An Innovation of Bilateral Ventro-Intermediate Thalamus Stimulation for Action Myoclonus in Sialidosis

Sialidosis is an autosomal recessive lysosomal storage disorder with mutation of the NEU1 gene on human chromosome 6. The core pathology is primary deficiency of the lysosomal neuraminidase which leads to accumulation of sialylated glucopeptides and oligosaccharides. Pathological findings are cytoplasmic vacuolation in the neurons of cerebral cortex, basal ganglia, thalamus and diffuse intracytoplasmic storage of lipofiscin-like pigment. Sialidosis can be further divided into two subtypes based on clinical phenotypes. Type 1 Sialidosis is characterized by macular cherry-red spots, myoclonus, ataxia and slower progression than type 2. Type 2 Sialidosis has a more severe clinical presentation and earlier onset. The action myoclonus is the most disable symptom in Sialidosis type 1. There is rare myoclonus at complete rest, but jerks can be elicited by tactile and loud acoustic stimuli. In advanced stage, patients usually lost the ability to walk and feed themselves. The efficacy of medical treatment is poor or absent. Suicidal syndrome relevant to the exhausted medical and social perspectives often complicates the situations. The pathophysiological mechanism of action myoclonus remains unclear. Several studies indicate that the major electrophysiological abnormalities of Sialidosis 1 is caused by the changes at a level above the brain stem. In addition, the dysfunction of the Ventro-intermediate (Vim) thalamus plays an important role in generating myoclonic jerks. It is also suggested that the cerebellar nuclei drives motor cortex through the Vim thalamus and causes myoclonic jerks. Deep brain stimulation (DBS) is an effective treatment for several movement disorders. Vim stimulation effectively controls various involuntary movements, such as Parkinsonism tremor, essential tremor, cerebellar tremor and action myoclonus caused by perinatal anoxia. This intervention has been reported to ameliorate myoclonic symptoms in patients with myoclonus dystonia syndrome. However, there is no study reported the efficacy of Vim stimulation on action myoclonus syndrome in Sialidosis patients. The aim of this study is three folds: Firstly, we will evaluate the acute and chronic therapeutic effect of innovative bilateral Vim stimulation for intractable action myoclonus in Sialidosis type1. The clinical features will be scored by using Unified Myoclonus Rating Scale (UMRS), neuropsychological test and polymyography (PMG). Secondly, we will further explore the electrophysiological mechanism of action myoclonus in Sialidosis type l patients by using simultaneously local field potential of Vim, electroencephalogram and PMG recordings. It is to test whether the action myoclonus and myoclonic cortical discharges are driven from cerebellum via Vim, which is the prevailing, but unproven view. Finally, stimulation at different frequencies may drive or modulate pathological activities in Vim. We will determine whether some frequencies of imposed synchronization have more therapeutic effects on the myoclonic syndrome in Sialidosis type l patients

Project ID:PC10108-1100
External Project ID:NSC101-2314-B182-087