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.

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society.

A Critical Evaluation of the Updated Evidence for Casting for Equinus Deformity in Children with Cerebral Palsy.

BACKGROUND AND PURPOSE: Equinus deformity is common in ambulant children with cerebral palsy (CP). Although lower leg casting is frequently used, the physiological basis for casting and effects beyond range of motion (ROM) gains are unclear. This review critically evaluates the updated evidence for casting in the management of ankle equinus in children with CP. METHODS: Comprehensive searches were conducted using electronic databases AMED, MEDLINE, CINAHL, Scopus, PEDro and the Cochrane Database of Systematic Reviews, publication years 2005-2014, in order to identify literature published since an earlier comprehensive systematic review. Only studies evaluating lower leg casting for conservative management of equinus deformity in children with CP were considered. Two independent raters critically appraised studies against the hierarchy of levels of evidence and rigour of study conduct questions proposed by the American Academy of Cerebral Palsy and Developmental Medicine's methodology for systematic review. RESULTS: Four relevant systematic reviews were identified, although these largely concerned earlier literature. Five original studies were included, all demonstrating improvement in dorsiflexion ROM. Combined treatment with botulinum toxin and casting offered greater and/or more sustained ROM gains than botulinum toxin alone in three studies. Effects on gait parameters and motor function were inconsistent. Participation outcomes were not evaluated. Methodological limitations make firm conclusions difficult. CONCLUSIONS: Recent years have offered little progress in the state of evidence for casting in the management of equinus deformity. Casting appears to offer at least short-term improvement in ankle dorsiflexion, although the proposition that this improves function or avoids surgery is not well substantiated. Future research needs to ensure more robust study design and broader evaluation across domains of the International Classification of Functioning, Disability and Health to determine the functional and long-term effect of casting for equinus deformity. Greater knowledge is required of the effect of casting on muscle structure and function in spastic CP. Copyright © 2015 John Wiley & Sons, Ltd.

Progression to musculoskeletal deformity in childhood dystonia.

AIM: Dystonia is a movement disorder characterized by involuntary muscle contractions, resulting in abnormalities of posture and movement. Children with dystonia are at risk of developing fixed musculoskeletal deformities (FMDs). FMDs cause pain, limit function and participation and interfere with care. We aimed to explore factors relating to the development of FMD in a large cohort of children with dystonia. METHOD: The case notes of all children referred to our Complex Motor Disorder service between July 2005 and December 2011 were reviewed. Data from 279 children (median age 9 years 10 months, Standard Deviation 4 years 2 months) with motor disorders including a prominent dystonic element were analyzed. Parametric accelerated failure time regression was used to identify the factors related to development of contractures. RESULTS: FMDs were present at referral in more than half (n = 163, 58%) of cases. Three quarters (n = 120, 74%) of children with FMD had deformities around the hip, and 42% had spinal deformity (n = 68). Compared to pure primary dystonia, FMD onset was earlier with a diagnosis of secondary or heredodegenerative dystonia, and a mixed spastic-dystonic phenotype (all p < 0.001). FMD onset was also earlier with increasing Gross Motor Function Classification System (GMFCS) level (p < 0.001). The effect of aetiological classification was lost when controlling for GMFCS level and motor phenotype. INTERPRETATION: Children with secondary or heredodegenerative dystonia are at greater risk of progression to FMD compared to primary dystonia, likely due to more severe dystonia within these groups. Children with additional spasticity are at particular risk, requiring close monitoring.

Rater reliability and scoring duration of the Quality Function Measure in ambulant children with hyperkinetic movement disorders.

AIM: To examine intra- and interrater reliability/agreement, and time taken to score, when the Quality Function Measure (QFM) is applied to children with hyperkinetic movement disorders (HMD; e.g. dystonia, chorea, athetosis, tremor, and myoclonus). METHOD: Fifteen ambulant children with HMD participated (eight males, seven females; mean age 13y 7mo, SD 3y 7mo). Three trained raters (two physiotherapists, one occupational therapist) independently scored the QFM using videos of each child performing Gross Motor Function Measure (GMFM) Stand and Walk/Run/Jump dimensions. Reliability was evaluated using intraclass correlation coefficient (ICC) model 2.1, Standard Error of Measurement (SEM), and Bland-Altman methods. RESULTS: Rater reliability was excellent for all five QFM attributes: intrarater ICCs ≥0.98 (95% confidence interval [CI] 0.83-1.00), and interrater ICCs ≥0.96 (95% CI 0.91-1.00). SEM varied from 2.07% to 4.72% points for intra- and interrater scores across QFM attributes. Bland-Altman tests demonstrated close agreement between ratings, with absolute mean differences varying from 0.34% to 3.23% (intrarater) to 1.67% to 3.82% (interrater). Median scoring duration time was 83 minutes (range 56-144min, SD 16.02). INTERPRETATION: Low measurement error attributable to rater effects suggests the QFM has potential as an evaluative measure in research studies involving children with HMD, though its lengthy scoring requirements are an important consideration for clinical practice. Evaluation of test-retest reliability and responsiveness is required.

Intrathecal baclofen trials: complications and positive yield in a pediatric cohort.

OBJECT Intrathecal baclofen (ITB) is an effective management option for childhood hypertonia. Given the potential complications of implanted ITB pumps, trials of ITB are usually performed as part of the workup for ITB pumps. Two methods are used for ITB trials, lumbar puncture (LP) and catheter insertion into the intrathecal space. Little has been written to date on the number of positive trials and complications in trials. This study aimed to report the outcomes and complications in ITB trials for childhood hypertonia (dystonia, spastic, or mixed). METHODS A retrospective case notes review was conducted of all patients who underwent ITB trials at the Evelina London Children's Hospital between 2005 and 2012 (inclusive). Positive trials were defined as a reduction in Modified Ashworth Scale by a minimum of 1 point in at least 2 muscle groups and improvement reported by the caregivers in the areas of goals agreed upon between professionals and the families. RESULTS Our patient group comprised children with dystonia (n = 7), mixed spasticity/dystonia (n = 29), spasticity (n = 4), and pain (n = 1). A total of 47 trials were attempted in 41 children. Forty trials were successfully completed, with 39 being positive. Thirty-three were catheter trials, and 14 were LPs. The overall complication rate in the 47 attempted trials was 53%: 61% in catheter trials, and 36% in LP trials. This difference was not statistically significant. The most common complications were vomiting (n = 9) and CSF leak (n = 4). The most serious complication was meningitis (n = 1) in a catheter trial. No patients experienced a permanent injury. CONCLUSIONS There is a high risk of minor self-limiting complications with ITB trials, which needs to be factored into the decision process of progression to trials. The rate of positive trials in this study was 98%, of which 21% did not progress to pump implantation. While the authors would still advocate for ITB trials prior to ITB pump insertion to aid parental decision-making, this figure suggests that with good patient selection, ITB pumps could be placed without a preceding trial.

Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

AIM: Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. METHOD: Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. RESULTS: All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, p<0.001), with worse dystonia severity implying worse function. Secondary dystonias had worse dystonia and less function than primary dystonias (p<0.001). A longer proportion of life lived with dystonia is associated with more severe dystonia (rs =0.42, p<0.001). INTERPRETATION: The BFM-M is strongly linked with the GMFCS, MACS, and CFCS, irrespective of aetiology. Each scale offers interrelated but complementary information and is applicable to all aetiologies. Movement disorders including cerebral palsy can be effectively evaluated using these scales.

Interventional studies in childhood dystonia do not address the concerns of children and their carers.

AIMS: This study aimed to determine the main concerns/priorities of the parents and carers of children with dystonia referred to our service and whether medical interventional studies addressed these concerns. METHODS: Records of children assessed by our service from June 2005-December 2012 were reviewed and expressed parental/carer concerns at initial assessment categorized using the International Classification of Functioning (ICF) Framework. Medline, CINAHL and Embase databases were searched for outcome measures of medical and surgical interventional studies in childhood dystonia. RESULTS: Data was collected from 273 children and young people with dystonia. The most commonly expressed concerns were: pain (104/273, 38.1%); difficulties in delivering activities of daily-living (66/273, 24.2%), difficulties with hand-use (59/273, 21.6%) and seating (41/273, 15.0%). Literature review identified 70 interventional studies, 46 neurosurgical and 24 pharmacological. The majority of neurosurgical studies (34/46) used impairment scales to measure change, with pharmacological studies typically reporting more subjective changes in motor symptoms. Only a minority of studies used assessments or scales capable of objectively addressing the concerns reported by our cohort. INTERPRETATIONS: Existing interventional studies in childhood dystonia poorly address the main concerns of children with dystonia and their carers, limiting the conclusions which may be drawn as to true impact of these interventions in childhood.

Evaluation of functional goal outcomes using the Canadian Occupational Performance Measure (COPM) following Deep Brain Stimulation (DBS) in childhood dystonia.

PURPOSE: To evaluate the functional goal-directed outcomes of Deep Brain Stimulation (DBS) in childhood dystonia according to aetiology and to explore relationship with a traditional impairment-based measure. METHOD: This is a prospective case series study involving thirty children with dystonia with a 1-year follow-up post-DBS. The Canadian Occupational Performance Measure (COPM) and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were used as primary outcome measures. Results were analysed based on aetiology in 3 groups: 1. primary/primary plus dystonia; 2. secondary dystonia-cerebral palsy (CP); 3. secondary dystonia-non-CP group. Correlation between functional outcome using COPM and dystonia improvement as captured by BFMDRS was measured. RESULTS: All groups demonstrated significant improvement in individualised goal attainment, measured with the COPM, at 1-year post-DBS. The secondary dystonia-CP group also achieved significant improvement at 6 months for performance and satisfaction scores. In the majority of secondary dystonias, the BFMDRS failed to demonstrate significant improvement. A linear correlation between change in BFMDRS and COPM scores was observed when the entire cohort was analysed. INTERPRETATION/CONCLUSIONS: DBS improved functional performance, independently of the dystonic phenotype. Improvements in individualized COPM functional goal areas were seen in the absence of significant changes in BFMDRS scores, highlighting the relative insensitivity of impairment scales in this patient group.

Proportion of life lived with dystonia inversely correlates with response to pallidal deep brain stimulation in both primary and secondary childhood dystonia.

AIM: The aim of this study was to examine the impact of dystonia aetiology and duration, contracture, and age at deep brain stimulation (DBS) surgery on outcome in a cohort of children with medically refractory, disabling primary, secondary-static, or secondary-progressive dystonias, including neurodegeneration with brain iron accumulation (NBIA). METHOD: Dystonia severity was assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score at baseline and 6 and 12 months postoperatively in a cohort of 70 consecutive children undergoing DBS between June 2005 and July 2011. RESULTS: Two children (3%) received unilateral DBS for hemidystonia and were excluded and five (7%) developed infections requiring part-DBS removal within 6 months, leaving 63 children (90%) undergoing bilateral DBS for follow-up (34 males, 29 females; mean age at surgery for the whole group 10y 4mo, SD 4y 2mo, range 1-14y). Seventeen children were classified with primary dystonia: mean age 12 years 11 months, SD 4 years 6 months range 4 years 6 months to 17 years 3 months; 28 as having secondary-static dystonia: mean age 10 years 2 months, SD 4 years 9 months (range 3y 3mo-20y); five as having secondary-progressive dystonia: mean age 8 years 11 months, SD 3 years 9 months (range 5y 5mo-13y 1mo); and 13 as having NBIA dystonia: mean age 10 years 2 months, SD 3 years 11 months (range 1-14y). Children with primary dystonias demonstrated greater improvements in BFMDRS motor score than those in the other aetiological categories (Kruskal-Wallis test, p<0.001), which correlated negatively with dystonia duration and more strongly still against the ratio of dystonia duration normalized to age at surgery (DD/AS ratio) at 1 year (Spearman's rank correlation coefficient 0.4752 and -0.599 respectively). A similar significant negative correlation was found in the secondary-static dystonia group between outcome at 1 year and DD/AS ratio (-0.461). Poorer outcome in secondary dystonia coincided with the absence of a period of normal motor development in comparison with the primary dystonia group. A significant improvement in BFMDRS motor score was seen in the NBIA group at 6, but not 12 months (Wilcoxon signed rank test p=0.028, p=0.85 respectively). No reduction in efficacy was seen in children with a musculoskeletal deformity at the time of surgery. CONCLUSION: Response to pallidal DBS in the treatment of dystonia declines with the proportion of life lived with dystonia in primary and secondary dystonia. Other intrinsic factors reduce the median magnitude of reduction in secondary dystonia after DBS. DBS should be offered early, preferably within 5 years of onset, to maximize benefits and reduce the childhood experience of dystonia, including musculoskeletal deformity. Other multidimensional assessments are required to understand how DBS improves the lives of children with dystonia.

Improvement in upper limb function in children with dystonia following deep brain stimulation.

BACKGROUND: Childhood dystonia can severely impact upper limb function. Deep brain stimulation (DBS) has been shown to be effective in reducing dystonic symptoms in childhood. Functional recovery following DBS is however not well understood. AIMS: To explore changes in upper limb function following DBS in paediatric dystonia. METHODS: Upper limb outcomes, using the Melbourne Assessment of Unilateral Upper Limb Function, are reported in 20 cases of childhood dystonia (unilateral n = 1, four limb n = 19) at 6 and 12 months following DBS. RESULTS: Improvement in at least in one upper limb was seen in the majority of cases (n = 17, 85%) at 12 months following DBS. Deterioration of scores in both upper limbs was seen in 3 children with progressive disorders. Grouping the children aetiologically, a significant improvement in the dominant hand was obtained for the primary dystonia/dystonia-plus group at both six (p = 0.018) and twelve months (p = 0.012). In secondary dystonia due to a static disorder, improvement was also seen at 6 (p = 0.043) and 12 months (p = 0.046) in the non-dominant hand. No significant change was found in the group of children with progressive disorders. CONCLUSIONS: DBS has the potential to alter upper limb function in children with primary and secondary dystonia. The dominant hand improved most in children with primary dystonias, with greater improvement in the non-dominant hand in secondary-static cases.

Functional priorities in daily life for children and young people with dystonic movement disorders and their families.

PURPOSE: This study aims to describe the most prevalent functional concerns of a group of young people with dystonia and their primary carers, and to explore the relationship between concerns, aetiology, severity of motor disability and manual ability. METHOD: The Canadian Occupational Performance Measure (COPM) was completed with 57 children with dystonic movement disorders (65% males/35% females, mean 11.2 years (3.5-18.1)): 25% had primary dystonia, 75% secondary dystonia. Gross motor and manual function were classified using the Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS). COPM concerns were analysed with respect to aetiology and severity of motor disability. RESULTS: Almost three quarters of the respondents were GMFCS/MACS IV-V. All respondents had at least one concern around self-care. Other concerns included access to assistive technology, pain, dressing activities, use of tools and social participation. The nature and presence of concerns did not statistically differ according to the severity of gross motor or manual function impairment, though qualitative differences were noted. No statistical difference was found in relation to aetiology. INTERPRETATION: Children and young people with dystonia have common functional concerns and priorities independent of the cause of dystonia, gross motor severity or manual function ability.

Beyond the Burke-Fahn-Marsden Dystonia Rating Scale: deep brain stimulation in childhood secondary dystonia.

PURPOSE: Deep brain stimulation is now widely accepted as an effective treatment for children with primary generalized dystonia. More variable results are reported in secondary dystonias and its efficacy in this heterogeneous group has not been fully elucidated. Deep brain stimulation outcomes are typically reported using impairment-focused measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, which provide little information about function and participation outcomes or changes in non-motor areas. The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulation. METHODS: Six paediatric cases who underwent deep brain stimulation surgery with a minimum of one year follow up were selected on the basis of apparent non-response to deep brain stimulation, defined as a clinically insignificant change in the Burke-Fahn-Marsden Dystonia Movement Scale (<20%), but where other evaluation measures demonstrated clinical efficacy across several domains. RESULTS: Despite no significant change in Burke-Fahn-Marsden Dystonia Rating Scale scores following deep brain stimulation, parallel outcome measures demonstrated significant benefit in a range of child and family-centred goal areas including: pain and comfort, school attendance, seating tolerance, access to assistive technology and in some cases carer burden. CONCLUSIONS: Sole use of impairment-focused measures, are limited in scope to evaluate outcome following deep brain stimulation, particularly in secondary dystonias. Systematic study of effects across multiple dimensions of disability is needed to determine what deep brain stimulation offers patients in terms of function, participation, care, comfort and quality of life. Deep brain stimulation may offer meaningful change across multiple domains of functioning, disability and health even in the absence of significant change in dystonia rating scales.