Upon awakening from electrode implantation, the patient was noted to have complete cessation of motor and vocal tics. Multiple attempts to elicit tics, including the use of intravenous steroids to minimize a possible inflammatory micro-lesion effect, stimulant medication, and environmental triggers, were unsuccessful. Only rare verbal tics without coprolalia or any clear pattern were noted to occur. Although a rare episode of coprolalia occurred on day 5 post-lead implantation, during a direct discussion regarding the patient’s tics and his emotional and physical stressors, coprolalia could not be otherwise elicited. At this time stimulation testing was initiated in order to evaluate for potential settings. Assessment of evoked potentials and local field potentials was repeated during this time. Tics began to appear with slightly increasing frequency on day 10 postoperatively, but still required specific elicitation such as emotional triggers for the patient. At no point did the tic severity return to the prior level, and coprolalia did not occur spontaneously during the hospitalization. Tics remained absent while the patient performed regular activities in the context of social interaction, family discussions, and playing video games. Notably, prior to surgery, the patient’s tics were so severe that they persisted even when the patient was alone and at rest, interfering with sleep onset. In order to evaluate the DBS effect on tics, the patient was hospitalized for approximately 2 weeks until tic frequency had increased to sufficient regularity for testing.
10 days after test lead implantation, stimulation was repeated to evaluate the effect on tic frequency. The greatest decrease in tic frequency was elicited with concurrent stimulation to bilateral GPi posterior and NA. Stimulation to CM parafascicular nuclei also had benefit, although slightly less. Optimal stimulation settings in GPi posterior (with 1 being the most distal contact) were 123-4+ at 3v, 120 μs, and 40 Hz bilateral. Optimal stimulation settings in left NA were 123-4+ at 5v, 120 μs, and 180 Hz. Optimal settings on right NA were 234-5+ at 5v, 120 μs, and 180 Hz. Externalized electrodes were removed 12 days after implantation. Worsening of motor tics was observed approximately 5 h after removal, with the progressive re-emergence of motor and vocal tics, including coprolalia, over subsequent days. The patient was discharged on post-operative day 12.
Recorded data from the MM16C micro-contacts showed variable activity in all recorded regions associated with voluntary movement. When tics recurred, widespread brief activity in NA and CMpf often occurred at the time of the tic, but not always preceding movement onset. Reliable analysis and presentation of the recorded data requires confirmation from further patients and will be reported subsequently. Nevertheless, the activity did seem to be consistent with a role of NA and GPi in the disorder.
Based on the results of testing in the NMU, and in conjunction with the patient and his family, the clinical care team decided to implant permanent electrodes in bilateral Gpi posterior and NA. This decision was based on these targets showing maximal efficacy without side effects. Four permanent Medtronic 3387 DBS leads were implanted and connected to two Medtronic ActivaRC pulse generators (Medtronic Inc., Minneapolis, MN, USA) in the left and right chest. Targeting of the 3387 leads was based on the location of the effective Adtech depth electrodes, as identified on the initial postoperative CT scan. The AC-PC coordinates for the Medtronic leads are shown in Table 2
. Standard stereotactic implantation procedures were followed, and both leads (NA and Gpi posterior) were implanted through a single burr-hole on each side of the head. Lead placement was confirmed with postoperative CT scan. Figure 2
depicts final permanent DBS lead placement location.
After implantation of permanent DBS leads and generators and activation of the pulse generators, the patient demonstrated substantial improvement in tics, with complete and persistent resolution of coprolalia. Initial setting of permanent electrodes were based on optimal settings noted in the NMU- with adjustments based on differing spacing on the Medtronic permanent electrode contacts from the macro-contacts on the sEEG leads as well as assessment of each contact at previous identified optimal frequency to find clinically effective contacts in each location. The patient was seen every 2–3 weeks during which voltage was gradually increased if indicated to sustain benefit. Adjustments in frequency and pulsewidth were made to assess for further benefit and limitation of side effects. Programming visits with a trained clinician (DF, JM, TS) continued every 2–6 weeks as indicated based on patient symptomatology. Intermittently during programming visits, blinded stimulation was performed to confirm results. The patient was noted to require a progressive increase in voltage in NA to maintain benefit. The Yale Global Tic Severity Scale (YGTSS) ratings were performed by a trained staff member (JM) and confirmed independently by the treating neurologist (TDS) (Table 3
). The 15 month assessment was delayed from the standard 12 month assessment due to patient’s delay in returning to clinic as a result of the COVID-19 pandemic. The 57% reduction in tic severity exceeds the 25% threshold for positive response that has been proposed [16
]. The patient was able to return to school, with significant reduction in overall tic severity and complete response of coprolalia that has been maintained up to two years post-surgery. Intermittent motor and simple verbal tics persist. The patient and parents stated strong satisfaction with the surgery, and there has been a self-reported reduction in anxiety and depressive symptoms.