Dual-Target Deep Brain Stimulation for Obsessive-Compulsive Disorder and Tourette Syndrome

To the Editor:

Deep brain stimulation (DBS) has been used effectively for both treatment-resistant obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) (1,2). While DBS of the anterior limb of the internal capsule is Food and Drug Administration approved for use in OCD under a Humanitarian Device Exemption, DBS for TS is still considered investigational (3,4). Several DBS targets for TS have been studied, most prominently the globus pallidus internus (GPi) and centromedian/parafascicular thalamus, though no single best target has emerged (2,5). Up to two-thirds of patients with TS present with comorbid OCD (6). In many cases, treatment-resistant dual-diagnosis patients have been treated with one pair of leads in the hope of improving both. In an attempt to optimize outcomes for both disorders, and given the increasing utilization of multilead implantation strategies (7-10), we opted for a dual-target strategy in 2 patients with severe TS and OCD. We also utilized recently available sensing-capable implantable pulse generators (IPGs), which present a unique opportunity to study the disease-modifying effects of DBS on OCD- and TS-associated neurophysiology.

Patient 1 is a 42-year-old right-handed Hispanic woman with a 34-year history of OCD, TS, and major depression. Her TS symptoms consisted of simple and complex motor (e.g., blinking, head rolling/turning) and vocal tics (e.g., sneezing/gasping). Her OCD symptoms included intrusive thoughts and obsessions related to her tics. These were relieved by tic compulsions, which had to be completed until she felt “just right.” Often, they were repeated to the point of self-injury, even requiring surgery (e.g., cervical fusion). The patient also experienced contamination obsessions with cleaning compulsions and harm obsessions such as thoughts of harm coming to her parents, all of which exacerbated her tics. Her symptoms were severe, with a baseline Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (11) score of 40, a Yale Global Tic Severity Scale (YGTSS) (12) score of 80, and a Hamilton Depression Rating Scale (13) score of 28.

Patient 2 is a 20-year-old right-handed White man with a 16-year history of OCD and TS. His TS consisted of complex motor (e.g., eye rolling/shutting, jaw excursion, teeth grinding, nose poking/pushing) and phonic (e.g., snorting) tics. His OCD symptoms involved completing tics regardless of time and circumstance until feeling “just right.” He also reported needing to repeat or rewrite words he heard or read until achieving symptom relief. The severity and frequency of his OCD and TS symptoms had detrimental effects on all aspects of his functioning, including inability to finish high school, social isolation, and inability to drive. By his estimation, he spent ~90% of his waking hours performing the OCD and TS behaviors. His baseline Y-BOCS score was 34 and his YGTSS score was 94.

Both patients had extensive treatment histories including failed medication trials with selective serotonin reuptake inhibitors (e.g., fluoxetine), clomipramine, adjunctive atypical antipsychotics (e.g., aripiprazole), and VMAT2 inhibitors (e.g., tetrabenazine). Both also had expert exposure and response prevention therapy for their OCD. Despite this extensive treatment history, neither patient demonstrated significant clinical improvement. Based on their histories of severe OCD and TS and multiple failed treatments, our multidisciplinary team concluded that both patients qualified as candidates for DBS for both disorders.

Using our standard robotic DBS procedure (14), we targeted the bilateral ventral capsule/ventral striatum (VC/VS) for OCD (15) and posteroventral (motor) GPi for TS (2,16-18) (Figure 1A). Each patient received 2 IPGs (Percept PC; Medtronic), 1 for each pair of leads.

Figure 1.

Patient 1 (left), patient 2 (right). (A) Multi-Modality Visualization Tool reconstructions of patient brains showing frontal and superior views of cortical surfaces, labeled subcortical structures, and deep brain stimulation (DBS) leads. (B) Clinical scores over time (days since lead implantation). Vertical lines (black) indicate when stimulation was turned on at each anatomic target; lines are initially dotted for patient 2 to indicate lack of data during that time, and color-coded dotted lines for each clinical scale indicate threshold for response to treatment. (C) Timeline indicating patient programming visits and use of event markers (by anatomic target) and surveys completed over time; four example power spectral densities (PSDs) are shown for select event markers and surveys for each patient. ERP, exposure and response prevention; GPi, globus pallidus internus; HAMD, Hamilton Depression Rating Scale; VC, ventral capsule; VS, ventral striatum; YBOCS, Yale-Brown Obsessive Compulsive Scale; YGTSS, Yale Global Tic Severity Scale.

At 4 months, patient 1 met response criteria for both OCD [defined as $35% reduction in Y-BOCS (19); ΔY-BOCS = −53%] and TS [defined as ≥25% reduction in YGTSS (20); ΔYGTSS = −79%] (Figure 1B, left). However, she subsequently lost her job and experienced worsening OCD and major depressive symptoms. Fortunately, she slowly recovered, and by 17 months she again achieved and has so far maintained OCD and TS responder status (Y-BOCS = 24; ΔY-BOCS = −40%; YGTSS = 51; ΔYGTSS = −36%). Of note, her major depression has also improved significantly (Hamilton Depression Rating Scale = 15; Δ Hamilton Depression Rating Scale = −46%). Patient 2 was also a responder for OCD and TS at 4 months, and this response was sustained at 10 months (Y-BOCS = 15; ΔY-BOCS = −56%; YGTSS = 19; ΔYGTSS = −80%) (Figure 1B, right).

The sensing-capable IPGs allowed us to collect time and frequency domain electrophysiological data from VC/VS and GPi leads using both clinician- and patient-triggered recordings. We collected neural recordings (107 sessions; 1–5 minutes each) during VC/VS and GPi DBS programming visits and exposure and response prevention sessions (Figure 1C). At home, we instructed patients to mark changes in symptoms related to mood, tics, or OCD by using a built in customizable event button on their patient programmers to trigger a 30-second local field potential recording that is converted to a frequency domain power spectral density estimate and saved onboard the device. Each IPG accommodates only 4 event options. In order to acquire richer behavioral data, we created a set of online surveys that assess more granular changes in symptoms and programmed a survey event to allow us to capture neural data at the time of each online survey administration. Here, we show example power spectral density data from various patient-triggered events. Analysis of the oscillatory activity associated with each self-reported symptom may lead to biomarker identification. Recent work from Provenza et al. (15) and Vissani et al. (21) has identified candidate biomarkers of OCD symptoms in VC/VS delta (0–4 Hz) and alpha (8–15 Hz) frequency bands using data collected onboard sensing-capable IPGs during concurrent stimulation. Our data, simultaneously collected from 2 regions in the basal ganglia, present a unique opportunity for analyzing the interaction between the VC/VS and GPi during OCD- and TS-relevant behaviors. Ongoing work will focus on analysis of these data to investigate the brain-behavior relationships underlying OCD and TS. Improvements in on-device electrophysiologic recording technology and development of objective, time-resolved measures of psychiatric symptomatology will advance our understanding of these disorders (15,22-24).

In sum, we report favorable outcomes in the first 2 patients to receive dual-target DBS for OCD and TS targeting the VC/VS and GPi, respectively, and demonstrate the feasibility of using sensing-capable IPGs to gather data that could further our understanding of the neurophysiological bases of these complex neuropsychiatric disorders.