Chronic Outcome Monitoring for DBS in Dystonia

Dystonia is a hyperkinetic movement disorder that can have various clinical phenotypes, from isolated cervical dystonia to severe generalized dystonia. Deep brain stimulation (DBS) is an effective therapy for dystonic symptoms and has been successfully used for more than 20 years. However, clinical optimization can be a complicated and lengthy process, and to date there is no closed-loop stimulation paradigm automatically adapting to current disease states.

Previous electrophysiological research using intracranial local field potential (LFP) recordings from DBS electrodes in the internal pallidal globe (GPi) has identified low-frequency activity in the theta/alpha band (7-12 Hz) as a physiomarker for symptom severity, although stimulation effects on the neurophysiology have only been investigated indirectly to date. Interestingly, stimulation-induced bradykinesia was correlated with increased beta-band activity, pointing towards transdiagnostic biomarkers. With the Percept neurostimulator (Medtronic Inc., Minnesota, USA) high resolution electrophysiological recordings, also during stimulation, and chronic biomarker tracking have become more accessible, also allowing for investigation of long-term dynamics such as circadian variations. To date, in dystonia, only case-reports have been published using this device.

Here, the development of electrophysiological biomarkers are systematically investigated during the first post-operative year. The aim is to, firstly, characterize the potential of low-frequency activity as a biomarker for adaptive algorithms. Secondly, neurophysiological signatures (e.g. low-frequency, gamma band activity) that are predictive of symptom improvement will be characterized, which might lead to electrophysiology-guided acceleration of therapy optimization.

All patients with dystonia, regardless of the dystonia type, between the age of 5-80 years, receiving surgery for pallidal deep brain stimulation electrode implantation and the Percept device are screened to participate in the study. Participants, and if applicable the legal guardians, will provide informed consent according to the ethics approval (EA1/164/23 and EA2/163/25). The aim is to include 20-30 patients with various types of dystonia.

The first dataset will be continuously recorded biomarker activity in the low-frequency range and beta band, to also assess development of stimulation-induced beta increases. Recordings will be done using the Percept Chronic BrainSense feature that allows for continuous assessment of peak biomarker activity at an investigator-selected peak at a 5 Hz window and a temporal resolution of one mean value/10min. For symptomatic correlation, subjective (patient reported outcome (PRO) questionnaire) and objective (video-based kinematic analysis) will be collected. The PRO will cover motor symptoms as well as non-motor symptoms such as mood and pain.

The second data set will be high-resolution local-field potential recordings at monthly lab visits. Here, different therapy states (ON/OFF DBS) will be recorded during rest (comfortably seated with open eyes) and a movement task (finger tapping). Additionally, standardized clinical scales such as the Burke-Fahn-Marsden-Dystonia-Rating Scale (BFMDRS) and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) will be assessed by clinicians.

Inclusion criteria

• Ability to give informed consent for the study, or in pediatric patients, legal guardian or parent willing to give informed consent
• Diagnosis of dystonia, which may be isolated or generalized
• Wish to receive surgical intervention with DBS to the internal pallidal globe (GPi)
• Decision to receive the sensing-enabled neurostimulator (Percept neurostimulator) PC/RC
• Age 5-80 years

Exclusion criteria

• Severe psychiatric disorders (BDI>20)
• Other severe medical conditions, that may interfere with the successful paritcipation in the study protocol
• No consent given