Search

Clinical Vignette: A 23-year-old woman with pantothenate kinase-associated neurodegeneration (PKAN) presented with medication-refractory generalized dystonia and an associated gait impairment., Clinical Dilemma: Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) can be an effective treatment for dystonia. However, outcomes for PKAN DBS have been variable and there are no standardized criteria for patient selection., Clinical Solution: Bilateral GPi DBS implantation resulted in improvement in dystonia and gait. The benefit has persisted over one year after implantation., Gap in Knowledge: PKAN is a rare neurodegenerative disorder and evidence supporting the use of PKAN DBS has been largely limited to case reports and case series. Consequently, there is a paucity of long-term data, especially on gait-related outcomes., Expert Commentary: The clinical characteristics of dystonia that respond to DBS tend to respond in PKAN. Clinicians counselling patients about the effects of DBS for PKAN should thoughtfully discuss gait and postural instability as important aspects to consider, especially as the disease will progress post-DBS., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia., Methods: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist., Results: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes., Conclusion: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SAJEA Lagerweij reports a grant from the Stichting Wetenschapsfonds Dystonie and a personal grant from the University of Groningen. The funder was not involved in the study. M Smit, LM Centen, JW Elting and JMC van Dijk report no disclosures. ME van Egmond participated in a training program sponsored by Medtronic and received a grant from the Stichting Wetenschapsfonds Dystonie. MAJ Tijssen reports grants from the Netherlands Organisation for Health Research and Development Domain: NWO-TTW (2022–9), ZonMW Topsubsidie (91218013) and ZonMW Program Translational Research(40–44,600–98-323). She also received two European Fund for Regional Development from the European Union (01492947 & DIMATIO (EFRO-0059) and a European Joint Programme on Rare Diseases (EJP RD) Networking Support Scheme. A grant from the Health Holland and the PPP allowance program (PPP-2023-00).Furthermore, from the the province of Friesland, the Stichting Wetenschapsfonds Dystonie and unrestricted grants from Ipsen, Actelion and Merz. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking., Objectives: To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia., Methods: Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously., Results: DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations., Conclusions: This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach., (© 2024 International Parkinson and Movement Disorder Society.)

Introduction: Deep Brain Stimulation (DBS) is an established therapeutic approach for the treatment of dystonia. However, to date, no large-scale or comprehensive DBS dystonia patient registry has been yet undertaken. Here, we describe the protocol for a world-wide registry of clinical outcomes in dystonia patients implanted with DBS., Methods and Analysis: This protocol describes a multicenter, international clinical outcomes registry consisting of up to 200 prospectively enrolled participants at up to 40 different sites to be implanted with a constant-current, multiple independent current controlled (MICC) DBS device (Vercise DBS Systems, Boston Scientific) for treatment of dystonia. Key inclusion criteria for registry candidates include the following: understanding of study requirements and treatment procedures, a signed written informed consent form prior to participation, and meeting all criteria established in the locally applicable Instructions for Use (IFU) for the implanted DBS system. Key clinical endpoints include (but are not limited to) the evaluation of disease state (Burke-Fahn-Marsden Dystonia Rating Scale [BFMDRS], Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), quality of life (Short Form Health Survey-36, Short Form Health Survey-10), and treatment satisfaction (Clinical Global Impression of Change [CGI-Clinician; CGI-Subject; CGI-Caregiver]) at 6-months, 12-months, 2-years, and 3-years post-lead placement. Adverse events are documented and reported using structured questionnaires., Perspectives: Treatment of patients with dystonia using DBS has progressed considering recent technological advances. This international dystonia outcomes registry aims to collect and evaluate real-world clinical data derived from patients who have been implanted with a constant-current, MICC-equipped DBS system (with available directional capabilities), per standard of care., Competing Interests: No authors have competing interests., (Copyright: © 2024 Albanese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deep brain stimulation of the subthalamic nucleus and globus pallidus internus is approved by the Food and Drug Administration for treating dystonia. Both targets have shown effectiveness in improving symptoms, but post-operative outcomes can vary significantly among patients. This variability has led researchers to explore alternative neuromodulation targets that might offer more consistent results. Emerging research has highlighted several promising new targets for DBS in dystonia. This review examines pre-clinical and clinical data on novel DBS targets for dystonia and explores non-invasive neuromodulation studies that shed light on the disease's underlying pathological circuitry., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) and subthalamic nucleus (STN) is employed for the treatment of dystonia. Pallidal low-frequency oscillations have been proposed as a pathophysiological marker for dystonia. However, the role of subthalamic oscillations and STN-GPi coupling in relation to dystonia remains unclear., Objective: We aimed to explore oscillatory activities within the STN-GPi circuit and their correlation with the severity of dystonia and efficacy achieved by DBS treatment., Methods: Local field potentials were recorded simultaneously from the STN and GPi from 13 dystonia patients. Spectral power analysis was conducted for selected frequency bands from both nuclei, while power correlation and the weighted phase lag index were used to evaluate power and phase couplings between these two nuclei, respectively. These features were incorporated into generalized linear models to assess their associations with dystonia severity and DBS efficacy., Results: The results revealed that pallidal theta power, subthalamic beta power and subthalamic-pallidal theta phase coupling and beta power coupling all correlated with clinical severity. The model incorporating all selected features predicts empirical clinical scores and DBS-induced improvements, whereas the model relying solely on pallidal theta power failed to demonstrate significant correlations., Conclusions: Beyond pallidal theta power, subthalamic beta power, STN-GPi couplings in theta and beta bands, play a crucial role in understanding the pathophysiological mechanism of dystonia and developing optimal strategies for DBS., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units ( p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

Objective: Dystonia is among the most common pediatric movement disorders and can manifest with a range of debilitating symptoms, including sleep disruptions. The duration and quality of sleep are strongly associated with quality of life in these individuals and could serve as biomarkers of dystonia severity and the efficacy of interventions such as deep brain stimulation (DBS). Thus, this study investigated sleep duration and its relationship to disease severity and DBS response in pediatric dystonia., Methods: Actigraphs (wearable three-axis accelerometers) were used to record multiday sleep data in 22 children with dystonia, including 6 patients before and after DBS implantation, and age- and sex- matched healthy controls. Data were preprocessed, and metrics of sleep duration and quality were extracted. Repeated-measures statistical analyses were used., Results: Children with dystonia slept less than typically developing children (p = 0.009), and shorter sleep duration showed trending correlation with worse dystonia severity (r = -0.421, p = 0.073). Of 4 patients who underwent DBS and had good-quality data, 1 demonstrated significantly improved sleep (p < 0.001) postoperatively. Reduction in dystonia severity strongly correlated with increased sleep duration after DBS implantation (r = -0.965, p = 0.035)., Conclusions: Sleep disturbances are an underrecognized marker of pediatric dystonia severity, as well as the effectiveness of interventions such as DBS. They can serve as objective biomarkers of disease burden and symptom progression after treatment.

Background: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor., Methods: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters., Results: Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups., Conclusions: GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

While biallelic POLR3A loss-of-function variants are traditionally linked to hypomyelinating leukodystrophy, patients with a specific splice variant c.1909+22G>A manifest as adolescent-onset spastic ataxia without overt leukodystrophy. In this study, we reported eight new cases, POLR3A-related disorder with c.1909+22 variant. One of these patients showed expanded phenotypic spectrum of generalised dystonia and her sister remained asymptomatic except for hypodontia. Two patients with dystonic arm tremor responded to deep brain stimulation. In our systemic literature review, we found that POLR3A-related disorder with c.1909+22 variant has attenuated disease severity but frequency of dystonia and upper limb tremor did not differ among genotypes., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

A neurological condition called dystonia results in abnormal, uncontrollable postures or movements because of sporadic or continuous muscular spasms. Several varieties of dystonia can impact people of all ages, leading to severe impairment and a decreased standard of living. The discovery of genes causing variations of single or mixed dystonia has improved our understanding of the disease's etiology. Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3. Diagnosis of dystonia is primarily based on clinical symptoms, which can be challenging due to overlapping symptoms with other neurological conditions, such as Parkinson's disease. This review aims to summarize recent advances in the genetic origins and management of focal dystonia.

One of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with 'traditional' healthcare providers; about the role of the European Reference Networks (ERNs); if remote care can retain a human touch and stay patient centric. The manuscript is one of the results of the European Brain Council (EBC) Value of Treatment research project on rare brain disorders focusing on progressive ataxias, dystonia and phenylketonuria with the support of Academic Partners and in collaboration with European Reference Networks (ERNs) experts, applying empirical evidence from different European countries. The main purpose of this work is to investigate the impact of the COVID-19 pandemic on the continuity of care for ataxias, dystonia and phenylketonuria (PKU) in Europe. The analysis carried out makes it possible to highlight the critical points encountered and to learn from the best experiences. Here, we propose a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards. This work showed that the implementation of telemedicine services was the main measure that healthcare providers (HCPs) put in place and adopted for mitigating the effects of disruption or discontinuity of the healthcare services of people with rare neurological diseases and with neurometabolic disorders in Europe., (© 2024. The Author(s).)

Background and Purpose: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome., Methods: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation., Results: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported., Conclusions: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms., (© 2023. The Author(s).)

Background: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with an experienced physician - an important barrier to widespread adoption in medication-refractory dystonia patients., Objective: Here we prospectively tested the best machine-predicted programming settings in a dystonia cohort treated with GPi-DBS against the settings derived from clinical long-term care in a specialised DBS centre., Methods: Previously, we reconstructed an anatomical map of motor improvement probability across the pallidal region using individual stimulation volumes and clinical outcomes in dystonia patients. We used this to develop an algorithm that tests in silico thousands of putative stimulation settings in de novo patients after reconstructing an individual, image-based anatomical model of electrode positions, and suggests stimulation parameters with the highest likelihood of optimal symptom control. To test real-life application, our prospective study compared results in 10 patients against programming settings derived from long-term care., Results: In this cohort, dystonia symptom reduction was observed at 74.9 ± 15.3% with C-SURF programming as compared to 66.3 ± 16.3% with clinical programming (p < 0.012). The average total electrical energy delivered (TEED) was similar for both the clinical and C-SURF programming (262.0 μJ/s vs. 306.1 μJ/s respectively)., Conclusion: Our findings highlight the clinical potential of machine-based programming in dystonia, which could markedly reduce the programming burden in postoperative management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FL reports grants from Boston Scientific not relevant to the submitted manuscript. MMR reports grants and personal fees from Boston Scientific and Medtronic, not relevant to the submitted work. MJR reports grants and personal fees from Boston Scientific, Medtronic and Zambon, not relevant to the submitted work. JV reports grants and personal fees from Medtronic, personal fees from St. Jude, grants and personal fees from Boston Scientific, personal fees from UCB, personal fees from Merz, personal fees from Allergan, personal fees from TEVA, personal fees from Novartis, personal fees from AbbVie and personal fees from Grünenthal, all outside the submitted work. All other authors report no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior., Objective/hypothesis: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS., Methods: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life., Results: Patients (n = 21) who were enrolled in adaptive DBS trials for Parkinson's disease, essential tremor, obsessive-compulsive disorder, Tourette's syndrome, or dystonia participated. Qualitative data revealed that participants, in general, reported positive experiences with alterations in what was described as 'personality, mood, and behavior changes.' The majority of participants reported increases in quality of life. No participants reported 'regretting the decision to undergo DBS.', Conclusion(s): The findings from this patient sample do not support the narrative that DBS results in substantial adverse changes to dimensions of personality, mood, and behavior. Changes reported as "negative" or "undesired" were few in number, and transient in nature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The balance between neural oscillations provides valuable insights into the organisation of neural oscillations related to brain states, which may play important roles in dystonia. We aim to investigate the relationship of the balance in the globus pallidus internus (GPi) with the dystonic severity under different muscular contraction conditions., Methods: Twenty-one patients with dystonia were recruited. All of them underwent bilateral GPi implantation, and local field potentials (LFPs) from the GPi were recorded via simultaneous surface electromyography. The power spectral ratio between neural oscillations was computed as the measure of neural balance. This ratio was calculated under high and low dystonic muscular contraction conditions, and its correlation with the dystonic severity was assessed using clinical scores., Results: The power spectral of the pallidal LFPs peaked in the theta and alpha bands. Within participant comparison showed that the power spectral of the theta oscillations significantly increased during high muscle contraction compared with that during low contraction. The power spectral ratios between the theta and alpha, theta and low beta, and theta and high gamma oscillations were significantly higher during high contraction than during low contraction. The total score and motor score were associated with the power spectral ratio between the low and high beta oscillations, which was correlated with the dystonic severity both during high and low contractions. The power spectral ratios between the low beta and low gamma and between the low beta and high gamma oscillations showed a significantly positive correlation with the total score during both high and low contractions; a correlation with the motor scale score was found only during high contraction. Meanwhile, the power spectral ratio between the theta and alpha oscillations during low contraction showed a significantly negative correlation with the total score. The power spectral ratios between the alpha and high beta, alpha and low gamma, and alpha and high gamma oscillations were significantly correlated with the dystonic severity only during low contraction., Conclusion: The balance between neural oscillations, as quantified by the power ratio between specific frequency bands, differed between the high and low muscular contraction conditions and was correlated with the dystonic severity. The balance between the low and high beta oscillations was correlated with the dystonic severity during both conditions, making this parameter a new possible biomarker for closed-loop deep brain stimulation in patients with dystonia., Competing Interests: Declaration of Competing Interest Nothing to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Neural oscillatory activities in basal ganglia have prominent roles in cognitive processes. However, the characteristics of oscillatory activities during cognitive tasks have not been extensively explored in human Globus Pallidus internus (GPi). This study aimed to compare oscillatory characteristics of GPi between dystonia and Parkinson's Disease (PD). A dystonia and a PD patient performed the Intra-Extra-Dimension shift (IED) task during both on and off-medication states. During the IED task, patients had to correctly choose between two visual stimuli containing shapes or lines based on a hidden rule via trial and error. Immediate auditory and visual feedback was provided upon the choice to inform participants if they chose correctly. Bilateral GPi Local Field Potentials (LFP) activity was recorded via externalized DBS leads. Transient high gamma activity (~ 100-150 Hz) was observed immediately after feedback in the dystonia patient. Moreover, these bursts were phase synchronous between left and right GPi with an antiphase clustering of phase differences. In contrast, no synchronous high gamma activity was detected in the PD patient with or without dopamine administration. The off-med PD patient also displayed enhanced low frequency clusters, which were ameliorated by medication. The current study provides a rare report of antiphase homotopic synchrony in human GPi, potentially related to incorporating and processing feedback information. The absence of these activities in off and on-med PD patient indicates the potential presence of impaired medication independent feedback processing circuits. Together, these findings suggest a potential role for GPi's synchronized activity in shaping feedback processing mechanisms required in cognitive tasks., (© 2023. The Author(s).)

Background: Role of radiosurgical lesioning in functional disorders has been restricted because of development of deep brain stimulation (DBS) techniques. However, many elderly patients with comorbidities and coagulation abnormalities may not be eligible for DBS. Radiosurgical lesioning may be a good alternative in such cases. The objective of the study was to review the role of radiosurgical lesioning for functional targets in common functional disorders., Materials and Methods: Literature reports pertaining to common disorders were reviewed. Disorders included are tremors (essential tremors, tremor-dominant Parkinson's disease [PD], multiple sclerosis [MS] related refractory tremors), Parkinson's disease (for rigidity, bradykinesia, drug-induced dyskinesias), dystonia, and obsessive-compulsive disorder (OCD)., Results: The most commonly performed procedure was ventral intermediate nucleus (VIM) lesioning for essential tremors and tremor-dominant PD, with about 90% patients demonstrating improvement. Intractable OCD with 60% responders is a promising indication. Other disorders are less commonly treated, with dystonia being the least commonly treated entity. Subthalamic nucleus (STN) and globus pallidus interna/posteroventral pallidum (GPi) lesioning are very rarely reported, and the available literature suggests caution due to high rates of adverse effects., Conclusions: Outcomes for radiosurgical lesioning for essential tremors (VIM) and OCD (anterior limb of internal capsule [ALIC]) are encouraging. Radiosurgical lesioning offers a lower immediate risk profile in patient population with several comorbidities; however, long-term adverse effects due to radiation are a concern, especially for STN and GPi lesioning.

Background: Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable., Objective: To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement., Methods: The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects., Results: Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery ( p  = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement ( p  = 0.003)., Conclusions: These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Deep brain stimulation (DBS) is an established treatment in patients of various ages with pharmaco-resistant neurological disorders. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures, and on electrode connectivity to a specific distribution pattern within brain networks. Such information is usually collected using group-level analysis, which relies on the availability of normative imaging resources (atlases and connectomes). Analysis of DBS data in children with debilitating neurological disorders such as dystonia would benefit from such resources, especially given the developmental differences in neuroimaging data between adults and children. We assembled pediatric normative neuroimaging resources from open-access datasets in order to comply with age-related anatomical and functional differences in pediatric DBS populations. We illustrated their utility in a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources., Methods: An average pediatric brain template (the MNI brain template 4.5-18.5 years) was implemented and used to localize the DBS electrodes in 20 patients from the GEPESTIM registry cohort. A pediatric subcortical atlas, analogous to the DISTAL atlas known in DBS research, was also employed to highlight the anatomical structures of interest. A local pallidal sweetspot was modeled, and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcomes. Additionally, a pediatric functional connectome of 100 neurotypical subjects from the Consortium for Reliability and Reproducibility was built to allow network-based analyses and decipher a connectivity fingerprint responsible for the clinical improvements in our cohort., Results: We successfully implemented a pediatric neuroimaging dataset that will be made available for public use as a tool for DBS analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46, permuted p = 0.019). The functional connectivity fingerprint of DBS outcomes was determined to be a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30, permuted p = 0.003)., Conclusions: Local sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcomes in dystonia using pediatric neuroimaging surrogate data. Implementation of this pediatric neuroimaging dataset might help to improve the practice and pave the road towards a personalized DBS-neuroimaging analyses in pediatric patients., Competing Interests: Declaration of Competing Interest AAK received honoraria from Medtronic and Boston Scientific, not related to this work. AK is a principal investigator in the STIM-CP trial, partly sponsored by Boston Scientific. JKK is a consultant to Medtronic, Boston Scientific, aleva and Inomed. LT serves as the vice president of the German Neurological Society. TAD has received speaker honoraria from Medtronic & Boston Scientific. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

During the last decades deep brain stimulation (DBS) has become an important treatment option for a variety of neurological disorders such as drug-intractable dystonia. Yet, the mechanisms of action of DBS are still largely unknown. Dystonia is a heterogenous movement disorder characterized by involuntary muscle contractions causing abnormal movements, postures, or both. The underlying pathophysiological processes remain unclear, but a dysfunction of the basal ganglia circuit is critically involved as supported by the effectiveness of DBS of the globus pallidus internus (GPi) in various types of dystonia. However, the degree of clinical improvement differs among the types of dystonia, as well as from patient to patient, and the delayed response to GPi-DBS in dystonia patients hampers the adjustment and optimization of stimulation parameters. Preclinical studies in suitable animal models can contribute decisively to detect the underlying mechanisms of DBS and biomarkers, to identify new possible stimulation targets and to optimize stimulation patterns. In this review, we give an overview of previous research on DBS in animal models of dystonia. With regard to the aims of research we discuss the opportunities and limitations concerning different available animal models of dystonia and technical challenges., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Dystonia is a clinical sign and main feature of many movement disorders in humans as well as veterinary species. It is characterized by sustained or intermittent involuntary muscle contractions causing abnormal (often repetitive) movements, postures, or both. This review discusses the terminology and definition of dystonia, its phenomenology, and its pathophysiology, and provides considerations regarding the diagnosis and treatment of dystonia in dogs and cats. In addition, currently recognized or reported disorders in dogs and cats in which dystonia is a particular or main feature are discussed and comparisons are made between disorders featuring dystonia in humans and animals. We suggest that when describing the phenomenology of dogs and cats with dystonia, if possible the following should be included: activity being performed at onset (e.g., resting or running or exercise-induced), body distribution, duration, responsiveness (subjective), severity, temporal pattern (i.e., paroxysmal or persistent, severity at onset and at later stages), presence or absence of autonomic signs (e.g., salivation), presence or absence of preceding signs (e.g., restlessness), presence or absence of signs after dystonia subsides (e.g., sleepiness), coexistence of other movement disorders, any other neurological manifestations, and possible links to administered medications, intoxications or other associated factors. We also suggest that dystonia be classified based on its etiology as either structural genetic, suspected genetic, reactive, or unknown., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: Dystonias are relatively rare disorders characterized by sustained or intermittent muscle contractions causing abnormal movements or postures. Generalized dystonia is a therapeutic challenge because medications are unable to control dystonia adequately in most patients. These patients may be candidates for surgical therapy. The commonly used surgical procedures in these patients are pallidotomy and deep brain stimulation. Limited studies are available on the role of pallidotomy in children with acquired/heredodegenerative generalized dystonia. The objective of this study was to describe the authors' experience with bilateral pallidotomy in this group of patients., Methods: The authors retrospectively reviewed all pediatric patients (less than 18 years of age) with acquired/heredodegenerative generalized dystonia who underwent bilateral simultaneous pallidotomy at their center between January 2014 and January 2021. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores before and after surgery were recorded. Complications arising after the procedure were recorded as well., Results: Ten patients (8 male and 2 female) with a mean (range) age of 11.1 (5-17) years were included in this study. The mean duration between disease onset and surgical intervention was 3.9 years. Two patients presented in status dystonicus. The mean ± SD (range) preoperative BFMDRS score of the patients without status dystonicus (n = 8) was 80 ± 18.9 (59.5-108). The mean ± SD BFMDRS score at the time of discharge from the hospital after surgery was 58.8 ± 37.9. Three patients had more than 20% change in BFMDRS score at the time of discharge from the hospital. The mean improvement was 25.5% at the end of 1 year. Of 5 surviving patients in the non-status dystonicus group, 3 patients had more than 40% change in BFMDRS score while the other 2 patients developed recurrence at the last follow-up (4.5 years). Status dystonicus abated after bilateral pallidotomy in both patients. Permanent bulbar complications were seen in 2 patients., Conclusions: Bilateral pallidotomy may result in clinically significant improvement in children with acquired/heredodegenerative generalized dystonia, although the benefits should be closely weighed against the risk of irreversible bulbar dysfunction. It is a viable option for children in resource-limited settings.

Background: DYT6 dystonia belongs to a group of isolated, genetically determined, generalized dystonia associated with mutations in the THAP1 gene., Case Presentation: We present the case of a young patient with DYT6 dystonia associated with a newly discovered c14G>A (p.Cys5Tyr) mutation in the THAP1 gene. We describe the clinical phenotype of this new mutation, effect of pallidal deep brain stimulation (DBS), which was accompanied by two rare postimplantation complications: an early intracerebral hemorrhage and delayed epileptic seizures. Among the published case reports of patients with DYT6 dystonia, the mentioned complications have not been described so far., Conclusions: DBS in the case of DYT6 dystonia is a challenge to thoroughly consider possible therapeutic benefits and potential risks associated with surgery. Genetic heterogeneity of the disease may also play an important role in predicting the development of the clinical phenotype as well as the effect of treatment including DBS. Therefore, it is beneficial to analyze the genetic and clinical relationships of DYT6 dystonia., (© 2022. The Author(s).)

Background: Deep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms., Objectives: The aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome., Methods: This open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity)., Results: Compared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls., Conclusions: All in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)-being lower in samples with late or incomplete penetrance-thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD) including dystonia. Dystonic features in JE are uncommon. Here, we have tried to summarize the clinical features and management of dystonia among JE patients with a comprehensive literature search., Methods: Various databases, including PubMed, Embase, and Google Scholar, were searched against the predefined criteria using suitable keywords combination and boolean operations. Relevant information from observational and case studies was extracted according to the author, dystonic features, radiological changes in the brain scans, treatment options, and outcome wherever provided., Result: We identified 19 studies with a total of 1547 JE patients, the diagnosis of which was confirmed by IgM detection in serum and/or cerebrospinal fluid in the majority of the patients (88.62%). 234 (15.13%) of JE patients had dystonia with several types of focal dystonia being present in 131 (55.98%) either alone or in combination. Neuroimaging showed predominant involvement of thalami, basal ganglia, and brainstem. Oral medications including anticholinergics, GABA agonists, and benzodiazepines followed by botulinum toxin were the most common treatment modalities., Conclusion: Dystonia can be a disabling consequence of JE, and various available medical therapies can significantly improve the quality of life. Owing to insufficient studies on the assessment of dystonia associated with JE, longitudinal studies with a larger number of patients are warranted to further clarify the clinical course, treatment, and outcome of dystonia., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: Globus 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 Methods: Five 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., Results: BFMDRS 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., Conclusion: Unilateral 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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Background: Task-specific dystonia (TSD) is a form of focal dystonia that occurs in the context of the performance of selective, highly skilled, often repetitive, motor activity. TSD may be apparent during certain tasks such as writing, playing musical instruments, or other activities requiring fine motor control, but may also occur during certain sports, and maybe detrimental to professional athletes' careers. Therefore, sports physicians and movement disorder neurologists need to be aware of the presentation and phenomenology of sports-related dystonia (SRD), the topic of this review., Methods: A broad PubMed search using a wide range of keywords and combinations was done in October 2021 to identify suitable articles for this review., Results: Most of the publications are on yips in golfers and on runners' dystonia. Other sports in which SRD has been reported are ice skating, tennis, table tennis, pistol shooting, petanque, baseball, and billiards., Discussion: Yips, which may affect up to half of the golfers and rarely athletes in other sports (e.g., baseball, cricket, basketball, speed skating, gymnastics) seems to be a multi-factorial form of TSD that is particularly troublesome in highly skilled professional golfers. Runners' dystonia, affecting the foot, leg, and hip (in decreasing order), may evolve into more generalized and less specific dystonia. The pathophysiologic mechanisms of SRD are not well understood. Botulinum toxin has been reported to alleviate dystonia in golfers', runners', and other forms of SRD. Future studies should utilize neurophysiologic, imaging, and other techniques to elucidate mechanisms of this underrecognized group of movement disorders., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Context: Movement disorders represent a common presentation in pediatrics and are often a source of clinical and diagnostic dilemmas. In this review, we provide an overview of common causes along with simplified clinical approach and management options for major movement disorders., Sources: This narrative review is based on contemporary evidence and personal experience. Medline was searched for recent advances, current understanding and consensus on classification, clinical features, diagnosis and treatment., Results: Movement disorders are classified as hyperkinetic and hypokinetic disorders, the latter being rare in childhood. The hyperkinetic disorders include dystonia, chorea, athetosis, tics and tremor, stereotypies, myoclonus, startle syndromes and functional disorders. Some movement disorders can be benign and developmental. A large proportion of conditions are genetic in origin with a guarded prognosis. Some of the conditions may be post-infectious, immune-mediated or drug induced. Multiple types of movement disorders are present in many conditions. The age at onset, type and distribution of abnormal movements and presence of associated neurological and systemic features help in narrowing the differential diagnosis. The pharmacotherapy of movement disorders is complex and evolving., Conclusion: A synopsis of movement disorders presenting in pediatric age has been provided, incorporating the latest evidence. A simplified approach for clinical diagnosis has been developed for dystonia and chorea.

Aim: To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia., Method: Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE., Results: Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis., Interpretation: Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson's disease, local field potentials (LFPs) excessively synchronized in the beta band (13-35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13-20 Hz) and high frequency gamma facilitation (35-250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4-13 Hz), beta and gamma (60-90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.

There is no available data on the journey of dystonia patients once referred to a tertiary center to undergo deep brain stimulation (DBS). We hypothesized that some patients might be incorrectly diagnosed while others might decline the procedure or experience significant benefit with switching to a different botulinum neurotoxin (BoNT). This is a single-center, retrospective study of dystonia patients who were referred to the DBS program between January 2014 and December 2018. We collected data on the surgical decision as well as factors influencing this decision. Sixty-seven patients were included (30 males, mean age: 48.3 ± 20.1 years, disease duration: 16.9 ± 15.3 years). Thirty-three (49%) patients underwent DBS. Four (6%) patients were awaiting the procedure while the remaining 30 patients (45%) did not undergo DBS. Reasons for DBS decline were patient refusal (17, 53%), functional dystonia (6, 20%), and successful use of AbobotulinumtoxinA (3, 10%) in patients who had failed other BoNTs. Our study highlights the importance of structured patient education to increase acceptance of DBS, as well as careful patient evaluation, particularly with respect to functional dystonia. Finally, changing BoNT formulation might be beneficial in some patients.

Pallidal deep brain stimulation (DBS) is an important option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the globus pallidus internus (GPi). The mechanisms of GPi-DBS are far from understood. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown. We hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal function. We tested this hypothesis in the dt sz hamster, an animal model of inherited generalised, paroxysmal dystonia. Hamsters (dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes in the GPi. DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 h. Synaptic cortico-striatal field potentials, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurones were recorded in brain slice preparations obtained immediately after EPN-DBS. The main findings were as follows: a. DBS increased cortico-striatal evoked responses in healthy, but not in dystonic tissue. b. Commensurate with this, DBS increased inhibitory control of these evoked responses in dystonic, and decreased inhibitory control in healthy tissue. c. Further, DBS reduced mEPSC frequency strongly in dystonic, and less prominently in healthy tissue, showing that also a modulation of presynaptic mechanisms is likely involved. d. Cellular properties of medium-spiny neurones remained unchanged. We conclude that DBS leads to dampening of cortico-striatal communication, and restores intrastriatal inhibitory tone., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

We present the case of a 70-year-old woman with treatment-refractory diaphragmatic dystonia. Patient initially presented with blepharospasms followed by development of involuntary inspiratory spasms during speech. Her symptoms were drug-refractory, and she therefore underwent awake bilateral pallidal deep brain stimulation with microelectrode recording. No intraoperative or postoperative complications or adverse events occurred, and there were no undesired effects of stimulation. Using contacts in bilateral dorsal globus pallidus interna and ventral globus pallidus externa, symptoms alleviated after a latency period of 2-4 weeks. At 5-month follow-up, the patient maintained a 16.5-point reduction in Burke-Fahn-Marsden movement scale (from 20/120 to 3.5/120) with resolution of blepharospasm, irregular inspirations and broken and irregular speech., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.