Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation.

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor.

OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.

Perceptions of Playing-Related Musculoskeletal Disorders (PRMDs) in Irish traditional musicians: a focus group study.

BACKGROUND: Playing-related musculoskeletal disorders (PRMDs) are common in musicians and interfere with the ability to play an instrument at the accustomed level. There is limited research into injuries affecting folk musicians. OBJECTIVE: To explore the Irish traditional musicians' experience of PRMDs. METHODS: Focus group interviews were conducted in 2011 and 2012, in two venues in Ireland. Data were recorded and transcribed verbatim. Data collection ended when no new findings emerged from the analysis of interviews. The inclusion criteria were: males or females aged 18 and above, and who taught or played Irish traditional music on any instrument. The data were analysed using the interpretative phenomenological method. RESULTS: All participants (n=22) believed there was a link between playing music and musculoskeletal problems. The main body areas affected were the back, shoulders, arms and hands. The main theme that emerged was: 'PRMDs are an integral part of being a traditional musician', and that the musical experience was generally prioritised over the health of the musician. There were sub-themes of 'fear' and 'stresses that contributed to PRMDs'. CONCLUSIONS: PRMDs are an occupational hazard for Irish musicians. There is an awareness of PRMDs, but changes (technique, environment) may threaten identity.

Status dystonicus: a practice guide.

Status dystonicus is a rare, but life-threatening movement disorder emergency. Urgent assessment is required and management is tailored to patient characteristics and complications. The use of dystonia action plans and early recognition of worsening dystonia may potentially facilitate intervention or prevent progression to status dystonicus. However, for established status dystonicus, rapidly deployed temporizing measures and different depths of sedation in an intensive care unit or high dependency unit are the most immediate and effective modalities for abating life-threatening spasms, while dystonia-specific treatment takes effect. If refractory status dystonicus persists despite orally active anti-dystonia drugs and unsuccessful weaning from sedative or anaesthetic agents, early consideration of intrathecal baclofen or deep brain stimulation is required. During status dystonicus, precise documentation of dystonia sites and severity as well as the baseline clinical state, using rating scales and videos is recommended. Further published descriptions of the clinical nature, timing of evolution, resolution, and epidemiology of status dystonicus are essential for a better collective understanding of this poorly understood heterogeneous emergency. In this review, we provide an overview of the clinical presentation and suggest a management approach for status dystonicus.

Acute complications of movement disorders surgery: effects of age and comorbidities.

The most common indication for movement disorder surgery is Parkinson's disease (PD), and the incidence of PD increases with age. The analysis reported here was undertaken with the primary goal of examining whether there is a relationship between peri-operative complications and age. The Nationwide Inpatient Sample (Agency for Healthcare Research and Quality, Rockville, MD, USA) was queried for 10 years beginning in 1999 for patients undergoing deep brain stimulator insertion, pallidotomy, and thalamotomy for treatment of PD, essential tremor, and dystonia. Inpatient complications, including death, stroke (both ischemic and hemorrhagic), and other overall complications were examined. The relative risks associated with advanced age; primary diagnosis; treatment modality; the diagnoses of hypertension, diabetes, and nicotinism; and the cumulative number of comorbidities were examined. There were 5464 patients who met inclusion criteria, including 4145 patients treated for PD and 4961 patients treated with deep brain stimulation (DBS). Overall in-hospital mortality was 0.26%, with 0.15% related to surgical factors. There was a correlation between in-hospital mortality, increasing age, and number of medical comorbidities. After multivariate regression no factor remained predictive of mortality. Having more than 1 medical comorbidity or PD increased the risk of in-hospital complications. Patients with PD were more likely to suffer hemorrhage or stroke. Hypertension, diabetes, nicotinism, and modality of treatment were not associated with increased mortality, hemorrhage or stroke risk, or in-hospital mortality in univariate or multivariate analysis. Both age and medical comorbidity are correlated with in-hospital complications, but age appears to serve as a surrogate for comorbidity. Surgery for PD appears to carry an increased risk of hemorrhage or stroke and in-hospital complications.

A combination of constraint-induced therapy and motor control retraining in the treatment of focal hand dystonia in musicians.

UNLABELLED: Focal hand dystonia (FHD) in musicians is a painless task-specific motor disorder characterized by an involuntary loss of control of individual finger movements. The aim of this study was to investigate the effects of an innovative behavioural therapy intervention, aimed at normalising movement patterns, in musicians affected by FHD. METHODS: Eight musicians volunteered to take part in this retraining protocol. Intensive constraint-induced therapy and motor control retraining at slow speed were the interventions. Video recordings of the subjects playing two pieces were used for data analysis. The Frequency of Abnormal Movements scale (FAM), the change in metronome speed achieved during motor control retraining, and two ordinal dystonia evaluation scales were chosen as outcome measures. It was hypothesised that there would be significant differences in the FAM scores and metronome speeds over a 12-month period. RESULTS: For the main outcome measure, the FAM scale scores, the two-factor repeated measures ANOVA revealed a very significant decrease in the number of abnormal movements per second of instrumental playing over the 12-month period (F = 6.32, df = 7, p < 0.001). Tukey's post-hoc tests carried out for the FAM scores revealed that significant changes occurred after 8 months of therapy. DISCUSSION: These results suggest that a combination of constraint-induced therapy and specific motor control retraining may be a successful strategy for the treatment of musicians' FHD. Furthermore, the results suggest that retraining strategies may need to be carried out for at least 8 months before statistically significant changes are noted.

Selective lateral laser thyroarytenoid myotomy for adductor spasmodic dysphonia.

OBJECTIVE: Selective lateral laser thyroarytenoid myotomy is a conceptually sound, simple, minimally invasive, repeatable and predictable new surgical procedure for treating adductor spasmodic dysphonia. This paper aims to introduce and describe the surgical technique, and to present a clinical case series and its outcomes. STUDY DESIGN: A prospective, clinical case series treated with selective lateral laser thyroarytenoid myotomy, with follow up of 2.5 years. METHOD: Pre- and post-operative data were collected prospectively for patients undergoing selective lateral laser thyroarytenoid myotomy. These data included patient demographics, previous interventions for adductor spasmodic dysphonia, technical aspects of surgery and clinical outcome. Outcome data included clinical assessment, voice handicap index, need for further intervention, and patient satisfaction assessed by subjective improvement (detailed subjectively by the patients themselves and objectively using the Glasgow benefit inventory). RESULTS: Four patients (two men and two women; mean age 65 years; age range 41-80 years) were included. The mean duration of adductor spasmodic dysphonia was 11 years. All patients had previously been treated with botulinum toxin A. All patients reported improvement in voice quality, fluency, sustainability and elimination of voice breaks over 2.5 years' follow up. Clinical assessment revealed no alteration in mucosal wave, and complete relief of hyperadduction was observed on phonation. No patients required supplementary botulinum toxin treatment during follow up. CONCLUSION: Selective lateral laser thyroarytenoid myotomy seems to represent a curative procedure for adductor spasmodic dysphonia, a chronic, debilitating condition. This procedure is conceptually simple, minimally invasive and repeatable. It also seems to offer a safe and lasting alternative to botulinum toxin therapy.

Disrupted thalamic prefrontal pathways in patients with idiopathic dystonia.

There are quantifiable abnormalities in water diffusion properties of the white matter in thalamic and prefrontal areas in patients with idiopathic dystonia (ID). However, it is unclear which pathways are disrupted in these patients. Using probabilistic tractography of high resolution DTI, we reconstructed thalamic prefrontal pathways in seven patients with ID and seven matched controls. Resulting fibers were registered onto the stereotaxic space and submitted to a voxel-wise statistical analysis comparing patients and controls. Patients with ID exhibited less thalamic prefrontal connections, particularly involving fibers traveling from the thalamus to the middle frontal gyrus. These results corroborate neurophysiologic findings of reduced and asynchronous thalamic prefrontal input, and emphasize the structural correlates of the pathophysiology of ID.

A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome.

Mutations in the epsilon-sarcoglycan (SGCE) gene have been associated with DYT11 myoclonus-dystonia syndrome (MDS). The aim of this study was to characterize myoclonus in 9 patients with DYT11-MDS presenting with predominant myoclonus and mild dystonia by means of neurophysiological techniques. Variously severe multifocal myoclonus occurred in all of the patients, and included short (mean 89.1 +/- 13.3 milliseconds) electromyographic bursts without any electroencephalographic correlate, sometimes presenting a pseudo-rhythmic course. Massive jerks could be evoked by sudden stimuli in 5 patients, showing a "startle-like" muscle spreading and latencies consistent with a brainstem origin. Somatosensory evoked potentials and long-loop reflexes were normal, as was silent period and long-term intracortical inhibition evaluated by means of transcranial magnetic stimulation; however, short-term intracortical inhibition revealed subtle impairment, and event-related synchronization (ERS) in the beta band was delayed. Blink reflex recovery was strongly enhanced. Myoclonus in DYT11-MDS seems to be generated at subcortical level, and possibly involves basal ganglia and brainstem circuitries. Cortical impairment may depend from subcortical dysfunction, but it can also have a role in influencing the myoclonic presentation. The wide distribution of the defective SCGE in DYT11-MDS may justify the involvement of different brain areas.

[Stereotactic pallidotomy and thalamotomy in the treatment of primary dystonia]. / Leczenie dystonii pierwotnej stereotaktyczna palidotomia i talamotomia.

BACKGROUND AND PURPOSE: The goal of the study was to assess the results of the stereotactic pallidotomy and thalamotomy in the treatment of primary dystonia. MATERIAL AND METHODS: Thirty patients with primary dystonia underwent twenty-eight stereotactic pallidotomies and twenty two thalamotomies. The operations were based on the fused images of computed tomography and magnetic resonance imaging, and were verified by an intraoperative neurophysiological investigation. Neurological and neuropsychological assessments were performed before surgery and at 3 days, 3 and 6 months after the operation. The Mann-Whitney U test was used to find out statistic differences between subgroups and the Wilcoxon test to compare results between particular assessments. RESULTS: The statistic analysis showed postsurgical amelioration of the neurological state lasting at least 6 months. A better long-term outcome was revealed in the subgroup of pallidotomies vs. thalamotomies, in the subgroup with the onset of dystonia after the age of 35 vs. earlier onset, and in the subgroup of the focal and local dystonia vs. generalized dystonia. The statistically significant improvement was achieved at a depression level and the statistically significant deterioration was not stated in the mental status after the operations. A very low percentage of neurological complications after the operations was found in the study. CONCLUSIONS: The stereotactic pallidotomies and thalamotomies are effective and safe options in the treatment of the intractable cases of primary dystonia. Both resulted predominantly in contralateral improvement of motor functions. However, the results of pallidotomies are better than thalamotomies six months after the surgery. The improvement of the mood without cognitive deterioration was revealed in the neuropsychological tests after the operations. Only few, persistent and mild complications were ascertained in the study.

Sporadic rapid-onset dystonia-parkinsonism syndrome: failure of bilateral pallidal stimulation.

We report on a woman who had a severe sporadic nonprogressive dystonia-parkinsonism syndrome with rapid onset of symptoms at age 21. Secondary causes for dystonia were ruled out. No response to levodopa/carbidopa was seen. The patient fulfilled all diagnostic criteria of rapid-onset dystonia-parkinsonism, except for autosomal-dominant inheritance. Bilateral deep brain stimulation of the globus pallidus failed to alleviate her symptoms.

Life-threatening dystonia-dyskinesias in a child: successful treatment with bilateral pallidal stimulation.

We report a 13-year-old boy who developed severe, refractory dystonia-dyskinesias as an abrupt worsening of a previously nonprogressive movement disorder. The movements became continuous, requiring artificial respiration and continuous sedation in the intensive-care unit. Various drugs and drug combinations failed to achieve control. The child was then treated successfully with bilateral pallidal (GPi) stimulation as shown in the videotape. Four months later and without medication, the boy regained autonomous gait and audible speech; his neurologic condition continues to improve.