Pallidal Deep Brain Stimulation Research Articles

Bilateral Pallidal Deep Brain Stimulation in Meige Syndrome: Effects on Motor Function, Neuropsychological Status, and Mood.

Bilateral pallidal deep brain stimulation (DBS) has been broadly accepted as a feasible surgical procedure for treating various forms of dystonia, but its effects on motor function, neuropsychological status, and mood in patients with Meige syndrome have rarely been examined. To evaluate the effects of bilateral globus pallidus internus DBS (GPi-DBS) on the motor performance, quality of life, neuropsychological status, and mood of patients with primary Meige syndrome. Between January 2015 and April 2019, the database of 35 patients with Meige syndrome who underwent bilateral GPi-DBS in our institution was retrospectively reviewed. The severity of dystonia, health-related quality of life, cognitive function, and mood were assessed using standardized and validated rating scales at baseline. Repeat assessment of the same domains was performed at 1 year and 3 years after neurostimulation in a similar manner. One year and 3 years after bilateral GPi-DBS, Burke-Fahn-Marsden Dystonia Rating Scale movement scores were improved by 65% and 72% and Burke-Fahn-Marsden Dystonia Rating Scale disability scores were improved by 49% and 57%, respectively. The significant improvement in health-related quality of life observed at 1 year was sustained at 3 years. Relative to baseline and to the 1-year assessment, cognitive functions and mood remained stable after 3 years of neurostimulation. No deaths or life-threatening events were reported over the study period. Bilateral GPi-DBS is a safe and effective approach for medically refractory Meige syndrome that can improve motor function and quality of life without cognitive and mood side effects.

Does Pallidal Physiology Determine the Success of Unilateral Deep Brain Stimulation in Cervical Dystonia?

Pallidal deep brain stimulation is a well-known surgical treatment for cervical dystonia. The resolution of dystonia typically requires bilateral pallidal stimulation, but in some instances, unilateral stimulation has been successful. In such instances, generally, the stimulated hemisphere was contralateral to the dystonic sternocleidomastoid, but rarely it was ipsilateral. We sought for the physiological features that determine the basis for success and laterality of deep brain stimulation for cervical dystonia with prominent torticollis. We found that pallidal physiology such as high burst to tonic ratio and significant interhemispheric differences in the neuronal firing rate and regularity are critical determinants of successful treatment with unilateral deep brain stimulation. We also found that higher lateralized differences in pallidal physiological parameters predict more robust improvement. In three out of four patients, the stimulation of the hemisphere ipsilateral to the dystonic sternocleidomastoid muscle was effective. These patients did not have any structural brain abnormalities on clinically available imaging studies. One patient responded to the unilateral deep brain stimulation in the hemisphere contralateral to the dystonic sternocleidomastoid. This patient had a structural putamen lesion on brain MRI. These results provide objective parameters determining the success of pallidal deep brain stimulation for treatment of cervical dystonia. The results also depict differences in the pallidal physiology in patients where ipsilateral versus contralateral deep brain stimulation was effective.

Long-term efficacy of pallidal deep brain stimulation in tardive dystonia: A case report and follow-up of 4 years

Long-term efficacy of pallidal deep brain stimulation in tardive dystonia: A case report and follow-up of 4 years

Short- and long-term outcomes of chronic pallidal deep brain stimulation in the dystonic dtsz hamster

Short- and long-term outcomes of chronic pallidal deep brain stimulation in the dystonic dtsz hamster

Subthalamic Nucleus Deep Brain Stimulation for Dystonia: Evidence, Pros and Cons

The primary target for deep brain stimulation (DBS) for medication refractory dystonia has traditionally been the globus pallidus internus (GPi), however alternate targets have also been explored with the hope they might offer similar or superior outcomes with less side effects and reduced battery demands. Recent studies have shown comparable outcomes with both pallidal and subthalamic (STN) DBS, although the level of evidence is still superior for the GPi. There may not be an “optimal target” for all dystonia patients, with both targets offering the potential for excellent control of dystonia but more comparison studies are needed. In this review, we will discuss the history, efficacy, as well as target specific benefits and possible side effects of STN DBS for dystonia.

Long-Term Outcomes of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series.

Among dystonia patients receiving globus pallidus internus (GPi) deep brain stimulation (DBS), long-term outcomes remain to be established. To report the long-term outcomes of GPi DBS in a patient cohort with idiopathic and acquired dystonia. In this long-term follow-up cohort, there were 4 patients with idiopathic dystonia and 2 patients with acquired dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale was used to evaluate 6 consecutive patients preoperatively and at 6months, 12months, and the last follow-up. The relationship between etiology and clinical improvement was analyzed. Stimulation parameters were evaluated for similarities and differences among these patients. The mean follow-up of our cohort was 65.3months (median 40.5months). The average improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (mean±SEM) were 56%±7.6, 67%±6.8 and 66%±9.7 at 6months, 12months, and the last follow-up, respectively. There was greater improvement during the long-term follow-up in the 4 patients with idiopathic dystonia than in the 2 patients with acquired dystonia. The 2 most ventral electrodes (contact 0 and 1) were activated in all 11 leads in this cohort. The average stimulation intensity, pulse width and frequency were 2.0±0.24mA, 252±43μs, and 99±6.0Hz, respectively. Isolated dystonia, either monogenic or idiopathic, usually responds better to GPi DBS than to acquired dystonia. Selection of patients by dystonia etiology, accurate placement of DBS leads in GPi targets, and proper stimulation programming are crucial to achieve better long-term outcomes.

O032 / #633 PALLIDAL DEEP BRAIN STIMULATION EVOKES RESONANT NEURAL ACTIVITY IN PARKINSON’S DISEASE: TRACK 2: DEEP BRAIN STIMULATION FOR MOVEMENT DISORDERS

Objective markers of therapeutic deep brain stimulation (DBS) for Parkinson’s disease (PD) are needed to tailor stimulation on a patient-specific basis. Recent studies suggest that subthalamic nucleus DBS evoked resonant neural activity (ERNA) may be used to refine targeting and possibly identify therapeutic stimulation parameters [1]. However, ERNA has not been studied in the pallidum, and whether it could be used to guide intraoperative targeting or stimulation programming is unknown. We aimed to determine if ERNA is present with pallidal DBS and if pallidal ERNA features are correlated with baseline PD neurophysiology.

Outcomes of pallidal deep brain stimulation for treating pure blepharospasm

Objective: Blepharospasm (BSP) is a disease in which the closure rate of the bilateral eyelids increases, mainly due to involuntary contraction of the orbicularis oculi, procerus, and corrugator muscles. The objective of this study was to report postoperative outcomes after deep brain stimulation (DBS) in 10 cases of pure BSP after at least 12 months of follow-up.Methods: Ten patients with pure BSP who underwent bilateral globus pallidus interna (GPi) DBS at The Catholic University of Korea, Incheon St. Mary’s Hospital, between 2019 and 2021 were included. The Burke-Fahn-Marsden dystonia rating scale (BFMDRS), Blepharospasm Disability Index, and Jankovic Rating Scale were used for analysis before surgery, at 6 months of follow-up as short-term outcomes, and at follow-up over 1 year (12–37 months) as long-term results. Results: The median age of patients at surgery was 56.5 years (interquartile range [IQR], 50.5–65.8 years) and the median length of time from disease onset to the time of surgery was 58.0 months (IQR, 46.8–64.3 months). The median postoperative follow-up period was 22.5 months (IQR, 15.3–29.0 months). The median BFMDRS movement subscale scores at the three time points (preoperative baseline, 6 months, and over 1 year of follow-up) were 7.0 (IQR, 6.0–8.0), 4.5 (IQR, 3.9–6.0; 35.7% improvement, p<0.001), and 3.8 (IQR, 2.8–5.3; 45.7% improvement, p=0.002), respectively.Conclusion: Bilateral GPi DBS for pure BSP can be effective if conservative treatment options fail. Its benefit is not only observed in the short term, but is also maintained during long-term follow-up.

A case of novel DYT6 dystonia variant with serious complications after deep brain stimulation therapy: a case report

BackgroundDYT6 dystonia belongs to a group of isolated, genetically determined, generalized dystonia associated with mutations in the THAP1 gene.Case presentationWe present the case of a young patient with DYT6 dystonia associated with a newly discovered c14G>A (p.Cys5Tyr) mutation in the THAP1 gene. We describe the clinical phenotype of this new mutation, effect of pallidal deep brain stimulation (DBS), which was accompanied by two rare postimplantation complications: an early intracerebral hemorrhage and delayed epileptic seizures. Among the published case reports of patients with DYT6 dystonia, the mentioned complications have not been described so far.ConclusionsDBS in the case of DYT6 dystonia is a challenge to thoroughly consider possible therapeutic benefits and potential risks associated with surgery. Genetic heterogeneity of the disease may also play an important role in predicting the development of the clinical phenotype as well as the effect of treatment including DBS. Therefore, it is beneficial to analyze the genetic and clinical relationships of DYT6 dystonia.

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms. ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome. MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity). ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls. ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.

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.

Retrospective Multicenter Study on Outcome Measurement for Dyskinesia Improvement in Parkinson's Disease Patients with Pallidal and Subthalamic Nucleus Deep Brain Stimulation.

Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson’s disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-Ⅲ) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006).

Freezing of Gait as a Complication of Pallidal Deep Brain Stimulation in DYT‐KMT2B Patients with Evidence of Striatonigral Degeneration

Freezing of Gait as a Complication of Pallidal Deep Brain Stimulation in <scp>DYT‐<i>KMT2B</i></scp> Patients with Evidence of Striatonigral Degeneration

Adjuvant medical therapy in cervical dystonia after deep brain stimulation: A retrospective analysis.

BackgroundThere is limited information on optimization of symptomatic management of cervical dystonia (CD) after implantation of pallidal deep brain stimulation (DBS).ObjectivesTo describe the long-term, “real-world” management of CD patients after DBS implantation and the role of reintroduction of pharmacologic and botulinum toxin (BoNT) therapy.MethodsA retrospective analysis of patients with focal cervical or segmental craniocervical dystonia implanted with DBS was conducted.ResultsNine patients were identified with a mean follow-up of 41.7 ± 15.7 months. All patients continued adjuvant oral medication(s) to optimize symptom control post-operatively. Three stopped BoNT and four reduced BoNT dose by an average of 22%. All patients remained on at least one medication used to treat dystonia post-operatively.ConclusionOptimal symptom control was achieved with DBS combined with either BoNT and/or medication. We suggest utilization of adjuvant therapies such as BoNT and/or medications if DBS monotherapy does not achieve optimal symptom control.

Neural Correlates of Optimal Deep Brain Stimulation for Cervical Dystonia.

A total of 15 individuals with cervical dystonia and good outcome after pallidal deep brain stimulation underwent resting-state functional magnetic resonance imaging under three conditions: stimulation using a priori clinically determined optimal settings (ON-Op), non-optimal settings (ON-NOp), and stimulation off (OFF). ON-Op > OFF and ON-Op > ON-NOp were both associated with significant deactivation within sensorimotor cortex (changes not seen with ON-NOp > OFF). Brain responses to stimulation were related to individual long-term clinical improvement (R = 0.73, R2 = 0.53, p = 0.001). The relationship was consistent when this model included four additional patients with generalized or truncal dystonia. These findings highlight the potential for immediate imaging-based biomarkers of clinical efficacy. ANN NEUROL 2022;92:418-424.

Outcome of pallidal deep brain stimulation for treating isolated orofacial dystonia.

Isolated orofacial dystonia is a rare segmental neurological disorder that affects the eye, mouth, face, and jaws. Current literature on pallidal surgery for orofacial dystonia is limited to case reports and small-scale studies. This study was to investigate clinical outcomes of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with isolated orofacial dystonia. Thirty-six patients who underwent GPi DBS at Incheon St. Mary's Hospital, The Catholic University of Korea, between 2014 and 2019 were included in this study. Burke-Fahn-Marsden Dystonia Rating Scale, Unified Dystonia Rating Scale, and Global Dystonia Severity Rating Scale were retrospectively retrieved for analysis before surgery, at 6-month follow-up as short-term outcome, and at follow-up over 1year (12months to 69months) as long-term results. Mean total BFMDRS-M scores at the three time points (baseline, 6months, and over 1year follow-up) were 11.6 ± 4.9, 6.1 ± 5.2 (50.3 ± 29.9% improvement, p < 0.05), and 4.3 ± 4.2 (65.0 ± 24.2% improvement, p < 0.05), respectively. In terms of UDRS and GDS, improvement rates were 45.1% (p < 0.001) and 47.7% (p < 0.001) at 6months, and 63.8% (p < 0.001) and 65.7% (p < 0.001) at over 1year after surgery, respectively. Bilateral GPi DBS in isolated orofacial dystonia can be effective if conservative treatment option fails. Its benefit is not only observed in a short term, but also maintained in a long-term follow-up.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia.

ObjectiveTo investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN).MethodsWe reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke–Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRS-D scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively.ResultsFive classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities.ConclusionThe benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease.

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

Difference in the effectiveness of subthalamic nucleus and globus pallidus deep brain stimulation in Parkinson’s disease

Deep brain stimulation (DBS) is regarded as a feasible Parkinson’s disease (PD) treatment option. The subthalamic nucleus (STN) and globus pallidus (GPi) are the two most common sites for DBS. The following criteria were used to select studies that examined the Unified PD Rating Scale (UPDRS) III: (1) had at least three months of follow-up; (2) compared both GPi and STN-DBS; (3) each group included at least five individuals; (4) were conducted after 2010. The majority of studies found no statistically significant difference in UPDRS score improvements between groups. Although there were some encouraging findings in terms of action tremor, rigidity, and urinary symptoms, indicating that STN-DBS would be a better alternative, GPi appeared to be better in terms of side effects; nonetheless, it cannot be said that it is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are required to determine which target is more effective for stimulation and has fewer negative side effects on patients. Keywords: Deep brain stimulation, globus pallidus, Parkinson’s disease, subthalamic nucleus, UPDRS

DBS emergency surgery for treatment of dystonic storm associated with rhabdomyolysis and acute colitis in DYT-GNAO1

IntroductionPatients with variants in the GNAO1 gene may present with life-threatening dystonic storm. There is little experience using pallidal deep brain stimulation (DBS) as an emergency treatment in such cases.Case descriptionWe report on a 16-year-old girl with a variant in the GNAO1 gene (c.626G > T; p.(Arg209Leu)) who was admitted to the intensive care unit with medically refractory dystonic storm with secondary complications inducing rhabdomyolysis and acute colitis. Emergency pallidal DBS resulted in rapid improvement of dystonic storm and the subsidence of rhabdomyolysis and colitis. There were no further episodes of dystonic storm during follow-up of 2 years.ConclusionPallidal DBS is a useful treatment option for GNAO1-related dystonic storm with secondary complications which can be performed as an emergency surgery.