Severity Of Dystonia Research Articles

Comparison of Burke‐Fahn‐Marsden Dystonia Severity, Gross Motor, Manual Abilities and Communication Function Classification Scales in childhood hyperkinetic movement disorders including cerebral palsy: a Rosetta Stone Study

Comparison of Burke‐Fahn‐Marsden Dystonia Severity, Gross Motor, Manual Abilities and Communication Function Classification Scales in childhood hyperkinetic movement disorders including cerebral palsy: a Rosetta Stone Study

Gabapentin can significantly improve dystonia severity and quality of life in children.

Gabapentin has been used in the management of neuropathic pain, epilepsy and occasionally movement disorders. A four-year retrospective, observational study analysed the use of gabapentin for severe dystonia in children at the Evelina London Children's Hospital. Motor severity was classified according to the Gross Motor Function Classification System (GMFCS), Dystonia Severity Assessment Plan (DSAP) and levels of impairment in activities of daily living were graded according to the WHO International Classification of Functioning, Disability and Health, Children & Youth version (ICF-CY) before and after gabapentin. The majority of the 69 children reported were level 5 GMFCS (non-ambulant). The DSAP grade fell significantly from grade 3 before to grade 1 after gabapentin. Significant improvements in median ICF-CY grades were seen following gabapentin in sleep quality, sleep amount, mood & agreeableness, pain, general muscle tone, involuntary muscle contractions and seating tolerance (p<0.01 in all areas). A significantly higher mean dose of 18.1mg/kg/dose (SD: 13.3) for dystonia, compared to 7.61mg/kg/dose (SD: 4.14) for pain relief without dystonia (z=-2.54, p=0.011) was noted. Gabapentin may significantly ameliorate dystonia severity and improve activities of daily living and quality of life in children with severe dystonia.

Strategies for treatment of dystonia.

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Effect of Transcranial Direct Current Stimulation on Neurorehabilitation of Task-Specific Dystonia: A Double-Blind, Randomized Clinical Trial.

Task-specific focal hand dystonia can disable affected individuals. Although neurorehabilitation techniques such as sensory motor retuning can result in complete recovery in some patients, it requires many months of treatment. Combining transcranial direct current stimulation (tDCS) with neurorehabilitation is a new and promising approach that can help these patients. However, the results in different studies are contradictory. Analyze whether delivering tDCS (cathode over left and anode over right parietal region) during the neurorehabilitation process for musicians with dystonia can increase the effectiveness of therapy. A parallel double-blind randomized design was used to study 30 musicians with right-hand primary focal dystonia. All patients underwent a 2-week course of neurorehabilitation based on sensory motor retuning therapy coupled with either real or sham tDCS for the first 30 minutes of each daily 1-hour therapy session (total 10 sessions). The therapist and patient were blind to the tDCS condition. A dystonia severity score was obtained before and after the 2-week protocol. The therapist also rated the evolution of each patient. Both groups significantly improved their dystonia severity score during the 2 weeks. Score differences were 88.23 (±40.51) and 63.36 (±30.57) for the active and sham groups, respectively. The active group showed a statistically significant greater improvement. Biparietal tDCS with left-sided cathode is a safe technique that does not interfere with the neurorehabilitation procedure and can increase therapy effectiveness in rehabilitation patients with right-hand task-specific focal dystonia.

Clinical course of psychiatric disorders in patients with cervical dystonia

We assessed the course of psychiatric disorders in 23 cervical dystonia patients by using the structured clinical interview for DSM-IV and different rating scales. Patients were studied on two occasions 5 years apart. There were no differences in psychiatric disorders and severity of psychiatric symptoms between the two evaluations, whereas the severity of dystonia was milder at the second evaluation. Psychiatric symptoms likely represent a primary disorder in cervical dystonia patients.

Preserved dichotomy but highly irregular and burst discharge in the basal ganglia in alert dystonic rats at rest

Despite its prevalence, the underlying pathophysiology of dystonia remains poorly understood. Using our novel tri-component classification algorithm, extracellular neuronal activity in the globus pallidus (GP), STN, and the entopeduncular nucleus (EP) was characterized in 34 normal and 25 jaundiced dystonic Gunn rats with their heads restrained while at rest. In normal rats, neurons in each nucleus were similarly characterized by two physiologically distinct types: regular tonic with moderate discharge frequencies (mean rates in GP, STN and EP ranging from 35–41 spikes/s) or irregular at slower frequencies (17–20 spikes/s), with a paucity of burst activity. In dystonic rats, these nuclei were also characterized by two distinct principal neuronal patterns. However, in marked difference, in the dystonic rats, neurons were primarily slow and highly irregular (12–15 spikes/s) or burst predominant (14–17 spikes/s), with maintained modest differences between nuclei. In GP and EP, with increasing severity of dystonia, burstiness was moderately further increased, irregularity mildly further increased, and discharge rates mildly further reduced. In contrast, these features did not appreciably change in STN with worsening dystonia. Findings of a lack of bursting in GP, STN and EP in normal rats in an alert resting state and prominent bursting in dystonic Gunn rats suggest that cortical or other external drive is normally required for bursting in these nuclei and that spontaneous bursting, as seen in dystonia and Parkinson׳s disease, is reflective of an underlying pathophysiological state. Moreover, the extent of burstiness appears to most closely correlate with the severity of the dystonia.

Coordination of Reach-to-Grasp Kinematics in Individuals With Childhood-Onset Dystonia Due to Hemiplegic Cerebral Palsy.

Functional reaching is impaired in dystonia. Here, we analyze upper extremity kinematics to quantify timing and coordination abnormalities during unimanual reach-to-grasp movements in individuals with childhood-onset unilateral wrist dystonia. Kinematics were measured during movements of both upper limbs in a patient group ( n = 11, age = 17.5 ±5 years), and a typically developing control group ( n = 9, age = 16.6 ±5 years). Hand aperture was computed to study the coordination of reach and grasp. Time-varying joint synergies within one upper limb were calculated using a novel technique based on principal component analysis to study intra-limb coordination. In the non-dominant arm, results indicate reduced coordination between reach and grasp in patients who could not lift the grasped object compared to those who could lift it. Lifters exhibit incoordination in distal upper extremity joints later in the movement and non-lifters lacked coordination throughout the movement and in the whole upper limb. The amount of atypical coordination correlates with dystonia severity in patients. Reduced coordination during movement may reflect deficits in the execution of simultaneous movements, motor planning, or muscle activation. Rehabilitation efforts can focus on particular time points when kinematic patterns deviate abnormally to improve functional reaching in individuals with childhood-onset dystonia.

Do clinical features of Lesch-Nyhan disease correlate more closely with hypoxanthine or guanine recycling?

Lesch-Nyhan disease (LND) is a rare, X-linked recessive neurodevelopmental disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGprt), an enzyme in the purine salvage pathway. HGprt has two functions; it recycles hypoxanthine and guanine. Which of these two functions is more relevant for pathogenesis is unclear because some evidence points to hypoxanthine recycling, but other evidence points to guanine recycling. In this study, we selectively assayed hypoxanthine (Hprt) and guanine (Gprt) recycling in skin fibroblasts from 17 persons with LND, 11 with an attenuated variant of the disease (LNV), and 19 age-, sex-, and race-matched healthy controls (HC). Activity levels of both enzymes differed across groups (p < 0.0001), but only Gprt distinguished patients with LND from those with LNV (p < 0.05). Gprt also showed slightly stronger correlations than Hprt with 13 of 14 measures of the clinical phenotype, including the severity of dystonia, cognitive impairment, and behavioral abnormalities. These findings suggest that loss of guanine recycling might be more closely linked to the LND/LNV phenotype than loss of hypoxanthine recycling.

Multimodal Physiotherapy as an Add-On Treatment to Botulinum Neurotoxin A-Therapy in Patients with Cervical Dystonia

<b>Background:</b> The treatment of choice for cervical dystonia comprises a local injection of botulinum neurotoxin type A (BoNT-A). Whether additional physiotherapy can achieve better results is not clearly documented in the literature. The present study aims to show possible effects of physiotherapy as an add-on treatment to therapy with botulinum neurotoxin type A in terms of pain, severity of dystonia, statics and function of the cervical spine as well as the quality of life in order to optimize the treatment of cervical dystonia. <b>Design/Methods:</b> This is a prospective, single-center, interventional study of a target patient population comprising 20 participants. The study is divided into 2 phases, with each phase lasting for 3 months. During the first phase, the usual BoNT-A will be applied. In addition, the baseline values will be collected and these assessments will be repeated at an interval of 6 weeks. In the second phase, participants will undergo a physiotherapy program consisting of two 45 min sessions per week in addition to the BoNT-A treatment. The assessments will be undertaken at the same intervals as in the first phase. <b>Analysis:</b> In order to determine the effect of the add-on physiotherapy program, the following parameters will be measured for each assessment: quality of life using the SF- 36 score and the range of motion determined by the ZEBRIS measurement system which will comprise the primary endpoints. Furthermore, for each assessment the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and electrical activity from the trapezius and the sternocleidomastoid muscles measured by a surface electromyography will be recorded. Descriptive statistical analysis will be performed for all of the collected data. Possible changes in the measured values will be compared to the baseline values over the 2 periods by means of the Wilcoxon-test at a significance level of p<0.05. For the statistical analysis the software SPSS 22.0 will be used. <b>Trial registration:</b> Deutsches Register Klinischer Studien: DRKS00006562

Brain Stimulation for Torsion Dystonia.

Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used. To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action. PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined. Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients. Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative.

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia.

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer’s dystonia, 3 musician’s dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer’s Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

Role of ¹⁸F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation.

No current neuroimaging modality offers mechanistic or prognostic information to guide management in paediatric dystonia. We assessed F-fluorodeoxyglucose (¹⁸F-FDG) PET/computed tomography (CT) brain imaging in childhood primary dystonia (PDS) and neurodegeneration with brain iron accumulation (NBIA) to determine whether it would identify altered metabolism and hence constitute a potentially useful 'biomarker' indicating functional disturbances associated with dystonia and severity of the disease. A total of 27 children (15 PDS and 12 NBIA) underwent brain ¹⁸F-FDG PET/CT imaging under anaesthesia during acquisition. The images were assessed visually and the two groups were compared quantitatively with statistical parametric mapping. PET/CT images were spatially transformed to Montreal Neurological Institute standard space. Voxelwise ¹⁸F-FDG uptake was normalized to whole-brain uptake. Data of both groups were correlated separately with duration and severity of dystonia as assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Visual inspection did not identify any abnormalities in ¹⁸F-FDG uptake within the cerebral cortex, basal ganglia, or thalami in either group. Quantitative analysis identified higher uptake in the posterior cingulate and bilateral posterior putamina but decreased uptake in the occipital cortex and cerebellum in NBIA compared with PDS. The NBIA group had more severe dystonia scores compared with the PDS group. BFMDRS was negatively correlated with age but not with duration of dystonia. Compared with PDS, NBIA is dominated by relative overactivity in the putamen and by cerebellar underactivity, patterns that may reflect the increased severity of dystonia in NBIA cases. Hence, there is a potential role for ¹⁸F-FDG PET/CT imaging in paediatric dystonia, particularly in the NBIA group.

PP06.5 – 2643: Clinical profile and radiological characteristics of children with dyskinetic cerebral palsy – An observational study

Objective To study the clinical profile, etiology, radiological characteristics, motor functional ability and severity of dystonia in children with dyskinetic CP. Methods This was an observational study. Sixty-five consecutive children with dyskinetic CP seen between January 2013 and December 2013 were evaluated. For all patients, neuroimaging was done; gross motor function was evaluated using Gross Motor Function Classification System (GMFCS). Video-recordings of each child were made to evaluate resting and task-based dyskinesia using Burke–Fahn–Marsden Scale (BFMS). Results Majority of the dyskinetic children was termborn (80%), weighed >2500 g (72%), age-group 1–2 years (55.4%) and were boys (77%). Dystonia was predominant (91%) as compared to choreo-athetosis (9%). Commonest neonatal problems were neonatal jaundice (79%), sepsis (40%) and birth asphyxia (26%). Main parental concerns were developmental delay (97%), dystonia (60%) and speech problems (26%). 83% were severely disabled and non-ambulatory (level V and IV GMFCS); only onetenth achieved ambulation (Level I and II GMFCS). Mean BFMS score was 45.8+19. Nearly 90% of dystonic children were at level IV and V GMFCS; 67% of choreo-athetotic children were ambulatory. Etiologically, hyperbilirubinemia (66%) and perinatal asphyxia (30%) were predominant. In children with hyperbilirubinemia, mean serum bilirubin was 31+9.4 mg/dL, exchange transfusion done in 60.7%, and 21.5% were G-6-PD deficient. Radiologically, this predominantly involved globus pallidum, substantia nigra and subthalamus; normal scans were seen in 2 children. Perinatal asphyxia led to periventricular-white-matter, putaminal and thalamic changes. The mean dystonia scales were higher in the hyperbilirubinemia group as compared to perinatal asphyxia group. Conclusion Hyperbilirubinemia contributes significantly to severely disabling dyskinetic CP in developing countries. Distinctive radiological patterns of injury help identify the nature of insult. Significant motor impairments and dystonia impair functional abilities of these dyskinetic children.

PP12.1 – 2938: Comparison of Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Abilities and Communication Function classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a Rosetta Stone study

Objective The Burke-Fahn-Marsden Dystonia Rating Scale-Movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability in paediatric movement disorders (PMD). The Gross Motor Classification System (GMFCS), Manual Ability Classification System (MACS) and Communication Function Classification System (CFCS) are widely used in the cerebral palsy (CP) literature to classify functional ability. This study explores the concordance of the three functional scales in a large sample of PMD and the impact of dystonia severity on these functional scales. Methods Children with PMD (n=161, median age 10y3mo SD 4y) were assessed using the BFM-M, and classified using the 3 scales. Data analysis was performed using the R language and environment for statistical computing, version 3.01 RDev. Overall relationships between BFM-M and categorical variables were evaluated with the Kruskal-Wallis Rank Sum Test and the proportion variation explained (R b ). Relationships between two categorical variables were assessed using Pearson's chi-squared test and Pearson residuals. Spearman correlations (rs) were also provided as an estimate of the strength of the association between variables. The information provided by these scales is compared. Results Of the 161 children included, secondary dystonias (n=125, 78%) included those of both static (n=99, 61%), including dystonic/dyskinetic CP (n=75, 47%), and progressive (n=26, 16%) dystonia. All four scales were strongly associated (all rS>0.72, p Conclusion The BFM-M is strongly linked with the GMFCS, MACS and CFCS, irrespective of aetiology. PMD other than CP could be effectively evaluated using these scales. The ability of the BFM-M scale to discriminate between GMFCS levels in this sample offers the possibility to compare samples across different studies. However, the similarity between MACS I-III in terms of BFM-M scores indicates that non-motor components such as process skills and planning are required for functional activities and cannot be explained by dystonia alone.

TMS-evoked twitches in the passive limb change direction according to muscle activation of the active limb

s / Brain Stimulation 8 (2015) 326e342 330 The cerebellum may provide a therapeutic target for non-invasive stimulation in people with cervical dystonia (CD). This study assessed the effect of 10 sessions of intermittent theta-burst stimulation (iTBS) of the cerebellum on symptoms, quality of life and cortical neurophysiology. Fourteen participants (to date) were randomised into intermittent (n 1⁄4 7) or sham (n 1⁄4 7) TBS groups. TMS was used to elicit MEPs from upper trapezius muscles. Dystonia severity and quality of life were assessed using TWSTRS (primary outcome) and CDQ24 questionnaires, pre intervention (pre), after five (mid) and ten (post1) interventions. The CDQ24 was also assessed 4 (post2) and 12 (post3) weeks later. Questionnaire datawere analysed using non-parametric tests. The Mann-Whitney test revealed no difference between groups for the TWSTRS (all P > 0.66). Friedman test showed a reduction in the iTBS group (X2 (2) 1⁄4 8.86, P 1⁄4 0.012), but not in the sham group (X2 (2) 1⁄4 0.67, P 1⁄4 0.72). For TWSTRS pain subsection, there was a group difference at post1 (iTBS -2.93 0.74; sham TBS 0.053 0.94, P 1⁄4 0.046) and a reduction from baseline across time after iTBS (X2 (2) 1⁄4 8.67, P 1⁄4 0.013), but not sham TBS (X2 (2) 1⁄4 4.26, P 1⁄4 0.12). For CDQ-24, the groups differed at post3 (P 1⁄4 0.029) with a trend toward a group difference at post2 (P1⁄4 0.063). Therewas a difference from baseline across time for iTBS (X2 (4)1⁄4 11.14, P1⁄4 0.025), but not sham TBS (X2 (4)1⁄4 4.69, p1⁄4 0.32). MEPs were unaffected by iTBS or sham TBS (all P > 0.21). These preliminary results suggest iTBS may provide an effective intervention for people with CD, particularly for symptoms of pain and for quality of life.

Pallidal stimulation for acquired dystonia due to cerebral palsy: beyond 5 years.

There is increasing evidence that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is effective in patients with idiopathic or inherited generalized dystonia. There is comparatively less experience about the effects of GPi DBS on acquired dystonia, particularly dystonia due to cerebral palsy (DCP). Clinical and demographic outcome predictors for DBS in dystonia syndromes are also poorly defined. Our aim was to examine the efficacy and safety of GPi DBS for the treatment of generalized DCP. Fifteen patients with DCP up to 6.2years after DBS surgery were studied. Only mild limb spasticity or mild static brain magnetic resonance imaging abnormalities were acceptable for inclusion. Dystonia severity and disability were assessed by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS), and health-related quality of life was assessed by the Short Form General Health Survey (SF-36) scale. The amount of energy delivered was calculated, and adverse events and side effects were collected. At last follow-up, BFMDRS motor score improved on average by 49.5%, and the disability score improved by 30%. Health-related quality of life improved in most patients. Age at implant, age at onset and disease duration did not correlate to outcome, whilst higher pre-operative dystonia severity and occurrence of spasticity were associated with poorer outcome. The patients received a stable amount of energy after the first 2years post-implant and throughout all the observation period. There were few serious adverse events or side effects. The outcome was encouraging in the majority of DCP patients, with a stable outlook and a good safety profile.

Young Adults with Dyskinetic Cerebral Palsy Improve Subjectively on Pallidal Stimulation, but not in Formal Dystonia, Gait, Speech and Swallowing Testing

Background: Pharmacological treatment of dyskinetic cerebral palsy (CP) is often ineffective. Data about outcome of deep brain stimulation (DBS) in these patients remains scarce. Methods: Eight patients with dyskinetic CP and DBS of the Globus Pallidus internus were investigated. Using pre- and postoperative videos the severity of dystonia and changes thereof during standardized settings (‘on') and after the stimulator had been switched off (‘off') were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Furthermore, subjective impression (SI) of the extent of postoperative change as well as gait (Leonardo Mechanograph® Gangway), speech (Frenchay Dysarthria) and swallowing performances (fiberoptic laryngoscopy) were assessed during ‘on' and ‘off'. Results: When comparing pre- and postoperative as well as ‘on' and ‘off', the BFMDRS and most of the gait, speech, and swallowing parameters did not differ significantly. In contrast, patients reported significant improvement of their SI postoperatively (3.1 on a 10-point-scale). Conclusion: Data show that our CP-patients did not benefit from GPi-DBS when tested formally for dystonia, gait, speech and swallowing. In stark contrast, these patients reported significant subjective improvement. Taken together, and in light of current unsatisfactory medical treatment options, our data suggest that further assessment of the effects of GPi-DBS in dyskinetic CP is warranted.

Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial

Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment. In this randomised, sham-controlled trial, we recruited patients with cervical dystonia from centres in Germany, Norway, and Austria. Eligible patients (ie, those aged 18-75 years, disease duration ≥3 years, Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score ≥15 points) were randomly assigned (1:1) to receive active neurostimulation (frequency 180 Hz; pulse width 120 μs; amplitude 0·5 V below adverse event threshold) or sham stimulation (amplitude 0 V) by computer-generated randomisation lists with randomly permuted block lengths stratified by centre. All patients, masked to treatment assignment, were implanted with a deep brain stimulation device and received their assigned treatment for 3 months. Neurostimulation was activated in the sham group at 3 months and outcomes were reassessed in all patients after 6 months of active treatment. Treating physicians were not masked. The primary endpoint was the change in the TWSTRS severity score from baseline to 3 months, assessed by two masked dystonia experts using standardised videos, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148889. Between Jan 19, 2006, and May 29, 2008, we recruited 62 patients, of whom 32 were randomly assigned to neurostimulation and 30 to sham stimulation. Outcome data were recorded in 60 (97%) patients at 3 months and 56 (90%) patients at 6 months. At 3 months, the reduction in dystonia severity was significantly greater with neurostimulation (-5·1 points [SD 5·1], 95% CI -7·0 to -3·5) than with sham stimulation (-1·3 [2·4], -2·2 to -0·4, p=0·0024; mean between-group difference 3·8 points, 1·8 to 5·8) in the intention-to-treat population. Over the course of the study, 21 adverse events (five serious) were reported in 11 (34%) of 32 patients in the neurostimulation group compared with 20 (11 serious) in nine (30%) of 30 patients in the sham-stimulation group. Serious adverse events were typically related to the implant procedure or the implanted device, and 11 of 16 resolved without sequelae. Dysarthria (in four patients assigned to neurostimulation vs three patients assigned to sham stimulation), involuntary movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression (one vs two) were the most common non-serious adverse events reported during the course of the study. Pallidal neurostimulation for 3 months is more effective than sham stimulation at reducing symptoms of cervical dystonia. Extended follow-up is needed to ascertain the magnitude and stability of chronic neurostimulation effects before this treatment can be recommended as routine for patients who are not responding to conventional medical therapy. Medtronic.

The clinical utility of botulinum toxin injections targeted at the motor endplate zone in cervical dystonia.

Cervical dystonia (CD) patients usually receive repeated botulinum neurotoxin (BoNT) injections. The aims of this study were to evaluate the feasibility of motor endplate zone (MEZ) detection of relevant cervical muscles in CD patients receiving chronic BoNT treatment and to compare the treatment effect of half-dosed, endplate-targeted injections to standard BoNT injections. In study 1, high-density surface electromyography (HD-sEMG) was recorded from the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in 18 CD patients with ongoing BoNT treatment, by which the location of the MEZ was determined. In study 2, nine additional patients with rotational-type CD participated in a treatment effect study where they received either half of their regular BoNT dose through endplate-targeted injections or their normal BoNT dose through standard injections (crossover design). Dystonia severity was recorded before and 4weeks after each treatment session (Toronto Western Spasmodic Torticollis Rating Scale severity subscore). In the SCM muscle the MEZ was located at the lower border of the superior third part of the muscle, and in the SC muscle at half muscle length. Endplate-targeted, half-dosed BoNT injection resulted in a similar treatment effect to injecting the full dose in the standard technique. Half-dosed, endplate-targeted BoNT injections lead to a similar treatment effect to the standard BoNT injection protocol. MEZ detection confronts the clinician with some technical challenges, such as the ability of accurate and technically optimal placement of the electrode grid and correct interpretation of the HD-sEMG signal.

The effects of electroconvulsive therapy on tardive dystonia or dyskinesia induced by psychotropic medication: a retrospective study.

BackgroundTardive dystonia and dyskinesia are potentially irreversible neurological syndromes. Successful electroconvulsive treatment (ECT) has been reported by multiple sources; however, the existing retrospective reviews and open prospective trials provide little information on the response rate.MethodsEighteen consecutive patients with tardive dystonia or dyskinesia received a standard course of ECT to treat abnormal movement. The severity of the tardive dystonia and dyskinesia was evaluated using the Abnormal Involuntary Movement Scale (AIMS) before and after the course of ECT. The patients who displayed a greater than 50% improvement in the AIMS score were classified as the responders.ResultsThe mean AIMS score decreased from 19.1±4.7 to 9.6±4.2. There were seven responders among the 18 patients, which yielded a 39% response rate.ConclusionECT has a moderate but significant effect on tardive dystonia and dyskinesia.