Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

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.

Quality of life outcomes after deep brain stimulation in acquired dystonia: a systematic review and meta-analysis.

BACKGROUND: Dystonia is a condition that affects the ability to control the movement and function of the body's muscles. It can cause not only physical problems, but also mental problems, resulting in impaired health-related quality of life (HRQoL). However, the effect of deep brain stimulation on quality of life in acquired dystonia remains unclear. METHODS: We conducted a systematic literature review from January 2000 to October 2022，determined the eligible studies, and performed a meta-analysis of HRQoL outcomes based on the Short-Form Health Survey-36 (SF-36) after DBS to evaluate the effects of DBS on physical and mental QoL. RESULTS: A total of 14 studies met the inclusion criteria and were systematically reviewed. A comprehensive meta-analysis was performed for 9 studies that reported physical and psychological data or physical component summary (PCS), or mental component summary (MCS) for SF-36. The mean (SD) age at DBS implantation was 34.29 (10.3) years, and the follow-up period after implantation was 2.21 (2.80) years. The random effects model meta-analysis revealed that both physical and mental domains of the SF-36 improved following DBS. There was no statistically significant difference between the physical domains (effect size=1.34; p<0.0001) and the mental domains (effect size=1.38; p<0.0001). CONCLUSION: This is the first meta-analysis that demonstrates significant benefits in HRQoL following DBS in patients with acquired dystonia. There were significant improvements in both physical QoL and mental QoL.

Brain Shift during Staged Deep Brain Stimulation for Movement Disorders.

INTRODUCTION: Deep brain stimulation (DBS) is a routine neurosurgical procedure utilized to treat various movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. Treatment efficacy is dependent on stereotactic accuracy of lead placement into the deep brain target of interest. However, brain shift attributed to pneumocephalus can introduce unpredictable inaccuracies during DBS lead placement. This study aimed to determine whether intracranial air is associated with brain shift in patients undergoing staged DBS surgery. METHODS: We retrospectively evaluated 46 patients who underwent staged DBS surgery for PD, ET, and dystonia. Due to the staged nature of DBS surgery at our institution, the first electrode placement is used as a concrete fiducial marker for movement in the target location. Postoperative computed tomography (CT) images after the first electrode implantation, as well as preoperative, and postoperative CT images after the second electrode implantation were collected. Images were analyzed in stereotactic targeting software (BrainLab); intracranial air was manually segmented, and electrode shift was measured in the x, y, and z plane, as well as a Euclidian distance on each set of merged CT scans. A Pearson correlation analysis was used to determine the relationship between intracranial air and brain shift, and student's t test was used to compare means between patients with and without radiographic evidence of intracranial air. RESULTS: Thirty-six patients had pneumocephalus after the first electrode implantation, while 35 had pneumocephalus after the second electrode implantation. Accumulation of intracranial air following the first electrode implantation (4.49 ± 6.05 cm3) was significantly correlated with brain shift along the y axis (0.04 ± 0.35 mm; r (34) = 0.36; p = 0.03), as well as the Euclidean distance of deviation (0.57 ± 0.33 mm; r (34) = 0.33; p = 0.05) indicating statistically significant shift on the ipsilateral side. However, there was no significant correlation between intracranial air and brain shift following the second electrode implantation, suggesting contralateral shift is minimal. Furthermore, there was no significant difference in brain shift between patients with and without radiographic evidence of intracranial air following both electrode implantation surgeries. CONCLUSION: Despite observing volumes as high as 22.0 cm3 in patients with radiographic evidence of pneumocephalus, there was no significant difference in brain shift when compared to patients without pneumocephalus. Furthermore, the mean magnitude of brain shift was <1.0 mm regardless of whether pneumocephalus was presenting, suggesting that intracranial air accumulation may not produce clinical significant brain shift in our patients.

Deep brain stimulation in pediatric dystonia: calls for therapeutic realism over nihilism.

PURPOSE: Pediatric dystonia (PD) has a significant negative impact on the growth and development of the child. This study was done retrospectively to analyze functional outcomes in pediatric patients with dystonia who underwent deep brain stimulation. METHODS: In this retrospective analytical study, all the patients of age less than 18 years undergoing deep brain stimulation (DBS) for dystonia between 2012 and 2020 in a single center were analyzed and their functional outcomes were measured by the Burke-Fahn-Marsden-dystonia-rating-scale (BFMDRS). RESULTS: A total of 10 pediatric patients were included with a mean age of onset, duration of disease, and age at surgery being 5.75 years, 7.36 years, and 13.11 years, respectively, with a mean follow-up of 23.22 months. The mean pre-DBS motor score was 75.44 ± 23.53 which improved significantly at 6-month and 12-month follow-up to 57.27 (p value 0.004) and 50.38 (p value < 0.001), respectively. Limbs sub-scores improved significantly at both the scheduled intervals. There was a significant improvement in disability at 1-year follow-up with significant improvement in feeding, dressing, and walking components. There was a 27.34% and 36.64% improvement in dystonia with a 17.37% and 28.86% reduction in disability at 6 months and 12 months, respectively. There was a positive correlation between the absolute reduction of the motor score and improvement in disability of the patients at 6 months (rho = 0.865, p value 0.003). CONCLUSIONS: DBS in PD has an enormous role in reducing disease burden and achieving a sustainable therapeutic goal.

Actigraph-based quantification of sleep in children with dystonia undergoing deep brain stimulation.

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.

Femur Fractures in 5 Individuals With Pantothenate Kinase-associated Neurodegeneration: The Role of Dystonia and Suggested Management.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes. METHODS: A retrospective case review was conducted on 5 patients (ages 10 to 20 y) with PKAN with a femur fracture requiring surgical intervention. Data regarding initial presentation, surgical treatment, complications, and outcomes were obtained. RESULTS: All patients were non-ambulatory, with 4 of 5 patients sustaining an atraumatic femur fracture in the setting of dystonia episode. One patient had an additional contralateral acetabular fracture. Postoperatively, 4 of the 5 patients sustained orthopaedic complications requiring surgical revision, with 3 of these secondary to dystonia. Overall, 4 required prolonged hospitalization in the setting of refractory dystonia. CONCLUSION: Femur fractures in PKAN present distinct challenges for successful outcomes. A rigid intramedullary rod with proximal and distal interlocking screws is most protective against surgical complications associated with refractory dystonia occurring during the postoperative period. Multidisciplinary planning for postoperative care is essential and may include aggressive sedation and pain management to decrease the risk of subsequent injuries or complications. LEVEL OF EVIDENCE: Level IV.

Chronic Pallidal Local Field Potentials Are Associated With Dystonic Symptoms in Children.

BACKGROUND: Novel deep brain stimulation devices can record local field potentials (LFPs), which represent the synchronous synaptic activity of neuronal populations. The clinical relevance of LFPs in patients with dystonia remains unclear. OBJECTIVES: We sought to determine whether chronic LFPs recorded from the globus pallidus internus (GPi) were associated with symptoms of dystonia in children. MATERIALS AND METHODS: Ten patients with heterogeneous forms of dystonia (genetic and acquired) were implanted with neurostimulators that recorded LFP spectral snapshots. Spectra were compared across parent-reported asymptomatic and symptomatic periods, with daily narrowband data superimposed in 24 one-hour bins. RESULTS: Spectral power increased during periods of registered dystonic symptoms: mean increase = 102%, CI: (76.7, 132). Circadian rhythms within the LFP narrowband time series correlated with dystonic symptoms: for delta/theta-waves, correlation = 0.33, CI: (0.18, 0.47) and for alpha waves, correlation = 0.27, CI: (0.14, 0.40). CONCLUSIONS: LFP spectra recorded in the GPi indicate a circadian pattern and are associated with the manifestation of dystonic symptoms.

Deep Brain Stimulation for GNAO1-Associated Dystonia: A Systematic Review and Meta-Analysis.

OBJECTIVES: Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients. RESULTS: The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients. CONCLUSION: Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.

Genetic Update and Treatment for Dystonia.

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.

Electrophysiological insights into deep brain stimulation of the network disorder dystonia.

Deep brain stimulation (DBS), a treatment for modulating the abnormal central neuronal circuitry, has become the standard of care nowadays and is sometimes the only option to reduce symptoms of movement disorders such as dystonia. However, on the one hand, there are still open questions regarding the pathomechanisms of dystonia and, on the other hand, the mechanisms of DBS on neuronal circuitry. That lack of knowledge limits the therapeutic effect and makes it hard to predict the outcome of DBS for individual dystonia patients. Finding electrophysiological biomarkers seems to be a promising option to enable adapted individualised DBS treatment. However, biomarker search studies cannot be conducted on patients on a large scale and experimental approaches with animal models of dystonia are needed. In this review, physiological findings of deep brain stimulation studies in humans and animal models of dystonia are summarised and the current pathophysiological concepts of dystonia are discussed.

Balance between pallidal neural oscillations correlated with dystonic activity and severity.

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.

New developments in diagnostics and treatment of adult-onset focal dystonia.

PURPOSE OF REVIEW: The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia. RECENT FINDINGS: Accurate phenotyping of focal dystonia is essential in the process of finding an underlying cause, including acquired, genetic, and idiopathic causes. Motor symptoms as well as the associated nonmotor symptoms and their detrimental impact on quality of life have received increased interest over the last years. The diagnostic process is complicated by the steadily increasing numbers of newly discovered genes associated with dystonia. Recent efforts have been aimed at further developing recommendations and algorithms to aid in diagnosis and in navigating the use of diagnostic tools. In terms of treatment, research on DBS is advancing towards a better understanding of the most effective stimulation locations within the globus pallidus. Moreover, with the introduction of the LFP-recording devices, the search continues for an accurate electrophysiological biomarker for dystonia. SUMMARY: Accurate phenotyping and (sub)classification of patients with dystonia is important for improving diagnosis, subsequent treatment effect and population-based study outcomes in research. Medical practitioners should be attentive to the presence of nonmotor symptoms in dystonia.

Pallidal Beta Activity Is Linked to Stimulation-Induced Slowness in Dystonia.

BACKGROUND: Pallidal deep brain stimulation (DBS) effectively alleviates symptoms in dystonia patients, but may induce movement slowness as a side-effect. In Parkinson's disease, hypokinetic symptoms have been associated with increased beta oscillations (13-30 Hz). We hypothesize that this pattern is symptom-specific, thus accompanying DBS-induced slowness in dystonia. METHODS: In 6 dystonia patients, pallidal rest recordings with a sensing-enabled DBS device were performed and tapping speed was assessed using marker-less pose estimation over 5 time points following cessation of DBS. RESULTS: After cessation of pallidal stimulation, movement speed increased over time (P < 0.01). A linear mixed-effects model revealed that pallidal beta activity explained 77% of the variance in movement speed across patients (P = 0.01). CONCLUSIONS: The association between beta oscillations and slowness across disease entities provides further evidence for symptom-specific oscillatory patterns in the motor circuit. Our findings might help DBS therapy improvements, as DBS-devices able to adapt to beta oscillations are already commercially available. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Subthalamic Nucleus Stimulation-Induced Local Field Potential Changes in Dystonia.

BACKGROUND: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a physiomarker for adaptive stimulation. OBJECTIVE: We aimed to explore if enhanced theta power was also present in STN and if stimulation-induced spectral changes that were previously reported for Parkinson's disease would occur in dystonia. METHODS: We recorded LFPs from 7 patients (12 hemispheres) with isolated craniocervical dystonia whose electrodes were placed such that inferior, middle, and superior contacts covered STN, zona incerta, and thalamus. RESULTS: We did not observe prominent theta power in STN at rest. STN stimulation induced similar spectral changes in dystonia as in Parkinson's disease, such as broadband power suppression, evoked resonant neural activity (ERNA), finely-tuned gamma oscillations, and an increase in aperiodic exponents in STN-LFPs. Both power suppression and ERNA localize to STN. Based on this, single-pulse STN stimulation elicits evoked neural activities with largest amplitudes in STN, which are relayed to the zona incerta and thalamus with changing characteristics as the distance from STN increases. CONCLUSIONS: Our results show that STN stimulation-induced spectral changes are a nondisease-specific response to high-frequency stimulation, which can serve as placement markers for STN. This broadens the scope of STN stimulation and makes it an option for other disorders with excessive oscillatory peaks in STN. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Globus pallidus internus versus subthalamic nucleus deep brain stimulation for isolated dystonia: A 3-year follow-up.

BACKGROUND AND PURPOSE: Bilateral deep brain stimulation (DBS) surgery targeting the globus pallidus internus (GPi) or the subthalamic nucleus (STN) is widely used in medication-refractory dystonia. However, evidence regarding target selection considering various symptoms remains limited. This study aimed to compare the effectiveness of these two targets in patients with isolated dystonia. METHODS: This retrospective study evaluated 71 consecutive patients (GPi-DBS group, n = 32; STN-DBS group, n = 39) with isolated dystonia. Burke-Fahn-Marsden Dystonia Rating Scale scores and quality of life were evaluated preoperatively and at 1, 6, 12, and 36 months postoperatively. Cognition and mental status were assessed preoperatively and at 36 months postoperatively. RESULTS: Targeting the STN (STN-DBS) yielded effects within 1 month (65% vs. 44%; p = 0.0076) and was superior at 1 year (70% vs. 51%; p = 0.0112) and 3 years (74% vs. 59%; p = 0.0138). For individual symptoms, STN-DBS was preferable for eye involvement (81% vs. 56%; p = 0.0255), whereas targeting the GPi (GPi-DBS) was better for axis symptoms, especially for the trunk (82% vs. 94%; p = 0.015). STN-DBS was also favorable for generalized dystonia at 36-month follow-up (p = 0.04) and required less electrical energy (p < 0.0001). Disability, quality of life, and depression and anxiety measures were also improved. Neither target influenced cognition. CONCLUSIONS: We demonstrated that the GPi and STN are safe and effective targets for isolated dystonia. The STN has the benefits of fast action and low battery consumption, and is superior for ocular dystonia and generalized dystonia, while the GPi is better for trunk involvement. These findings may offer guidance for future DBS target selection for different types of dystonia.

American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.

Dystonias: Clinical Recognition and the Role of Additional Diagnostic Testing.

Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles. Diagnosis is challenging. We provide a comprehensive appraisal of the epidemiology and an approach to the phenomenology and classification of dystonia, based on the clinical characteristics and underlying etiology of dystonia syndromes. We discuss the features of common idiopathic and genetic forms of dystonia, diagnostic challenges, and dystonia mimics. Appropriate workup is based on the age of symptom onset, rate of progression, whether dystonia is isolated or combined with another movement disorder or complex neurological and other organ system features. Based on these features, we discuss when imaging and genetic should be considered. We discuss the multidisciplinary treatment of dystonia, including rehabilitation and treatment principles according to the etiology, including when pathogenesis-direct treatment is available, oral pharmacological therapy, chemodenervation with botulinum toxin injections, deep brain stimulation and other surgical therapies, and future directions.

Blood DNA methylation provides an accurate biomarker of KMT2B-related dystonia and predicts onset.

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.

Elective and Emergency Deep Brain Stimulation in Refractory Pediatric Monogenetic Movement Disorders Presenting with Dystonia: Current Practice Illustrated by Two Cases.

BACKGROUND: Dystonia is characterized by sustained or intermittent muscle contractions, leading to abnormal posturing and twisting movements. In pediatric patients, dystonia often negatively influences quality of life. Pharmacological treatment for dystonia is often inadequate and causes adverse effects. Deep brain stimulation (DBS) appears to be a valid therapeutic option for pharmacoresistant dystonia in children. METHODS: To illustrate the current clinical practice, we hereby describe two pediatric cases of monogenetic movement disorders presenting with dystonia and treated with DBS. We provide a literature review of similar previously described cases and on different clinical aspects of DBS in pediatric dystonia. RESULTS: The first patient, a 6-year-old girl with severe dystonia, chorea, and myoclonus due to an ADCY5 gene mutation, received DBS in an elective setting. The second patient, an 8-year-old boy with GNAO1-related dystonia and chorea, underwent emergency DBS due to a pharmacoresistant status dystonicus. A significant amelioration of motor symptoms (65% on the Burke-Fahn-Marsden Dystonia Rating Scale) was observed postoperatively in the first patient and her personal therapeutic goals were achieved. DBS was previously reported in five patients with ADCY5-related movement disorders, of which three showed objective improvement. Emergency DBS in our second patient resulted in the successful termination of his GNAO1-related status dystonicus, this being the eighth case reported in the literature. CONCLUSION: DBS can be effective in monogenetic pediatric dystonia and should be considered early in the disease course. To better evaluate the effects of DBS on patients' functioning, patient-centered therapeutic goals should be discussed in a multidisciplinary approach.

Deep brain stimulation in Lesch-Nyhan syndrome: a systematic review.

Given the good results of deep brain stimulation (DBS) in the treatment of movement disorders, DBS was initially tried to treat Lesch-Nyhan syndrome (LNS) with the aim to alleviate LNS-related dystonia. Some cases have reported clinical results of DBS in LNS thus far. This systematic review was conducted to comprehensively summarize cases of LNS treated with DBS and evaluate the efficacy and safety of DBS in LNS. Eight publications covering 12 LNS patients were included in this review. DBS improved dystonia of the LNS to varying degrees. All the included cases achieved partial or complete control of self-injurious behavior (SIB). Overall, DBS is a promising treatment for both motor and behavior disorders of LNS patients, but the results reported thus far have varied widely, especially for motor outcomes. The ultimate clinical benefits in LNS patients were still unpredictable. DBS-related complications were rather common, which raised questions about the safety of the procedure in LNS. More research is needed to further clarify the safety and effectiveness of this treatment.