Can Short Latency Afferent Inhibition Give us Clues to Better DYT 1 Dystonia Treatments?

Study Overview
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Brief Summary
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This is a research study using transcranial magnetic stimulation (TMS) to investigate interactions between the sensory system and the motor cortex in primary generalized dystonia (DYT1 dystonia) subjects who undergo deep brain stimulation (DBS) surgery. The sensory system is the body's sense organs - smell, sight, sound, etc. - and the motor cortex is the part of your brain where nerve impulses control voluntary muscle activity.

Detailed Description
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The cause of DYT1 dystonia is not clear. DYT1 dystonia symptoms include abnormal posture or repetitive twisting movements affecting one body part; in some patients, the entire body can twist and contort painfully. Magnetic resonance imaging (MRI) studies are normally used to evaluate changes in brain structure in DYT1 dystonia. Transcranial magnetic stimulation (TMS) is a painless, non-invasive method to test how your brain conducts electrical messages to the rest of your body, including your muscles. If you are a DYT1 dystonia patient, then this study involves up to three visits. The first visit (before DBS surgery) will last about 4 hours and the second and third visits (after DBS surgery) will last about 4 hours as well. These visits will include a complete physical and neurological exam, video recorded dystonia and mood rating scales, followed by electromyography (EMG) and TMS sessions. Subjects who have already undergone DBS surgery may participate in applicable visits based on the length of time since their DBS surgery. If you are a control subject, this study involves one visit, about 4 hours long. This visit will include TMS and EMG sessions.

Official Title
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Can Short Latency Afferent Inhibition Give us Clues to Better Dystonia Treatments?

Conditions
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DYT-1, DYT1, DYT 1, Dystonia

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Between the ages of 10 and 80 years. (CONTROL SUBJECTS between 18-80 years) Diagnosis and genetic test results confirming diagnosis of DYT1 dystonia. Currently treated with medications and enrolled in evaluation process for DBS surgery to confirm candidacy - OR - Previous DBS surgery EXCLUSION CRITERIA: Implanted pacemaker, medication pump, vagal stimulator, Transcutaneous electrical nerve stimulation (TENS) unit or ventriculoperitoneal shunt. Family or personal history of medication refractory epilepsy. Pregnancy: due to the frequent visits over a prolonged period and the lack of Information on the safety of TMS during pregnancy, pregnant women will not be eligible to participate in this study. Women of childbearing potential will be eligible to participate, provided that they are using adequate contraception during TMS treatments. This study is accepting healthy volunteers, aged 18-80, as control subjects. Control subjects will not undergo DBS surgery. EXCLUSION CRITERIA (as it applies to healthy control subjects): Cannot have family history or personal history of medication refractory epilepsy

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DYT-1 Postive<br>This group includes those participants who enroll having a genetically confirmed primary generalized dystonia diagnosis. | |
| Control<br>This group includes healthy subjects between the ages of 18 and 80. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in amplitude, at 3 and 6+ months, of motor evoked potentials (MEPs) with median nerve stimulation (SAI) and simultaneous median nerve and ulnar nerve stimulation (SAIdualstim) | Surface electromyography (EMG) will be recorded from the first dorsal interosseous muscle to determine the amplitude of potentials evoked in two ways - SAI and SAIdualstim. For SAI, potentials will be evoked with median nerve stimulation preceding TMS by the N20 latency plus 3 ms. For SAI dualstim, simultaneous stimulation of median and ulnar nerves will precede TMS by the N20 latency plus 3 ms. | 3 and 6+ months post-DBS surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of change in evoked potential amplitudes and clinical measures at 3 and 6+ months | The changes, from baseline to 3 and 6+ months post-operation, in amplitudes recorded during SAI and SAIdualstim testing will will be correlated with the changes in the clinical measures taken at the same timepoints. The Spearman correlation test will be used for this analysis. | 3- and 6+-months post-DBS surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBS, DYT-1, DYT1, DYT 1, dystonia, deep brain stimulation, TMS, transcranial magnetic stimulation