Monica Volz

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes

Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising new procedure for the treatment of dystonia. The authors present their technical approach for placement of electrodes into the GPi in awake patients with dystonia, including the methodology used for electrophysiological mapping of the GPi in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients who had various forms of dystonia were included in this study. Baseline neurological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia is technically feasible in the awake state in most cases, with low morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than by rates. Active electrode locations associated with robust improvement (> 50% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance of 3.7 mm from the pallidocapsular border. Patients with juvenile-onset primary dystonia and those with the tardive form benefited greatly from this procedure, whereas benefits for most secondary dystonias and the adult-onset craniocervical form of this disorder were more modest.

Pallidal deep brain stimulation in patients with cranial–cervical dystonia (Meige syndrome)

Idiopathic cranial–cervical dystonia (ICCD) is an adult‐onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke–Fahn–Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.

Subthalamic nucleus deep brain stimulation in primary cervical dystonia

Objectives: The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies. Methods: In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patients preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured. Results: STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation. Conclusions: This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia. Classification of evidence: This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.

Interventional MRI–guided deep brain stimulation in pediatric dystonia: first experience with the ClearPoint system

OBJECT The placement of deep brain stimulation (DBS) leads in adults is traditionally performed using physiological confirmation of lead location in the awake patient. Most children are unable to tolerate awake surgery, which poses a challenge for intraoperative confirmation of lead location. The authors have developed an interventional MRI (iMRI)-guided procedure to allow for real-time anatomical imaging, with the goal of achieving very accurate lead placement in patients who are under general anesthesia. METHODS Six pediatric patients with primary dystonia were prospectively enrolled. Patients were candidates for surgery if they had marked disability and medical therapy had been ineffective. Five patients had the DYT1 mutation, and mean age at surgery was 11.0 ± 2.8 years. Patients underwent bilateral globus pallidus internus (GPi, n = 5) or sub-thalamic nucleus (STN, n = 1) DBS. The leads were implanted using a novel skull-mounted aiming device in conjunction with dedicated software (ClearPoint system), used within a 1.5-T diagnostic MRI unit in a radiology suite, without physiological testing. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used at baseline, 6 months, and 12 months postoperatively. Further measures included lead placement accuracy, quality of life, adverse events, and stimulation settings. RESULTS A single brain penetration was used for placement of all 12 leads. The mean difference (± SD) between the intended target location and the actual lead location, in the axial plane passing through the intended target, was 0.6 ± 0.5 mm, and the mean surgical time (leads only) was 190 ± 26 minutes. The mean percent improvement in the BFMDRS movement scores was 86.1% ± 12.5% at 6 months (n = 6, p = 0.028) and 87.6% ± 19.2% at 12 months (p = 0.028). The mean stimulation settings at 12 months were 3.0 V, 83 μsec, 135 Hz for GPi DBS, and 2.1 V, 60 μsec, 145 Hz for STN DBS). There were no serious adverse events. CONCLUSIONS Interventional MRI-guided DBS using the ClearPoint system was extremely accurate, provided real-time confirmation of DBS placement, and could be used in any diagnostic MRI suite. Clinical outcomes for pediatric dystonia are comparable with the best reported results using traditional frame-based stereotaxy. Clinical trial registration no.: NCT00792532 ( ClinicalTrials.gov ).

Subthalamic nucleus deep brain stimulation in isolated dystonia: A 3-year follow-up study

Objective: To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604). Results: Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia). Conclusions: This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia. Classification of evidence: This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia.

Deep brain stimulator implantation in a diagnostic MRI suite: infection history over a 10-year period

OBJECTIVE The objective of this study was to assess the incidence of postoperative hardware infection following interventional (i)MRI-guided implantation of deep brain stimulation (DBS) electrodes in a diagnostic MRI scanner. METHODS A diagnostic 1.5-T MRI scanner was used over a 10-year period to implant DBS electrodes for movement disorders. The MRI suite did not meet operating room standards with respect to airflow and air filtration but was prepared and used with conventional sterile procedures by an experienced surgical team. Deep brain stimulation leads were implanted while the patient was in the magnet, and patients returned 1-3 weeks later to undergo placement of the implantable pulse generator (IPG) and extender wire in a conventional operating room. Surgical site infections requiring the removal of part or all of the DBS system within 6 months of implantation were scored as postoperative hardware infections in a prospective database. RESULTS During the 10-year study period, the authors performed 164 iMRI-guided surgical procedures in which 272 electrodes were implanted. Patients ranged in age from 7 to 78 years, and an overall infection rate of 3.6% was found. Bacterial cultures indicated Staphylococcus epidermis (3 cases), methicillin-susceptible Staphylococcus aureus (2 cases), or Propionibacterium sp. (1 case). A change in sterile practice occurred after the first 10 patients, leading to a reduction in the infection rate to 2.6% (4 cases in 154 procedures) over the remainder of the procedures. Of the 4 infections in this patient subset, all occurred at the IPG site. CONCLUSIONS Interventional MRI-guided DBS implantation can be performed in a diagnostic MRI suite with an infection risk comparable to that reported for traditional surgical placement techniques provided that sterile procedures, similar to those used in a regular operating room, are practiced.

Bilateral Ventral Intermediate Nucleus Thalamic Deep Brain Stimulation in Orthostatic Tremor

Background: Orthostatic tremor (OT) is characterized by high-frequency leg tremor when standing still, resulting in a sense of imbalance, with limited treatment options. Ventral intermediate (Vim) nucleus thalamic deep brain stimulation (DBS) has been reported as beneficial in a few cases. Objective: To report clinical outcomes, lead locations, and stimulation parameters in 2 patients with severe medication-refractory OT treated with Vim DBS. Methods: The patients underwent surface electromyography (EMG) to confirm the OT diagnosis. Outcomes were measured as change in tolerated standing time at the last follow-up. Lead locations were quantified using postoperative MRI. Results: Vim DBS was well tolerated and resulted in improvement in standing time (patient 1: 50 s at baseline to 15 min 16 months after surgery; patient 2: 34 s at baseline to 4.2 min 7 months after surgery). Postoperative surface EMG for patient 1 demonstrated a delayed onset of tremor, lower-amplitude tremor, and periods of quiescence, but an unchanged tremor frequency. Conclusion: These cases provide further support for Vim DBS to improve standing time in severe medication-refractory OT. The location of the effective thalamic target for OT does not differ from the effective target for essential tremor.

Intractable Blepharospasm Treated with Bilateral Pallidal Deep Brain Stimulation

Background Blepharospasm can be present as an isolated dystonia or in conjunction with other forms of cranial dystonia, causing significant disability. Case Report We report a case of a 69-year-old male with craniocervical dystonia, manifesting primarily as incapacitating blepharospasm refractory to medical treatments. He underwent bilateral globus pallidus (GP) deep brain stimulation (DBS) with complete resolution of his blepharospasm and sustained benefit at 12 months postoperatively. Discussion This case illustrates successful treatment of blepharospasm with pallidal stimulation. GP-DBS should be considered a reasonable therapeutic option for intractable blepharospasm.