Burke-Fahn-Marsden Dystonia Rating Scale Motor Research Articles

Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

Superior cerebellar peduncle deep brain stimulation for cerebral palsy.

Patients with coexisting spastic cerebral palsy (CP) and dystonia have limited treatment options. In this study, the authors aimed to evaluate the efficacy of deep brain stimulation (DBS) targeting the superior cerebellar peduncles (SCPs) in adults with CP. Five patients with CP and medically refractory dystonia and spasticity underwent SCP DBS. Assessments included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), modified Ashworth scale (mAS), and tests of cognition, mental status, and quality of life preoperatively and at 3, 6, and 12 months postoperatively (in both DBS ON and OFF states, double blinded). Active contacts and fiber bundles were examined. Four patients completed follow-up. The BFMDRS motor score decreased from 74 to 52 at 12 months postoperatively (30%, p = 0.008). The mean mAS score indicated significant spasticity reduction (from 2.9 ± 0.9 to 1.9 ± 0.6 after 12 months, p = 0.0454). Quality of life improved (p < 0.01), while cognition remained unaffected. Active contacts were found within the dentato-rubro-thalamic tract, with variable efficiency in decussating and nondecussating portions. In this pilot trial, SCP DBS showed promise as a well-tolerated treatment for CP, improving dystonic symptoms, spasticity, quality of life, and functional capacities. However, caution is needed when interpreting the results given the small sample size and heterogeneous motor outcomes.

A localized pallidal physiomarker in Meige syndrome.

Oscillatory patterns in local field potentials (LFPs) have been recognized as disease-specific physiomarkers, particularly in the context of Parkinson's disease and cervical dystonia. This characteristic oscillatory feature is currently employed in adaptive deep brain stimulation (aDBS). However, for other types of dystonia, especially Meige syndrome, a distinct physiomarker of this nature is yet to be identified. Local field potentials were recorded during microelectrode-guided deep brain stimulation surgery from 28 patients with primary Meige syndrome. Before surgery, the severity of patients' motor syndrome were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M). An instantaneous oscillation detection method was employed to identify true narrowband oscillations. Subsequently, a linear mixed effects model was utilized to examine the relationship between oscillatory activities (including power amplitude and burst duration) and symptom severity. The focal peaks of "oscillatory activities" detected were predominantly concentrated in the narrow theta band (4-8 Hz), constituting 81.5% of the total detected oscillations in all recording sites near active DBS contacts in the globus pallidus internus (GPi). The linear mixed effects model revealed a positive correlation between the theta burst duration and the severity of preoperative motor impairment, but no correlation with postoperative motor scores. Additionally, there was no significant lateralization effect observed between the left and right GPi. Our findings suggest that the exaggerated narrowband theta activity (mainly the burst duration) in the GPi is predictive of dystonia symptom severity and may be used as a physiomarker for optimized DBS target during surgery and adaptive DBS for the treatment of Meige syndrome.

Cranial geometry in patients with dystonia and Parkinson’s disease

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = − 0.282, p = 0.016). The Burke–Fahn–Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.

The minimal clinically important change in the motor section of the Burke-Fahn-Marsden Dystonia Rating Scale for generalized dystonia: Results from deep brain stimulation

BackgroundThe minimal clinically important difference (MCID) describes the smallest change in an outcome that is considered clinically meaningful. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is the most frequently rating scale assessing the efficacy of deep brain stimulation therapy (DBS) for dystonia. To expand our understanding, we evaluated the MCID thresholds for the BFMDRS motor subscale (MS) using physician-reported outcomes. MethodsWe assessed the MCID thresholds for the BFMDRS using movement disorder specialist ratings of videotapes from patients with genetically determined dystonia (Tor1A and THAP1) who underwent bilateral globus pallidum internum (GPi) DBS. We calculated the effect size of the BFMDRS-MS change and determined the MCID thresholds using the Clinical Global Impression of Change (CGIC). ResultsTwelve participants with a median age at DBS of 44.5 (range:27–68) had baseline and follow-up BFMDRS-MS with a median post-DBS follow-up of 5.5 years. Based on descriptive analysis, patients with good improvement after DBS according to the CGIC [8/12 (67%)] had a median BFMDRS-MS score reduction of 77% [Interquartile range (IQR):66.2;91.0) with an effect size of 0.39, and those with non-improvement [4/12 (33%)], had a median BFMDRS-MS score reduction of 62% (IQR:36.6;83.6). ConclusionsOur MCID estimates can be utilized in clinical practice in judging clinical relevance. However, further larger, powered studies are needed to simultaneously determine and compare MCID using patient and physician-reported outcomes in segmental and generalized dystonia in genetic and non-genetic populations.

Identification of TH Variants in Chinese Dopa-Responsive Dystonia Patients and Long-Term Outcomes.

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder.Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke–Fahn–Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared).Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG.Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.

The Efficacy and Predictors of Using GPi-DBS to Treat Early-Onset Dystonia: An Individual Patient Analysis.

Objective To compare the efficacy in patients with different genotypes, identify the potential predictive factors, and summarize the complications of globus pallidus deep brain stimulation (GPi-DBS) treating early-onset dystonia. Methods Three electronic databases (PubMed, Embase, and Cochrane databases) were searched with no publication data restriction. The primary outcomes were the improvements in Burke–Fahn–Marsden Dystonia Rating Scale motor (BFMDRS-M) and disability (BFMDRS-D) score. Pearson's correlation coefficients and a metaregression analysis were used to identify the potential predictive factors. This article was registered in Prospero (CRD42020188527). Results Fifty-four studies (231 patients) were included. Patients showed significant improvement rate in BFMDRS-M (60.6%, p < 0.001) and BFMDRS-D (57.5%, p < 0.001) scores after treatment with GPi-DBS. BFMDRS-M score improved greater in the DYT-1-positive (p = 0.001) and DYT-11-positive (p = 0.008) patients compared to DYT-6-positive patients. BFMDRS-D score improved greater in the DYT-11 (+) compared to DYT-6 (+) patients (p = 0.010). The relative change of BFMDRS-M (p = 0.002) and BFMDRS-D (p = 0.010) scores was negatively correlated with preoperative BFMDRS-M score. In the metaregression analysis, the best predictive model showed that preoperative BFMDRS-M, disease duration (p = 0.047), and the age at symptom onset (p = 0.027) were important. Conclusion Patients with early-onset dystonia have a significant effect after GPi-DBS treatment, and DYT-1 (+) and DYT-11 (+) patients are better candidates for GPi-DBS. Lower preoperative score, later age of onset, and an earlier age at surgery probably predict better clinical outcomes.

Asleep Deep Brain Stimulation in Patients With Isolated Dystonia: Stereotactic Accuracy, Efficacy, and Safety

ObjectivesLead placement for deep brain stimulation (DBS) is routinely performed using neuroimaging or microelectrode recording (MER). Recent studies have demonstrated that DBS under general anesthesia using an imaging-guided target technique (“asleep” DBS) can be performed accurately and effectively with lower surgery complication rates than the MER-guided target method under local anesthesia (“awake” DBS). This suggests that asleep DBS may be a more acceptable method. However, there is limited direct evidence focused on isolated dystonia using this method. Therefore, this study aimed to investigate the clinical outcomes and targeting accuracy in patients with dystonia who underwent asleep DBS. Materials and MethodsWe examined 56 patients (112 leads) with isolated dystonia who underwent asleep DBS targeting in the globus pallidus internus (GPi) and subthalamic nucleus (STN). The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were assessed preoperatively and at 12-month follow-up (12 m-FU). The lead accuracy was evaluated by comparing the coordinates of the preoperative plan with those of the final electrode implantation location. Other measures analyzed included stimulation parameters and adverse events (AEs). ResultsFor both GPi and STN cohorts, mean BFMDRS motor scores were significantly lower at 12 m-FU (8.9 ± 10.9 and 4.6 ± 5.7 points) than at baseline (22.6 ± 16.4 and 16.1 ± 14.1 points, p < 0.001). The mean difference between the planned target and the distal contact of the leads was 1.33 ± 0.54 mm for the right brain electrodes and 1.50 ± 0.57 mm for the left, determined by Euclidian distance. No perioperative complications or AEs related to the device were observed during the complete follow-up. However, AEs associated with stimulation occurred in 12 and 6 patients in the GPi and STN groups, respectively. ConclusionsAsleep DBS may be an accurate, effective, and safe method for treating patients with isolated dystonia regardless of the stimulation target.

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

To establish the prevalence of dystonic pain in children and their response to deep brain stimulation (DBS). Dystonic pain was assessed in a cohort of 140 children, 71 males and 69 females, median age 11years 11months (range 3y-19y 1mo), undergoing DBS in our centre over a period of 10years. 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). 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 1year 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. 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.

Subthalamic Nucleus Stimulation in Pediatric Isolated Dystonia: A 10-Year Follow-up.

To evaluate the short-term and long-term clinical effectiveness and safety of subthalamic nucleus deep brain stimulation (STN-DBS) for medically intractable pediatric isolated dystonia. Using a longitudinal retrospective design, we assessed the clinical outcomes of nine patients who underwent STN-DBS for treatment-refractory pediatric isolated dystonia one decade ago (mean age at surgery: 15.9 ± 4.5 years). The primary clinical outcome used was assessed by retrospective video analyses of patients' dystonia symptoms using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Clinical assessments were performed at baseline, 1-year follow-up (1-yr FU), and 10-year follow-up (10-yr FU). Adverse side effects, including surgery-related, device-related, and stimulation-related effects, were also documented. After STN-DBS surgery, the mean improvement in the BFMDRS motor score was 77.1 ± 26.6% at 1-yr FU and 90.4 ± 10.4% at 10-yr FU. Similarly, the mean BFMDRS disability score was improved by 69.5 ± 13.6% at 1-yr FU and by 86.5 ± 13.9% at 10-yr FU. The clinical improvements gained at 10-yr FU were significantly larger than those observed at 1-yr FU. Negative correlations were found between the duration of disease to age at surgery ratio (DD/AS) and the improvements in the BFMDRS motor score and total score at 1-yr FU and 10-yr FU. To our knowledge, this study provides the first clinical evidence for the short- and long-term effectiveness and safety of STN-DBS for pediatric isolated dystonia. Additionally, putative evidence is provided that earlier STN-DBS intervention in patients with refractory pediatric isolated dystonia may improve short- and long-term clinical outcomes.

Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis

ObjectiveGenetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common...

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

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

Long-term follow-up of bilateral subthalamic deep brain stimulation for refractory tardive dystonia

BackgroundNo effective treatment for tardive dystonia (TD) has been well established. Deep brain stimulation (DBS) can ameliorate motor manifestations in primary dystonia, and may also be an effective approach for TD. ObjectivesThis study aimed to illuminate the long-term efficacy and safety of subthalamic nucleus (STN)-DBS in treating TD. MethodsTen patients with refractory TD underwent STN-DBS therapy and were assessed by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS), Abnormal Involuntary Movement Scale (AIMS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and the Short Form (36) Health Survey (SF-36) at four time points: pre-operation, 1 week post-operation, 6 months post-operation, and at a final long-term postsurgical follow-up time point. ResultsThe mean follow-up time was 65.6 ± 30.4 months (range, 12–105 months). At the first follow-up, BFMDRS motor and disability scores had improved by 55.9± 28.3% and 62.6± 32.0%, respectively, while AIMS scores improved by 53.3± 26.7%. At the second follow-up, BFMDRS motor and disability scores improved further, by 87.3± 17.0% and 84.3% ± 22.9%, respectively, while AIMS scores improved by 88.4 ± 16.1%. At the last follow-up, this benefit was sustained and had plateaued. Quality of life was improved significantly at the long-term follow-up, and the HAMA and HAMD scores displayed a significant reduction that persisted after the first follow-up. ConclusionSTN-DBS may be an effective and acceptable procedure for TD, leading to persistent and significant improvement in both movement and psychiatric symptoms.

Considerations in deep brain stimulation (DBS) for pediatric secondary dystonia.

There is a paucity of effective long-term medication treatment for secondary dystonias. In situations where significantly impairing secondary dystonias fail to respond to typical enteral medications and intrathecal (or even intraventricular) baclofen, consideration should be given to the use of deep brain stimulation (DBS). While Level I evidence and long-term follow-up clearly demonstrate the efficacy of DBS for primary dystonia, the evidence for secondary dystonia remains mixed and unclear. In this study, we report our experience with pediatric subjects who have undergone DBS for secondary dystonia. We discuss the indications and outcomes of DBS procedures completed at our center. We also present a detailed discussion of the considerations in the management of these patients as well as a literature review. Of the four cases retrospectively examined here, all subjects experienced reductions in the severity of their dystonia (ranging from 0 to 100% on both the Barry-Albright Dystonia (BAD) and Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) scales). Pallidal DBS should be considered among children with functionally debilitating, medication-resistant secondary dystonia. Patients without fixed skeletal deformities who have experienced a short duration of symptoms are most likely to benefit from this intervention.

Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis.

The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi‐DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta‐regression. In total, 24 studies were included in the meta‐analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow‐up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4–30.8] and 65.2% (95% CI, 59.6–70.7), respectively. The corresponding changes in disability score at the last follow‐up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0–7.8) and 58.6% (95% CI, 50.3–66.9). Multivariate meta‐regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow‐up. Reporting of safety data was frequently inconsistent and could not be included in the meta‐analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi‐DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.

Subthalamic nucleus deep brain stimulation in isolated dystonia: A 3-year follow-up study.

To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS). Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604). Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia). This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia. This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia.

Long-term results of deep brain stimulation in a cohort of eight children with isolated dystonia.

Pallidal deep brain stimulation (DBS) is an established treatment for patients with severe isolated dystonia. However, clinical evidence for the long-term use of DBS in children is limited and controlled trials have not yet been conducted. Here, we provide the long-term results of up to 13years of pallidal DBS in eight pediatric patients with generalized idiopathic or hereditary isolated dystonia (five males, mean age at surgery 12.5±3.5years), as assessed by retrospective video rating. Video rating was performed at three time points: pre-operative, 1-year short-term follow-up (1y-FU) and long-term last FU (LT-FU, up to 13years). Symptom severity and disability were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Disability scores were obtained from clinical charts and during the last FU. The mean improvement in BFMDRS motor score was 54.4±8.9% at 1y-FU and 42.9±11.6% at LT-FU; the disability scores improved by 59.8±10.3 and 63.3±7.8%, respectively. Electrode dislocation was noted in one patient and implantable pulse generator dislocation in another, both requiring surgical intervention; no further serious adverse events occurred. Our study presents the first blinded video rating assessment of the short- and long-term effects of pallidal DBS in children with idiopathic or hereditary isolated dystonia. Results confirm that pallidal DBS is a safe and efficacious long-term treatment in children, with overall motor improvement similar to that described in controlled trials in adults.

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.

Cognitive impairment in rapid‐onset dystonia‐parkinsonism

Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation-negative controls. We studied 22 familial RDP patients, 3 non-motor-manifesting mutation-positive family members, 29 mutation-negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia-parkinsonism. The affected RDP patients performed more poorly, on average, than mutation-negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P ≤ 0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP.

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

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). Dystonia severity was assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score at baseline and 6 and 12months postoperatively in a cohort of 70 consecutive children undergoing DBS between June 2005 and July 2011. Two children (3%) received unilateral DBS for hemidystonia and were excluded and five (7%) developed infections requiring part-DBS removal within 6months, 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 12years 11months, SD 4years 6months range 4years 6months to 17years 3months; 28 as having secondary-static dystonia: mean age 10years 2months, SD 4years 9months (range 3y 3mo-20y); five as having secondary-progressive dystonia: mean age 8years 11months, SD 3years 9months (range 5y 5mo-13y 1mo); and 13 as having NBIA dystonia: mean age 10years 2months, SD 3years 11months (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 1year (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 1year 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 12months (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. 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 5years 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.