Pallidal Neurostimulation Beneficial in Cervical Dystonia

Megan Brooks

October 02, 2014

Bilateral pallidal deep-brain stimulation (DBS) reduced dystonia severity and related disability and improved quality of life in patients with medication-refractory cervical dystonia participating in the first sham stimulation controlled clinical trial.

"The improvements were significantly better than those associated with sham stimulation," Jens Volkmann, MD, Department of Neurology, Christian Albrechts University, Kiel, Germany, and colleagues report.

"Extended follow-up is needed to ascertain the magnitude and stability of chronic neurostimulation effects before this treatment can be recommended as routine for patients who are not responding to conventional medical therapy," the authors conclude.

Their findings are published in the September issue of Lancet Neurology.

When Botulinum Toxin Fails

Cervical dystonia is the most common type of dystonia. Repeated injections of botulinum toxin to denervate dystonic neck muscles are the first-line treatment option for most patients, but some patients do not respond.

DBS of the globus pallidus internus (GPi) has proven to be an effective and relatively safe treatment for patients with severe generalized dystonia or segmental dystonia. Results of small retrospective cohort studies and a controlled trial with 10 patients also suggest a benefit in cervical dystonia.

Dr Volkmann and colleagues compared active and sham GPi DBS in 62 patients with medication-refractory cervical dystonia recruited from centers in Germany, Norway, and Austria. The patients were 18 to 75 years old, had had cervical dystonia for at least 3 years, and had a severity score of at least 15 points on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS).

All patients, masked to treatment assignment, were implanted with the DBS device and received active stimulation at a frequency of 180 Hz or sham stimulation for 3 months. At 3 months, neurostimulation was activated in the sham group and outcomes were reassessed in all patients after 6 months of active treatment.

At 3 months, the reduction in TWSTRS severity score (the primary outcome assessed by 2 masked dystonia experts by intention-to-treat analysis) was significantly greater (P = .0024) with active (–5.1 points; 95% confidence interval [CI], –7.0 to – 3.5) than with sham stimulation (–1.3; 95% CI, –2.2 to –0.4).

Patients receiving active stimulation also had a substantially greater percentage improvement in TWSTRS disability score (41% vs 11%) and Bain tremor score (61% vs 16%) at 3 months.

Six months after activation of the neurostimulation device, patients initially assigned to sham stimulation had improved by 5.0 points (26% improvement) on the TWSTRS severity score since the 3-month visit, while patients originally assigned to active DBS had only minor additional benefit from an extra 3 months of treatment (3% improvement).

A post hoc comparison of outcomes at baseline and after 6 months of active DBS support the beneficial effects of active GPi DBS, the researchers say.

"The symptomatic improvements had a significant bearing on quality of life as assessed by the Craniocervical Dystonia Questionnaire-24 (28% score reduction)," the investigators report.

During the study, 21 adverse events (5 serious) were reported in 11 (34%) patients in the active stimulation group compared with 20 (11 serious) in 9 (30%) patients in the sham stimulation group. Serious adverse events were typically related to the implant procedure or the implanted device, and 11 of 16 resolved without sequelae.

The most common nonserious adverse events were dysarthria (in four patients assigned to active DBS vs three patients assigned to sham stimulation), involuntary movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression (one vs two).

The researchers say a strength of the study is the sham controlled design and large sample size (the largest to date of DBS in cervical dystonia). A limitation is the short observational period, which didn't allow optimization of stimulation parameters. They say longer follow-up is also needed to establish the magnitude and stability of long-term neurostimulation effects.

"Strong Proof of Efficacy"

In an accompanying editorial, Alberto Albanese, MD, Università Cattolica del Sacro Cuore, Milan, Italy, says the study shows that GPi DBS is a "worthy contender for the treatment of patients with cervical dystonia."

 
These data will likely lead to changes in neurological practice for cervical dystonia and reposition the indications for DBS and botulinum toxin. Dr. Alberto Albanese
 

The study provides "strong proof of efficacy for GPi DBS in the most common dystonia type. These data will likely lead to changes in neurological practice for cervical dystonia and reposition the indications for DBS and botulinum toxin," Dr Albanese writes.

Commenting on the findings for Medscape Medical News, Michele Tagliati, MD, director of the Movement Disorders Program at Cedars-Sinai Medical Center, Los Angeles, California, said this "elegant study clearly supports the use of deep brain stimulation (DBS) for cervical dystonia. It's a good option for patients who do not respond to botulinum toxin." Dr Tagliati wasn't involved in the study.

The study was funded by Medtronic. Several of the authors have disclosed relationships with Medtronic and other companies. See the original article for a complete list. Dr Albanese has received personal fees from Medtronic and Boston Scientific.

Lancet Neurol. 2014;13:875-884. Abstract Comment

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