergics benzhexol seem to be the most effective, with both typical and atypical antipsychotics, dopamine depletors, levodopa, and baclofen also utilised. However, none of these agents has been tested in rigorously controlled clinical trials [19] . When evaluated in patients with segmental cranio-cervical dystonia, the blepharospasm component was found to be more responsive than the oromandibular region although this clinical impression is only supported by limited evidence involving a small number of patients and short follow-up visits [20] , [21] .…”