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Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions of the neck, leading to abnormal head postures and movement, pain and impaired motor function. Current treatments for CD, such as botulinum toxin injections and physical therapy, may not always provide sufficient relief of symptoms and may fail to offer long-term benefits for patients. As a result, new therapeutic approaches are needed. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates neuronal activity. Recent neurophysiological studies suggest that cerebellar tDCS (ctDCS), in particular, could be beneficial in modulating the activity of the sensorimotor network in CD. This clinical trial aims to investigate the effects of ctDCS on the excitability of the sensorimotor network and motor symptom severity in CD patients. Applying transcranial magnetic stimulation (TMS) we will evaluate the effects of anodal, cathodal and sham ctDCS to improve the understanding of the neurophysiological mechanisms underlying CD and the potential therapeutic role of ctDCS.
Dystonia is a movement disorder characterized by involuntary, sustained or intermittent muscle contractions, resulting in abnormal movements and postures. CD is the most common form of focal dystonia. It is characterized by abnormal postures or movements of the head. Standard treatment in patients with CD includes regular botulinum toxin injections and physical therapy, but many patients continue to experience symptoms, especially towards the end of the treatment cycle, highlighting the need for alternative treatment options.
One of the challenges in treating CD is the incomplete understanding of its underlying neurophysiological mechanisms. Recently, CD has been recognized as a network disorder, affecting the basal ganglia, the brainstem, the sensorimotor cortex and the cerebellum. So far, there is increasing evidence supporting the role of the cerebellum in the pathophysiology of dystonia, including animal models, neuroimaging and neurophysiological studies, but the exact the role in the proposed dystonia network is only incompletely understood.
TDCS is a form of non-invasive brain stimulation modulating the excitability of superficially located neurons. CtDCS is known to modulate the excitability of neurons of the cerebellar cortex, while the cerebellar nuclei and the brain stem remain unaffected. It has been shown that anodal ctDCS increases and cathodal ctDCS decreases the excitability of the cerebellum.
This randomized and sham-controlled clinical trial aims to investigate the effects of anodal and cathodal ctDCS in CD patients, focusing on both the sensorimotor network excitability and motor symptom severity. Participants will undergo three separated experimental sessions separated by one week, each with a different stimulation condition: anodal, cathodal, and sham ctDCS. Both, the study participants and the experimenter will be blinded to the order of stimulation mode.
The outcome measures will include:
Changes in the sensorimotor network before and after ctDCS stimulation, assessed by TMS. Measurements include four main metrics to determine the neurophysiological properties of the sensorimotor network in different ways:
Clinical motor symptom severity, assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and after each session.
This study aims to improve the understanding of the neurophysiological mechanisms and clinical effects of ctDCS in isolated CD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anodal ctDCS | Active Comparator | Patients receive anodal ctDCS stimulation for 20 minutes with 2 mA |
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| Cathodal ctDCS | Active Comparator | Patients receive cathodal ctDCS stimulation for 20 minutes with 2 mA |
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| Sham stimulation | Sham Comparator | Patients receive ctDCS stimulation for 20 minutes with 0 mA |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anodal and cathodal ctDCS | Device | CtDCS will be delivered using an DC-stimulator and two saline-soaked sponge electrodes: one electrode placed 3 cm lateral to the right of the inion, the other electrode on the right buccinator muscle. A 2 mA current will be delivered through these electrodes for a duration of 20 minutes with a 8-second fade-in and fade-out. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in sensorimotor network | Before and after each tDCS intervention, TMS will be used to assess the neurophysiological properties of the sensorimotor network with four main metrics:
To assess CBI, a conditioning stimulus will be applied over the right cerebellar hemisphere using a second magnetic coil, followed by a cortical test stimulus over the left primary motor cortex. | Baseline (pre-intervention) and immediately after the intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical symptom severity | Each session will begin and end with a clinical evaluation using the TWSTRS to quantify motor symptom severity, disability and pain associated with CD. | Baseline (pre-intervention) and immediately after the intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology, University Medical Center Hamburg-Eppendorf | Hamburg | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 7778843 | Result | Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation over the cerebellum in humans. Ann Neurol. 1995 Jun;37(6):703-13. doi: 10.1002/ana.410370603. | |
| 30682155 | Result | Porcacchia P, Alvarez de Toledo P, Rodriguez-Baena A, Martin-Rodriguez JF, Palomar FJ, Vargas-Gonzalez L, Jesus S, Koch G, Mir P. Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia. PLoS One. 2019 Jan 25;14(1):e0211367. doi: 10.1371/journal.pone.0211367. eCollection 2019. |
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Double blind
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| Sham stimulation | Device | The tDCS procedure will be identical to the active (anodal and cathodal) stimulation condition, but stimulation will cease after 30 seconds. |
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| 10990547 | Result | Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x. |
| 22473780 | Result | Hamada M, Strigaro G, Murase N, Sadnicka A, Galea JM, Edwards MJ, Rothwell JC. Cerebellar modulation of human associative plasticity. J Physiol. 2012 May 15;590(10):2365-74. doi: 10.1113/jphysiol.2012.230540. Epub 2012 Apr 2. |
| 37641392 | Result | Grimm K, Prilop L, Schon G, Gelderblom M, Misselhorn J, Gerloff C, Zittel S. Cerebellar Modulation of Sensorimotor Associative Plasticity Is Impaired in Cervical Dystonia. Mov Disord. 2023 Nov;38(11):2084-2093. doi: 10.1002/mds.29586. Epub 2023 Aug 28. |
| 18815775 | Result | Brighina F, Romano M, Giglia G, Saia V, Puma A, Giglia F, Fierro B. Effects of cerebellar TMS on motor cortex of patients with focal dystonia: a preliminary report. Exp Brain Res. 2009 Feb;192(4):651-6. doi: 10.1007/s00221-008-1572-9. Epub 2008 Sep 25. |
| 23649720 | Result | Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6. |