Globus Pallidus Internus Stimulation Research Articles

Globus pallidus internus deep brain stimulation improves axial symptoms of Parkinson patients after long-term subthalamic nucleus stimulation: A case series study

IntroductionSome patients with advanced Parkinson's disease (PD) develop refractory axial symptoms and motor complications following initially effective subthalamic nucleus (STN) deep brain stimulation (DBS). We aim to determine whether globus pallidus internus (GPi) stimulation can improve refractory axial symptoms and dyskinesia, as well as psychosocial functioning and quality of life, in this group of patients who no longer benefit from STN DBS. MethodsIn this pilot study, bilateral pallidal stimulation treatment was given to 7 patients with advanced PD who had developed refractory axial symptoms, including speech and swallowing difficulties, and painful dyskinesia, after long-term (>5 y) subthalamic stimulation. The follow-up period was 6 months. Primary clinical outcome measures focused on motor symptom severity, motor complications, psychosocial function, and quality of life. Secondary outcome measures included daily dose of antiparkinsonian medication and patient's body weight. ResultsAfter pallidal stimulation, patients showed an overall 44% improvement in motor symptom scores at 6-month follow-up along with a 49% improvement in dyskinesia, a 33% improvement in psychosocial functioning, and a 42% improvement in quality of life. No adverse events occurred during the study. ConclusionsThese initial results indicate that bilateral GPi DBS could provide significant clinical benefits to patients whose axial symptoms cannot or can no longer be controlled by STN DBS.

The pedunculopontine region and breathing in Parkinson's disease.

ObjectiveRespiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers.MethodsNine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition.Results PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = −2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7–11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = −2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096).Interpretation PPNr stimulation in PD improves indices of upper airway function. Increased alpha‐band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.

Deep brain stimulation of the globus pallidus internus versus the subthalamic nucleus in isolated dystonia.

Surgical procedures involving deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) are well-established treatments for isolated dystonia. However, selection of the best stimulation target remains a matter of debate. The authors' objective was to compare the effectiveness of DBS of the GPi and the STN in patients with isolated dystonia. In this matched retrospective cohort study, the authors searched an institutional database for data on all patients with isolated dystonia who had undergone bilateral implantation of DBS electrodes in either the GPi or STN in the period from January 30, 2014, to June 30, 2017. Standardized assessments of dystonia and health-related quality of life using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and SF-36 were conducted before and at 1, 6, and 12 months after surgery. No patients were lost to the 6-month follow-up; 5 patients were lost to the 12-month follow-up. Both GPi (14 patients) and STN (16 patients) stimulation produced significant improvement in dystonia and quality of life in all 30 patients found in the database search. At the 1-month follow-up, however, the percentage improvement in the BFMDRS total movement score was significantly (p = 0.01) larger after STN DBS (64%) than after GPi DBS (48%). At the 12-month follow-up, the percentage improvement in the axis subscore was significantly (p = 0.03) larger after GPi DBS (93%) than after STN DBS (83%). Also, the total amount of electrical energy delivered was significantly (p = 0.008) lower with STN DBS than with GPi DBS (124 ± 52 vs 192 ± 65 μJ, respectively). The GPi and STN are both effective targets in alleviating dystonia and improving quality of life. However, GPi stimulation may be better for patients with axial symptoms. Moreover, STN stimulation may produce a larger clinical response within 1 month after surgery and may have a potential economic advantage in terms of lower battery consumption.

Deep brain stimulation for dystonia-choreoathetosis in cerebral palsy: Pallidal versus thalamic stimulation

IntroductionDystonia-choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some effect, but there is still a need to optimize treatment strategies. We aimed to assess whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in dystonia-choreoathetosis. MethodsThree patients with cerebral palsy and dystonia-choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with corresponding clinical outcomes were assessed. ResultsOne patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued. In one patient Vim was chosen as initial target for chronic DBS. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further mild clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 82). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 135, GPi DBS 121). ConclusionsThe GPi still represents the most convenient DBS target in patients with dystonia-choreoathetosis. Vim DBS did not show a relevant long-term advantage in everyday life in our patients. Further alternative DBS targets need to be considered in acquired dystonia.

Neural State of Globus Pallidus Internus Local Field Potential Predicting Outcome of Deep Brain Stimulation in Primary Dystonia

Background. Deep brain stimulation (DBS) of globus pallidus internus (GPi) has been used to treat primary dystonia for many years. However, patients respond differently to DBS. Some patients could not benefit much from it. Classification of local field potential (LFP) neural state in GPi may provide a new method to identify the differences in neuropathophysiological mechanisms, which may predict DBS outcome and investigate neurobiological marker of dystonia for adaptive-DBS.

Pallidal Deep Brain Stimulation in Patients With Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center. We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months. All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 μsec to 98 μsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes.

Comparison of Short-Term Stimulation of the Globus Pallidus Interna and Subthalamic Nucleus for Treatment of Primary Dystonia

To compare the efficacy and side effects of bilateral globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in the same patient with primary dystonia. Patients with primary dystonia from the department of functional neurosurgery in Beijing Tiantan Hospital were recruited for the study. Four electrodes were bilaterally implanted in the GPi and STN. A trial stimulation was applied to determine the preliminary therapeutic effects. Five evaluations were conducted: preoperative, postoperative (before stimulation), after sham stimulation, and after stimulation for 24 hours of GPi and STN using optimal parameters, judged by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS movement score decreased after both short-term GPi stimulation (from 15.3 ± 6.9 to 7.6 ± 4.2, P < 0.05) and short-term STN stimulation (from 15.3 ± 6.9 to 8.6 ± 5.0, P < 0.05). There were significant reductions in facial (eyes and mouth) movement scores after short-term GPi and STN DBS compared with baseline (P < 0.05), but not in cervical symptoms (P > 0.05). The cervical symptoms of tonic dystonia had an improvement after long-term DBS treatment (P < 0.05). There were more adverse events with STN DBS; however, most side effects could be ameliorated by adjusting stimulation parameters. Both short-term GPi and STN stimulation improved the motor symptoms of dystonia, but there was no significant difference between GPi DBS and STN DBS. There were more side effects associated with STN stimulation.

The long-term efficacy of deep brain stimulation for medically refractory primary generalized dystonia

Objective To evaluate the long-term efficacy of deep brain stimulation (DBS) in treatment of medically refractory primary generalized dystonia (PGD) and to compare the effect of stimulation of subthalamic nucleus (STN) with that of globus pallidus internus (GPi) in the treatment of dystonia. Methods Twenty-one cases of PGD underwent STN-DBS or GPi-DBS at Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University from December 2004 to April 2013 and were enrolled into this study. Among them, 11 patients underwent STN stimulation (STN-DBS group) and the other 10 cases received GPi stimulation (GPi-DBS group). Pre- and postoperative severity of dystonia were assessed by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Results The average improvement rates of BFMDRS movement subscale in the 21 cases of PGD were 63.7±14.2 % and 66.5±13.7 % at 1 and 3 years post operation, respectively. Meanwhile, the disability scores were reduced by 43.7±13.8 % and 49.1±12.4 %, respectively. The movement scores in STN-DBS group were 56.9±20.9 prior to surgery and 18.3±6.8 at 3 years post operation, and the average improvement rate was 64.6±15.2 %. Their disability scores were 20.0(11.0) prior to surgery and 8.0(4.0) points at 3 years post operation, and the average improvement rate was 54.5 %(15.0 %). In the GPi-DBS group, the movement scores were 60.8±19.3 before surgery and 18.3±7.9 at 3 years post surgery, and the average improvement rate was 68.6±12.5 %. Their disability scores were 17.5±5.4 before surgery and 8.9±2.5 post surgery, and the average improvement rate was 47.2±12.8 %. There was no statistically significant difference in the improvement rates of BFMDRS movement and disability scores between 2 targets at 1 year and 3 years after surgery (both P>0.05). Conclusions The effect of DBS in the treatment of medically refractory seems to be significant and sustained. Our preliminary results suggest that there is no significant difference in the long-term efficacy between stimulation of STN and stimulation of GPi for dystonia. Key words: Deep brain stimulation; Subthalamic nucleus; Globus pallidus; Primary dystonia; Treatment outcome

337 Pallidocortical Beta Coherence Decreases with Pallial Deep Brain Stimulation in Parkinson Disease

Abstract INTRODUCTION Deep Brain Stimulation (DBS) of Globus Pallidus internus (GPi) is an effective therapy to manage Parkinson disease (PD) symptoms. Despite its documented clinical efficacy, the underlying neural oscillatory mechanisms of GPi-DBS is still not well understood. In this study, we evaluate the hypothesis that therapeutic effects of DBS are mediated by changes in the cortical-subcortical coherence. METHODS Seven patients with PD underwent GPi-DBS implantation. Simultaneous recordings of GPi local field potentials (LFPs) and ipsilateral motor cortex electrocorticography (ECoG) were obtained intra-operatively both off and on GPi stimulation. Eighteen seconds of data were used for each condition and the mean coherence was calculated over five different frequency bands of Alpha (8-12 Hz), Low Beta (13-20 Hz), High Beta (21-35 Hz), Low Gamma (36-80 Hz), and High Gamma (81-100 Hz). RESULTS &gt;We found a statistically significant (p-value corrected &lt;0.02, Friedman test) reduction of pallidocortical coherence in the High Beta frequency band. No statistically significant difference was observed in the other frequency bands between off and on DBS conditions. This decrease was specific to the primary motor cortex, and no statistical cortical-subcortical coherence difference was observed at the premotor and sensorimotor sites between the two conditions. CONCLUSION These findings suggest pallidocortical High Beta coupling may be a critical mechanism in the pathophysiology of PD. GPi-DBS might, therefore, exert their therapeutic effect by inhibition of this exaggerated pallidocortical High Beta coupling. A better understanding of the DBS mechanisms on the alleviation of PD symptoms can contribute to the development of closed-loop DBS in which the patients' neurophysiological parameters will be considered in optimizing the DBS parameters.

Subthalamic nucleus and globus pallidus internus stimulation for the treatment of Parkinson's disease: A systematic review.

ObjectiveDeep brain stimulation (DBS) for treatment of advanced Parkinson’s disease (PD) has two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). The clinical effectiveness of these two stimulation targets was compared in the present study.MethodsA systematic review and meta-analysis was performed to evaluated the postoperative changes in the United Parkinson’s Disease Rating Scale (UPDRS) on- and off-phase, on-stimulation motor scores; activities of daily living score (ADLS); and levodopa equivalent dose (LED) after STN and GPI stimulation. Randomized and nonrandomized controlled trials of PD treated by STN and GPI stimulation were considered for inclusion.ResultsEight published reports of eligible studies involving 599 patients met the inclusion criteria. No significant differences were observed between the STN and GPI groups in the on-medication, on-stimulation UPDRS motor score [mean difference, 2.15; 95% confidence interval (CI), −0.96–5.27] or ADLS (mean difference, 3.40; 95% CI, 0.95–7.76). Significant differences in favor of STN stimulation were noted in the off-medication, on-stimulation UPDRS motor score (mean difference, 1.67; 95% CI, 0.98–2.37) and LED (mean difference, 130.24; 95% CI, 28.82–231.65).ConclusionThe STN may be the preferred target for DBS in consideration of medication reduction, economic efficiency, and motor function improvement in the off phase. However, treatment decisions should be made according to the individual patient’s symptoms and expectations.

Holmes' Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus.

A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

Result of Pallidotomy in Parkinson’s Disease in Nepal

Surgical treatment of Parkinsons disease (PD) has already been an established treatment. Currently pallidotomy, Deep Brain Stimulation (DBS) of Globus pallidus internus (GPi) and Subthalamic nucleus (STN) are available mode of surgical treatment of PD. We have included all patients of idiopathic Parkinosons disease who underwent pallidotomy in Annapurna Neurological Institute and Allied Sciences since 2014. The demographics of the patients have been shown and the patient’s improvement has been shown by Unifi ed Parkinsons Disease Rating Score (UPDRS). We have found that pallidotomy is still a promising surgical modality but it is advised to perform either unilaterally or staged bilaterally with at least 3 months gap inbetween.Nepal Journal of Neuroscience. Vol. 13, No. 2, 2016, Page: 68-72

Hypometric anticipatory postural adjustments in dystonia are not affected by deep brain stimulation of globus pallidus internus

BackgroundDystonia is a movement disorder with patterned, directional, and often sustained muscle contractions that produce abnormal postures or repetitive movements. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and safe treatment for medically refractory dystonia. However, recent studies reported gait problems, gait freezing and falls in patients treated with DBS. Because these symptoms may point to deficient gait initiation processes, we systematically assessed the anticipatory postural adjustments (APAs) prior to stepping in dystonia patients with GPi-DBS. MethodsThirteen patients with focal/segmental dystonia under GPi-DBS and twelve healthy control subjects were included in the study. Data were collected using pressure sensitive sensors and APAs were studied by centre of pressure measures. We compared APAs of both groups and analysed the influence of GPi-DBS on APAs in patients. ResultsMedio-lateral and antero-posterior COP displacements, total COP path, maximal APA velocity and 1st step length were all smaller in patients for both ON (p=0.006, p=0.018, p=0.002, p=0.016, p=0.04) and OFF (p=0.001, p=0.01, p=0.001, p=0.03, p=0.024) condition compared to healthy subjects. GPi-DBS did not change APA parameters in patients. ConclusionsObservations that APAs are impaired in dystonia and are at the same time not affected by the stimulation current are compatible with the assumption that APAs and dystonic symptoms may rely on distinct networks, possibly within the same cortical and basal ganglia structures. With no effect of stimulation on APAs it is unlikely that this would be a mechanism of impaired balance in the patients after the surgery.

GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up.

Editors' Note: In reference to “GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up,” Drs. Sidiropoulos and LeWitt suggest that the study findings could be due to suboptimal globus pallidus internus (GPi) programming and targeting imprecision. Odekerken et al., authors of the study, disagree and offer several arguments to support their findings, which showed superiority of subthalamic nucleus (STN) over GPi deep brain stimulation. Commenting on “Statin pretreatment is associated with better outcomes in large artery atherosclerotic stroke,” Dr. Goldstein further discusses the benefit of statin on cerebrovascular events and functional outcome, citing 2 exploratory analyses based on data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Tsivgoulis et al., authors of the study, suggest further research to establish the safety and efficacy of early statin treatment on the …

Influence of cognitive-motor interference on gait spatiotemporal parameters in children and adolescents with cerebral palsy: A preliminary study

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been established as an effective and safe treatment for dystonia. In general, side effects are rare, but there is increasing evidence that GPi DBS in dystonia can induce hypokinetic symptoms like micrographia or freezing of gait. We aimed to evaluate and quantify possible changes of gait following bilateral chronic GPi DBS for dystonia by computerized gait analyses.We prospectively performed computerized gait analysis in ten consecutive patients (mean age 57.8+/−14.3 years) with segmental dystonia but without involvement of lower trunk or legs who were treated with bilateral GPi DBS. Using pressure sensitive insoles, several parameters were measured preoperatively (pre-OP) and at a median of 7 months postoperatively.The mean step length significantly decreased from 60.0+/−6.9 cm pre-OP to 54.3+/−6.4 cm with GPi DBS (p < 0.01). Due to only small changes of walking distance and gait velocity, the cadence correspondingly increased from 105.6+/−9.2 steps/min to 111.3+/−11.4 steps/min (p < 0.05). More importantly, the variance of several gait parameters significantly decreased postoperatively.In patients with segmental dystonia, chronic DBS of the posteroventral lateral GPi is associated with only mild hypokinesia of gait, but with a relevant decrease in gait variability. Given other recently reported hypokinetic effects of GPi DBS for dystonia and recent results of electrophysiological coherence studies, these findings support the hypothesis of a general alteration of neuronal activity in striato-pallido-thalamo-cortical motor pathways following chronic stimulation of the posteroventral lateral GPi.

Hypokinetic gait changes induced by bilateral pallidal deep brain stimulation for segmental dystonia

BackgroundDeep brain stimulation (DBS) of the globus pallidus internus (GPi) has been established as an effective and safe treatment for dystonia. In general, side effects are rare, but there is increasing evidence that GPi DBS in dystonia can induce hypokinetic symptoms like micrographia or freezing of gait. We aimed to evaluate and quantify possible changes of gait following bilateral chronic GPi DBS for dystonia by computerized gait analyses. MethodsWe prospectively performed computerized gait analysis in ten consecutive patients (mean age 57.8+/−14.3 years) with segmental dystonia but without involvement of lower trunk or legs who were treated with bilateral GPi DBS. Using pressure sensitive insoles, several parameters were measured preoperatively (pre-OP) and at a median of 7 months postoperatively. ResultsThe mean step length significantly decreased from 60.0+/−6.9cm pre-OP to 54.3+/−6.4cm with GPi DBS (p<0.01). Due to only small changes of walking distance and gait velocity, the cadence correspondingly increased from 105.6+/−9.2 steps/min to 111.3+/−11.4 steps/min (p<0.05). More importantly, the variance of several gait parameters significantly decreased postoperatively. ConclusionsIn patients with segmental dystonia, chronic DBS of the posteroventral lateral GPi is associated with only mild hypokinesia of gait, but with a relevant decrease in gait variability. Given other recently reported hypokinetic effects of GPi DBS for dystonia and recent results of electrophysiological coherence studies, these findings support the hypothesis of a general alteration of neuronal activity in striato-pallido-thalamo-cortical motor pathways following chronic stimulation of the posteroventral lateral GPi.

Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome.

In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased. Our results provide substantial evidence that, in TS, brain perfusion is altered in the frontal cortex and the cerebellum and that these changes can be reversed by both GPi and CM/Voi DBS.

Deep brain stimulation of the internal globus pallidus for disabling haloperidol-induced tardive dystonia. Report of two cases

AimTardive dystonia (TD) represents a side effect of prolonged intake of neuroleptic drugs. TD can be a disabling movement disorder persisting despite available medical treatment. Deep brain stimulation (DBS) has been reported successful in this condition although the number of treated patients with TD is still limited to small clinical studies or case reports. In this study, we present 2 additional cases of patients after bilateral globus pallidus internus (GPi) stimulation. MethodsThe formal assessment included the Burke–Fahn–Dystonia Rating Scale (BFMDRS). The preoperative and postoperative functional and motor parts of this scale were compared in each patient. The postoperative assessments were done every 6 months. ResultsBoth patients underwent successful bilateral GPi DBS for TD. The postoperative motor score improved by 78% at 24 months in patient 1 and 69% at 12 months in patient 2. There were no surgical or hardware-related complications over follow-up period. ConclusionOur experience indicates that bilateral GPi DBS can be an effective treatment for disabling TD. The response of TD to bilateral GPi DBS is very rapid and occurs within days after the procedure.

Are there treatments for atypical parkinsonism? An update on actual options

Success in treating patients with atypical parkinsonism remains exceedingly low. It is particularly important for both neurologists and general practicians to have a guideline in the actual possible cure options. This study reviews the limited available literature reporting treatment trials about treatment in parkinsonism. Various therapeutical approaches have been tried with rasagiline, immunoglobulin, autologous mesenchymal stem cells, davunetide, lithium, and tideglusib. Recently, the transdermal rotigotine has been proposed for the treatment of atypical parkinsonism, as well as deep brain stimulation (DBS) of the peduncolopontine nucleus alone or combined with globus pallidus internus stimulation. The outcomes reviewed here highlight the need for the development of randomized, placebo-controlled trials to validate outcomes about rotigotine, DBS, and all other new therapies directed at altering the underlying biological mechanisms involved in the disease process.

High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide Functional or Morphological Neuroprotection from 6-Hydroxydopamine.

Deep brain stimulation (DBS) is the most common neurosurgical treatment for Parkinson’s disease (PD). Whereas the globus pallidus interna (GPi) has been less commonly targeted than the subthalamic nucleus (STN), a recent clinical trial suggests that GPi DBS may provide better outcomes for patients with psychiatric comorbidities. Several laboratories have demonstrated that DBS of the STN provides neuroprotection of substantia nigra pars compacta (SNpc) dopamine neurons in preclinical neurotoxin models of PD and increases brain-derived neurotrophic factor (BDNF). However, whether DBS of the entopeduncular nucleus (EP), the homologous structure to the GPi in the rat, has similar neuroprotective potential in preclinical models has not been investigated. We investigated the impact of EP DBS on forelimb use asymmetry and SNpc degeneration induced by 6-hydroxydopamine (6-OHDA) and on BDNF levels. EP DBS in male rats received unilateral, intrastriatal 6-OHDA and ACTIVE or INACTIVE stimulation continuously for two weeks. Outcome measures included quantification of contralateral forelimb use, stereological assessment of SNpc neurons and BDNF levels. EP DBS 1) did not ameliorate forelimb impairments induced by 6-OHDA, 2) did not provide neuroprotection for SNpc neurons and 3) did not significantly increase BDNF levels in any of the structures examined. These results are in sharp contrast to the functional improvement, neuroprotection and BDNF-enhancing effects of STN DBS under identical experimental parameters in the rat. The lack of functional response to EP DBS suggests that stimulation of the rat EP may not represent an accurate model of clinical GPi stimulation.