Secondary dystonia following parenchymal brain tumors.

BACKGROUND: Secondary dystonia has been associated with diverse etiologies. Dystonia associated with brain tumors has not been well characterized. OBJECTIVES: To characterize dystonia and relationship with parenchymal brain tumors. METHODS: We present six patients (1.03%) with dystonia related to parenchymal brain tumors, among 580 screened cases. RESULTS: Contralateral hemidystonia was observed in four cases, followed by focal limb (n = 1) and cervical dystonia (n = 1). Dystonia presented during the phase of tumor growth in four cases, and following tumor treatment in two, one case had re-emergent dystonia. Tumors were low-grade (WHO I or II) and located in the basal ganglia (n = 3), cortical areas (n = 2), thalamus (n = 1) and cerebral peduncle (n = 1). CONCLUSIONS: Secondary dystonia may be caused by brain tumors in diverse locations including basal ganglia, cortex and thalamus. It may be the presenting symptom of brain tumor or follow surgical resection combined with ancillary therapy.

Dystonia-like Movement Disorders Ameliorated by Shear Force and Pressure Stimulation after Small Infarction in the Left Posterolateral Thalamus.

Focal dystonia (FD) can develop after thalamic lesions. Abnormal somatic sensations were argued to be responsible for FD. Our patient experienced FD-like movement disorders, agraphesthesia, and a reduced sense of shear force on the skin and pressure to deep tissues of the right upper limb following a small infarction in the left posterolateral thalamus. FD-like symptoms improved while the skin was being pulled or the deep tissue was being pushed in a manner proportional to the strength of muscle contractions. Therefore, the lack of these sensations was suggested to be related to FD-like symptoms.

Deep Brain Stimulation and Thalamotomy for the Treatment of Dystonia Acquired by Moyamoya Disease with Stroke.

Background: Moyamoya disease (MMD) is a type of chronic cerebrovascular disease. Currently, revascularization surgery including direct/indirect procedure is recommended for symptomatic patients. However, some patients still respond poorly to the treatment or develop secondary symptoms. Case report: We report the first case of an MMD patient treated with deep brain stimulation (DBS) and thalamotomy. Symptoms of dystonia due to hemorrhage in the thalamus responded poorly to revascularization surgery, but were considerably alleviated by stereotactic neurosurgery. Discussion: Our case report provides a potential strategy for management of refractory symptomatic MMD patients with dystonia and also supports the combined efficacy of DBS with thalamotomies. Highlights: Approximately 30% of patients with Moyamoya disease (MMD) presenting movement symptoms do not respond well to revascularization surgery. We reported an MMD patient treated with deep brain stimulation (DBS) and thalamotomy with significant dystonia and dystonic tremor symptom amelioration. It indicates that DBS or stereotactic lesioning might be a potential treatment for the refractory movement symptoms of MMD.

Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review.

Cerebellar ataxia is a hallmark of coenzyme Q10 (CoQ10) deficiency associated with COQ8A mutations. We present four patients, one with novel COQ8A pathogenic variants all with early, prominent handwriting impairment, dystonia and only mild ataxia. To better define the phenotypic spectrum and course of COQ8A disease, we review the clinical presentation and evolution in 47 reported cases. Individuals with COQ8A mutation display great clinical variability and unpredictable responses to CoQ10 supplementation. Onset is typically during infancy or childhood with ataxic features associated with developmental delay or regression. When disease onset is later in life, first symptoms can include: incoordination, epilepsy, tremor, and deterioration of writing. The natural history is characterized by a progression to a multisystem brain disease dominated by ataxia, with disease severity inversely correlated with age at onset. Six previously reported cases share with ours, a clinical phenotype characterized by slowly progressive or static writing difficulties, focal dystonia, and speech disorder, with only minimal ataxia. The combination of writing difficulty, dystonia and ataxia is a distinctive constellation that is reminiscent of a previously described clinical entity called Dystonia Ataxia Syndrome (DYTCA) and is an important clinical indicator of COQ8A mutations, even when ataxia is mild or absent.

Deep Brain Stimulation of the Caudal Zona Incerta and Motor Thalamus for Postischemic Dystonic Tremor of the Left Upper Limb: Case Report and Review of the Literature.

BACKGROUND: Dystonic tremor is defined as a tremor occurring in a body region affected by dystonia. The pathophysiologic mechanisms behind dystonic tremor supposedly involve anomalies affecting the pallidothalamic-receiving area (for the dystonic component) and the ventralis intermedius-cortical loop (for the tremor component). Interest in posterior subthalamic area stimulation for various types of involuntary abnormal movements has arisen owing to positive results in patients affected by tremor refractory to ventralis intermedius deep brain stimulation. CASE DESCRIPTION: A 23-year-old man, with a 15-year history of left upper limb dystonic tremor due to a stroke in the right thalamus, underwent deep brain stimulation with a single electrode passing through the right ventralis oralis anterior/ventralis oralis posterior nuclei and caudal zona incerta. Objective movement outcomes were assessed through the Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor. The impact of tremor on activities of daily living was assessed with the ADL-T24 questionnaire, and quality of life was assessed with the Quality of Life Scale. All questionnaires were administered before deep brain stimulation and at 5-year follow-up. Unified Dystonia Rating Scale and Fahn-Tolosa-Marin Clinical Rating Scale for Tremor scores decreased from 14.5 to 4.5 and from 46 to 7, respectively. ADL-T24 score decreased from 19 to 3, whereas Quality of Life Scale score increased from 49 to 82. CONCLUSIONS: Stimulation of motor thalamus and caudal zona incerta could be a viable treatment for patients affected by tremor of various origins, including dystonic tremor, refractory to medical therapy.

Dystonia in Machado-Joseph disease: Clinical profile, therapy and anatomical basis.

INTRODUCTION: Dystonia is frequent in Machado-Joseph disease, but several important aspects are not yet defined, such as the detailed clinical profile, response to treatment and anatomical substrate. METHODS: We screened 75 consecutive patients and identified those with dystonia. The Burke-Marsden-Fahn Dystonia Rating Scale was employed to quantify dystonia severity. Patients with dystonia received levodopa 600 mg/day for 2 months and were videotaped before and after treatment. A blinded evaluator rated dystonia in the videos. Patients with disabling dystonia who failed to respond to levodopa treatment received botulinum toxin. Finally, volumetric T1 and diffusion tensor imaging sequences were obtained in the dystonic group using a 3T-MRI scanner to identify areas of gray and white matter that were selectively damaged. RESULTS: There were 21 patients with dystonia (28%): 9 classified as generalized and 12 as focal/segmental. Patients with dystonia had earlier onset and larger (CAG) expansions (28.9 ± 11.7 vs 40.6 ± 11.4; p < 0.001 and 75 vs 70; p < 0.001, respectively). Although group analyses failed to show benefit on levodopa (p = 0.07), some patients had objective improvement. In addition, ten patients received botulinum toxin resulting in a significant change in dystonia scores after 4 weeks (p = 0.03). Patients with dystonia had atrophy at pre- and paracentral cortices; whereas, non-dystonic patients had occipital atrophy. Basal ganglia volume was reduced in both groups, but atrophy at the thalami, cerebellar white matter and ventral diencephali was disproportionately higher in the dystonic group. CONCLUSION: Dystonia in Machado-Joseph disease is frequent and often disabling, but may respond to levodopa. It is associated predominantly with structural abnormalities around the motor cortices and in the thalami.

A prospective, randomized, blinded assessment of multitarget thalamic and pallidal deep brain stimulation in a case of hemidystonia.

OBJECTIVE: Dystonia is increasingly being interpreted as a multi-nodal "network" disorder. We aimed to investigate multitarget DBS (pallidal and thalamic) versus each target alone in a prospective, randomized, blinded trial in a case of hemidystonia secondary to putaminal stroke. METHODS: DBS leads were implanted in the GPi and Vim/Vop and each stimulation combination (GPi, Vim/Vop, and both) was tested for three months in a single patient. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Short-Form 36 (SF-36) were completed at the end of each trial period. RESULTS: Multitarget (GPi+Vim/Vop) stimulation was clinically the most effective treatment and resulted in the most improvement in function and quality of life. The patient's hemidystonia improved by 25% as measured by the BFMDRS during the multitarget stimulation trial period and at the 6-month follow-up. The patient's quality of life improved by 86% and 59% during the multitarget stimulation trial period and at the 6 month follow-up respectively. CONCLUSION: Multitarget thalamic and pallidal DBS proved to be the most effective therapy for this patient with secondary hemidystonia due to a putaminal stroke. A single-lead approach may not be sufficient in neuromodulating a highly disorganized motor network seen in hemidystonia. Multitarget DBS should be further explored in post-stroke dystonia and may offer improved outcome in other forms of secondary dystonia with limited response to GPi DBS.

Pyruvate dehydrogenase deficiency presenting as isolated paroxysmal exercise induced dystonia successfully reversed with thiamine supplementation. Case report and mini-review.

BACKGROUND: Pyruvate dehydrogenase (PDH) deficiency is a disorder of energy metabolism with variable clinical presentations, ranging from severe infantile lactic acidosis to milder chronic neurological disorders. The spectrum of clinical manifestations is continuously expanding. METHODS AND RESULTS: We report on a 19-year-old intelligent female with PDH deficiency caused by a Leu216Ser mutation in PDHA1. She presented with recurrent hemidystonic attacks, triggered by prolonged walking or running, as the unique clinical manifestation that manifested since childhood. Laboratory workup and neuroimages were initially normal but bilateral globus pallidum involvement appeared later on brain MRI. Dystonia completely remitted after high doses of thiamine, remaining free of symptoms after 3 years of follow up. We reviewed the literature for similar observations. CONCLUSIONS: Dystonia precipitated by exercise may be the only symptom of a PDH deficiency, and the hallmark of the disease as high serum lactate or bilateral striatal necrosis at neuroimaging may be absent. A high index of suspicion and follow up is necessary for diagnosis. The clinical presentation of this patient meets the criteria for a Paroxysmal Exercise induced Dystonia, leading us to add this entity as another potential etiology for this type of paroxysmal dyskinesia, which is besides a treatable condition that responds to thiamine supplementation.

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.

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.

Novel nonpharmacologic perspectives for the treatment of task-specific focal hand dystonia.

NARRATIVE REVIEW: The pathophysiology of focal hand dystonia (FHD) has not yet been completely clarified. Although there is a loss of inhibition at multiple levels of the central nervous system, maladaptive plasticity of the cerebral cortex as well as impairments in sensory and motor representations have also been reported. All of these abnormalities can be viewed as an epiphenomenon of the primary--still unknown--abnormality underlying focal dystonia. The purpose of this review is to describe the underlying constructs of novel nonpharmacologic approaches for the treatment of FHD. Alternative or complementary approaches to botulinum toxin injections such as behavioral training strategies and brain stimulation techniques are reviewed. None of the proposed treatments appears to be definitive and applicable to all patients with FHD. Each treatment strategy elicited some benefit in a fraction of patients. The combination of more than one approach (retraining, immobilization, botulinum toxin, neuromodulation, etc.) could lead to a better control of FHD.

Dystonia associated with pontomesencephalic lesions.

Secondary dystonia is well known subsequent to lesions of the basal ganglia or the thalamus. There is evidence that brainstem lesions may also be associated with dystonia, but little is known about pathoanatomical correlations. Here, we report on a series of four patients with acquired dystonia following brainstem lesions. There were no basal ganglia or thalamic lesions. Three patients suffered tegmental pontomesencephalic hemorrhage and one patient diffuse axonal injury secondary to severe craniocerebral trauma. Dystonia developed with a delay of 1 to 14 months, at a mean delay of 6 months. The patients' mean age at onset was 33 years (range 4-56 years). All patients presented with hemidystonia combined with cervical dystonia, and two patients had craniofacial dystonia in addition. Three patients had postural or kinetic tremors. Dystonia was persistent in three patients, and improved gradually in one. There was little response to medical treatment. One patient with hemidystonia combined with cervical dystonia improved after thalamotomy. Overall, the phenomenology of secondary dystonia due to pontomesencephalic lesions is similar to that caused by basal ganglia or thalamic lesions. Structures involved include the pontomesencephalic tegmentum and the superior cerebellar peduncles. Such lesions are often associated with fatal outcome. While delayed occurrence of severe brainstem dystonia appears to be rare, it is possible that mild manifestations of dystonia might be ignored or not be emphasized in the presence of other disabling deficits.

Atypical dystonic shoulder movements following neuralgic amyotrophy.

Peripherally induced movement disorders are relatively rare. Here, we present 3 patients who suffered a lesion of the brachial plexus because of neuralgic amyotrophy and developed involuntary movements of their shoulder muscles. The nature of the involuntary movements, which did not easily comply with classic descriptions of hyperkinetic movement disorders, is probably best referred to as dystonia.

Hemidystonia secondary to thalamic hemorrhage treated with GPi stimulation.

There have been few reports on the surgical treatment of secondary hemidystonias, most of which are due to basal ganglia stroke or trauma. We present 2 patients with hemidystonia secondary to thalamic hemorrhage whom we successfully treated with unilateral globus pallidus internus (GPi) stimulation. Case 1 is a 56-year-old man with abnormal posturing and intolerable muscle contraction pain in the left arm. Case 2 is a 73-year-old woman who developed severe abnormal posturing in the right arm and gait disturbance due to hyperextension of the right leg. The dystonic symptoms of both patients were refractory to medication. Three months after the inception of high frequency GPi stimulation, the motor scores on the Burke-Fahn-Marsden Dystonia Rating Scale were improved by 49.2% and 34.3% in Cases 1 and 2, respectively. We suggest GPi stimulation as a possible alternative to treat secondary hemidystonia.

Structural abnormalities in the cerebellum and sensorimotor circuit in writer's cramp.

BACKGROUND: Structural abnormalities were detected in bilateral primary sensorimotor areas in writer's cramp. Evidence in other primary dystonia, including blepharospasm and cervical dystonia, suggest that structural abnormalities may be observed in other brain areas such as the cerebellum in writer's cramp. OBJECTIVE: To test the hypothesis that structural abnormalities are present along the sensorimotor and cerebellar circuits in patients with writer's cramp. METHODS: Using voxel-based morphometry, the authors compared the brain structure of 30 right-handed patients with writer's cramp with that of 30 healthy control subjects matched for gender, age, and handedness. RESULTS: Gray matter decrease was found in the hand area of the left primary sensorimotor cortex, bilateral thalamus, and cerebellum (height threshold p < 0.01, cluster significant at p < 0.05 corrected for multiple comparisons). CONCLUSIONS: These results demonstrate in writer's cramp the presence of structural abnormalities in brain structures interconnected within the sensorimotor network including the cerebellum and the cortical representation of the affected hand. These abnormalities may be related to the pathophysiology of writer's cramp, questioning the role of the cerebellum, or to maladaptive plasticity in a task-related dystonia.