Recent Developments in Dystonia Treatment

Dystonia management requires a multifaceted approach aimed at alleviating symptoms, improving functional capacity, and enhancing overall wellbeing. Symptomatic treatments — including systemic pharmacological interventions, botulinum toxin (BTX) injections, neuromodulation (Deep Brain Stimulation — DBS) techniques, and physiotherapy — play important roles in addressing the various manifestations of dystonia. In addition to the ongoing search for effective pharmacotherapy, including improved BTX formulations, advances in DBS procedures (such as the use of rechargeable batteries with longer lifespans, improvements in planning and programming software, and progress in imaging techniques such as 7-Tesla MRI) will continue to benefit patients with dystonia.

Deep Brain Stimulation (DBS) in the Surgical Treatment of Dystonia

In dystonia treatment, DBS represents a highly powerful alternative when symptoms cannot be controlled despite effective, high-dose medical therapy. In patients with segmental or focal dystonia, botulinum toxin injection must have been attempted prior to DBS and found to provide insufficient benefit.

For dystonia patients being considered as DBS candidates, the following constitute contraindications: dementia, structural brain abnormality, major psychiatric disorders, and severe systemic illness. Patients with fixed contractures secondary to dystonia also do not benefit from DBS.

Unlike DBS applied in Parkinson's disease, symptomatic improvement following GPi DBS in dystonia occurs gradually over months. Some publications have also reported that the therapeutic effect persists for approximately 10 hours after stimulation is discontinued. This suggests that structural and functional changes in neural tissue at cortical and subcortical levels — secondary to electrical stimulation — continue for hours after stimulation has ceased.

Today, DBS targeting the GPi nucleus is highly effective and yields encouraging results, particularly for DYT-positive primary generalised dystonias.

Although the pathophysiology of dystonia is not yet fully understood, it is thought that increased activity in the GPi nucleus may be inversely proportional to the severity of dystonia. Beyond primary generalised dystonia, publications have reported that GPi DBS is effective in primary segmental dystonia, blepharospasm, cervical dystonia, Meige's syndrome, tardive dystonia, and certain forms of secondary dystonia.

However, Holloway et al. reported in a 2006 study that DBS was not effective in dystonias developing as a result of birth trauma.

In addition to the GPi, other targets such as the thalamus have been used in DBS for dystonia over the years. Mundinger et al. were the first to apply the DBS technique in 1977 in a patient with cervical torticollis, targeting the ventral intermediate/ventralis oralis anterior (Vim/Voa) nuclei of the thalamus and the zona incerta region. Since then, numerous authors and centres have published their series on DBS in dystonia.

Controlled studies in primary generalised dystonia report symptom improvement in the range of 30% to 60%. Rebound dystonia symptoms have been reported in patients following the discontinuation of chronic GPi DBS.

Furthermore, higher voltage and pulse width are used in dystonia patients compared to those with Parkinson's disease, resulting in shorter battery life. No adverse effect of GPi DBS on cognitive scoring and neuropsychiatric function has been observed — in contrast to what is occasionally seen in Parkinson's disease patients.

In 2012, Volkmann et al. published the results of a prospective, controlled, multicentre study involving 40 patients with primary generalised or focal dystonia who had undergone GPi DBS and were followed for 5 years post-surgery.

The study found that the efficacy of stimulation progressively increased over the years in patients with primary generalised dystonia, with a 67% improvement in motor scores observed at the end of the 5-year follow-up period. By contrast, improvement in focal dystonia patients remained relatively stable over the years.

Although most authors prefer GPi DBS for dystonia treatment, recent studies indicate that the subthalamic nucleus (STN) can also be used as a target. Recently, Schjerling et al. compared the clinical outcomes of 12 dystonia patients who had undergone STN DBS and GPi DBS in a double-blind, randomised study.

After a 6-month follow-up, patients treated with STN DBS and GPi DBS showed improvements of 13.8 and 9.1 points respectively on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).

Additionally, no significant difference was found between the two DBS targets in terms of their effects on patients' quality of life. DBS can also be applied in the treatment of secondary dystonias secondary to cerebral palsy, with successful outcomes.

Vidailhet et al. published the results of bilateral pallidal DBS applied to 13 patients with choreoathetotic dystonia and cerebral palsy in a multicentre prospective pilot study in 2009. At the end of the first year, statistically significant improvements were found in scores for functional disability, pain, and quality of life.

The authors also reported in this study that the most appropriate target for DBS in the treatment of dystonia secondary to cerebral palsy is the posterolateroventral region of the GPi nucleus.