Bilateral GPi-DBS Research Articles

Prognostic factors for long-term outcomes of bilateral pallidal deep brain stimulation in the treatment of Meige syndrome.

This study aimed to investigate the effects of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) on both motor and nonmotor symptoms in patients with Meige syndrome and to further explore prognostic factors for postoperative outcomes based on the long-term follow-up results. The authors retrospectively reviewed the medical records of a consecutive cohort of patients with refractory Meige syndrome who underwent GPi-DBS at their center from January 2016 to October 2023. Motor function, quality of life, neuropsychological status, and emotional state were assessed using standardized scales at baseline and every 3-6 months thereafter. Univariate and multivariate linear regression analyses were performed to identify independent risk factors affecting long-term motor function after GPi-DBS in patients with steady-state (stable) Meige syndrome. Fifty steady-state patients were ultimately included and assessed, with a mean follow-up duration of 62.9 ± 24.8 months. At the final postoperative evaluation, Burke-Fahn-Marsden Dystonia Rating Scale movement and disability scores showed improvements of 69% (p < 0.001) and 61% (p < 0.001), respectively. A significant improvement from baseline was observed in postoperative scores on the 36-item Short-Form General Health Survey. Throughout continuous neurostimulation, global cognitive function, neuropsychological status, and mood remained stable. Multivariate linear regression analysis revealed that longer disease duration (standardized β-coefficient -0.375, 95% CI -0.033 to -0.011; p < 0.001) and reduced volume of activated tissue within the sensorimotor subregion of the GPi (standardized β-coefficient 0.597, 95% CI 0.002-0.003; p < 0.001) were independently associated with worse long-term motor performance. Bilateral GPi-DBS is an effective, safe, and promising treatment option for intractable Meige syndrome and provides sustained benefits in motor function and quality of life without inducing cognitive or mood-related side effects. Early intervention and accurate electrode placement in the sensorimotor subregion of the GPi are essential for optimizing long-term therapeutic outcomes.

Clinical and Pathological Characterization of VPS16 Dystonia (P11-11.005)

<h3>Objective:</h3> To expand the clinical, radiologic and pathologic understanding of VPS16 related dystonia. <h3>Background:</h3> Variants in VPS16 have been associated with isolated dystonia in 35 cases from Chinese and European cohorts, including report of brainstem signal change on MRI. <h3>Design/Methods:</h3> We describe clinical features in 10 additional individuals with isolated dystonia and VPS16 variants, including neuroimaging on a subset and pathology in one, and perform pooled analysis with published cases. <h3>Results:</h3> 80% were men, mean age onset was 14.1 years (range 5–30), and mean age at exam was 35.89 years (range 11–73). Four began with arm, 3 with leg, and 3 with neck dystonia. Only one remained focal (arm); others became generalized (7), multifocal (1) or segmental (1). Brachial involvement was present in 90%, with 80% crural, 70% cranial/bulbar, and 50% cervical involvement. Two individuals underwent deep brain stimulation and one thalamotomy. Four cases were related, and five others had family history. MRI was available in two cases and demonstrated red nucleus and cerebral peduncle T2 hypointensity. Neuropathologic evaluation in one case (post bilateral GPi DBS) demonstrated asymmetric severe gliosis and marked neuronal loss of the left subthalamic nucleus with optically empty vacuoles and much less right-sided involvement. Pooled analysis with 34 additional published cases showed 62.22% male and average onset of 14.53 years (range 3–50). Onset site was 20.45% cranial/bulbar, 54.55% limb, and 36.36% axial (cervical or trunk); 75% of cases exhibited cranial/bulbar symptoms, 90.9% limb and 81.82% axial involvement. <h3>Conclusions:</h3> Expansion of known cases of VPS16 dystonia further support that it is a childhood-or adolescent-onset disorder, typically with limb or cervical onset that often spreads to the arm and leg. Additional histopathologic and metabolomic evaluation is underway to better understand the lysosomal and endolysosomal pathophysiology that may contribute to both vacuolization in the subthalamic nucleus as well as T2 brainstem hypointensities. <b>Disclosure:</b> The institution of Dr. Pullman has received research support from Empire Clinical Research Investigator Program. The institution of Ms. Raymond has received research support from NIH. Dr. Molofsky has nothing to disclose. Dr. Lubarr has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for applied therapeutics. Dr. Leaver has nothing to disclose. Roberto Ortega has nothing to disclose. Ms. Rawal has nothing to disclose. The institution of Dr. Bennett has received research support from Prevail. Mr. Bushnik has nothing to disclose. Dr. Khorsandi has nothing to disclose. Fedor Panov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for neuropace. Fedor Panov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for zimmer biomet. Jean Paul Vonsattel has nothing to disclose. The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program. The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH .

Pallidal deep brain stimulation for tardive dystonia: meta-analysis of clinical outcomes.

Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series. We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach. We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study. The searching strategy resulted in a total of n = 78 studies, which were screened for eligibility criteria resulting in the inclusion of n = 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (n = 4) or lack of improvement (n = 3) following GPi-DBS. Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.

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 in Huntington's disease: a literature review.

Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral changes. The complex constellation of clinical symptoms still makes the therapeutic management challenging. In the new era of functional neurosurgery, deep brain stimulation (DBS) may represent a promising therapeutic approach in selected HD patients. Articles describing the effect of DBS in patients affected by HD were selected from Medline and PubMed by the association of text words with MeSH terms as follows: "Deep brain stimulation," "DBS," and "HD," "Huntington's disease," and "Huntington." Details on repeat expansion, age at operation, target of operation, duration of follow-up, stimulation parameters, adverse events, and outcome measures were collected. Twenty eligible studies, assessing 42 patients with HD, were identified. The effect of globus pallidus internus (GPi) DBS on Unified Huntington's Disease Rating Scale (UHDRS) total score revealed in 10 studies an improvement of total score from 5.4 to 34.5%, and in 4 studies, an increase of motor score from 3.8 to 97.8%. Bilateral GPi-DBS was reported to be effective in reducing Chorea subscore in all studies, with a mean percentage reduction from 21.4 to 73.6%. HD patients with predominant choreic symptoms may be the best candidates for surgery, but the role of other clinical features and of disease progression should be elucidated. For this reason, there is a need for more reliable criteria that may guide the selection of HD patients suitable for DBS. Accordingly, further studies including functional outcomes as primary endpoints are needed.

Electrophysiological signatures predict clinical outcomes after deep brain stimulation of the globus pallidus internus in Meige syndrome

ObjectiveDeep brain stimulation (DBS) of the globus pallidus internus (GPi) has been shown to be a safe and effective alternative therapy for ameliorating medically refractory primary Meige syndrome. However, the associations between DBS target position and surrounding electrophysiological properties as well as patients’ clinical outcomes remains largely unknown. In a large number of patients, we investigated electrophysiological features around stimulation targets and explored their roles in predicting clinical outcomes following bilateral GPi-DBS. MethodsThe locations of DBS active contacts along the long axis of the GPi in a standard space were calculated and compared among three groups with different clinical outcomes. The firing rates of individual neurons within the GPi were calculated for each patient and compared across the three groups. ResultsCompared with the bad group (poor clinical outcome), active contacts in the good group (good clinical outcome) and the best group (best clinical outcome) were located in the more posterior GPi. The average firing rates in the good and best groups were significantly higher than in the bad group, and this difference was pronounced within the ventral GPi. For the bad group, the average firing rates were significantly lower in the ventral than in the dorsal GPi. ConclusionsThis study suggests that DBS of the posterior GPi may produce better clinical outcomes during primary Meige syndrome treatment and that higher GPi neuronal activity, particularly within the ventral part, can be used as a biomarker to guide DBS electrode implantation during surgery.

Dysarthria and Speech Intelligibility Following Parkinson's Disease Globus Pallidus Internus Deep Brain Stimulation.

Although earlier studies reported variable speech changes following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients, the effects of globus pallidus internus (GPi) DBS on speech performance in PD remain largely unknown. We aimed to characterize speech changes following PD GPi-DBS. We retrospectively analyzed clinical and speech outcomes of 25 PD patients treated with bilateral GPi-DBS at a single center. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), speech subsystem domains (respiratory, laryngeal, resonance, orofacial, rate, prosody, rhythm, and naturalness), and overall speech intelligibility. Scores at baseline were compared with those at 6 months, 1 year, and the longest clinical follow-up available. In the off-medication state, activities of daily living and motor function based on UPDRS II and III significantly improved postoperatively. We observed unique patterns of speech changes in patients with PD following GPi-DBS in the short- (n = 25) and longer-term (n = 8) follow-up periods. Velopharyngeal (resonance), laryngeal components, and prosody worsened after bilateral GPi-DBS (p < 0.015). Speech intelligibility did not worsen after GPi-DBS in the short-term, but there was a trend to deteriorate at long-term follow-up (e.g., one year and beyond). We observed worsening of hypokinetic dysarthria in individual patients. Also, a minority of patients developed stuttering, spastic dysarthria, or ataxic dysarthria. Bilateral GPi-DBS worsened several modalities of parkinsonian speech without compromising overall speech intelligibility. GPi-DBS can potentially worsen or induce hypokinetic dysarthria, stuttering, spastic dysarthria, or ataxic dysarthria. GPi-DBS may have different and variable effects on speech function when compared to STN-DBS.

Deep brain stimulation of the internal globus pallidus does not affect the limbic circuit in patients with Parkinson's disease: a PET study.

Internal globus pallidus (GPi) deep brain stimulation (DBS) is a safe and effective alternative treatment in Parkinson's disease (PD) for patients with cognitive impairment. However, no study has yet investigated metabolic changes within a large series of patients undergoing GPi stimulation. We assessed motor, cognitive and psychiatric changes, as well as modifications in brain glucose metabolism measured with FDG-PET, before and after bilateral GPi-DBS. In the same week, 32 patients with PD underwent a motor, cognitive and psychiatric assessment and a resting-state FDG-PET scan, 4months before and 4months after GPi-DBS surgery. For the voxelwise metabolic change assessment, the p value was controlled for multiple comparisons using the family wise error rate. After GPi-DBS surgery, patients showed a significant overall improvement in motor status. No cognitive or psychiatric changes were observed after surgery. Nor were any clusters with significantly relative metabolic changes found in the limbic circuit after surgery. Clusters with significantly relative metabolic changes were observed in the left and right Brodmann area (BA) 6, the right BA 9, the right and left BA 39 and the left BA 17. The present study confirmed that GPi-DBS is an effective treatment in patients with advanced PD, owing to metabolic changes in the areas involved in motor execution. The absence of relative metabolic decrease in the limbic circuit and the few changes affecting the associative circuit could explain why GPi-DBS is cognitively safe.

Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes

ObjectiveWe aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making. MethodsThis single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes. ResultsFor the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes. ConclusionBilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.

Three-Year Gait and Axial Outcomes of Bilateral STN and GPi Parkinson's Disease Deep Brain Stimulation.

Objective: To examine the short- and long-term clinical outcomes of the bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on gait and axial symptoms in Parkinson’s disease (PD) patients. Available data have been inconsistent and mostly short-term regarding the effect of both brain targets on gait and axial symptoms. We aimed to identify potential target specific differences at 3-year follow-up from a large single-center experience.Methods: We retrospectively reviewed short-term (6-month follow-up) and long-term (36-month follow-up) changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III total scores of 72 PD patients (53 with bilateral STN-DBS and 19 with bilateral GPi-DBS). An interdisciplinary team made target-specific decisions for each DBS patient. We analyzed changes in gait and axial subscores derived from UPDRS II and III.Results: In both the STN- and GPi-DBS cohorts, we observed no significant differences in gait and axial UPDRS derived subscores in the off-med/on stimulation state at long-term follow-up when compared to baseline. On-med axial scores remained similar in the short-term but worsened in both groups (STN, 2.23 ± 3.43, p < 0.001; GPi, 2.53 ± 2.37, p < 0.01) in the long-term possibly due to disease progression. At long-term follow-up, the UPDRS III off-med/on stimulation scores worsened but were persistently improved from baseline in both groups (−9.07 ± 13.9, p < 0.001).Conclusions: The study showed that long-term both STN- and GPi-DBS had a similar effect on gait and axial symptoms in UPDRS derived subscores at 36-month follow-up despite potential baseline differences in criteria for selection of each target. More sophisticated measures of gait and balance beyond the categorical UPDRS score will be needed for future studies.

Kinematic and electromyographic assessment in isolated generalized dystonia: posture and gait changes in response to bilateral GPiDBS

Kinematic and electromyographic assessment in isolated generalized dystonia: posture and gait changes in response to bilateral GPiDBS

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary.

Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease? When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease? There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease? When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I). Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease? If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I). Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson's disease? If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I). Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson's disease? There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events. The full guideline can be found at: https://www.cns.org/guidelines/deep-brain-stimulation-parkinsons-disease.

International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease.

The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

Long-term clinical outcome of bilateral pallidal stimulation for intractable craniocervical dystonia (Meige syndrome). Report of 6 patients

BackgroundThe aim of the present study was to report the short-term as well long-term results of bilateral pallidal stimulation in 6 consecutive patients for severe debilitating craniocervical dystonia (Meige syndrome) using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). MethodsWe evaluated 6 consecutive patients with the diagnosis of intractable long-standing craniocervical dystonia. The formal objective assessment included the motor and disability BFMDRS scores. The BFMDRS assessment was performed before and after it roughly annually up to 60months when bilateral pallidal stimulation was switched on and compared to baseline BFMDRS scores. We present short-term (3months postoperatively) follow-up as well long-term (from 6 to 60months) results. Baseline BFMDRS scores and subsequent follow-up BFMDRS scores were compared with the use of a Wilcoxon signed-rank test for matched pairs. A two-tailed probability level of 5% (p<0.05) was considered significant. ResultsBilateral GPi DBS improved the BFMDRS total movement score by 65% at short-term follow-up and by 53% at long-term follow-up when compared to baseline scores. Subscores for eyes at short-term follow-up were reduced by 78%, for mouth by 58%, and for speech/swallowing by 49%. This improvements for individual subscores were maintained at long-term follow-up and were as follows for eyes by 67%, mouth by 50% and speech/swallowing by 39%. The BFMDRS disability score was reduced by 48% at short-term follow-up and by 55% at long-term follow-up when compared to baseline scores. ConclusionOur results showed that bilateral GPi DBS in craniocervical dystonia is effective and safe. Phasic dystonic movements like blepharospasm or oromandibular dystonia responded very fast and favorable to pallidal stimulation reducing disabilities.

Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature.

BackgroundPost-hypoxic myoclonus (PHM) is a syndrome that occurs when a patient has suffered hypoxic brain injury. The myoclonus is usually multifocal and generalized, often stemming from both cortical and subcortical origins. In severe cases, pharmacological treatments with antiepileptic medications may not satisfactorily control the myoclonus.MethodsWe present a case of a 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). We review the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature.ResultsThis patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response.DiscussionWe demonstrate a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus.

A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study.

Dystonia often has inconsistent benefits and requires more energy-demanding DBS settings. Studies suggest that squared biphasic pulses could provide significant clinical benefit; however, dystonia patients have not been explored. To assess safety and tolerability of square biphasic DBS in dystonia patients. This study included primary generalized or cervical dystonia patients with bilateral GPi DBS. Square biphasic pulses were implemented and patients were assessed at baseline, immediately postwashout, post-30-minute washout, 1 hour post- and 2 hours postinitiation of investigational settings. Ten participants completed the study. There were no patient-reported or clinician-observed side effects. There was improvement across time on the Toronto Western Spasmodic Torticollis Rating Scale (χ2 = 10.7; P = 0.031). Similar improvement was detected in objective gait measurements. Square biphasic stimulation appears safe and feasible in dystonia patients with GPi DBS. Further studies are needed to evaluate possible effectiveness particularly in cervical and gait features. © 2016 International Parkinson and Movement Disorder Society.

Deep Brain Stimulation in Rare Inherited Dystonias.

Rare causes of inherited movement disorders often present with a debilitating phenotype of dystonia, sometimes combined with parkinsonism and other neurological signs. Since these disorders are often resistant to medications, DBS may be considered as a possible treatment. Patients with identified genetic diseases (ataxia-telangiectasia, chorea-achantocytosis, dopa-responsive dystonia, congenital nemaline myopathy, methylmalonic aciduria, neuronal ceroid lipofuscinosis, spinocerebellar ataxia types 2 and 3, Wilson's disease, Woodhouse-Sakati syndrome, methylmalonic aciduria, and X trisomy) and disabling dystonia underwent bilateral GPi DBS (bilateral thalamic Vim nucleus in 1 case). The primary outcome was the difference in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) between baseline, 1 year and last available follow-up. Preoperative factors such as age at surgery, disease duration at surgery, proportion of life lived with dystonia and severity of dystonia were correlated to the primary outcome. Eleven patients were operated between February 2003 and December 2013. Age and duration of disease at time of surgery were 30 ± 19 and 12.5 ± 15.7 years, respectively. DBS effects on dystonia severity were variable but overall marginally effective, with a mean improvement of 7.9% (p = 0.39) at 1-year follow-up and 16.7% (p = 0.46) at last follow-up (mean 47.3 ± 19.9 months after surgery). No preoperative factors were identified to predict the surgical outcome. Our findings support the current knowledge that DBS is modestly effective in treating rare inherited dystonias with a combined phenotype. However, the BFMDRS might not be the best tool to measure outcome in these severely affected patients.

EP 9. GPi Deep Brain Stimulation for the treatment of status distonicus in tardive dystonia

Introduction Dystonia is a movement disorder due to sustained muscle contractions that cause twisting and repetitive movements conditioning abnormal postures. Tardive dystonia generally follows long treatment with neuroleptics. An extreme condition called status distonicus may even be life threatening, determining spasm of axial musculature leading to respiratory or cardiac arrest. Bilateral pallidotomy provided significant benefit to dystonic symptoms in some patients; moreover, in recent years, pallidotomy has been replaced from pallidal DBS; pallidal DBS is particularly effective both in primitive generalized dystonia and in tardive dystonia consequent to neuroleptics. Objectives To report DBS for the treatment of severe iatrogenic dystonia refractory to medical treatment. Patient and methods A 19 years-old boy affected by severe behavior disorder was treated with neuroleptic drugs (haloperidole). After three years of treatment, appeared severe neck and axial dystonia with initial involvement of the extremities. The change in the pharmacological treatment led to an initial improvement, followed by a progressive and relentless worsening and loss of motor autonomy. The patient also experimented severe dysphagia and several episodes of ab-ingestis pneumonia. Anticholinergic and dopaminergic treatment failed to improve symptoms. The patient progressively felt in a generalized status distonicus. At admission, F-M DRS was 74. For this potentially threatening for life condition, he was candidated for bilateral GPi DBS. After stereotactic localization of ventro-mesial-posterior part of Gpi on volumetric isotropic T1 MRi coupled with Shaltenbrandt & Wahren atlas, bilateral DBS was performed in general sedation, with intraoperative neurophysiology. A couple of quadripolar electrodes were inserted and immediately connected with IPG (Activa RC Medtronic). Results Stimulation started during postoperative day 2. After initial adjustment of the stimulation parameters we appreciated a clear reduction in the intensity and frequency of dystonic spasms, without surgical complication or adverse effects. At discharge the patient was able to walk without help, no dysphagia has been complained for and dystonic spasms were absent. Stimulation parameters were settled as following: left GPi 1- case positive, 2.0 V, 210 μs, 130 Hz; right GPi 9-case positive, 2.0 V, 210 μs, 130 Hz. At one year follow-up F-M DRS is 20. Conclusion The role of DBS in secondary dystonia is still debated because of several failures; important factors in the surgical outcome are: the etiology of dystonia, the absence of skeletal deformity, younger age at surgery and shorter duration of disease. Another topic is the time of early efficacy of DBS, very varying among different reports, but generally considered in the span of weeks or months. Tardive dystonia, due to neuroleptic therapy, seems to be affected from DBS, better than other secondary forms. GPi DBS has also been described to be effective in the treatment of status distonicus and it is considered the treatment of choice in the acute management of this life-threatening condition. In this case we found a striking improvement in F-M DRS, since the first days, with prompt resolution of status distonicus. We suggest the indication to acute treatment with DBS in case of status distonicus in course of tardive dystonia.

Twiddler’s Syndrome in a Patient with Dystonic Tremor Treated with DBS

Background and Importance: Twiddler’s syndrome is a rare complication of DBS. This condition occurs when the IPG is consciously or inadvertently rotated in its pocket, resulting in torsion and possible dislodgement of implanted electrodes, with subsequent loss of function. Methods: Here we present a patient diagnosed with Twiddler’s syndrome. The patient presented with straining cables at the neck five months after bilateral Gpi DBS and an x-ray demonstrated Twiddler’s syndrome. Initial revision with preventive measures proved futile. After some time the condition recurred, now with dislocation of one of the intracerebral electrodes. In a second revision the IPG was placed under the pectoralis muscle, which has so far prevented further rotation. Results and Conclusion: While Twiddler’s syndrome is fairly uncommon, it remains to be a risk associated with DBS, recognizing the potential risks and signs might allow for preventive measures avoiding dislocation of the intracerebral electrodes.

Deep brain stimulation in critical care conditions

Some neurological conditions require admission to an intensive care unit (ICU) where deep sedation and mechanical ventilation are administered to improve the patient's condition. Nevertheless, these treatments are not always helpful in disease control. At this stage, deep brain stimulation (DBS) could become a viable alternative in the treatment of critical neurological conditions with long-lasting clinical benefit. The value of deep brain stimulation has been investigated in the treatment of patients who had undergone surgical electrode implants as an emergency procedure to treat acute life-threatening conditions requiring admission to neurological ICU (NICU). A before-and-after perspective study was examined of seven patients who were treated with DBS for status dystonicus (SD) and post-stroke severe hemiballismus. Bilateral globus pallidus internus (GPi) DBS was performed in five SD patients and unilateral ventralis oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post-stroke hemiballismus patients. Bilateral GPi-DBS allowed SD resolution in a time lapse varying from 1week to 3months. No clear improvements compared to the baseline clinical condition were observed. Unilateral Voa/Vop-DBS intervention controlled hemiballismus after 10h, and the patient was discharged in 2days. The other patient was transferred from the NICU to the neurosurgery ward after 13days. No surgical complications were observed in any of the above procedures. Neurostimulation procedures could represent a valuable choice in critical care conditions, when involuntary movements are continuous, life-threatening and refractory to intensive care procedures. DBS is feasible, safe and effective in selected cases.