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ABSTRACT & COMMENTARY
By Alexander Shtilbans, MD, PhD
Assistant Professor of Neurology, Weil Cornell Medical College
Dr. Shtilbans reports no financial relationships relevant to this field of study.
SYNOPSIS: Myoclonus-dystonia is characterized by specific neurophysiological dysfunctions that appear to be different from the ones seen in other dystonias.
SOURCE: Popa T, et al. The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias. JAMA Neurol 2014;71:612-619.
Myoclonus-dystonia is a movement disorder characterized by a combination of rapid, brief muscle contractures and sustained repetitive movements resulting in abnormal postures. Loss-of-function mutations or deletions in the ε-sarcoglycan (SGCE) gene on chromosome 7 have been implicated in 50% of the cases (DYT 11). The function of SGCE in the brain is presently unknown. Genetic defects in other locations presumably account for the rest of the cases (DYT 15). Aside from the abnormal movements, the patients frequently have psychiatric problems including depression, anxiety, and obsessive-compulsive disorder.
The objective of this study was to evaluate the neurophysiological characteristics of myoclonus dystonia due to SGCE defects. The authors studied 12 myoclonus-dystonia patients from 11 unrelated families with genetic defects in SGCE gene compared with 12 healthy volunteers. The pharmacological treatments of the patients were discontinued at least 1 week prior to the beginning of the study. The patients and controls were assessed by clinical examination and rating, MRI of the brain, and electrophysiological testing including resting motor threshold, active motor threshold, short-interval intracortical inhibition, and short-interval intracortical facilitation. Assessments of the left primary motor cortex excitability using transcranial magnetic stimulation and cerebellar-dependent eye-blink classic conditioning were conducted as well. Electrophysiological data were correlated with clinical scores in the patient group. Contrary to the previous findings in other forms of dystonia, these authors detected low membrane excitability of the corticocortical axons and normal intracortical GABA inhibition. However, there was enhanced responsiveness of the motor cortex to plasticity noted, as well as abnormal response to cerebellar conditioning in the patient group. The authors concluded that cerebellar dysfunction plays a role in pathophysiology of dystonia and that their findings support parasagittal cerebellum involvement in pathogenesis of myoclonus-dystonia, which the authors believe to be different from other types of dystonia based on the neurophysiological characteristics.
The authors of the current study evaluated neurophysiological features in patients with myoclonus-dystonia harboring a defect in SGCE gene (DYT-11). While the study was small and did not include patients with other genetic defects, such as seen in DYT 15, it was well designed and showed differences in some characteristics from other dystonias. Namely, the patients had low membrane excitability of the corticocortical axons while their intracortical GABA inhibition was normal. Also, myoclonus-dystonia patients showed enhanced tendency of the motor cortex to develop plasticity and cerebellar dysfunction compared to controls. While not much is known about the pathophysiology of myoclonus-dystonia, a possible explanation for these differences could be that abnormalities of myoclonus and dystonia could originate anywhere in the wide functional motor network including sensorimotor cortex, cerebellum, brainstem, and spinal cord, besides basal ganglia. It is still unclear whether the noted changes are causative or compensatory.
Despite the noted cerebellar dysfunction in the patient group as well as in other types of dystonia, the lack of clinical cerebellar signs on exam could be related to distortion of the cerebellar output, which could minimize the clinical picture.
Interestingly, the global disability score had discrepant results between the patient self-rating scores and the ones done by a neurologist. Indeed, the biphasic active motor threshold correlated with the self-rated but not the neurologist-rated global disability score. The authors rightfully argue that the self-rated scores might be more accurate given variations of the patients’ symptoms throughout the day.
Overall, the demonstrated neurophysiological differences in patients with myoclonus-dystonia compared to other forms of dystonia are important and warrant further studies in larger and more genetically diverse groups of patients to evaluate the functional significance of these changes, which can help understand the pathophysiology of the disease and lead to effective treatment.