Targeting Accuracy and Clinical Outcomes of Awake versus Asleep Interventional Magnetic Resonance Imaging-Guided Deep Brain Stimulation for Parkinson's Disease: The University of California, San Francisco Experience.

BACKGROUND: Interventional MRI (iMRI)-guided implantation of deep brain stimulator (DBS) leads has been developed to treat patients with Parkinson's disease (PD) without the need for awake testing. OBJECTIVE: Direct comparisons of targeting accuracy and clinical outcomes for awake stereotactic with asleep iMRI-DBS for PD are limited. METHODS: We performed a retrospective review of patients with PD who underwent awake or iMRI-guided DBS surgery targeting the subthalamic nucleus or globus pallidus interna between 2013 and 2019 at our institution. Outcome measures included Unified Parkinson's Disease Rating Scale Part III scores, levodopa equivalent daily dose, radial error between intended and actual lead locations, stimulation parameters, and complications. RESULTS: Of the 218 patients included in the study, the iMRI cohort had smaller radial errors (iMRI: 1.27 ± 0.72 mm, awake: 1.59 ± 0.96 mm, P < .01) and fewer lead passes (iMRI: 1.0 ± 0.16, awake: 1.2 ± 0.41, P < .01). Changes in Unified Parkinson's Disease Rating Scale were similar between modalities, but awake cases had a greater reduction in levodopa equivalent daily dose than iMRI cases ( P < .01), which was attributed to the greater number of awake subthalamic nucleus cases on multivariate analysis. Effective clinical contacts used for stimulation, side effect thresholds, and complication rates were similar between modalities. CONCLUSION: Although iMRI-DBS may result in more accurate lead placement for intended target compared with awake-DBS, clinical outcomes were similar between surgical approaches. Ultimately, patient preference and surgeon experience with a given DBS technique should be the main factors when determining the "best" method for DBS implantation.

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial.

OBJECTIVE: The aim of this study was to evaluate the feasibility and preliminary efficacy and safety of combined bilateral ventralis oralis posterior/ventralis intermedius (Vop/Vim) deep brain stimulation (DBS) for the treatment of acquired dystonia in children and young adults. Pallidal DBS is efficacious for severe, medication-refractory isolated dystonia, providing 50%-60% long-term improvement. Unfortunately, pallidal stimulation response rates in acquired dystonia are modest and unpredictable, with frequent nonresponders. Acquired dystonia, most commonly caused by cerebral palsy, is more common than isolated dystonia in pediatric populations and is more recalcitrant to standard treatments. Given the limitations of pallidal DBS in acquired dystonia, there is a need to explore alternative brain targets. Preliminary evidence has suggested that thalamic stimulation may be efficacious for acquired dystonia. METHODS: Four participants, 3 with perinatal brain injuries and 1 with postencephalitic symptomatic dystonia, underwent bilateral Vop/Vim DBS and bimonthly evaluations for 12 months. The primary efficacy outcome was the change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) scores between the baseline and 12-month assessments. Video documentation was used for blinded ratings. Secondary outcomes included evaluation of spasticity (Modified Ashworth Scale score), quality of life (Pediatric Quality of Life Inventory [PedsQL] and modified Unified Parkinson's Disease Rating Scale Part II [UPDRS-II] scores), and neuropsychological assessments. Adverse events were monitored for safety. RESULTS: All participants tolerated the procedure well, and there were no safety concerns or serious adverse events. There was an average improvement of 21.5% in the BFMDRS motor subscale score, but the improvement was only 1.6% according to the BADS score. Following blinded video review, dystonia severity ratings were even more modest. Secondary outcomes, however, were more encouraging, with the BFMDRS disability subscale score improving by 15.7%, the PedsQL total score by 27%, and the modified UPDRS-II score by 19.3%. Neuropsychological assessment findings were unchanged 1 year after surgery. CONCLUSIONS: Bilateral thalamic neuromodulation by DBS for severe, medication-refractory acquired dystonia was well tolerated. Primary and secondary outcomes showed highly variable treatment effect sizes comparable to those of pallidal stimulation in this population. As previously described, improvements in quality of life and disability were not reflected in dystonia severity scales, suggesting a need for the development of scales specifically for acquired dystonia.Clinical trial registration no.: NCT03078816 (clinicaltrials.gov).

Recommendations for Deep Brain Stimulation Device Management During a Pandemic.

Most medical centers are postponing elective procedures and deferring non-urgent clinic visits to conserve hospital resources and prevent spread of COVID-19. The pandemic crisis presents some unique challenges for patients currently being treated with deep brain stimulation (DBS). Movement disorder (Parkinson's disease, essential tremor, dystonia), neuropsychiatric disorder (obsessive compulsive disorder, Tourette syndrome, depression), and epilepsy patients can develop varying degrees of symptom worsening from interruption of therapy due to neurostimulator battery reaching end of life, device malfunction or infection. Urgent intervention to maintain or restore stimulation may be required for patients with Parkinson's disease who can develop a rare but potentially life-threatening complication known as DBS-withdrawal syndrome. Similarly, patients with generalized dystonia can develop status dystonicus, patients with obsessive compulsive disorder can become suicidal, and epilepsy patients can experience potentially life-threatening worsening of seizures as a result of therapy cessation. DBS system infection can require urgent, and rarely emergent surgery. Elective interventions including new implantations and initial programming should be postponed. For patients with existing DBS systems, the battery status and electrical integrity interrogation can now be performed using patient programmers, and employed through telemedicine visits or by phone consultations. The decision for replacement of the implantable pulse generator to prevent interruption of DBS therapy should be made on a case-by-case basis taking into consideration battery status and a patient's tolerance to potential therapy disruption. Scheduling of the procedures, however, depends heavily on the hospital system regulations and on triage procedures with respect to safety and resource utilization during the health crisis.

Surgical Treatment of Parkinson Disease.

Surgery in Parkinson disease is effective for a select group of patients when optimal medical management is not sufficient. Functional neurosurgery can be used as either a salvage therapy in patients with disabling symptoms or to maintain quality of life and independence before progression to severe disability in high-functioning patients. With recent technological advancements in imaging and targeting as well as novel neuromodulation paradigms, there are numerous options for targeted brain lesions and deep brain stimulation. Surgical decision making and postoperative management in Parkinson disease therefore often requires a multidisciplinary team effort with neurology, neurosurgery, neuropsychology, and psychiatry.

Benefits and risks of unilateral and bilateral ventral intermediate nucleus deep brain stimulation for axial essential tremor symptoms.

INTRODUCTION: Many experts assume bilateral deep brain stimulation (DBS) is necessary to improve axial tremor in essential tremor (ET). In the largest clinical trial of DBS for ET to date evaluating a non-directional, constant current device, we studied the effects of unilateral and staged bilateral DBS on axial tremor. METHODS: We included all participants from the original trial with unilateral ventral intermediate nucleus (VIM) DBS and 90-day follow up at minimum. Primary outcomes were changes in pooled axial subscores in the Clinical Rating Scale for Tremor (CRST) at 90 and 180 days after activation of unilateral VIM DBS compared to pre-operative baseline (n=119). Additionally, we performed within-subject analyses for unilateral versus bilateral DBS at 180 days in the cohort who underwent staged surgery to bilateral DBS (n=39). RESULTS: Unilateral VIM DBS improved midline tremor by 58% at 90 days (median[IQR]) (3[3] to 1[2], p<0.001) and 65% at 180 days (3[3] to 1[2], p<0.001) versus pre-op baseline. In the staged to bilateral DBS cohort, midline tremor scores further improved after bilateral DBS at 180 days by 63% versus unilateral DBS (3[3] to 1[3], p=0.007). There were, however, 35 additional DBS and surgery-related adverse events, 14 related to incoordination, gait impairment, or speech impairment, versus 6 after unilateral DBS. CONCLUSION: Unilateral VIM DBS for ET significantly improved associated axial tremor. Staged bilateral DBS was associated with additional axial tremor improvement but also additional adverse events. Unilateral VIM DBS may be sufficient to achieve a goal of contralateral limb and axial tremor attenuation.

Cortical Potentials Evoked by Subthalamic Stimulation Demonstrate a Short Latency Hyperdirect Pathway in Humans.

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.

Physiological effects of subthalamic nucleus deep brain stimulation surgery in cervical dystonia.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) surgery is clinically effective for treatment of cervical dystonia; however, the underlying physiology has not been examined. We used transcranial magnetic stimulation (TMS) to examine the effects of STN DBS on sensorimotor integration, sensorimotor plasticity and motor cortex excitability, which are identified as the key pathophysiological features underlying dystonia. METHODS: TMS paradigms of short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) were used to examine the sensorimotor integration. Sensorimotor plasticity was measured with paired associative stimulation paradigm, and motor cortex excitability was examined with short interval intracortical inhibition and intracortical facilitation. DBS was turned off and on to record these measures. RESULTS: STN DBS modulated SAI and LAI, which correlated well with the acute clinical improvement. While there were no changes seen in the motor cortex excitability, DBS was found to normalise the sensorimotor plasticity; however, there was no clinical correlation. CONCLUSION: Modulation of sensorimotor integration is a key contributor to clinical improvement with acute stimulation of STN. Since the motor cortex excitability did not change and the change in sensorimotor plasticity did not correlate with clinical improvement, STN DBS demonstrates restricted effects on the underlying physiology. CLINICAL TRIAL REGISTRATION: NCT01671527.

Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease: A Review.

Importance: Selection of the best deep brain stimulation (DBS) target-subthalamic nucleus (STN) or globus pallidus interna (GPi)-for treatment of motor complications in Parkinson disease remains a matter of debate. Observations: Increasing evidence from randomized clinical trials indicates that motor benefit is similar between both targets, including an effect on dyskinesia and improvement in quality of life. Deep brain stimulation of the STN offers consistently greater dopaminergic medication reduction, possible mild benefit in nonmotor domains, and potential economic advantage. Deep brain stimulation of the GPi provides a probable advantage in dyskinesia suppression, management of symptoms with unilateral leads, and flexibility in medications and programming adjustments. Overall, STN DBS is at potentially higher or equal risk for neuropsychiatric changes compared with GPi DBS. Conclusions and Relevance: Both GPi and STN DBS provide similar, consistent, marked motor benefits, but subtle target differences exist. Target selection should be tailored to each patient's clinical presentation, neuropsychiatric profile, and goals of surgery, allowing customization of this therapy and improved individual outcomes.

Parkinson's disease patient preference and experience with various methods of DBS lead placement.

INTRODUCTION: Physiology-guided deep brain stimulation (DBS) surgery requires patients to be awake during a portion of the procedure, which may be poorly tolerated. Interventional MRI-guided (iMRI) DBS surgery was developed to use real-time image guidance, obviating the need for patients to be awake during lead placement. METHODS: All English-speaking adults with PD who underwent iMRI DBS between 2010 and 2014 at our Center were invited to participate. Subjects completed a structured interview that explored perioperative preferences and experiences. We compared these responses to patients who underwent the physiology-guided method, matched for age and gender. RESULTS: Eighty-nine people with PD completed the study. Of those, 40 underwent iMRI, 44 underwent physiology-guided implantation, and five underwent both methods. There were no significant differences in baseline characteristics between groups. The primary reason for choosing iMRI DBS was a preference to be asleep during implantation due to: 1) a history of claustrophobia; 2) concerns about the potential for discomfort during the awake physiology-guided procedure in those with an underlying pain syndrome or severe off-medication symptoms; or 3) non-specific fear about being awake during neurosurgery. CONCLUSION: Participants were satisfied with both DBS surgery methods. However, identification of the factors associated with a preference for iMRI DBS may allow for optimization of patient experience and satisfaction when choices of surgical methods for DBS implantation are available.

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial.

INTRODUCTION: This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). METHODS: A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. RESULTS: 127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). CONCLUSION: Unilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET.

Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

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.

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease.

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.

Pallidal stimulation for Holmes tremor: clinical outcomes and single-unit recordings in 4 cases.

OBJECT: Holmes tremor (HT) is characterized by irregular, low-frequency (< 4.5 Hz) tremor occurring at rest, with posture, and with certain actions, often affecting proximal muscles. Previous reports have tended to highlight the use of thalamic deep brain stimulation (DBS) in cases of medication-refractory HT. In this study, the authors report the clinical outcome and analysis of single-unit recordings in patients with medication-refractory HT treated with globus pallidus internus (GPi) DBS. METHODS: The authors retrospectively reviewed the medical charts of 4 patients treated with pallidal DBS for medication-refractory HT at the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center. Clinical outcomes were measured at baseline and after surgery using an abbreviated motor-severity Fahn-Tolosa-Marin (FTM) tremor rating scale. Intraoperative microelectrode recordings were performed with patients in the awake state. The neurophysiological characteristics identified in HT were then also compared with characteristics previously described in Parkinson's disease (PD) studied at the authors' institution. RESULTS: The mean percentage improvement in tremor motor severity was 78.87% (range 59.9%-94.4%) as measured using the FTM tremor rating scale, with an average length of follow-up of 33.75 months (range 18-52 months). Twenty-eight GPi neurons were recorded intraoperatively in the resting state and 13 of these were also recorded during contralateral voluntary arm movement. The mean firing rate at rest in HT was 56.2 ± 28.5 Hz, and 63.5 ± 19.4 Hz with action, much lower than the GPi recordings in PD. GPi unit oscillations of 2-8 Hz were prominent in both patients with HT and those with PD, but in HT, unlike PD, these oscillations were not suppressed by voluntary movement. CONCLUSIONS: The efficacy of GPi DBS exceeded that reported in prior studies of ventrolateral thalamus DBS and suggest GPi may be a better target for treating HT. These clinical and neurophysiological findings help illuminate evolving models of HT and highlight the importance of cerebellar-basal ganglia interactions.

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain.

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 ).

Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia.

BACKGROUND: Subthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters. OBJECTIVE: Here we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia. METHODS: Seven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient's pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery. RESULTS: Patients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments. CONCLUSION: This study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation.

Neuromodulation for dystonia: target and patient selection.

Treatment of dystonia refractory to oral medications or botulinum toxin injections includes the use of deep brain stimulation (DBS). Expectations should be established based on patient-related factors, including type of dystonia, genetic cause, target symptoms, age at the time of surgery, disease duration, or the presence of fixed skeletal deformities. Premorbid conditions such as psychiatric illness and cognitive impairment should be considered. Target selection is an emerging issue in DBS for dystonia. Although efficacy has been established for targeting the globus pallidus internus for dystonia, other brain targets such as the subthalamic nucleus, thalamus, or cortex may be promising alternatives.

Predictive factors of outcome in primary cervical dystonia following pallidal deep brain stimulation.

BACKGROUND: Improvement after bilateral globus pallidus internus deep brain stimulation (DBS) in primary generalized dystonia has been negatively associated with disease duration and age, but no predictive factors have been identified in primary cervical dystonia (CD). METHODS: Patients treated with bilateral globus pallidus internus DBS for primary CD from 2 DBS centers with preoperative and postoperative Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) were studied retrospectively to explore possible predictors of response. RESULTS: Patients showed significantly improved TWSTRS total and severity scores (n = 28, mean 55.6% and 50.8%, respectively, both P < .001). Patients with lateral shift at baseline had less improvement in TWSTRS severity subscores (P = .02). No correlations between outcomes and disease duration, age at dystonia onset or surgery, baseline scores, or other included variables were found. CONCLUSIONS: Although this is the largest study supporting efficacy of bilateral pallidal DBS in primary CD, no major clinical predictive outcomes of surgical benefit were identified.

Use of pallidal deep brain stimulation in postinfarct hemidystonia.

BACKGROUND/AIMS: Reports of outcomes in treating dystonia secondary to stroke with deep brain stimulation (DBS) are limited. We report our experience with 3 patients, all with infarcts involving the striatum, who developed hemidystonia and were treated with unilateral globus pallidus interna DBS. METHODS: Case series describing characteristics and outcomes based on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores before and after DBS at 3, 6 and at least 12 months. RESULTS: All patients reported subjective improvements after surgery. At 1 year or more after surgery, none of the 3 patients displayed a measureable improvement in the BFMDRS movement score. CONCLUSION: Our findings are consistent with previous reports of limited benefits from pallidal DBS in secondary dystonia. Future work should focus on predictive factors for DBS outcomes and the development of more sensitive assessment tools specifically for secondary dystonias as well as the exploration of alternative brain targets for stimulation.