Pallidal Deep Brain Stimulation Research Articles

FV 23 POSe EstimatoR for Cervical Dystonia (POSER-CD): Automatized assessment of clinical severity and kinematic pathosignatures of Cervical Dystonia using convolutional neural networks

Background: Phenomenological description, diagnosis and assessment of disease development, as well as treatment effects, of movement disorders still heavily relies on clinical assessment using scoring scales. However, these scales are inherently prone to rater biases, thereby negatively affecting their reliability and comparability. Objective: To leverage recent advances in computer vision and artificial neural networks to devise a video-based movement analysis, which allows the quantitative measurement of cervical dystonia during clinical scoring of severity using the Toronto Western Spasmodic Torticollis Rating Scale (“TWSTRS-S”) before and after pallidal deep brain stimulation (DBS). Methods: 303 videos documenting the longitudinal TWSTRS-S assessment of 94 individuals who had undergone pallidal deep brain stimulation in the context of three multicentric studies, in addition to 22 standardized videos of healthy subjects (HS) were available for analysis. Clinical videos were retrospectively scored by two independent movement disorder specialists using the TWSTRS-S. HS videos and a subset of clinical videos were used for supervised training of a convolutional neural network for movement classification (MC-CNN) to segment 7 movement states along three axes (pitch, yaw, tilt) mapping to TWSTRS subscore dimensions (head inclination/reclination, turning, tilting). A total of 2178 frames from the video dataset were annotated to train a recurrent CNN for tracking of anatomical landmark points in the videos (R-CNN). Subsequently, coordinate time series were transformed into an anatomically inspired, multidimensional kinematic feature space (i. e. angles, velocities, ratios) to characterize MC-CNN classified movement states relevant to the TWSTRS-S. Results: MC-CNN reached ∼90% accuracy on a held-out test data set. The pose tracking R-CNN achieved train/ test errors of 0.5/ 9.5 mm, corresponding to 1.67/ 7.36 pixels (mean Euclidean distance). Movement classification analysis identified abnormal coherence between face-forward and the rotation and tilt (both left and right) movement states respectively, that are reminiscent of dystonic overflow phenomena and decreased range of motion which could be significantly attenuated by DBS (p<.005 for all comparisons). Furthermore, DBS reversed an abnormal degree of asymmetry in movement representations in 2/3 planes (pitch: p=.009, yaw: p= .011, roll: p= .828). Conclusions: We provide evidence that computer-assisted movement analysis using CNNs is a novel avenue to overcome metrological challenges in the field of movement disorders. CNNs may help derive and analyze patient and/or diagnosis-specific kinematic pathosignatures which can be integrated with multidimensional neural data and may contribute to “precision Neurology”.

FV 5 Striato-pallidal connectivity in oscillatory activity of patients with dystonia

Introduction: Dystonia is a network disorder in which aberrant signaling maybe associated with an imbalance between direct and indirect pathway activity. Invasive recordings from the internal pallidum (Globus pallidus internus, GPi), the major output structure of the basal ganglia, have described exaggerated oscillatory activity in the low frequency (LF) band (4-12 Hz). Oscillatory activity of the human striatum, as its major input structure, and its role in the generation and propagation of pathological LF activity is not well characterized. We hypothesize that i) the basal ganglia are functionally coupled within the LF band, ii) this connectivity is driven by the striatum and iii) LF activity could either be generated or amplified within the direct pathway. Patients & Methods: Rest recordings of local field potentials were performed in 11 patients undergoing pallidal deep brain stimulation (DBS) for cervical, segmental or generalized dystonia in the 1-7 days following surgery while DBS leads were externalized. The lead model used was DB-2201-45Bc, with 8 circular contacts spanning over 15.5 mm. DBS-leads were localized using the open-source software Lead-DBS and bipolar recordings from adjacent electrodes were assigned accordingly to either the putamen, Globus oallidus externus (GPe) or GPi. Power spectra were calculated for recordings from each structure, as well as the imaginary part of coherence (iCOH) as measure of functional connectivity and granger causality to assess directionality of coupling between structures in the LF band. Results: In all patients, one contact pair per hemisphere was localized in each structure of interest, namely the putamen, GPe and GPi. LF peaks could be detected in all structures of both hemispheres in all patients. LF- activity was coupled between all structures of one hemisphere (putamen-GPi, putamen-GPe, GPi-GPe) as assessed by iCOH and higher than coherence in shuffled data. Specifically the extent of coherence between putamen and GPi showed a positive correlation with motor symptom severity (R=0.63, P=.03). Directionality analyses were less consistent, with a trend towards striatum leading LF activity of internal and external pallidum that did not reach significance (P>0.05). Conclusion: We showed for the first time, that i) LF-activity can also be detected in the striatum of dystonia patients and ii) that striatum, GPe and GPi are coupled in this frequency band. However, only functional coupling in the LF-band between striatum and GPi significantly correlated with motor symptoms. This provides further evidence for the hypothesis that dystonia might be associated with aberrant signaling within the direct pathway. Regarding the directionality of LF-activity within the BG-loop, our preliminary results are less consistent and further analyses are needed. Taken together, these findings give insight to the pathophysiology of dystonia and the striatum as a potential target for neuromodulation.

Initial Clinical Outcome With Bilateral, Dual-Target Deep Brain Stimulation Trial in Parkinson Disease Using Summit RC + S.

Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and globus pallidus (GP) DBS show equivalent efficacy in PD, combined stimulation may demonstrate synergism. To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for adaptive DBS therapy in an observational study. We performed a pilot trial (n = 3) of implanting bilateral STN and GP DBS leads, connected to a bidirectional implantable pulse generator (Medtronic Summit RC + S; NCT03815656, IDE No. G180280). Initial 1-year outcome in 3 patients included Unified PD Rating Scale on and off medications, medication dosage, Hauser diary, and recorded beta frequency spectral power. Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating Scale with multiple electrodes activated (mean difference from off stimulation off medications -18.2, range -25.5 to -12.5) than either STN (-12.8, range -20.5 to 0) or GP alone (-9, range -11.5 to -4.5). Combined DBS resulted in a greater reduction of beta oscillations in STN in 5/6 hemispheres than either site alone. Adverse events occurred in 2 patients, including a small cortical hemorrhage and seizure at 24 hours postoperatively, which resolved spontaneously, and extension wire scarring requiring revision at 2 months postoperatively. Patients with PD preferred combined DBS stimulation in this preliminary cohort. Future studies will address efficacy of adaptive DBS as we further define biomarkers and control policy.

Deep Brain Stimulation in childhood-onset dystonia due to brain pathology. A long-term study.

Pallidal Deep Brain Stimulation (DBS) is an established treatment option for isolated, inherited or idiopathic dystonia, however data on its safety and efficacy in other forms of dystonia are more limited. Retrospective analysis of motor and non-motor outcomes in pediatric onset refractory dystonia due to static or progressive brain disorders in a cohort of patients with a DBS treatment duration ≥12 months. Multidisciplinary assessments including standardised scales/tests of motor function, pain, quality of life, cognition and language were carried out before implantation and longitudinally afterwards. 9 patients were included, 7 had cerebral palsy. Mean age at implantation was 209 months±156, mean treatment duration 84±37 months. DBS was well tolerated and positively affected both motor and non-motor functions. In particular, statistically significant improvements were documented in Burke-Fahn-Marsden Scale scores (- 19.9% p 0.01031) at 12 months and in long-term quality of life (+28.6%, p 0.0292). DBS may be a useful treatment option in generalized dystonia associated with brain pathology. Even when the motor benefits are limited, improvements in quality of life and non-motor functions, or the possible prevention of serious dystonia-related complications, may have a significant impact on overall clinical status.

Pallidal and Cortical Oscillations in Freely Moving Patients With Dystonia

ObjectivesTo evaluate the correlation between the pallidal local field potentials (LFPs) activity and the cortical oscillations (at rest and during several motor tasks) in two freely moving patients with generalized dystonia and pallidal deep brain stimulation (DBS). Materials and MethodsTwo women with isolated generalized dystonia were selected for bilateral globus pallidus internus (GPi) DBS. After the electrodes' implantation, cortical activity was recorded by a portable electroencephalography (EEG) system simultaneously with GPi LFPs activity, during several motor tasks, gait, and rest condition. Recordings were not performed during stimulation. EEG and LFPs signals relative to each specific movement were coupled together and grouped in neck/upper limbs movements and gait. Power spectral density (PSD), EEG-LFP coherence (through envelope of imaginary coherence operator), and 1/f exponent of LFP-PSD background were calculated. ResultsIn both patients, the pallidal LFPs PSD at rest was characterized by prominent 4–12 Hz activity. Voluntary movements increased activity in the theta (θ) band (4–7 Hz) compared to rest, in both LFPs and EEG signals. Gait induced a drastic raise of θ activity in both patients' pallidal activity, less marked for the EEG signal. A coherence peak within the 8–13 Hz range was found between pallidal LFPs and EEG recorded at rest. ConclusionsNeck/upper limbs voluntary movements and gait suppressed the GPi-LFPs—cortical-EEG coherence and differently impacted both EEG and LFPs low frequency activity. These findings suggest a selective modulation of the cortico-basal ganglia network activity in dystonia.

HP08: Deep Brain Stimulation Evoked Potentials in Children with dystonia

Pallidal Deep Brain Stimulation (DBS) is an established therapy for dystonia. Stimulation parameters are currently determined empirically. Recording the cortical response to the pallidal stimulus, known as Deep Brain Stimulation Evoked Potentials (DBSEPs) could provide a more objective measure of optimal contact selection (Tisch et al, MovDisord 2008;23:265-73; Bhanpuri et al, BrainStim 2014;7:718-26). Methods: Fifteen children with dystonia participated (age 7-19years), all with bilateral pallidal DBS implanted at least 6 months previously. Scalp EEG (10-20 system) was sampled at 5KHz. Contacts from each stimulating electrode were tested separately, using 6Hz bipolar stimulation. Pairs of electrode contacts were tested sequentially using combinations of cathodal stimulation (2 volts) with an adjacent anode, and pulse width at the patient’s therapeutic level. Each combination was recorded for 3 minutes, giving >1000 stimuli per contact pair. Therapeutic settings were restored on study completion. Offline, the DBS stimulus artefact was used to segment EEG data into epochs (10ms pre-stimulus, 150ms post-stimulus). After artefact rejection, 900-1100 epochs were averaged to obtain the DBSEP for each contact pair. Results: Clear DBSEPs were obtained in 12/15 patients on one or both sides, with peak latency of 20ms, and largest amplitude over the ipsilateral central/centro-parietal region, concordant with adult literature. In 3/15 patients no convincing DBSEP was obtained. Conclusion: To our knowledge this is the largest study of DBSEPs in dystonia and confirms the feasibility and tolerability of this technique in children. Future work will investigate potential clinical applications of DBSEPs to inform an individualised approach to DBS parameter selection.

Effectiveness of Low-Frequency Pallidal Deep Brain Stimulation at 65 Hz in Tourette Syndrome

ObjectivesPallidal deep brain stimulation (DBS) for refractory Tourette syndrome (TS) is often applied using a high frequency. The effectiveness of low-frequency long-term stimulation is unknown. We aimed to evaluate the clinical efficacy of low-frequency DBS applied to the globus pallidus pars internus (GPi) at 65 Hz for the treatment of TS, with long-term follow-up, to provide data for the optimization of stimulation parameters. Materials and MethodsA total of six patients with refractory TS were implanted with electrodes in the GPi and were assigned to receive low-frequency (65 Hz) DBS programming. Assessments were performed pre-DBS and at 3, 12, and a median of 34 (range 26–48) months post-DBS. The primary outcome was tic severity, as assessed by the Yale Global Tic Severity Scale (YGTSS), and the secondary outcomes were comorbid behavioral disorders, mood, functioning, and quality of life. ResultsWe noted significant differences in the YGTSS scores between the baseline and the post-DBS follow-ups (p = 0.01). At the final follow-up, four of six (66.6%) patients had a greater than 50% reduction in the YGTSS score, whereas the remaining two patients showed a mild worsening of tic severity. The secondary outcome measures also showed remarkable improvements in associated behavioral disorders, mood, functioning, and quality of life. Stimulation-induced adverse effects were not reported, although a device-related complication (an uncomfortable feeling in the neck) occurred in one patient. ConclusionsThe results of this study indicated that low-frequency DBS represents an effective and practical treatment for refractory TS with comparable efficacy to high-frequency DBS.

Long-term effects of pallidal deep brain stimulation in tardive dystonia: a follow-up of 5–14 years

IntroductionPallidal DBS is an established treatment for severe isolated dystonia. However, its use in disabling and treatment-refractory tardive syndromes (TS) including tardive dyskinesia and tardive dystonia (TD) is less well investigated and long-term data remain sparse. This observational study evaluates long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with medically refractory TS.MethodsWe retrospectively analyzed a cohort of seven TD patients with bilateral GPi-DBS. Involuntary movements, dystonia and disability were rated at long-term follow-up (LT-FU) after a mean of 122 ± 33.2 SD months (range 63–171 months) and compared to baseline (BL), short-term (ST-FU; mean 6 ± 2.0 SD months) and 4-year follow-up (4y-FU; mean 45 ± 12.3 SD months) using the Abnormal Involuntary Movement Scale (AIMS) and the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), respectively. Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires, respectively.ResultsAt LT-FU patients had improved by 73% ± 14.2 SD in involuntary movements and 90% ± 1.0 SD in dystonia. Mood had improved significantly whereas quality of life remained unchanged compared to baseline. No serious long-lasting stimulation-related adverse events (AEs) were observed. Three patients of this cohort presented without active stimulation and ongoing symptom relief at long-term follow-up after 3–10 years of continuous DBS.ConclusionPallidal DBS is a safe and effective long-term TD treatment. Even more interesting, three of our patients could stop stimulation after several years of DBS without serious relapse. Larger studies need to explore the phenomenon of ongoing symptom relief after DBS cessation.

Deep brain stimulation for chorea-acanthocytosis: a systematic review.

Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We aimed to investigate the safety and efficacy of DBS for ChAc by systematically reviewing literature through PubMed and EMBASE. Inclusion criteria were reports on the efficacy or safety of DBS for ChAc and English language articles, and exclusion criteria were other movement disorders, non-human subjects, and studies without original data. Most studies were published as case reports, and we therefore pooled these cases in one cohort. Twenty studies with 34 patients were included. The mean age of symptom onset was 29.3years (range, 17-48). The median follow-up was 12months (range, 2-84). Twenty-nine patients underwent GPi-DBS, two received STN-DBS, and one underwent Vop-DBS. Electrodes were implanted into the ventralis oralis complex of the thalamus and the pallidal in two patients. Symptoms seemed to be easier relieved in chorea (88.5%) and dystonia (76.9%) but dysarthria of most patients (85.7%) was no response after DBS. The Unified Huntington's Disease Rating Scale-Motor Score was used to assess the efficacy of DBS in 25 patients; the mean score decreased from 43.2 to 22.3 and the median improvement rate was 46.7%. Of 24 patients with data on adverse events, complications occurred in 9 patients (37.5%; mostly transient and mild events). DBS is a promising treatment for ChAc with satisfactory efficacy and safety based on the review. Pallidal and thalamic DBS have been applied in ChAc; GPi-DBS seems to be more widely used.

Dual Pallidal and Thalamic Deep Brain Stimulation for Complex Ipsilateral Dystonia.

PurposeGlobus pallidus pars interna (GPi) has become an established target for deep brain stimulation (DBS) in dystonia. Previous studies suggest that targeting the ventralis oralis (Vo) complex nucleus improves dystonic tremor or even focal dystonia. Research has also demonstrated that multi-target DBS shows some benefits over single target DBS. In this study, we reviewed patients who had undergone unilateral DBS targeting the GPi and Vo.Materials and MethodsFive patients diagnosed with medically refractory upper extremity dystonia (focal or segmental) underwent DBS. Two DBS electrodes each were inserted unilaterally targeting the ipsilateral GPi and Vo. Clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Disability Rating Scale.ResultsBFMDRS scores decreased by 55% at 1-month, 56% at 3-month, 59% at 6-month, and 64% at 12-month follow up. Disability Rating Scale scores decreased 41% at 1-month, 47% at 3-month, 50% at 6-month, and 60% at 12-month follow up. At 1 month after surgery, stimulating both targets improved clinical scores better than targeting GPi or Vo alone.ConclusionUnilateral thalamic and pallidal dual electrode DBS may be as effective or even superior to DBS of a single target for dystonia. Although the number of patients was small, our results reflected favorable clinical outcomes.

Both subthalamic and pallidal deep brain stimulation are effective for GNAO1-associated dystonia: three case reports and a literature review.

Background:Mutations in the G-protein subunit alpha o1 (GNAO1) gene have recently been shown to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. The clinical manifestations of GNAO1-associated movement disorders are highly heterogeneous. However, the genotype–phenotype correlations in this disease remain unclear, and the treatments for GNAO1-associated movement disorders are still limited.Objective:The objective of this study was to explore diagnostic and therapeutic strategies for GNAO1-associated movement disorders.Methods:This study describes the cases of three Chinese patients who had shown severe and progressive dystonia in the absence of epilepsy since early childhood. We performed genetic analyses in these patients. Patients 1 and 2 underwent globus pallidus internus (GPi) deep brain stimulation (DBS) implantation, and Patient 3 underwent subthalamic nucleus (STN) DBS implantation. In addition, on the basis of a literature review, we summarized and discussed the clinical characteristics and outcomes after DBS surgery for all reported patients with GNAO1-associated movement disorders.Results:Whole-exome sequencing (WES) analysis revealed de novo variants in the GNAO1 gene for all three patients, including a splice-site variant (c.724–8G > A) in Patients 1 and 3 and a novel heterozygous missense variant (c.124G > A; p. Gly42Arg) in Patient 2. Both GPi and STN DBS were effective in improving the dystonia symptoms of all three patients.Conclusion:DBS is effective in ameliorating motor symptoms in patients with GNAO1-associated movement disorders, and both STN DBS and GPi DBS should be considered promptly for patients with sustained refractory GNAO1-associated dystonia.

Long-Term Efficacy of Pallidal Deep Brain Stimulation in a Patient with DYT-THAP1 (DYT-6) Dystonia from India.

Long-Term Efficacy of Pallidal Deep Brain Stimulation in a Patient with DYT-THAP1 (DYT-6) Dystonia from India.

Intraoperative vs. Postoperative Side-Effects-Thresholds During Pallidal and Thalamic DBS.

Background: It is currently unknown whether results from intraoperative test stimulation of two types of Deep Brain Stimulation (DBS), either during awake pallidal (GPi) or thalamic (Vim), are comparable to the results generated by chronic stimulation through the definitive lead.Objective: To determine whether side-effects-thresholds from intraoperative test stimulation are indicative of postoperative stimulation findings.Methods: Records of consecutive patients who received GPi or Vim were analyzed. Thresholds for the induction of either capsular or non-capsular side-effects were compared at matched depths and at group-level.Results: Records of fifty-two patients were analyzed (20 GPis, 75 Vims). The induction of side-effects was not significantly different between intraoperative and postoperative assessments at matched depths, although a large variability was observed (capsular: GPi DBS: p = 0.79; Vim DBS: p = 0.68); non-capsular: GPi DBS: p = 0.20; and Vim DBS: p = 0.35). Linear mixed-effect models revealed no differences between intraoperative and postoperative assessments, although the Vim had significantly lower thresholds (capsular side-effects p = 0.01, non-capsular side-effects p < 0.01). Unpaired survival analyses demonstrated lower intraoperative than postoperative thresholds for capsular side-effects in patients under GPi DBS (p = 0.01), while higher intraoperative thresholds for non-capsular side-effects in patients under Vim DBS (p = 0.01).Conclusion: There were no significant differences between intraoperative and postoperative assessments of GPi and Vim DBS, although thresholds cannot be directly extrapolated at an individual level due to high variability.

GPi-DBS for KMT2B-Associated Dystonia: Systematic Review and Meta-Analysis.

Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT-KMT2B. We aimed to conduct a systematic review and meta-analysis to assess outcomes and identify predictors of good outcome following GPi-DBS in DYT-KMT2B. We searched MEDLINE, Cochrane and MDS-abstracts databases using the MeSH terms "KMT2B and DYT28". We included studies that reported objective outcomes following GPi-DBS in DYT-KMT2B. The BFMDRS-M (Burke-Fahn-Marsden Dystonia Rating Scale- Movement) total scores pre- and post-surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta-analysis and used meta-regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS-M). Initial searches screened 132 abstracts of which 34 full-text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow-up was 12months (range: 1-264months). GPi-DBS resulted in median BFMDRS-M improvement of 42.7% (range: -103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS-M was 41% (95% CI: 27%-57%). Male gender [β: 22.6, 95% CI: 8.0-37.3, P=0.004), and higher pre-operative BFMDRS-M score [β: 0.62, 95% CI: 0.36-0.87, P < 0.001) were independently associated with better outcome. KMT2B-associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline.

Can pallidal deep brain stimulation generate high-frequency oscillations in basal ganglia in dystonia? A case report

Can pallidal deep brain stimulation generate high-frequency oscillations in basal ganglia in dystonia? A case report

Marie Vidailhet: recognising the importance of teamwork

The city of Toulouse in southern France is filled with a rich history of heroes, adventure, and challenges; where Concorde made its first test flight and the French National Centre for Space Studies obtained stunning satellite images of Earth. It is also the birthplace of Marie Vidailhet, professor of neurology and head of the Movement Disorders and Parkinson's Disease department at the Salpêtrière Hospital—the “cradle of neurology” in France (Sorbonne University, Paris). Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a prospective 3 year follow-up studyBilateral pallidal stimulation provides sustained motor benefit after 3 years. Mild long-term improvements in quality of life and attention were also observed. Full-Text PDF Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot studyBilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome. Full-Text PDF

TOR1A mutation-related isolated childhood-onset generalised dystonia in South Africa.

Childhood-onset generalised dystonia is commonly caused by TOR1A mutations and is known to respond well to pallidal deep-brain stimulation (DBS) surgery. The incidence and prevalence of monogenic dystonia in individuals from Africa and specifically of African ancestry are unknown, and no local cases of TOR1A mutation dystonia are found in the literature. To describe our experience with the outcome of TOR1A mutation-positive patients with isolated generalised dystonia (IGD) of childhood onset who were treated with pallidal DBS. All patients with TOR1A mutations from Steve Biko Academic Hospital and the Pretoria Neurology Institute in Pretoria, South Africa (SA), who underwent DBS for IGD of childhood onset were identified. We conducted a retrospective analysis of their demographics, clinical presentation and time to generalisation, genetic status and family history, and response to DBS treatment of the internal segment of the globus pallidus (GPi), utilising pre- and post-surgical scores of the United Dystonia Rating Scale (UDRS). Three patients, all of black African ancestry, were identified. The median age at onset was 12 years and the median time to surgery from dystonia generalisation was 3 years. Two children presented with cervical-onset dystonia. Two patients were related, representing the only two with a positive family history. All three patients had a positive outcome after surgery, with improvement of 67 - 90% on the UDRS recorded at last follow-up. TOR1A mutations are found in SA patients of black African ancestry, with age of onset and generalisation comparable to those described in international studies. However, onset with cervical dystonia was more common than previously reported. Response to GPi DBS was excellent in all patients.

Predicting Outcome in a Cohort of Isolated and Combined Dystonia within Probabilistic Brain Mapping.

BackgroundProbabilistic brain mapping is a promising tool to estimate the expected benefit of pallidal deep brain stimulation (GPi‐DBS) in patients with isolated dystonia (IsoD).ObjectivesTo investigate the role of probabilistic mapping in combined dystonia (ComD).MethodsWe rendered the pallidal atlas and the volume of tissue activated (VTA) for a cohort of patients with IsoD (n = 20) and ComD (n = 10) that underwent GPi‐DBS. The VTA was correlated with clinical improvement. Afterwards, each VTA was applied on the previously published probabilistic model (Reich et al., 2019). The correlation between predicted and observed clinical benefit was studied in a linear regression model.ResultsA good correlation between observed and predicted outcome was found for both patients with IsoD (n = 14) and ComD (n = 7) (r2 = 0.32; P < 0.05). In ComD, 42% of the variance in DBS response is explained by VTA‐based outcome map.ConclusionA probabilistic model would be helpful in clinical practice to circumvent unpredictable and less impressive motor results often found in ComD.

Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

Suppression and Rebound of Pallidal Beta Power: Observation Using a Chronic Sensing DBS Device.

Pallidal deep brain stimulation (DBS) is an increasingly used therapy for Parkinson’s disease (PD). Here, we study the effect of DBS on pallidal oscillatory activity as well as on symptom severity in an individual with PD implanted with a new pulse generator (Medtronic Percept system) which facilitates chronic recording of local field potentials (LFP) through implanted DBS lead. Pallidal LFPs were recorded while delivering stimulation in a monopolar configuration using stepwise increments (0.5 mA, every 20 s). At each stimulation amplitude, the power spectral density (PSD) was computed, and beta power (13–30 Hz) was calculated and correlated with the degree of bradykinesia. Pallidal beta power was reduced when therapeutic stimulation was delivered. Beta power correlated to the severity of bradykinesia. Worsening of parkinsonism when excessive stimulation was applied was associated with a rebound in the beta band power. These preliminary results suggest that pallidal beta power might be used as an objective marker of the disease state in PD. The use of brain sensing from implanted neural interfaces may in the future facilitate clinical programming. Detection of rebound could help to optimize benefits and minimize worsening from overstimulation.