Globus Pallidus Internus Stimulation Research Articles

Pallidal and Thalamic Deep Brain Stimulation in the Treatment of Unilateral Dystonia: A Prospective Assessment.

The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking. To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia. Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously. DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations. This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach.

Unilateral globus pallidus internus combined contralateral subthalamic nucleus deep brain stimulation in the treatment of cervical dystonia: a case report and literature review

Background: Deep brain stimulation (DBS) is an effective treatment modality for medication-refractory cervical dystonia (CD). In recent years, the asymmetric targets for lead implantation of DBS have become a more valued topic. Objectives: To explore the efficacy of the asymmetric targets for lead implantation of DBS. Methods: A patient with CD underwent unilateral globus pallidus internus (GPi) combined contralateral subthalamic nucleus (STN) deep brain stimulation. Results: Although neither unilateral GPi nor STN stimulation relieved the patient’s clinical symptoms during temporary testing after surgery, the positive effect of bilateral stimulation was substantial. At the 12-month postoperative evaluation, the patient’s clinical symptoms improved remarkably, with an improvement rate of 78% compared with the preoperative assessment. Conclusions: Combined with the previous kinds of literature we reviewed in this article, we propose that in addition to conventional lead implantation, the option of using asymmetric targets for lead implantation can be considered when physicians encounter special conditions and can also be effective in relieving clinical symptoms in patients with CD.

Effect of Deep Brain Stimulation on Parkinson Disease Dementia: A Systematic Review and Meta-analysis.

Patients in the early stages of Parkinson disease (PD) may have subtle cognitive deficits, while overt cognitive deficits are usually manifestations of late-stage PD. There is still a debate on the outcome of deep brain stimulation (DBS) on the cognitive function of PD patients. This study aimed to investigate the effect of subthalamic nucleus (STN)-DBS on the dementia of PD patients after surgery compared to medical therapy and other procedures. We searched PubMed, Scopus, Cochrane Library, and Web of Science database on October 2020, with keywords: "Deep brain stimulation," "Parkinson disease," "dementia," and "memory." Reviews, abstracts, case presentations, and letters were excluded. In total, 491 studies were screened after removing the duplicates. The screening results yielded 81 articles to be screened for eligibility. Finally, 6 studies were included in this meta-analysis for synthesis. Overall, 800 patients were included in this meta-analysis, using the Mattis dementia rating scale (MDRS) and descriptive data from the articles extracted to assess global dementia. Our results suggest that the STN-DBS group showed a larger cognitive decline than the patients receiving the best medical treatment (BMT). However, comparing STN-DBS with globus pallidus interna stimulation and pallidotomy could not demonstrate a significant statistical effect on the global dementia of patients. More long-term studies with larger sample sizes are needed to validate current findings.

The use of flexible botulinum toxin type A inter-injection intervals after removal of deep brain stimulation due to infection in patient with DYT-THAP1 (DYT6)

Deep brain stimulation of globus pallidus internus is a safe and effective method of treatment of isolated generalized dystonia. Abrupt discontinuation of stimulation can lead to a sharp increase in the severity of the condition with a significant increase in the risk of dystonic status. Correction of the condition by selecting conservative therapy is often insufficient. Based on the description of a clinical observation, we demonstrated the possibility of effective use of flexible botulinum toxin type A inter-injection intervals after removal of deep brain stimulation due to infection in patient with DYT-THAP1 (DYT6). Due to the high risk of formation of antibodies to botulinum toxin type A when using short intervals, as well as when using high doses, preference was given to a drug with proven low immunogenicity — incobotulotoxin A. Incobotulotoxin A was administered once a month in a total dose of 400 units to various muscle groups (head, neck, trunk, limbs). At the time of publication, the duration of follow-up was six months, six procedures were performed, a total of 2,400 units of incobotulotoxin A. No significant side effects were noted. Evaluation of the effectiveness of the therapy was carried out by calculating the points of the Burke–Fahn–Marsden Dystonia Rating Scale. There was a decrease from 34 points (the indicator at the time of termination of neurostimulation) to 13.5 points (after six months of therapy). The therapy allowed the patient to maintain motor activity during the waiting period for repeated deep brain stimulation.

The Effects of Deep Brain Stimulation on Mood and Quality of Life in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Deep brain stimulation (DBS) is extensively used to treat motor and non-motor symptoms in Parkinson's disease (PD). The aim of this study was to investigate the difference between subthalamic (STN) and globus pallidus internus (GPi) DBS on mood and quality of life with reference to minimal clinically important differences (MCID). A systematic literature search for articles published until November 2022 yielded 14 studies meeting the eligibility criteria, with a total of 1,088 patients undergoing STN (n=571) or GPi (n=517) stimulation. Baseline patient and clinical characteristics were comparable between the two groups. Results showed that GPi stimulation demonstrated a greater reduction in the Beck depression inventory (mean difference (MD)=1.68) than STN stimulation (MD=0.84). Hospital anxiety and depression scale showed a 2.69- and 3.48-point decrease by the GPi group in the depression and anxiety categories, respectively. The summary index (SI) of the PD questionnaire depicted a greater improvement in the GPi group from baseline (mean=41.01, 95% CI 34.89, 47.13) to follow-up (mean=30.85, 95% CI 22.08, 39.63) when compared to the STN group (baseline mean=42.43, 95% CI 34.50, 50.37; follow-up mean=34.21, 95% CI 25.43, 42.99). The emotions category also demonstrated a similar trend. However, STN stimulation showed greater reductions in motor symptoms and medication than GPi stimulation. This meta-analysis demonstrated that GPi stimulation seems to offer an advantage over STN stimulation in improving mood and quality of life in PD, but those effects must be further validated by larger studies.

Deep Brain Stimulation in the Treatment of Tardive Dyskinesia.

Tardive dyskinesia (TD) is a phenomenon observed following the predominantly long-term use of dopamine receptor blockers (antipsychotics) widely used in psychiatry. TD is a group of involuntary, irregular hyperkinetic movements, mainly in the muscles of the face, eyelid, lips, tongue, and cheeks, and less frequently in the limbs, neck, pelvis, and trunk. In some patients, TD takes on an extremely severe form, massively disrupting functioning and, moreover, causing stigmatization and suffering. Deep brain stimulation (DBS), a method used, among others, in Parkinson's disease, is also an effective treatment for TD and often becomes a method of last resort, especially in severe, drug-resistant forms. The group of TD patients who have undergone DBS is still very limited. The procedure is relatively new in TD, so the available reliable clinical studies are few and consist mainly of case reports. Unilateral and bilateral stimulation of two sites has proven efficacy in TD treatment. Most authors describe stimulation of the globus pallidus internus (GPi); less frequent descriptions involve the subthalamic nucleus (STN). In the present paper, we provide up-to-date information on the stimulation of both mentioned brain areas. We also compare the efficacy of the two methods by comparing the two available studies that included the largest groups of patients. Although GPi stimulation is more frequently described in literature, our analysis indicates comparable results (reduction of involuntary movements) with STN DBS.

Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus and Globus Pallidus Internus in Parkinson's Disease: A Meta-Analysis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder typically manifested by its motor symptoms. In addition, PD patients also suffer from many nonmotor symptoms (NMSs), such as apathy. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the globus pallidus internus (GPi) are recommended as therapeutic interventions for PD, given their pronounced benefit in reducing troublesome dyskinesia. Apathy, a mood disorder recognized as a NMS of PD, has a negative impact on the prognosis of PD patients. However, the effect of STN-DBS and GPi-DBS on apathy is controversial. In the current meta-analysis, we analyzed apathy following bilateral STN-DBS and GPi-DBS in PD patients. Relevant literature was retrieved from public databases, including PubMed, Cochrane Library, and Embase. Studies were included in our analysis based on the following criterion: such studies should report apathy scores presurgery and postsurgery determined by using the Starkstein Apathy Scale or Apathy Evaluation Scale in patients receiving STN or GPi-DBS with at least three months of follow-up. Upon applying this strict criterion, a total of 13 out of 302 studies were included in our study. A mean difference (MD) and 95% confidence interval (CI) were calculated to show the change in apathy scores. We found a statistically significant difference between the presurgery and postsurgery scores in patients receiving STN-DBS (MD = 2.59, 95% CI = 2.23–2.96, P < 0.00001), but not in patients receiving GPi-DBS (MD = 0.32, 95% CI = −2.78–3.41, P=0.84). STN-DBS may worsen the condition of apathy, which may result from the reduction of dopaminergic medication. In conclusion, STN-DBS seems to relatively worsen the condition of apathy compared to GPi-DBS. Further studies should focus on the mechanisms of postoperatively apathy and the degree of apathy in STN-DBS versus GPi-DBS.

Combined thalamic and pallidal deep brain stimulation for dystonic tremor

BackgroundDeep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets. ObjectivesTo report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated. MethodsThree patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition. ResultsThe Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed. ConclusionCombined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them.

First case of new-onset psychosis due to DBS in the ventralis intermediate nucleus (Vim) of the thalamus

IntroductionKnown risk factors for developing of first-time psychosis in patients with deep brain stimulator (DBS) include older age, short time after implant placement and cerebral target for stimulation. In particular, stimulation of subtalamic nucleus and globus pallidus internus has been shown to elicit psychotic symptoms in various case reports. To date, there are no cases describing onset of psychosis due to DBS in the ventralis intermediate nucleus (Vim) of the thalamus.ObjectivesCase describtion of psychotic episode provoked by DBS in Vim regionMethodsCase report of 70 y.o. female with unilateral DBS from 2012 in Vim for essential tremor, who developed therapy resistant psychotic symptoms right after adjusted settings of the DBS.ResultsPsychotic onset of otherwise healthy 70 y.o. patient occurred and gradually worsened after adjustment of DBS settings in absence of other iatrogenic factors, including medication and comorbidity, and required involuntary hospitalization one week after beginning of psychosis. Treatment after hospitalization comprised olanzapine 10 mg. 1dd1 did not cause resolvent of psychosis. Because of therapy resistance to psychofarmaca and worsening of psychotic symptoms, by way of exception neurologists had to change the settings back to basic leading to complete and sustained remission of psychosis within two days.ConclusionsAmong side effects of DBS in Vim, psychotic symptoms have never been reported. However, as in our patient, psychosis occurred after changes of settings in DBS and presented acutely, was severe, resulted in involuntary hospitalization and was therapy resistant. Pathophysiology of DBS-induced psychosis in Vim region is not known and requires further investigation.DisclosureNo significant relationships.

Utility of GPI+VIM dual-lead deep brain stimulation for Parkinson's disease patients with significant residual tremor on medication.

Randomized controlled trials have demonstrated that deep brain stimulation (DBS) of both the globus pallidus internus (GPI) and subthalamic nucleus (STN) for Parkinson's disease (PD) is superior to the best medical therapy. Tremor is particularly responsive to DBS, with reports of 70%-80% improvement. However, a small number of patients do not obtain the expected response with both STN and GPI targets. Indeed, the authors' patient population had a similar 81.2% tremor reduction with a 9.6% failure rate. In an analysis of these failures, they identified patients with preoperative on-medication tremor who subsequently received a GPI lead as a subpopulation at higher risk for inadequate tremor control. Thereafter, STN DBS was recommended for patients with on-medication tremor. However, for the patients with symptoms and comorbidities that favored GPI as the target, dual GPI and ventral intermediate nucleus of the thalamus (VIM) leads were proposed. This report details outcomes for those patients. This is a retrospective review of patients with PD who met the criteria for and underwent simultaneous GPI+VIM DBS surgery from 2015 to 2020 and had available follow-up data. The preoperative Unified Parkinson's Disease Rating Scale scores were obtained with the study participants on and off their medication. Postoperatively, the GPI lead was kept on at baseline and scores were obtained with and without VIM stimulation. Thirteen PD patients with significant residual preoperative tremor on medication underwent simultaneous GPI+VIM DBS surgery (11 unilateral, 2 bilateral). A mean 90.6% (SD 15.0%) reduction in tremor scores was achieved with dual GPI+VIM stimulation compared to a 21.8% (SD 71.9%) reduction with GPI stimulation alone and a 30.9% (SD 37.8%) reduction with medication. Although rigidity and bradykinesia reductions were accomplished with just GPI stimulation, 13 of the 15 hemispheres required VIM stimulation to achieve excellent tremor control. GPI+VIM stimulation was required to adequately control tremor in all but 2 patients in this series, substantiating the authors' hypothesis that, in their population, medication-resistant tremor does not completely respond to GPI stimulation. Dual stimulation of the GPI and VIM proved to be an effective option for the patients who had symptoms and comorbidities that favored GPI as a target and had medication-resistant tremor.

Early Deep Brain Stimulation of Globus Pallidus Internus in Primary Meige s Syndrome: a successful case report and literature review

Welcome to BRAZILIAN JOURNAL OF NEUROSURGERY (JBNC), the official journal of the Brazilian Academy of Neurosurgery, is the oldest Neurosurgery journal in our country. It started in 1973 with the name of “Seara Médica Neurocirúrgica” and, since the beginning, it has been an extremely important information organ for Brazilian neurosurgeons. Brazil is the country with the third largest number of neurosurgeons in the world. Despite this large number of colleagues working in the specialty, we still do not have any journal indexed in PubMedTM, which is considered the most important database for medical journals in the world. Bem-vindo ao Jornal Brasileiro de Neurocirurgia - JBNC. Welcome to Brazilian Journal of Neurosurgery. O JORNAL BRASILEIRO DE NEUROCIRURGIA (JBNC), órgão oficial da Academia Brasileira de Neurocirurgia, é a revista de neurocirurgia mais antiga do nosso país. Iniciou no ano de 1973 com o nome de “Seara Médica Neurocirúrgica” e desde o início tem sido um órgão de informação de extrema importância para os neurocirurgiões brasileiros.

Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia.

We review the findings for motor cortical excitability, plasticity and evoked potentials in dystonia. Plasticity can be induced and assessed in cortical areas by non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and the invasive technique of deep brain stimulation (DBS), which allows access to deep brain structures. Single-pulse TMS measures have been widely studied in dystonia and consistently showed reduced silent period duration. Paired pulse TMS measures showed reduced short and long interval intracortical inhibition, interhemispheric inhibition, long-latency afferent inhibition and increased intracortical facilitation in dystonia. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex improved handwriting with prolongation of the silent period in focal hand dystonia patients. Continuous theta-burst stimulation (cTBS) of the cerebellum or cTBS of the dorsal premotor cortex improved dystonia in some studies. Plasticity induction protocols in dystonia demonstrated excessive motor cortical plasticity with the reduction in cortico-motor topographic specificity. Bilateral DBS of the globus pallidus internus (GPi) improves dystonia, associated pain and functional disability. Local field potentials recordings in dystonia patients suggested that there is increased power in the low-frequency band (4-12Hz) in the GPi. Cortical evoked potentials at peak latencies of 10 and 25ms can be recorded with GPi stimulation in dystonia. Plasticity induction protocols based on the principles of spike timing dependent plasticity that involved repeated pairing of GPi-DBS and motor cortical TMS at latencies of cortical evoked potentials induced motor cortical plasticity. These studies expanded our knowledge of the pathophysiology of dystonia and how cortical excitability and plasticity are altered with different treatments such as DBS.

Efficacy of deep brain stimulation of the anterior-medial globus pallidus internus in tic and non-tic related symptomatology in refractory Tourette syndrome

IntroductionAlthough refractory Tourette Syndrome (TS) is rare, it poses great challenges in clinical practice. Co-morbid psychiatric symptoms often occur, negatively impacting quality of life. Deep brain stimulation (DBS) targeting different brain structures seems effective for tics, but specific literature regarding response of psychiatric symptoms is more limited.This study aimed to assess the outcome of tics and non-tic related symptomatology in refractory TS treated with antero-medial globus pallidus interna (amGPi) DBS. MethodsWe included all patients with refractory TS (January 2013–August 2020) from the Brain Nerve Centre and Steve Biko Academic Hospital, Pretoria, South Africa, treated with bilateral amGPi DBS; retrospective baseline, early (up to 3 months) post-DBS follow-up assessment data, as well as prospective data from the latest follow-up (mean 37.4 months) were collected using standardised scoring tools and scales. ResultsFive patients were identified. Tics decreased by 63,9% (p = 0,002); quality of life improved by 39,8% (p = 0,015); self-injurious behaviour ceased; obsessive–compulsive symptoms resolved in all but one. The number of different chronic medications used more than halved. Transient stimulation-related adverse events occurred in four patients. ConclusionThis study contributes to the data of the efficacy of amGPi-targeted DBS in refractory TS, showing improvement in quality of life and both tic- and non-tic-related symptomatology..

Deep Brain Stimulation of Globus Pallidus

The globus pallidus internus(GPi)has evolved as a potential target for deep brain stimulation(DBS)in patients with advanced Parkinson's disease(PD). GPi stimulation has a significant impact on intractable hyperkinetic movement disorders. Optimal surgical procedures require a combination of image-based targeting and intraoperative microelectrode recording(MER)strategies. Provocation with stimulation through microelectrode or a DBS electrode is also crucial for refining the appropriate electrode position and obtaining a wide therapeutic window of stimulation parameters. In patients with PD, the best target for deep brain stimulation, whether subthalamic nucleus(STN)or the GPi, has been a subject of interest in recent medical literature. STN remains the preferred target for DBS in patients with advanced PD worldwide. In postoperative medication reduction, numerous data support that STN stimulation reduces the total dose of anti-parkinsonian drugs compared to GPi stimulation. However, GPi stimulation has shown a direct anti-dyskinetic effect, without reducing levodopa. Thus, GPi stimulation might be recommended for patients with neurocognitive or neuropsychiatric issues. GPi stimulation has a potential for treating hyperkinetic movement disorders. In patients with PD, STN stimulation is preferred worldwide; however, GPi stimulation has a clinical advantage only for select patients.

Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation for Treatment of Parkinson Disease: A Pilot Study of Symptom-Tailored Stimulation.

BACKGROUNDSubthalamic nucleus (STN) and globus pallidus interna (GPi) are the most effective targets in deep brain stimulation (DBS) treatment for Parkinson disease (PD). However, the individualized selection of targets remains a clinical challenge.OBJECTIVETo combine unilateral STN and contralateral GPi stimulation (STN DBS in one brain hemisphere and GPi DBS in the other) to maximize the clinical advantages of each target while inducing fewer adverse side effects in selected patients with PD because each target has its own clinical effects and risk profiles.METHODSWe reviewed the clinical outcomes of 8 patients with idiopathic PD treated with combined unilateral STN and contralateral GPi DBS. Clinical outcome assessments, focusing on motor and nonmotor symptoms, were performed at baseline and 6-mo and 12-mo follow-up. We performed the assessments under the following conditions: medication on and off (bilateral stimulation on and off and unilateral STN stimulation on).RESULTSPatients showed a significant improvement in motor symptoms, as assessed by the Unified Parkinson Disease Rating Scale III (UPDRS-III) and Timed Up-and-Go Test (TUG), in the off-medication/on-stimulation state at 6-mo and 12-mo follow-up. Also, patients reported a better quality of life, and their intake of levodopa was reduced at 12-mo follow-up. In the on-medication condition, bilateral stimulation was associated with an improvement in axial symptoms, with a 64% improvement in measures of gait and falls at 12-mo follow-up. No irreversible adverse side effects were observed.CONCLUSIONOur findings suggest that combined unilateral STN and contralateral GPi DBS could offer an effective and well-tolerated DBS treatment for certain PD patients.

Application of Machine Learning Using Decision Trees for Prognosis of Deep Brain Stimulation of Globus Pallidus Internus for Children With Dystonia.

Background: While Deep Brain Stimulation (DBS) of the Globus pallidus internus is a well-established therapy for idiopathic/genetic dystonia, benefits for acquired dystonia are varied, ranging from modest improvement to deterioration. Predictive biomarkers to aid DBS prognosis for children are lacking, especially in acquired dystonias, such as dystonic Cerebral Palsy. We explored the potential role of machine learning techniques to identify parameters that could help predict DBS outcome.Methods: We conducted a retrospective study of 244 children attending King's College Hospital between September 2007 and June 2018 for neurophysiological tests as part of their assessment for possible DBS at Evelina London Children's Hospital. For the 133 individuals who underwent DBS and had 1-year outcome data available, we assessed the potential predictive value of six patient parameters: sex, etiology (including cerebral palsy), baseline severity (Burke-Fahn-Marsden Dystonia Rating Scale-motor score), cranial MRI and two neurophysiological tests, Central Motor Conduction Time (CMCT) and Somatosensory Evoked Potential (SEP). We applied machine learning analysis to determine the best combination of these features to aid DBS prognosis. We developed a classification algorithm based on Decision Trees (DTs) with k-fold cross validation for independent testing. We analyzed all possible combinations of the six features and focused on acquired dystonias.Results: Several trees resulted in better accuracy than the majority class classifier. However, the two features that consistently appeared in top 10 DTs were CMCT and baseline dystonia severity. A decision tree based on CMCT and baseline severity provided a range of sensitivity and specificity, depending on the threshold chosen for baseline dystonia severity. In situations where CMCT was not available, a DT using SEP alone provided better than the majority class classifier accuracy.Conclusion: The results suggest that neurophysiological parameters can help predict DBS outcomes, and DTs provide a data-driven, highly interpretable decision support tool that lends itself to being used in clinical practice to help predict potential benefit of DBS in dystonic children. Our results encourage the introduction of neurophysiological parameters in assessment pathways, and data collection to facilitate multi-center evaluation and validation of these potential predictive markers and of the illustrative decision support tools presented here.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

IntroductionCognitive symptoms from Parkinson’s disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson’s disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3–8 Hz) and/or beta (10–30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

A pooled meta-analysis of GPi and STN deep brain stimulation outcomes for cervical dystonia.

To analyze deep brain stimulation (DBS) outcomes in patients with cervical dystonia (CD), the relationships between motor and disability/pain outcomes, and the differences in outcomes between globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS, and to identify potential outcome predictors. A systematic literature search identified individual patient data of CD patients who underwent DBS and whose outcomes were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Then, we performed a pooled meta-analysis on this cohort. A review of 39 papers yielded 208 patients with individual TWSTRS scores and demographic information. At a mean follow-up period of 23.3months after either GPi or STN DBS, the TWSTRS total (58.8%), severity (53.9%), disability (61.3%), and pain (46.6%) scores significantly improved compared to baseline status (all p < 0.001). There were no significant outcome differences between short-term (< 23.3months) and long-term (≥ 23.3months). The TWSTRS outcomes after GPi and STN DBS were comparable, whereas these two targets showed different adverse effect profiles. The rates of responders to DBS according to the TWSTRS total and severity (defined as ≥ 25% improvement) were both 89%. Regression analyses demonstrated motor benefits associated with disability improvement more than pain relief (R2 = 0.345 and 0.195, respectively). No clinically meaningful predictors for DBS outcomes were identified. DBS improves motor symptoms, disability, and pain in CD patients and may provide sustained benefits over 2years. GPi and STN appear to be equally effective targets with different adverse effect profiles.

Long-Term Efficacy of Deep Brain Stimulation of Bilateral Globus Pallidus Internus in Primary Meige Syndrome

Objective: Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) is an alternative therapy in ameliorating the clinical symptoms of primary Meige syndrome. Nevertheless, proof of its efficacy and safety is insufficient due to several case reports and small-sample clinical studies. This study aims to investigate postoperative long-term efficacy in patients undergoing DBS of the GPi for primary Meige syndrome. Methods: We performed a retrospective study to assess the efficacy and safety of bilateral GPi stimulation in 40 patients with primary Meige syndrome who responded poorly to medical treatments or botulinum toxin injections. All participants were postoperatively followed up at the outpatient clinic, and their motor functions were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The severity of patients’ dystonia was evaluated before surgery and at follow-up neurostimu­lation. Results: The implanted stimulator was turned on 1 month after surgery. All 40 patients received monopolar stimulation using the following parameters: voltage 2.5–3.5 V (average: 2.6 ± 0.8 V), frequency 60–160 Hz (average: 88.0 ± 21.3 Hz), and pulse width 60–185 μS (average: 90.0 ± 21.1 μS). In 28 of 40 patients, the symptoms had signifi­cantly improved within 1 week of stimulation. Most of the patients had been followed up for 6–24 months (average: 15.0 ± 7.8 months). The clinical symptoms of all patients had significantly improved. At 6, 12, and 24 months after surgery, the BFMDRS subscores of eyes, mouth, speech, and swallowing were significantly lower, and subscores of mouth movement showed progressively decreased with prolonged stimulation time. The overall improvement rate was 83%. Five adverse events occurred in the 40 patients; all of these events resolved without permanent sequelae. Conclusions: Bilateral GPi-DBS demonstrated satisfactory long-term efficacy in the treatment of primary Meige syndrome and could serve as an effective and safe option.

Globus pallidal deep brain stimulation for Tourette syndrome: Effects on cognitive function

IntroductionIn a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS. MethodsPatients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test). ResultsGPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test. ConclusionsThis study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.