Dystonia Image-based Programming of Stimulation: A Prospective, Randomized, Double-blind Crossover Trial

Dystonia is a neurological syndrome characterized by involuntary, sustained, or repetitive muscle contractions of opposing muscle groups that cause twisting movements and abnormal postures. Dystonias meet the prevalence criterion of a rare disorder, with prevalence estimates ranging from 0.2-5/100,000 for infantile or juvenile forms to 3-732/100,000 for dystonias manifesting in adults. In addition to motor impairments and mobility limitations, patients - especially young patients - suffer from non-motor symptoms: depression (> 15%), anxiety (> 25%), decreased sleep quality (> 70%), and pain (> 75%). In addition, there is a high risk of economic impairment, including job loss (> 55%), and decreased productivity are serious social consequences (> 50%). However, disability is usually secondary to motor impairment, and adequate treatment of motor symptoms can lead to profound improvements in quality of life (Skogseid et al. 2007). Currently, there is no cure for dystonia, and pharmacological symptom treatment is limited. Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recommended therapy for severe dystonia with Class I evidence for safety and efficacy (Vidailhet et al. 2005; Volkmann et al. 2012; Volkmann et al. 2014). However, clinical trials report up to 25% non-responders (<25% motor improvement) (Volkmann et al. 2012; Volkmann et al. 2014). Variability in electrode placement and inappropriate stimulation settings may explain much of this outcome variability (Reich et al. 2019). In addition, dystonia improves with a delay, often weeks after initiation or days after switching neurostimulation therapy, complicating clinical programming for DBS (Kupsch et al. 2011). Our group recently presented a novel approach based on empirical knowledge from a large cohort of chronically treated patients. We defined probabilistic maps of antidystonic effects using electrode position and volumes of tissue activation (VTA) from >100 patients. This method predicts a 16.3% better mean group improvement with computer-selected electrode choices compared with physician programming and a reduced proportion of non-responders from 25% to <5% (Reich et al. 2019). This potential advantage of computer-assisted programming capabilities will be tested in the study described here.

This study is supported by the Bundesministerium für Bildung und Forschung (BMBF): Förderkennzeichen: 01KG2032

Inclusion criteria

• Chronic deep brain stimulation (> 1 year) in the internal globus pallidus in patients with isolated dystonia.
• Deep brain stimulation settings and dystonia medication stable for > 3 months.
• Understanding about and consent to the study and signed informed consent form.

Exclusion criteria

• Relevant comorbidities that might interfere with study endpoints (esp. palliative disease and severe neurologic or psychiatric comorbidities).