Pharmacological and neurosurgical management of cerebral palsy and dystonia: Clinical practice guideline update.

Dystonia, typically characterized by slow repetitive involuntary movements, stiff abnormal postures, and hypertonia, is common among individuals with cerebral palsy (CP). Dystonia can interfere with activities and have considerable impact on motor function, pain/comfort, and ease of caregiving. Although pharmacological and neurosurgical approaches are used clinically in individuals with CP and dystonia that is causing interference, evidence to support these options is limited. This clinical practice guideline update comprises 10 evidence-based recommendations on the use of pharmacological and neurosurgical interventions for individuals with CP and dystonia causing interference, developed by an international expert panel following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The recommendations are intended to help inform clinicians in their use of these management options for individuals with CP and dystonia, and to guide a shared decision-making process in selecting a management approach that is aligned with the individual's and the family's values and preferences.

Probabilistic mapping of deep brain stimulation in childhood dystonia.

OBJECTIVES: In adults with dystonia Probabilistic Stimulation Mapping (PSM) has identified putative "sweet spots" for stimulation. We aimed to apply PSM to a cohort of Children and Young People (CYP) following DBS surgery. METHODS: Pre-operative MRI and post-operative CT images were co-registered for 52 CYP undergoing bilateral pallidal DBS (n = 31 genetic/idiopathic dystonia, and n = 21 Cerebral Palsy (CP)). DBS electrodes (n = 104) were automatically detected, and Volumes of Tissue Activation (VTA) derived from individual patient stimulation settings. VTAs were normalised to the MNI105 space, weighted by percentage improvement in Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS) at one-year post surgery and mean improvement was calculated for each voxel. RESULTS: For the genetic/idiopathic dystonia group, BFMDRS improvement was associated with stimulation across a broad volume of the GPi. A spatial clustering of the upper 25th percentile of voxels corresponded with a more delineated volume within the posterior ventrolateral GPi. The MNI coordinates of the centroid of this volume (X = -23.0, Y = -10.5 and Z = -3.5) were posterior and superior to the typical target for electrode placement. Volume of VTA overlap with a previously published "sweet spots" correlated with improvement following surgery. In contrast, there was minimal BFMDRS improvement for the CP group, no spatial clustering of efficacious clusters and a correlation between established "sweet spots" could not be established. CONCLUSIONS: PSM in CYP with genetic/idiopathic dystonia suggests the presence of a "sweet spot" for electrode placement within the GPi, consistent with previous studies. Further work is required to identify and validate putative "sweet spots" across different cohorts of patients.

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.

Mental health and behaviour in children with dystonia: Anxiety, challenging behaviour and the relationship to pain and self-esteem.

PURPOSE: To ascertain whether young people with dystonia are more likely than the general population to have mental health and/or behavioural difficulties, and to explore factors that may contribute to these difficulties. METHOD: Using a quasi-experimental design, 50 young people with dystonia aged 7-17 and their carers were recruited from the Evelina London Children's Hospital. Young people completed the Beck Youth Inventories and the Strengths and Difficulties Questionnaire. Carers completed the Strengths and Difficulties Questionnaire-Parent version and the Paediatric Pain Profile. Important medical factors, such as age of onset, motor severity and manual function were obtained from medical records. RESULTS: One sample z tests showed young people with dystonia self-reported significantly higher levels of anxiety (p < .001) and prosocial difficulties (p < .01), with 48% experiencing clinically significant anxiety levels. They experienced significantly lower levels of anger, disruptive behaviour and conduct problems (all p ≤ .01). Carers reported significantly higher rates of emotional problems, hyperactivity and peer problems, and significantly lower prosocial behaviours (all p ≤ .01). Pearson's correlation coefficients showed lower levels of self-esteem were related to higher levels of anxiety (p = .015). High levels of pain were related to parent-rated conduct problems (p = .004). Age of dystonia onset and motor severity did not correlate with any of the psychological or behavioural measures. INTERPRETATION/CONCLUSIONS: Our study suggests high rates of anxiety and behaviours that challenge in children with dystonia. Screening in movement clinics would be helpful in early identification and signposting for support.

Rehabilitation in childhood-onset hyperkinetic movement disorders including dystonia: Treatment change in outcomes across the ICF and feasibility of outcomes for full trial evaluation.

BACKGROUND: Childhood-onset hyperkinetic movement disorders (HMD), including dystonia are notoriously difficult to treat and there are limited studies showing successful medical, surgical or non-pharmacological interventions. METHODS: This prospective study used grouped data (n = 22) from two studies of the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach for patient-selected goals. Eligibility included aged 6-21 years, deep brain stimulation in place, with manual ability classification system level I-IV. Outcome was assessed on a range of patient-reported and clinician-rated measures across the International Classification of Function at end-treatment (10 weekly sessions) (series 1 and 2) and 3-month follow-up (series 1). Feasibility of outcomes to be used in a full trial were explored. FINDINGS: Nineteen participants completed the intervention and were included in the analysis. Of the primary outcome measures, the self-reported Canadian Occupational Performance Measure showed improvement in goal performance (mean change 4.08, 95% CI [3.37,4.79] post-; 4.18 [5.10,5.26] follow-up), and satisfaction (4.03 [3.04,5.03) post-; 4.44 [3.07,5.82] follow-up]. The Assessment of Motor and Process Skills showed improved motor score (0.52 [0.01,1.03] at follow-up only, while the process score did not change. Objective blind-rated pooled data using the Performance Quality Rating Scale-individualized indicated significant change for trained goals (3.79 [3.37,4.21] post-; (4.01,5.10) follow-up] and untrained goals (1.90 [1.24,2.55] post 1.91 [0.23,3.60] follow-up]. Motor impairment assessed by the Burke-Fahn Motor Disability Rating Scale was unchanged (-3.26 [-6.62,0.09] post-; -1.11 [-8.05,5.82] follow-up). Improvement was also observed in self-efficacy (0.97 [0.47,1.47] post-; 1.37 [1.91-0.83] follow-up) and Quality of Life (0.12 [0.03-0.22] follow-up). Goal improvement; self-efficacy and quality of life captured significant change post-intervention. This improvement was shown despite no change on impairment-related measures and were shown to be feasible measures to use in a larger study of CO-OP for this population.

Targeting accuracy of robot-assisted deep brain stimulation surgery in childhood-onset dystonia: a single-center prospective cohort analysis of 45 consecutive cases.

OBJECTIVE: Deep brain stimulation (DBS) is an established treatment for pediatric dystonia. The accuracy of electrode implantation is multifactorial and remains a challenge in this age group, mainly due to smaller anatomical targets in very young patients compared to adults, and also due to anatomical abnormalities frequently associated with some etiologies of dystonia. Data on the accuracy of robot-assisted DBS surgery in children are limited. The aim of the current paper was to assess the accuracy of robot-assisted implantation of DBS leads in a series of patients with childhood-onset dystonia. METHODS: Forty-five children with dystonia undergoing implantation of DBS leads under general anesthesia between 2017 and 2019 were included. Robot-assisted stereotactic implantation of the DBS leads was performed. The final position of the electrodes was verified with an intraoperative 3D scanner (O-arm). Coordinates of the planned electrode target and actual electrode position were obtained and compared, looking at the radial error, depth error, absolute error, and directional error, as well as the euclidean distance. Functional assessment data prospectively collected by a multidisciplinary pediatric complex motor disorders team were analyzed with regard to motor skills, individualized goal achievement, and patients' and caregivers' expectations. RESULTS: A total of 90 DBS electrodes were implanted and 48.5% of the patients were female. The mean age was 11.0 ± 0.6 years (range 3-18 years). All patients received bilateral DBS electrodes into the globus pallidus internus. The median absolute errors in x-, y-, and z-axes were 0.85 mm (range 0.00-3.25 mm), 0.75 mm (range 0.05-2.45 mm), and 0.75 mm (range 0.00-3.50 mm), respectively. The median euclidean distance from the target to the actual electrode position was 1.69 ± 0.92 mm, and the median radial error was 1.21 ± 0.79. The robot-assisted technique was easily integrated into the authors' surgical practice, improving accuracy and efficiency, and reducing surgical time significantly along the learning curve. No major perioperative complications occurred. CONCLUSIONS: Robot-assisted stereotactic implantation of DBS electrodes in the pediatric age group is a safe and accurate surgical method. Greater accuracy was present in this cohort in comparison to previous studies in which conventional stereotactic frame-based techniques were used. Robotic DBS surgery and neuroradiological advances may result in further improvement in surgical targeting and, consequently, in better clinical outcome in the pediatric population.

Deep Brain Stimulation of the Internal Pallidum in Lesch-Nyhan Syndrome: Clinical Outcomes and Connectivity Analysis.

BACKGROUND: Lesch-Nyhan syndrome (LNS) is a rare genetic disorder characterized by a deficiency of hypoxanthine-guanine phosphoribosyltransferase enzyme. It manifests during infancy with compulsive self-mutilation behavior associated with disabling generalized dystonia and dyskinesia. Clinical management of these patients poses an enormous challenge for medical teams and carers. OBJECTIVES: We report our experience with bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the management of this complex disorder. MATERIALS AND METHODS: Preoperative and postoperative functional assessment data prospectively collected by a multidisciplinary pediatric complex motor disorders team, including imaging, neuropsychology, and neurophysiology evaluations were analyzed with regards to motor and behavioral control, goal achievement, and patient and caregivers' expectations. RESULTS: Four male patients (mean age 13 years) underwent DBS implantation between 2011 and 2018. Three patients received double bilateral DBS electrodes within the posteroventral GPi and the anteromedial GPi, whereas one patient had bilateral electrodes placed in the posteroventral GPi only. Median follow-up was 47.5 months (range 22-98 months). Functional improvement was observed in all patients and discussed in relation to previous reports. Analysis of structural connectivity revealed significant correlation between the involvement of specific cortical regions and clinical outcome. CONCLUSION: Combined bilateral stimulation of the anteromedial and posteroventral GPi may be considered as an option for managing refractory dystonia and self-harm behavior in LNS patients. A multidisciplinary team-based approach is essential for patient selection and management, to support children and families, to achieve functional improvement and alleviate the overall disease burden for patients and caregivers.

The Relative Merits of an Individualized Versus a Generic Approach to Rating Functional Performance in Childhood Dystonia.

AIMS: The Performance Quality Rating Scale (PQRS) is an observational measure that captures performance at the level of activity and participation. Developed for use with the Cognitive Orientation to daily Occupational Performance (CO-OP), it is a highly individualized approach to measurement. CO-OP is currently being studied in childhood-onset hyperkinetic movement disorders (HMD) and deep brain stimulation. The purpose of this study was to compare two different approaches to rating performance, generic (PQRS-G) and individualized (PQRS-I), for children with childhood-onset hyperkinetic movement disorders (HMD) including dystonia. METHOD: Videotaped activity performances, pre and post intervention were independently scored by two blind raters using PQRS-G PQRS-I. Results were examined to determine if the measures identified differences in e performance on goals chosen by the participants and on change scores after intervention. Dependent t-tests were used to compare performance and change scores. RESULTS: The two approaches to rating both have moderate correlations (all data: 0.764; baseline: 0.677; post-intervention: 0.725) and yielded some different results in capturing performance. There was a significant difference in scores at pre-intervention between the two approaches to rating, even though post-intervention score mean difference was not significantly different. The PQRS-I had a wider score range, capturing wider performance differences, and greater change between baseline and post-intervention performances for children and young people with dystonic movement. CONCLUSIONS: Best practice in rehabilitation requires the use of outcome measures that optimally captures performance and performance change for children and young people with dystonic movement. When working with clients with severe motor-performance deficits, PQRS-I appears to be the better approach to capturing performance and performance changes.

Application of Machine Learning Using Decision Trees for Prognosis of Deep Brain Stimulation of Globus Pallidus Internus for Children With Dystonia.

BACKGROUND: While Deep Brain Stimulation (DBS) of the Globus pallidus internus is a well-established therapy for idiopathic/genetic dystonia, benefits for acquired dystonia are varied, ranging from modest improvement to deterioration. Predictive biomarkers to aid DBS prognosis for children are lacking, especially in acquired dystonias, such as dystonic Cerebral Palsy. We explored the potential role of machine learning techniques to identify parameters that could help predict DBS outcome. METHODS: We conducted a retrospective study of 244 children attending King's College Hospital between September 2007 and June 2018 for neurophysiological tests as part of their assessment for possible DBS at Evelina London Children's Hospital. For the 133 individuals who underwent DBS and had 1-year outcome data available, we assessed the potential predictive value of six patient parameters: sex, etiology (including cerebral palsy), baseline severity (Burke-Fahn-Marsden Dystonia Rating Scale-motor score), cranial MRI and two neurophysiological tests, Central Motor Conduction Time (CMCT) and Somatosensory Evoked Potential (SEP). We applied machine learning analysis to determine the best combination of these features to aid DBS prognosis. We developed a classification algorithm based on Decision Trees (DTs) with k-fold cross validation for independent testing. We analyzed all possible combinations of the six features and focused on acquired dystonias. RESULTS: Several trees resulted in better accuracy than the majority class classifier. However, the two features that consistently appeared in top 10 DTs were CMCT and baseline dystonia severity. A decision tree based on CMCT and baseline severity provided a range of sensitivity and specificity, depending on the threshold chosen for baseline dystonia severity. In situations where CMCT was not available, a DT using SEP alone provided better than the majority class classifier accuracy. CONCLUSION: The results suggest that neurophysiological parameters can help predict DBS outcomes, and DTs provide a data-driven, highly interpretable decision support tool that lends itself to being used in clinical practice to help predict potential benefit of DBS in dystonic children. Our results encourage the introduction of neurophysiological parameters in assessment pathways, and data collection to facilitate multi-center evaluation and validation of these potential predictive markers and of the illustrative decision support tools presented here.

Deep brain stimulation reduces pain in children with dystonia, including in dyskinetic cerebral palsy.

AIM: To establish the prevalence of dystonic pain in children and their response to deep brain stimulation (DBS). METHOD: Dystonic pain was assessed in a cohort of 140 children, 71 males and 69 females, median age 11 years 11 months (range 3y-19y 1mo), undergoing DBS in our centre over a period of 10 years. The cohort was divided into aetiological dystonia groups: 1a, inherited; 1b, heredodegenerative; 2, acquired; and 3, idiopathic. Motor responses were measured with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: Dystonic pain was identified in 63 (45%) patients, 38% of whom had a diagnosis of cerebral palsy (CP). Dystonic pain improved in 90% of children and in all aetiological subgroups 1 year after DBS, while the BFMDRS motor score improved in 70%. Statistically significant improvement (p<0.01) was noted for the whole cohort on the Numerical Pain Rating Scale (n=27), Paediatric Pain Profile (n=17), and Caregivers Priorities and Child Health Index of Life with Disabilities questionnaire (n=48). There was reduction of pain severity, frequency, and analgesia requirement. Findings were similar for the whole cohort and aetiological subgroups other than the inherited heredodegenerative group where the improvement did not reach statistical significance. INTERPRETATION: Dystonic pain is frequent in children with dystonia, including those with CP, who undergo DBS; this can be an important, realizable goal of surgery irrespective of aetiology. We encourage the use of multimodal approach in pain research to reduce the risk of bias.

Cognitive Strategy Training in Childhood-Onset Movement Disorders: Replication Across Therapists.

Objective: To explore preliminary effectiveness of the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach in improving outcomes in childhood-onset hyperkinetic movement disorders (HMDs) including dyskinetic cerebral palsy following deep brain stimulation (DBS) across UK clinical occupational therapists. Methods: Randomized, multiple-baseline, Single Case Experimental Design N-of-1 trial with replications across participants. Five self-selected goals were identified: three goals were worked on during CO-OP and two goals were left untreated and used to assess skills transfer. Participants were between 6 and 21 years and had received DBS surgery with baseline Manual Ability Classification System (MACS) levels I-IV. Participants were randomized to typical or extended baseline (2 vs. 6 weeks), followed by 10 weekly individual CO-OP sessions. The primary outcome was functional performance measured by the Performance Quality Rating Scale-Individualized (PQRS-I), assessed before, during, and following treatment. Outcome assessors were blinded to baseline allocation, session number, and assessment time. A non-overlapping index, Tau-U, was used to measure effect size. Results: Of the 12 participants recruited, 10 commenced and completed treatment. In total, 63% of trained goals improved with effect sizes 0.66-1.00 ("moderate" to "large" effect), seen for all children in at least one goal. Skills transfer was found in 37% of the untrained goals in six participants. Conclusions: Cognitive strategy use improved participant-selected functional goals in childhood-onset HMD, more than just practice during baseline. Preliminary effectiveness is shown when the intervention is delivered in clinical practice by different therapists in routine clinical settings.

Gross motor function outcomes following deep brain stimulation for childhood-onset dystonia: A descriptive report.

AIM: To examine the impact of deep brain stimulation (DBS) on gross motor function in children with dystonic movement disorders. METHOD: Prospective audit involving children implanted 2007-2015, followed for up to two years. Outcomes were evaluated across aetiological sub-groups (inherited, acquired, idiopathic) using the GMFM-88 and BFMDRS movement scale (BFM-M). The predictive value of proportion of life lived with dystonia (PLD) and baseline motor capacity were evaluated. RESULTS: Data was available for 60 children (median surgery age 10y11mo). Inherited monogenetic dystonias demonstrated a median increase in GMFM-88 scores of 6.9% (p = 0.021) and 14.5% (p = 0.116) at one and two years. Heredodegenerative and idiopathic dystonias showed disparate responses, with non-significant changes seen in GMFM-88 and BFM-M scores, with the exception of improved one-year BFM-M scores in the idiopathic group [median change 5.5, p = 0.021]. Median GMFM-88 and BFM-M change scores were near zero for acquired dystonias, though improvement was noted in 9/18 CP cases with one-year GMFM-88 data. No significant relationship was found between PLD, or baseline GMFM-88, and GMFM-88 change following DBS. CONCLUSION: Gross motor response to DBS is similar in profile to literature reporting results using impairment-based dystonia rating scales. Relatively consistent improvements were seen in inherited monogenetic ("primary") dystonias, while highly variable, often disappointing, gross motor responses were found in acquired, heredodegenerative, and idiopathic dystonias. In view of such response variability, alternatives to mean group studies, such as single case experimental designs with multiple replications, are needed to determine the efficacy of DBS in childhood-onset dystonias. Ongoing research is needed to identify factors that predict treatment response.

Cognitive approach to rehabilitation in children with hyperkinetic movement disorders post-DBS.

OBJECTIVE: This proof-of-concept feasibility trial examined the potential of the Cognitive Orientation to daily Occupational Performance Approach (CO-OP) to augment deep brain stimulation (DBS) outcomes in childhood-onset hyperkinetic movement disorders (HMD) including dystonia and dyskinetic cerebral palsy. METHODS: This is a single case experimental design using multiple baseline as n-of-1 trial comprising 10 intervention sessions, with replications across participants (n = 10). Treatment focused on 3 participant-selected goals. Transfer was assessed on 2 additional untreated goals. Individuals enrolled were 6-21 years of age and had DBS in situ and sufficient manual ability. Primary outcome was functional performance change on the Performance Quality Rating Scale-Individualized (PQRS-i) measured before, during, and posttreatment, and at 3-month follow-up. Assessors of outcome were blinded to time of assessment, number of intervention session, and treatment allocation. To measure effect size, a nonoverlapping index, Tau-U, was used. Feasibility measures were captured. RESULTS: One participant withdrew before baseline assessment. Effect sizes of at least 0.66 were seen at both posttreatment and follow-up with all participants showing improvements in at least one trained goal in PQRS-i. Six participants improved on all 3 goals and 2 improved on 2 trained goals. Two children showed deterioration in one trained goal each. Transfer to untrained goals was observed in 3 participants for a total of 5 goals. CO-OP was feasible and acceptable to all participants. CONCLUSION: A cognitive-based, task-oriented approach to support performance of personally relevant functional skills enabling participation is acceptable in childhood-onset HMD post-DBS. Further, preliminary efficacy to improve outcomes and proof of concept with CO-OP has been established in this population. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with HMD who had undergone DBS, CO-OP improves performance of personally relevant functional skills.

Protocol: Using Single-Case Experimental Design to Evaluate Whole-Body Dynamic Seating on Activity, Participation, and Quality of Life in Dystonic Cerebral Palsy.

Introduction: People with hyperkinetic movement disorders, including dystonia, experience often painful, involuntary movements affecting functioning. Seating comfort is a key unmet need identified by families. This paper reports a protocol to assess the feasibility and preliminary evidence for the efficacy of dynamic seating to improve functional outcomes for young children with dystonic cerebral palsy (DCP). Design: A series of single-case experimental design N-of-1 trials, with replications across participants, with a random baseline interval, and one treatment period (n = 6). Methods: Inclusion criteria: DCP; 21.5 cm < popliteal fossa to posterior sacrum < 35 cm; Gross Motor Function Classification System level IV-V; mini-Manual Ability Classification System level IV-V; difficulties with seating. Intervention: Trial of the seat (8 weeks), with multiple baseline before, during and after intervention and 2 month follow up. The baseline duration will be randomised per child (2-7 weeks). Primary outcomes: Performance Quality Rating Scale; Canadian Occupational Performance Measure; seating tolerance. The statistician will create the randomization, with allocation concealment by registration of participants prior to sending the allocation arm to the principal investigator. Primary outcomes will be assessed from video by an assessor blind to allocation. Analysis: Participant outcome data will be plotted over time, with parametric and non-parametric analysis including estimated size effect for N-of-1 trials.

Protocol for N-of-1 trials proof of concept for rehabilitation of childhood-onset dystonia: Study 1: Protocole des essais de validation à effectif unique pour la réadaptation de la dystonie débutant dans l'enfance : Étude 1.

BACKGROUND: Hyperkinetic movement disorders (HMD) are a heterogeneous group of neurological conditions among which dystonia is the predominant disorder and dyskinetic cerebral palsy the largest secondary dystonia group. Currently, there are no evidence-based, non-medical management options for childhood HMD. The Cognitive Orientation to daily Occupational Performance (CO-OP) Approach is a task-oriented, performance-based intervention that focuses on participation. PURPOSE: This paper reports the protocol for a proof-of-concept study to assess feasibility and preliminary evidence regarding efficacy of CO-OP for HMD following deep brain stimulation (DBS). METHOD: A series of N-of-1 trials with replications will be conducted with children, ages 6 and 21 years with HMD and DBS as indicated by the Manual Ability Classification System. Ten individualized CO-OP sessions, with multiple baselines before, during, and after, will be completed. The primary outcome measures are the Performance Quality Rating Scale and the Assessment of Motor and Process Skills. Outcome data will be plotted over time for each participant and supplemented with graph statistical analysis and effect size estimates. IMPLICATIONS: A written protocol will be developed based on evidence and feedback incorporating any changes to the CO-OP intervention for children and young people with HMD, as per the Medical Research Council's Framework for Complex Interventions.

Protocol for N-of-1 trials with replications across therapists for childhood-onset dystonia rehabilitation: Study 2: Protocole des essais à effectif unique avec répétitions par différents ergothérapeutes pour la réadaptation de la dystonie débutant dans l'enfance : Étude 2.

BACKGROUND: Currently, no evidence-based rehabilitation interventions are available for hyperkinetic movement disorders (HMD), including dyskinetic cerebral palsy (CP). Among these highly heterogeneous disorders, dystonia is the predominant disorder. The Cognitive Orientation to daily Occupational Performance (CO-OP) Approach-a task-oriented, performance-based intervention to enable participation-is currently being evaluated for its potential as an intervention option. PURPOSE: This paper reports the protocol for the second of two studies designed to evaluate the potential of CO-OP to improve functional outcomes for individuals with HMD following deep brain stimulation (DBS). This second study is a systematic replication across multiple treating therapists from multiple centres. METHOD: Systematic replications will be used across centres and treating therapists trained in the CO-OP, using a series of randomized multiple-baseline N-of-1 trials. Participants will be ages 6 to 21 years with HMD and DBS as indicated by the Manual Ability Classification System. Data collection will involve multiple data points collected at baseline, during intervention, and after intervention. The intervention will involve occupation-based goal setting followed by 10 individualized CO-OP sessions. The primary outcome measures are the Performance Quality Rating Scale and the Canadian Occupational Performance Measure. Outcome data will be plotted over time for each participant and supplemented with graph statistical analysis and estimate size effect for N-of-1 trials. IMPLICATIONS: The results of this study will help to inform future training procedures and future clinical trials.

Somatosensory Evoked Potentials and Central Motor Conduction Times in children with dystonia and their correlation with outcomes from Deep Brain Stimulation of the Globus pallidus internus.

OBJECTIVES: To report Somatosensory Evoked Potentials (SEPs) and Central Motor Conduction Times (CMCT) in children with dystonia and to test the hypothesis that these parameters predict outcome from Deep Brain Stimulation (DBS). METHODS: 180 children with dystonia underwent assessment for Globus pallidus internus (GPi) DBS, mean age 10 years (range 2.5-19). CMCT to each limb was calculated using Transcranial Magnetic Stimulation. Median and posterior tibial nerve SEPs were recorded over contralateral and midline centro-parietal scalp. Structural abnormalities were assessed with cranial MRI. One-year outcome from DBS was assessed as percentage improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m). RESULTS: Abnormal CMCTs and SEPs were found in 19% and 47% of children respectively and were observed more frequently in secondary than primary dystonia. Of children proceeding to DBS, better outcome was seen in those with normal (n = 78/89) versus abnormal CMCT (n = 11/89) (p = 0.002) and those with normal (n = 35/51) versus abnormal SEPs (n = 16/51) (p = 0.001). These relationships were independent of dystonia aetiology and cranial MRI findings. CONCLUSIONS: CMCTs and SEPs provide objective evidence of motor and sensory pathway dysfunction in children with dystonia and relate to DBS outcome. SIGNIFICANCE: CMCTs and SEPs can contribute to patient selection and counselling of families about potential benefit from neuromodulation for dystonia.

Bilateral globus pallidus internus deep brain stimulation for dyskinetic cerebral palsy supports success of cochlear implantation in a 5-year old ex-24 week preterm twin with absent cerebellar hemispheres.

BACKGROUND: Early onset dystonia (dyskinesia) and deafness in childhood pose significant challenges for children and carers and are the cause of multiple disability. It is particularly tragic when the child cannot make use of early cochlear implantation (CI) technology to relieve deafness and improve language and communication, because severe cervical and truncal dystonia brushes off the magnetic amplifier behind the ears. Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) neuromodulation can reduce dyskinesia, thus supporting CI neuromodulation success. METHODS: We describe the importance of the order of dual neuromodulation surgery for dystonia and deafness. First with bilateral GPi DBS using a rechargeable ACTIVA-RC neurostimulator followed 5 months later by unilateral CI with a Harmony (BTE) Advanced Bionics Hi Res 90 K cochlear device. This double neuromodulation was performed in series in a 12.5 kg 5 year-old ex-24 week gestation-born twin without a cerebellum. RESULTS: Relief of dyskinesia enabled continuous use of the CI amplifier. Language understanding and communication improved. Dystonic storms abated. Tolerance of sitting increased with emergence of manual function. Status dystonicus ensued 10 days after ACTIVA-RC removal for infection-erosion at 3 years and 10 months. He required intensive care and DBS re-implantation 3 weeks later together with 8 months of hospital care. Today he is virtually back to the level of functioning before the DBS removal in 2012 and background medication continues to be slowly weaned. CONCLUSION: This case illustrates that early neuromodulation with DBS for dystonic cerebral palsy followed by CI for deafness is beneficial. Both should be considered early i.e. under the age of five years. The DBS should precede the CI to maximise dystonia reduction and thus benefits from CI. This requires close working between the paediatric DBS and CI services.

The International Classification of Functioning (ICF) to evaluate deep brain stimulation neuromodulation in childhood dystonia-hyperkinesia informs future clinical & research priorities in a multidisciplinary model of care.

The multidisciplinary team (MDT) approach illustrates how motor classification systems, assessments and outcome measures currently available have been applied to a national cohort of children and young people with dystonia and other hyperkinetic movement disorders (HMD) particularly with a focus on dyskinetic cerebral palsy (CP). The paper is divided in 3 sections. Firstly, we describe the service model adopted by the Complex Motor Disorders Service (CMDS) at Evelina London Children's Hospital and King's College Hospital (ELCH-KCH) for deep brain stimulation. We describe lessons learnt from available dystonia studies and discuss/propose ways to measure DBS and other dystonia-related intervention outcomes. We aim to report on current available functional outcome measures as well as some impairment-based assessments that can encourage and generate discussion among movement disorders specialists of different backgrounds regarding choice of the most important areas to be measured after DBS and other interventions for dystonia management. Finally, some recommendations for multi-centre collaboration in regards to functional clinical outcomes and research methodologies for dystonia-related interventions are proposed.

Stable cognitive functioning with improved perceptual reasoning in children with dyskinetic cerebral palsy and other secondary dystonias after deep brain stimulation.

BACKGROUND: Dystonia is characterised by involuntary movements (twisting, writhing and jerking) and postures. Secondary dystonias are described as a heterogeneous group of disorders with both exogenous and endogenous causes. There is a growing body of literature on the effects of deep brain stimulation (DBS) surgery on the motor function in childhood secondary dystonias, however research on cognitive function after DBS is scarce. METHODS: Cognitive function was measured in a cohort of 40 children with secondary dystonia following DBS surgery using a retrospective repeated measures design. Baseline pre-DBS neuropsychological measures were compared to scores obtained at least one year following DBS. Cognitive function was assessed using standardised measures of intellectual ability and memory. RESULTS: There was no significant change in the assessed domains of cognitive function following DBS surgery. A significant improvement across the group was found on the Picture Completion subtest, measuring perceptual reasoning ability, following DBS. CONCLUSION: Cognition remained stable in children with secondary dystonia following DBS surgery, with some improvements noted in a domain of perceptual reasoning. Further research with a larger sample is necessary to further explore this, in particular to further subdivide this group to account for its heterogeneity. This preliminary data has potentially positive implications for the impact of DBS on cognitive functioning within the childhood secondary dystonia population.