Multitarget Stereotactic Electrophysiological Recording and Stimulation for Tourette Syndrome

The YGTSS is a 10-item semi-structured clinician-rating instrument that evaluates motor and phonic symptoms' number, frequency, intensity, complexity, and interference. The items about the tic ratings are scored on two subscales: motor tics and phonic tics. Behaviors are rated on a 6-point scale. The Total Tic Severity Score ranges from 0-50, with a higher score indicating a higher severity of symptoms.

The Modified Rush Video Rating Scale (MRVRS) is a validated, video-based instrument for objectively assessing tic severity in patients with Tourette Syndrome. The MRVRS evaluates motor and phonic tics using a revised scoring method that captures tic frequency, intensity, and complexity from a 5-minute video recording. The MRVRS ranges from 0-20, with a higher score indicating a higher severity of symptoms. In this study, trained, blinded evaluators will rate each participant's tic severity using the MRVRS at multiple time points. Assessments are performed at baseline, after 1 month of stimulation during each randomized crossover period (following New Target DBS Stimulation, CM DBS Stimulation, and Sham Stimulation), and again after 3 months of continuous optimal stimulation. A decrease in the MRVRS score from baseline will indicate an improvement in tic severity.

The Premonitory Urge Scale (PUTS) is a self-reported measure that evaluates the intensity of premonitory urges preceding tics in patients with Tourette Syndrome. The PUTS score ranges from 9-36, where higher values reflect more severe urges, will be recorded at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. Changes in the PUTS score will indicate alterations in the severity of premonitory urges.

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a clinician-rated instrument that assesses the severity of obsessive-compulsive disorder (OCD). Scores range from 0 (no symptoms) to 40 (severe symptoms). Assessments will be performed at baseline, after each 1-month randomized stimulation phase (following New Target DBS, CM DBS, and Sham stimulation), and after 3 months of continuous optimal stimulation. A reduction in the Y-BOCS score indicates an improvement in OCD symptoms.

The Conners' Adult ADHD Rating Scale (CAARS) will be used to evaluate the severity of attention deficit hyperactivity disorder (ADHD) , including inattention, hyperactivity, and impulsivity. The scale provides a score reflecting overall ADHD severity. Assessments will be conducted at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A decrease in the CAARS score indicates improvement in ADHD symptoms

The Hamilton Anxiety Scale (HAMA) is a clinician-rated scale used to assess the severity of anxiety symptoms, with scores ranging from 0 to 56. Higher scores indicate greater anxiety. HAMA assessments will be performed at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the HAMA score reflects a decrease in anxiety symptoms.

The Hamilton Depression Scale (HAMD) is used to assess the severity of depressive symptoms, with total scores ranging from 0 to 52. Higher scores indicate more severe depression. Evaluations will occur at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the HAMD score indicates an improvement in depressive symptoms.

The Young Mania Rating Scale (YMRS) is a clinician-administered instrument assessing the severity of manic symptoms, with scores ranging from 0 to 60. Higher scores indicate more severe mania. YMRS evaluations will be performed at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the YMRS score signifies an improvement in manic symptoms.

The Columbia Suicide Severity Rating Scale (C-SSRS) primarily evaluates the presence, severity, and frequency of suicidal ideation and behaviors rather than providing a single numerical range. Typically, higher scores indicate greater suicide risk, with severity rated individually per item rather than summed into a total score. The C-SSRS will be administered at baseline, after each 1-month stimulation period during the randomized crossover phase, and after 3 months of continuous optimal stimulation. A reduction in the C-SSRS score indicates an improvement in suicidal risk.

The Mini-Mental State Examination (MMSE) is a clinician-administered test that evaluates overall cognitive function. The MMSE provides a score ranging from 0 to 30, with lower scores indicating greater cognitive impairment. In this study, trained evaluators will assess the MMSE score at baseline, 3 months post-intervention, and 6 months post-intervention. The primary measure is the change in the MMSE score from baseline, which will reflect any improvement or decline in cognitive function due to the interventions.

The Montreal Cognitive Assessment Beijing Version (MoCA) is a brief screening tool that evaluates multiple cognitive domains, including memory, executive function, attention, language, and visuospatial abilities. The MoCA yields a total score from 0-30, with lower scores indicating more significant cognitive deficits. In this study, the MoCA will be administered by trained evaluators at baseline, 3 months post-intervention, and 6 months post-intervention. The outcome measure is the change in the MoCA score from baseline, which will help determine the effect of the interventions on cognitive performance.

Quality of life will be evaluated using the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL), a patient-reported measure that assesses the impact of TS on daily functioning and overall well-being. The scale yields a total score ranging from 0-108 where lower scores indicate a better quality of life. Assessments will be performed at baseline, after each 1-month randomized stimulation phase during the crossover period, and following 3 months of continuous optimal stimulation. A decrease in the GTS-QOL score from baseline indicates an improvement in quality of life.

Safety will be evaluated by recording the incidence, severity, and nature of treatment-related adverse events (AEs), including surgical complications, stimulation-related side effects, and device-related issues. Data will be collected at every follow-up visit and monitored throughout the study. This measure will provide an overall safety profile of the interventions.

This outcome measure assesses the effectiveness of electrophysiological brain mapping (using SEEG) in identifying a novel stimulation target. Success is defined as the reliable identification of a new target based on electrophysiological criteria during brain mapping and subsequent 24-hour stimulation. The proportion of patients with a successfully identified new target will be determined.