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.

Dystonia-like Movement Disorders Ameliorated by Shear Force and Pressure Stimulation after Small Infarction in the Left Posterolateral Thalamus.

Focal dystonia (FD) can develop after thalamic lesions. Abnormal somatic sensations were argued to be responsible for FD. Our patient experienced FD-like movement disorders, agraphesthesia, and a reduced sense of shear force on the skin and pressure to deep tissues of the right upper limb following a small infarction in the left posterolateral thalamus. FD-like symptoms improved while the skin was being pulled or the deep tissue was being pushed in a manner proportional to the strength of muscle contractions. Therefore, the lack of these sensations was suggested to be related to FD-like symptoms.

Harnessing cognitive strategy use for functional problems and proposed underlying mechanisms in childhood-onset dystonia.

BACKGROUND: There is a significant gap in knowledge about rehabilitation techniques and strategies that can help children and young people with hyperkinetic movement disorders (HMD) including dystonia to successfully perform daily activities and improve overall participation. A promising approach to support skill acquisition is the Cognitive Orientation to daily Occupational Performance (CO-OP) intervention. CO-OP uses cognitive strategies to help patients generate their own solutions to overcome self-identified problems encountered in everyday living. PURPOSE: 1. To identify and categorize strategies used by children with HMD to support skill acquisition during CO-OP; 2. To review the possible underlying mechanisms that might contribute to the cognitive strategies, in order to facilitate further studies for developing focused rehabilitation approaches. METHODS: A secondary analysis was performed on video-recorded data from a previous study exploring the efficacy of CO-OP for childhood onset HMD, in which CO-OP therapy sessions were delivered by a single occupational therapist. For the purpose of this study, we reviewed a total of 40 randomly selected hours of video footage of CO-OP sessions delivered to six participants (age 6-19 years) over ten intervention sessions. An observational recording sheet was applied to identify systematically the participants' or therapist's verbalizations of cognitive strategies during the therapy. The strategies were classified into six categories in line with published literature. RESULTS: Strategies used by HMD participants included distraction, externally focussed attention, internally focussed attention, emotion self-regulation, motor imagery and mental self-guidance. We postulate different underlying working mechanisms for these strategies, which have implications for the therapeutic management of children and young people with HMD including dystonia. CONCLUSIONS: Cognitive strategy training can fundamentally change and improve motor performance. On-going work will address both the underlying neural mechanisms of therapeutic change and the mediators and moderators that influence how change unfolds.

Vim-Thalamic Deep Brain Stimulation for Cervical Dystonia and Upper-Limb Tremor: Quantification by Markerless-3D Kinematics and Accelerometry.

Background: Deep Brain Stimulation (DBS) for dystonia is usually targeted to the globus pallidus internus (GPi), though stimulation of the ventral-intermediate nucleus of the thalamus (Vim) can be an effective treatment for phasic components of dystonia including tremor. We report on a patient who developed a syndrome of bilateral upper limb postural and action tremor and progressive cervical dystonia with both phasic and tonic components which were responsive to Vim DBS. We characterize and quantify this effect using markerless-3D-kinematics combined with accelerometry. Methods: Stereo videography was used to record our subject in 3D. The DeepBehavior toolbox was applied to obtain timeseries of joint position for kinematic analysis [1]. Accelerometry was performed simultaneously for comparison with prior literature. Results: Bilateral Vim DBS improved both dystonic tremor magnitude and tonic posturing. DBS of the hemisphere contralateral to the direction of dystonic head rotation (left Vim) had greater efficacy. Assessment of tremor magnitude by 3D-kinematics was concordant with accelerometry and was able to quantify tonic dystonic posturing. Discussion: In this case, Vim DBS treated both cervical dystonic tremor and dystonic posturing. Markerless-3D-kinematics should be further studied as a method of quantifying and characterizing tremor and dystonia.

Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia.

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.

Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus in Writer's Cramp: A Case Report.

Background: Globus pallidus internus (GPi) deep brain stimulation (DBS) and thalamotomy are interventions for writer's cramp (WC). Ventralis intermedius nucleus (VIM) DBS is targeted for tremor, however, many aspects of VIM DBS remained underexplored in WC. Case Report: A 62-year-old man with WC underwent DBS. Dystonic tremor improved intraoperatively with ventralis oralis anterior (VoA)/ventral oralis posterior (VoP) and with subthalamic nucleus stimulation; although greatest benefit was obtained with VIM stimulation. Sustained benefit with VIM DBS at ten months post-operative was obtained. Discussion: This case demonstrates an intraoperative approach in target selection and supports benefits of VIM DBS for WC. Highlights: This case highlights the intraoperative approach and clinical effects of VIM DBS in the treatment of medically refractory writer's cramp (WC). We contextualize our results from this case with previous reports of VoA/VoP stimulation for WC.

Deep Brain Stimulation and Thalamotomy for the Treatment of Dystonia Acquired by Moyamoya Disease with Stroke.

Background: Moyamoya disease (MMD) is a type of chronic cerebrovascular disease. Currently, revascularization surgery including direct/indirect procedure is recommended for symptomatic patients. However, some patients still respond poorly to the treatment or develop secondary symptoms. Case report: We report the first case of an MMD patient treated with deep brain stimulation (DBS) and thalamotomy. Symptoms of dystonia due to hemorrhage in the thalamus responded poorly to revascularization surgery, but were considerably alleviated by stereotactic neurosurgery. Discussion: Our case report provides a potential strategy for management of refractory symptomatic MMD patients with dystonia and also supports the combined efficacy of DBS with thalamotomies. Highlights: Approximately 30% of patients with Moyamoya disease (MMD) presenting movement symptoms do not respond well to revascularization surgery. We reported an MMD patient treated with deep brain stimulation (DBS) and thalamotomy with significant dystonia and dystonic tremor symptom amelioration. It indicates that DBS or stereotactic lesioning might be a potential treatment for the refractory movement symptoms of MMD.

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia.

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode's localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

Motor outcomes and adverse effects of deep brain stimulation for dystonic tremor: A systematic review.

Dystonic tremor (DT) is defined as the tremor in body parts affected by dystonia. Although deep brain stimulation (DBS) has been used to manage medically-refractory DT patients, its efficacy has not been well established. The objective of this study is to provide an up-to-date systematic review of DBS outcomes for DT patients. We conducted a literature search using Medline, Embase, and Cochrane Library databases in February 2020 according to the PRISMA guidelines. From 858 publications, we identified 30 articles involving 89 DT patients who received DBS of different targets. Thalamic DBS was the most common (n = 39) and improved tremor by 40-50% potentially in the long-term over five years with variable effects on dystonic symptoms. Globus pallidus internus (GPi), subthalamic, and subthalamic nucleus (STN) DBS improved both tremor and dystonic symptoms; however, data were limited. A few studies have reported better tremor and dystonia outcomes with combinations of different targets. Concerning adverse effects, gait/balance disorders, and ataxia seemed to be more common among patients treated with thalamic or subthalamic DBS, whereas parkinsonian adverse effects were observed only in patients treated with subthalamic or GPi DBS. Comparative benefits and limitations of these targets remain unclear because of the lack of randomized controlled trials. In conclusion, DBS of these targets may improve tremor with a variable effect on dystonia with different adverse effect profiles. The shortcomings in the literature include long-term motor outcomes, quality of life outcomes, optimal DBS targeting, and DBS programming strategy.

Neuromodulation: Deep Brain Stimulation for Treatment of Dystonia.

Dystonia is a heterogeneous, hyperkinetic movement disorder with sustained or intermittent abnormal postures, hyperkinetic muscle contractions, or repetitive movements. Classification of dystonia involves 2 axes: axis I and axis II, defining relevant clinical features and etiology, respectively. Medical therapy varies based on subtype and includes intramuscular botulinum toxin injections and oral anticholinergic pharmaceuticals. Deep brain stimulation became widely incorporated in 1999 after several landmark studies and has been effectively used in targets of the thalamus, pallidum, and subthalamic nucleus. New insights into pathophysiology of dystonia and genetic analysis continue to guide surgical technique toward ever-effective treatment.

Deep Brain Stimulation of the Caudal Zona Incerta and Motor Thalamus for Postischemic Dystonic Tremor of the Left Upper Limb: Case Report and Review of the Literature.

BACKGROUND: Dystonic tremor is defined as a tremor occurring in a body region affected by dystonia. The pathophysiologic mechanisms behind dystonic tremor supposedly involve anomalies affecting the pallidothalamic-receiving area (for the dystonic component) and the ventralis intermedius-cortical loop (for the tremor component). Interest in posterior subthalamic area stimulation for various types of involuntary abnormal movements has arisen owing to positive results in patients affected by tremor refractory to ventralis intermedius deep brain stimulation. CASE DESCRIPTION: A 23-year-old man, with a 15-year history of left upper limb dystonic tremor due to a stroke in the right thalamus, underwent deep brain stimulation with a single electrode passing through the right ventralis oralis anterior/ventralis oralis posterior nuclei and caudal zona incerta. Objective movement outcomes were assessed through the Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor. The impact of tremor on activities of daily living was assessed with the ADL-T24 questionnaire, and quality of life was assessed with the Quality of Life Scale. All questionnaires were administered before deep brain stimulation and at 5-year follow-up. Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor scores decreased from 14.5 to 4.5 and from 46 to 7, respectively. ADL-T24 score decreased from 19 to 3, whereas Quality of Life Scale score increased from 49 to 82. CONCLUSIONS: Stimulation of motor thalamus and caudal zona incerta could be a viable treatment for patients affected by tremor of various origins, including dystonic tremor, refractory to medical therapy.

Thalamus Stimulation for Myoclonus Dystonia Syndrome: Five Cases and Long-Term Follow-up.

BACKGROUND: Myoclonic dystonia syndrome (MDS) is a rare inherited movement disorder characterized by the coexistence of myoclonic jerks and dystonia. Deep brain stimulation (DBS) is a promising treatment for patients with MDS that targets the globus pallidus internus or ventral intermediate nucleus (Vim) of the thalamus. However, there are few studies regarding the long-term effects of Vim DBS in patients with MDS and even fewer in those without gene mutations. METHODS: Two positive and three negative SGCE mutation patients presenting with predominant myoclonus underwent Vim DBS. The Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were assessed pre- and postoperation. RESULTS: Over an average follow-up period of 50 months, the myoclonus improvement rate was 92.7%. The average improvement in the BFMDRS motor score was 71.4% and the average improvement in the BFMDRS disabling score was 75.8%. CONCLUSIONS: This study suggests that Vim DBS can be a safe and effective treatment option for patients with MDS. Vim DBS alone may be preferable for patients with myoclonus-dominated MDS regardless of the identification of an SGCE mutation. Additional globus pallidus internus DBS may be used for progressive dystonia after Vim DBS.

Both Deep Brain Stimulation and Thalamotomy in a 13-Year-Old Patient with Primary Dystonia.

BACKGROUND: Primary dystonia is a neurologic disease with characteristics of abnormal, involuntary twisting and turning movements, which greatly affect quality of life of patients. Treatments for dystonia consist of oral medications, botulinum neurotoxin injections, physical therapy, and surgery. For medication-refractory dystonia, surgery, especially deep brain stimulation (DBS), is the optimal option. CASE DESCRIPTION: The patient was a 13-year-old boy suffering from extremely severe primary dystonia, with a Burke-Fahn-Marsden Dystonia Rating Scale-motor score of 118 and a Toronto Western Spasmodic Torticollis Rating Scale-severity score of 29. The examination of 173 genes, including DYT, failed to identify any abnormality. He responded ineffectively to medications. After both bilateral subthalamic nucleus DBS and unilateral thalamic lesion in ventralis intermedius nucleus and ventralis oralis nucleus (Vim-Vo thalamotomy), his movement disorder improved dramatically. Four and 7 months after the operation, the scores of 2 rating scales sharply decreased. Potential brain structural changes were reflected in sensorimotor-related cortical thickness, surface area, and gray matter volume from magnetic resonance imaging, which may reveal a valid method to evaluate surgical effect on the brain with enough patients. CONCLUSIONS: DBS and thalamotomy is potentially an effective combination of treatments for severe medication-refractory dystonia.

Unilateral thalamic and pallidal deep brain stimulation for idiopathic hemidystonia: results of individual and combined stimulations. Case report.

Pallidal stimulation has been the usual surgical treatment for dystonia in the last decades. The continuous investigation of the physiopathology and the motor pathways involved leads to the search for complementary targets to improve results. The authors present the case of a 37-year-old woman who had suffered from idiopathic hemidystonia with hyperkinetic and hypokinetic movements for 11 years, and who was treated with deep brain stimulation. A brief literature review is also provided. The globus pallidus internus and the ventral intermediate/ventral oral posterior complex of the thalamus were stimulated separately and simultaneously for 3 months and compared using the Burke-Fahn-Marsden Dystonia Rating Scale and the Global Dystonia Severity Rating Scale, with a 3.5-year follow-up. The synergism of multiple-target stimulation resulted in a complete improvement of the mixed dystonic symptoms.

Combinación de tres técnicas en el reentrenamiento de un músico con distonía focal: estudio de un caso / The use of three combined techniques in the retraining of a mucisian with focal dystonia: a case study

La distonía resulta de una co-contracción sostenida de músculos agonistas y antagonistas que puede causar torsión, movimientos involuntarios o posturas anormales que interfieren con el control voluntario de la mano, u otro grupo muscular, involucrados en una determinada acción; por ejemplo, tocar un instrumento, o escribir.El presente estudio descriptivo, de caso único, buscó probar la efectividad de un tratamiento que combinó tres técnicas (técnica del umbral, imaginería, y relajación por neurofeedback) en el reentrenamiento de un concertista profesional con distonía focal. Según evaluación por jueces, los resultados después de dos semanas de tratamiento, no fueron concluyentes. Sin embargo, el reporte experiencial del propio músico dio cuenta de una clara mejoría. Ante la carencia de un método efectivo para larehabilitación demúsicos con distonía focal, la relevancia del presente estudio consistió en identificar y combinar técnicas específicas que pueden contribuir a ese propósito. En estudios futuros, sería de interés probar el efecto del mismo tratamiento,pero más prolongado; o el efecto de la incorporación de las técnicas en sucesión progresiva, iniciando siempre con la relajación por neurofeedback.

Focal dystonia results from a sustained simultaneous co-contraction of agonists and antagonists muscle fibers which can cause twisting, involuntary movements or abnormal postures that interfere with voluntary control of the hand, arm, mouth, or other muscle groups involved in a given action; for example, playing an instrument, or hand writing. This descriptive, single case study, sought to explore the effectiveness of a treatment that combined three procedures: the threshold technique, imagery, and neurofeedback induced relaxation, in retraining of a professional cello player with focal dystonia. After two weeks of treatment, experts judged the results inconclusive; however, the report from the actual patient accounted for a note worthy recovery over time. In the absence of an effective method to rehabilitate musicians with focal dystonia, the relevance of this study resided on thepossibility of identifying and combining specific techniques that could be effective. Future studies might want to explore these same or different techniques, but perhaps for a longer period of time.

A prospective, randomized, blinded assessment of multitarget thalamic and pallidal deep brain stimulation in a case of hemidystonia.

OBJECTIVE: Dystonia is increasingly being interpreted as a multi-nodal "network" disorder. We aimed to investigate multitarget DBS (pallidal and thalamic) versus each target alone in a prospective, randomized, blinded trial in a case of hemidystonia secondary to putaminal stroke. METHODS: DBS leads were implanted in the GPi and Vim/Vop and each stimulation combination (GPi, Vim/Vop, and both) was tested for three months in a single patient. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Short-Form 36 (SF-36) were completed at the end of each trial period. RESULTS: Multitarget (GPi+Vim/Vop) stimulation was clinically the most effective treatment and resulted in the most improvement in function and quality of life. The patient's hemidystonia improved by 25% as measured by the BFMDRS during the multitarget stimulation trial period and at the 6-month follow-up. The patient's quality of life improved by 86% and 59% during the multitarget stimulation trial period and at the 6 month follow-up respectively. CONCLUSION: Multitarget thalamic and pallidal DBS proved to be the most effective therapy for this patient with secondary hemidystonia due to a putaminal stroke. A single-lead approach may not be sufficient in neuromodulating a highly disorganized motor network seen in hemidystonia. Multitarget DBS should be further explored in post-stroke dystonia and may offer improved outcome in other forms of secondary dystonia with limited response to GPi DBS.

The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation.

BACKGROUND: In essential tremor (ET), the main target for deep brain stimulation (DBS) is the thalamic ventralis intermedius nucleus (Vim). This target cannot be identified on conventional magnetic resonance imaging (MRI). Therefore, targeting depends on probabilistic coordinates derived from stereotactic atlases. The goal of our study was to investigate the variability of atlas-based Vim targets in relation to surrounding major fibre tracts. METHODS: With the MRI and computed tomography (CT) scan data of ten patients who underwent DBS, we planned atlas based Vim targets in both hemispheres. We also performed deterministic fibre-tracking with diffusion tensor imaging (DTI) of the dentato-rubro-thalamic tract (DRTT), pyramidal tract (PT) and lemniscus medialis (LM) in all 20 hemispheres. Subsequently, we measured the distance from the atlas-based Vim target to each tract along the medial/lateral (x-coordinate), anterior/posterior (y-coordinate) and superior/inferior axis (z-coordinate). RESULTS: Seventeen out of 20 DRTTs could be depicted with our standardised DTI/fibre-tracking parameters. The PT and the LM could be displayed in all 20 hemispheres. The atlas-based Vim target was found inside the DRTT in 11 (concerning the x-coordinate) and 10 hemispheres (concerning the z-coordinate). Regarding the anterior/posterior direction, the target was posterior to the DRTT in 11 cases. In 19 hemispheres the Vim target was located medial and superior to the PT and in 17 hemispheres posterior to it. Concerning the LM, the Vim target was found inside the LM in 16 (regarding the x-coordinate) and in 14 cases (regarding the z-coordinate). In eight cases it was located inside and in 12 cases anterior to the LM concerning the y-coordinate. CONCLUSIONS: We found a considerable variability of the location of atlas-based target points of the ventralis intermedius nucleus in relation to neighbouring major fibre tracts in individual patients. These results suggest that individualised targeting to structures not directly visible on conventional MRI is necessary.