Dystonia Disorder
Conditions
Keywords
Transcranial Magnetic Stimulation, Heperkinetic Movement Disorder,Truncal (Axial) Dystonia, Abnormal Posture,Contractions of the chest, back,abdominal muscles
Brief summary
By tracking resting-state fMRI scans, we aim to discover how repetitive transcranial magnetic stimulation (rTMS) changes brain connectivity in individuals with dystonia.
Detailed description
Dystonia is a neurological movement disorder characterized by spontaneous involuntary muscle contractions that cause repetitive twisting motions. These involuntary movements affect various body regions, including the face (blepharospasm), jaw (bruxism, oromandibular dystonia), head and neck (torticollis), voice box (laryngeal spasm), hands (writer's cramp), or as multiple body segments simultaneously. Dystonia lacks defining neuropathological change, making diagnosis challenging, and rendering symptom management incomplete. Advanced imaging techniques, particularly spatial covariance analysis and graph theory computations have revealed insights into dystonia's underlying brain networks. This approach shows that the relative strength of the metabolic function at each brain region (called "hubs") regulates information flow within the network and between the network and the rest of the brain. The identification of accessible cortical hubs as integral parts of the dystonia network raises new therapeutic possibilities though non-invasive techniques. Continuous theta-burst stimulation (cTBS), a modified form of rTMS that mimics natural brain rhythms (theta 4-8Hz), can effectively inhibit the cortical hyperactivity in targeted hubs with shorter treatment times than traditional approaches. The rationale for this proposed pilot experiment is to combine advanced analysis of standard neuroimaging to refine target location for a test of whether the application of non-invasive rTMS (in the form of cTBS) modulates abnormal cortical regions or the entire brain network, or both, as these networks underlie dystonia. Our PET investigations of patients with dystonia (DYT1 carriers both symptomatic and non-symptomatic) have identified hyperactive subcortical regions including the lentiform nuclei, cerebellum, and supplementary motor cortex. The dystonia-related brain metabolic networks that we generated with PET scanning, can now be generated with rs-fMRI, a less invasive technique that avoids radiation exposure and blood sampling. Graph Theory analysis indicates that the bilateral motor cortex (spanning the inter-hemispheric sulcus) and the left pre-motor region serve as critical hyperactive hubs. We hypothesize that modulating these hubs will disrupt the information flow in patients with dystonia. Using frameless stereotaxic optical system (Polaris Vicra, BrainSight 2.2), we can precisely target these cortical hubs with cTBS, the inhibitory form of rTMS. We are encouraged by recent studies that showed that a single cTBS run (40sec) precisely targeted significantly modified brain networks in patients with dystonia. Ameliorating dystonia has been one of the most controversial and challenging topics in treating hyperkinetic movement disorders, because it is difficult to estimate the overall whole brain responses after focal alterations caused by brain stimulation techniques. Our approach offers several innovations: 1. Enhanced and personalized hypermetabolic cortical hub identification. 2. Use of independent component analysis and graph theory to optimize location for cTBS delivery. 3. Individual response to the single cTBS stimulation site will be used for customized modeling of the TMS effect. Although previous attempts to use TMS to improve dystonia have been inconsistent, our precisely targeted approach may improve outcomes. Success with this method could expand TMS application beyond its established use in depression to other neurological disorders. The shift from PET to rs-fMRI for network mapping represents a significant advance, making the technique/treatment more accessible and easier on patients.
Interventions
DEVICETranscranial Magnetic Stimulation
Continuous theta-burst stimulation (cTBS), a modified form of rTMS that mimics natural brain rhythms (theta 4-8Hz), can effectively inhibit the cortical hyperactivity in targeted hubs with shorter treatment times than traditional approaches. The rationale for this proposed pilot experiment is to combine advanced analysis of standard neuroimaging to refine target location for a test of whether the application of non-invasive rTMS (in the form of cTBS) modulates abnormal cortical regions or the entire brain network, or both, as these networks underlie dystonia. This pilot study will provide the basis for a controlled study to test the effectiveness and robustness of any positive influence that TMS might have on the patients' dystonia.
Sponsors
Northwell Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female * 18 and 80 years of age. * Patients who manifest dystonia - sustained involuntary movement of the head, neck, trunk or limbs. * The dystonia may be spontaneous or genetic, specifically DYT1 or DYT6 and then only those patients who are demonstrating dystonia. The patient/subject will have a normal neurological exam except for dystonia.
Exclusion criteria
* Heredodegenrative dystonia of the type DYT8,9 or 10. * Past history of head trauma, stroke, epilepsy, demyelinating disease * Hypertension in excess of 160mmHg systolic and 90mmHg diastolic * Congestive heart failure * Diabetes * Past psychiatric conditions: e.g., depression * Systemic metabolic disease: e.g., Wilson's disease, progressive neurodegenerative disease (like supranuclear palsy or corticobasal ganglionic degeneration) * Magnetizable incorporated metal parts - like pacemakers * History or diagnosis of Parkinson's disease * Presence of myoclonus * No previous surgery for dystonia * Long term exposure to benzodiazepines, neuroleptics or anticonvulsants * No botulinum toxin within 12 weeks of baseline assessment and fMRI. * Moderate to severe cognitive impairment (judged by a minimental status of \<24.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluating rs-fMRI Changes Following rTMS Treatment | Two to four weeks. | The primary objective is to identify and modify replicable brain networks in dystonia patients using rs-fMRI. These networks reflect underlying disease processes, clinical symptomatology or both. The primary endpoint is change in the rs-fMRI derived network after rTMS treatment for two or four weeks, or both. We expect there to be changes at two and four weeks. We will then analyze the robustness of these changes in the repeat fMRI one week after treatment ends. Initially, identification and validation of the dystonia pattern from the resting state MRI will occur; it is a task with which we are familiar and is detailed in our recent manuscript. |
Countries
United States
Contacts
CONTACTCelina B Fernandez, MS
CONTACTBruce T Volpe, MD
Outcome results
None listed