Dystonia, a movement disorder that features involuntary contractions of the muscles often leading to functional impairment, has many forms. Focal dystonia is localized to a single body part and cervical dystonia (torticollis) is the most common presentation of focal dystonia, often leading to painful twisting movements of the head and neck. The standard treatment for cervical dystonia is periodic injections of botulinum toxin to the affected muscles, an approach which appears to be more efficacious than anticholinergic oral medications. Volkmann and colleagues (2014) aimed to ascertain whether deep brain stimulation (DBS) would be effective for cervical dystonia cases that prove refractory to standard therapies.
The authors conducted a randomized, sham-controlled trial of patients with cervical dystonia in Europe. Enrolled patients were age 18–75 with disease duration >3 years and a severity score rating (using a standard cervical dystonia scale) of ≥15 points. All patients had a history of a poor response to oral treatment at the maximal effective dose and had not received botulinum toxin injections for at least 6 months. Those with previous neurosurgical procedures, cognitive impairment, moderate to severe depression, and other medical or psychiatric conditions that could interfere with the trial were excluded.
Within 6 weeks of baseline assessment, all patients underwent bilateral DBS placement in the posteroventrolateral globus pallidus internus. Half of the patients were then randomized to active stimulation and half to sham stimulation, where no activation of the DBS device occurred. The primary endpoint examined was the change in dystonia severity at 3 months. After the 3-month follow-up, neurostimulation was activated in the sham group as well. While the patients were blinded to their group assignment, treating physicians were not; however, assessment was made using videotaped examinations viewed by dystonia experts who were indeed blind to group assignment.
A total of 62 patients were enrolled in the study, and 30 patients in each group completed the 3-month evaluation. The primary outcome showed a 26% improvement in the neurostimulation group at 3 months compared with 6% in the sham stimulation group (p = .0024). The between-group difference in the mean change from baseline was 3.8 points (95% confidence interval, 1.76–5.84). Six months after activation of the device, the sham group (which now had the device activated) improved by 26% but there was only 3% additional improvement in the active stimulation group achieved during the extra 3 months of stimulation, suggesting that the benefit of DBS is uniform whether stimulation is started immediately or in a delayed fashion and that the benefit seen at 3 months is near the maximum a patient can expect.
Serious adverse events were related to the device implantation or device itself and therefore were similar in the two groups [16 of the 60 patients (27%)], although 11 of the 16 events resolved completely. Ongoing events included neck pain and electrode dislocation or misplacement. The most common non-serious adverse events were dysarthria, depression, and involuntary movements, all of which may in theory be mitigated or resolved with further refinement of the patient's stimulation settings.
This trial demonstrates that DBS can be effective for refractory cases of cervical dystonia. The magnitude of benefit here is similar to that found in trials of botulinum toxin, occurred in a population with severe and refractory disease, and is likely clinically meaningful. In these refractory patients, the risk-to-benefit ratio is likely favorable for DBS implantation. Whether this approach could become standard of care for more mild and nonrefractory cases of cervical dystonia will need to be explored in future trials. For now, clinicians caring for patients with refractory disease should consider referral to a tertiary movement disorders center for possible DBS evaluation.
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