Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region.

BACKGROUND: Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. OBJECTIVE: To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. METHODS: The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. RESULTS: Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). CONCLUSIONS: These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

ANTECEDENTES: A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. OBJETIVO: O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. MéTODOS: A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. RESULTADOS: Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00­98,00) e 20,60 ± 7,80 (13,00­32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). CONCLUSãO: Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Subthalamic Nucleus Deep Brain Stimulation Lessens Acquired Dystonia: Report of Two Patients and Systematic Review of Published Cases.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment of primary dystonia. Few studies have reported the effect of STN-DBS on secondary or acquired dystonia. METHODS: We reported 2 patients with acquired dystonia treated by subthalamic DBS and followed up for 24 months, besides providing a systematic review and meta-analysis of published series. RESULTS/CONCLUSIONS: Both patients had thalamic vascular or autoimmune lesions within the ventral and the pulvinar nuclei. A reduction of 67.2% on the Burke-Fahn-Marsden Dystonia Rating Scale and 90% improvement in disability scores were shown in the first patient, while the second patient showed a lower reduction in both dystonia symptoms (28.6%) and disability scores (44%). Both patients had a significant mean improvement in the quality of life (62.5% in the first and 57.9% in the second) and were free of drugs postoperatively. A systematic review showed a mean follow-up of 13 months in 19 patients, including our 2 patients. The review showed a significant Burke-Fahn-Marsden Dystonia Scale (BFMDRS) score median reduction of 19 points (52.4%; confidence interval [CI]: 11.0-25.0) and a significant median reduction of 6 points in disability scores (44.5%; 95% CI: 4.0-14.0), thereby improving quality of life. Age at surgery was inversely correlated with postoperative improvement (r = 0.63; p = 0.039). Hemidystonia had a nonsignificant better improvement than generalized dystonia (55.3 vs. 43.5%; p = 0.4433). No association between etiology and postoperative improvement and no serious complications were found. Although few data reported so far, subthalamic DBS is likely efficient for acquired dystonia.

Rescue Subthalamic Deep Brain Stimulation for Refractory Meige Syndrome.

Meige syndrome is a segmental form of dystonia. It is a disabling disease, especially when refractory to treatment with botulinum toxin. A well-established therapeutic option is deep brain stimulation (DBS), and the target in bilateral globus pallidus internus (GPi DBS) demonstrated satisfactory short- and long-term efficacy. However, some patients present minor or suboptimal responses after GPi DBS, and in those cases, rescue DBS may be appropriate. The present case illustrates a good outcome after subthalamic nucleus (STN) and not after GPi DBS (considering that both were well positioned and had adequate programming). The larger dimension of the GPi and its somatotopic organization, with the stimulation outside the "face region," could explain our outcomes.

Abnormal sensory thresholds of dystonic patients are not affected by deep brain stimulation.

BACKGROUND: Unlike motor symptoms, the effects of deep brain stimulation (DBS) on non-motor symptoms associated with dystonia remain unknown. METHODS: The objective of this study was to assess the effects of DBS on evoked experimental pain and cutaneous sensory thresholds in a crossover, double-blind on/off study and compare these results with those of healthy volunteers (HV). RESULTS: Sixteen patients with idiopathic dystonia (39.9 ± 13 years old, n = 14 generalized) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing and assessment using a pain top-down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were compared in on and off stimulation. The patients' results were compared to age- and sex-matched HV. Descending pain modulation CPM responses in dystonic patients (on-DBS, 11.8 ± 40.7; off-DBS, 1.8 ± 22.1) was abnormally low (defective) compared to HV (-15.6 ± 23.5, respectively p = .006 and p = .042). Cold pain threshold and cold hyperalgesia were 54.8% and 95.7% higher in dystonic patients compared to HV. On-DBS CPM correlated with higher Burke-Fahn-Marsden disability score (r = 0.598; p = .014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was abnormal in dystonic patients and tended to be aggravated by DBS. CONCLUSION: The analgesic effects after DBS do not seem to depend on short-duration changes in cutaneous sensory thresholds in dystonic patients and may be related to changes in the central processing of nociceptive inputs.

Non-invasive brain stimulation and kinesiotherapy for treatment of focal dystonia: Instrumental analysis of three cases.

Dystonia is a disabling movement disorder characterized by co-contraction of antagonist and agonist muscles, leading to abnormal sustained postures and impaired motor control. Cervical Dystonia (CD) and Hand Focal Dystonia (HFD) have been the most common forms of focal dystonia (FD). Do Non-Invasive Brain Neuromodulation (NIBS) such as Transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) modulate the excitability of the connections between the motor cortical areas and may represent a therapeutic alternative for focal dystonia? Herein, we reported three cases of focal dystonia, two of them with cervical dystonia (CD) and one with hand focal dystonia (HFD), treated with NIBS combined to kinesiotherapy. The patients were daily submitted to 15 sessions of NIBS combined simultaneously with kinesiotherapy. CD patients were treated with tDCS (2 mA, 20 min, over the primary motor cortex), and HFD patient with rTMS (1 Hz, 1200 pulses, 80% of resting motor threshold, over the premotor cortex). For the CD patient's assessment, the Modified Toronto Scale for Cervical Dystonia Assessment (MTS), quiet balance test, and visual postural assessment were applied to observe the therapeutic effects. Quality handwriting analysis, tremor acceleration amplitudes, and the Wrinter's Cramp Rating Scale (WCRS) were used to assess the NIBS effect on HFD symptoms. Patients were evaluated before (pretest), immediately after (posttest), and three months after treatment (retention). NIBS associated with kinesiotherapy produced a long-term improvement of dystonia symptoms in all three patients. rTMS and tDCS associated with kinesiotherapy showed to be useful and safe to relief the dystonia symptoms in individuals with different types of focal dystonia with distinct functional disorders. SIGNIFICANCE: The combined use of these intervention strategies seems to optimize and anticipate satisfactory clinical results in these neurological conditions, characterized by its difficult clinical management.

Safety of transcranial direct current stimulation in a patient with deep brain stimulation electrodes.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated in movement disorders, making it a therapeutic alternative in clinical settings. However, there is still no consensus on the most appropriate treatment protocols in most cases, and the presence of deep brain stimulation (DBS) electrodes has been regarded as a contraindication to the procedure. We recently studied the effects of cerebellar tDCS on a female patient already undergoing subthalamic nucleus deep brain stimulation (STN-DBS) for generalized dystonia. She also presented with chronic pain and depression. With STN-DBS, there was improvement of dystonia, and botulinum toxin significantly reduced pain. However, depressive symptoms were worse after STN-DBS surgery. METHODS: Neuromodulation with 2 mA anodal cerebellar tDCS was initiated, targeting both hemispheres in each daily 30 minute session: 15 minutes of left cerebellar stimulation followed by 15 minutes of right cerebellar stimulation. The DBS electrodes were in place and functional, but the current was turned off during tDCS. RESULTS: Although our goal was to improve dystonic movements, after 10 tDCS sessions there was also improvement in mood with normalization of Beck Depression Inventory scores. There were no complications in spite of the implanted STN-DBS leads. CONCLUSION: Our results indicate that tDCS is safe in patients with DBS electrodes and may be an effective add-on neuromodulatory tool in the treatment of potential DBS partial efficacy in patients with movement disorders.

Safety of transcranial direct current stimulation in a patient with deep brain stimulation electrodes / Segurança da estimulação transcraniana por corrente contínua em uma paciente com implante de eletrodos de estimulação cerebral profunda

ABSTRACT Background: Transcranial direct current stimulation (tDCS) has been investigated in movement disorders, making it a therapeutic alternative in clinical settings. However, there is still no consensus on the most appropriate treatment protocols in most cases, and the presence of deep brain stimulation (DBS) electrodes has been regarded as a contraindication to the procedure. We recently studied the effects of cerebellar tDCS on a female patient already undergoing subthalamic nucleus deep brain stimulation (STN-DBS) for generalized dystonia. She also presented with chronic pain and depression. With STN-DBS, there was improvement of dystonia, and botulinum toxin significantly reduced pain. However, depressive symptoms were worse after STN-DBS surgery. Methods: Neuromodulation with 2 mA anodal cerebellar tDCS was initiated, targeting both hemispheres in each daily 30 minute session: 15 minutes of left cerebellar stimulation followed by 15 minutes of right cerebellar stimulation. The DBS electrodes were in place and functional, but the current was turned off during tDCS. Results: Although our goal was to improve dystonic movements, after 10 tDCS sessions there was also improvement in mood with normalization of Beck Depression Inventory scores. There were no complications in spite of the implanted STN-DBS leads. Conclusion: Our results indicate that tDCS is safe in patients with DBS electrodes and may be an effective add-on neuromodulatory tool in the treatment of potential DBS partial efficacy in patients with movement disorders.

RESUMO Descrição: A estimulação transcraniana por corrente contínua (ETCC) tem sido investigada nos distúrbios de movimento, tornando-a uma alternativa terapêutica no contexto clínico. Contudo, não há consenso quanto aos protocolos mais apropriados na maioria dos casos e a presença de eletrodos de estimulação cerebral profunda (ECP) é geralmente considerada uma contraindicação. Recentemente, estudamos os efeitos da ETCC cerebelar em uma paciente do sexo feminino com implante de eletrodos de estimulação cerebral profunda (ECP) para distonia generalizada. Ela também apresentava dor crônica e depressão. A ETCC foi realizada dois anos após o implante de eletrodos de ECP. Com a ECP houve melhora da distonia e a toxina botulínica reduziu a dor. Contudo, os sintomas depressivos pioraram após a cirurgia de ECP. Métodos: Foi proposta ETCC cerebelar anódica de 2mA, sobre os dois hemisférios em cada sessão de 30min: 15 min de ETCC cerebelar esquerda seguida de 15min de ETCC cerebelar direita. Resultados: Embora o nosso objetivo tenha sido melhorar os movimentos distônicos, após 10 sessões de ETCC houve melhora também do humor da paciente. Não houve nenhuma complicação, apesar da presença de eletrodos de ECP. Conclusão: Nossos resultados apontam para a segurança da tDCS e sua aplicação potencial e efetiva como ferramenta neuromodulatória adicional no tratamento de possíveis sintomas persistentes após a ECP em pacientes com distúrbios de movimento.

Unilateral thalamic and pallidal deep brain stimulation for idiopathic hemidystonia: results of individual and combined stimulations. Case report.

Pallidal stimulation has been the usual surgical treatment for dystonia in the last decades. The continuous investigation of the physiopathology and the motor pathways involved leads to the search for complementary targets to improve results. The authors present the case of a 37-year-old woman who had suffered from idiopathic hemidystonia with hyperkinetic and hypokinetic movements for 11 years, and who was treated with deep brain stimulation. A brief literature review is also provided. The globus pallidus internus and the ventral intermediate/ventral oral posterior complex of the thalamus were stimulated separately and simultaneously for 3 months and compared using the Burke-Fahn-Marsden Dystonia Rating Scale and the Global Dystonia Severity Rating Scale, with a 3.5-year follow-up. The synergism of multiple-target stimulation resulted in a complete improvement of the mixed dystonic symptoms.

Distonía focal en músicos / FOCAL DYSTONIA IN MUSICIANS

The aim of this report was to describe the Focal dystonia in Musicians. Musician´s dystonia is a disorder characterized by abnormal movements, with excessive activation of muscular antagonists or co-contraction of antagonist muscles that are not required for a specific movement. Belongs to the group of occupational dystonias ; is a specific disorder of a determinated task in musicians, that include the absence of voluntary control of movements detailed determinated in the ejecution of an instrument, and manifiests itself by the deteriorization of his dexterity in the ejecution. Dystonia, including all his forms, is the third more frequent pathology of abnormal movements, after Parkinson´s disease and the essential trembling. Musician´s dystonia is a task-specific movement that manifiests itself as a loss of voluntary motor control in extensively trained movements. Approximately 1 % of all professional musicians develop musician´s dystrofia, and in many cases the disorder terminates the careers of affected musicians. Several theories have been referred related to the etiology. The aim of this report was to present the author´s casuistic of Focal dystonia in musicians in Argentina, considering the type of instrument, which kind of music is ejecuted ­classic or popular- and to inform the treatment proposed and the results obtained.

Combinación de tres técnicas en el reentrenamiento de un músico con distonía focal: estudio de un caso / The use of three combined techniques in the retraining of a mucisian with focal dystonia: a case study

La distonía resulta de una co-contracción sostenida de músculos agonistas y antagonistas que puede causar torsión, movimientos involuntarios o posturas anormales que interfieren con el control voluntario de la mano, u otro grupo muscular, involucrados en una determinada acción; por ejemplo, tocar un instrumento, o escribir.El presente estudio descriptivo, de caso único, buscó probar la efectividad de un tratamiento que combinó tres técnicas (técnica del umbral, imaginería, y relajación por neurofeedback) en el reentrenamiento de un concertista profesional con distonía focal. Según evaluación por jueces, los resultados después de dos semanas de tratamiento, no fueron concluyentes. Sin embargo, el reporte experiencial del propio músico dio cuenta de una clara mejoría. Ante la carencia de un método efectivo para larehabilitación demúsicos con distonía focal, la relevancia del presente estudio consistió en identificar y combinar técnicas específicas que pueden contribuir a ese propósito. En estudios futuros, sería de interés probar el efecto del mismo tratamiento,pero más prolongado; o el efecto de la incorporación de las técnicas en sucesión progresiva, iniciando siempre con la relajación por neurofeedback.

Focal dystonia results from a sustained simultaneous co-contraction of agonists and antagonists muscle fibers which can cause twisting, involuntary movements or abnormal postures that interfere with voluntary control of the hand, arm, mouth, or other muscle groups involved in a given action; for example, playing an instrument, or hand writing. This descriptive, single case study, sought to explore the effectiveness of a treatment that combined three procedures: the threshold technique, imagery, and neurofeedback induced relaxation, in retraining of a professional cello player with focal dystonia. After two weeks of treatment, experts judged the results inconclusive; however, the report from the actual patient accounted for a note worthy recovery over time. In the absence of an effective method to rehabilitate musicians with focal dystonia, the relevance of this study resided on thepossibility of identifying and combining specific techniques that could be effective. Future studies might want to explore these same or different techniques, but perhaps for a longer period of time.

Musicians and Dystonia: Is Sleep Part of the Problem?

We would like to congratulate Lee and Altenmüller for their recent study showing important findings about the characterization of a task-specific dystonia in a young professional percussionist. The authors presented in an elegant way the EMG investigation and treatment approach and the possible differential diagnoses, raising an important question about the need for physicians' awareness of this condition when considering musicians' health. We would like to add a new point of view in order to contribute with this discussion and provide critical thinking for a multidisciplinary approach to this type of dystonia, which may affect many individuals and result in severe compromise of musical technical performance. One factor that could also be potentially associated with the percussion-related dystonia is sleep.

Bilateral subthalamic nucleus stimulation for generalized dystonia after bilateral pallidotomy.

BACKGROUND: Thalamotomies and pallidotomies were commonly performed before the deep brain stimulation (DBS) era. Although ablative procedures can lead to significant dystonia improvement, longer periods of analysis reveal disease progression and functional deterioration. Today, the same patients seek additional treatment possibilities. METHODS: Four patients with generalized dystonia who previously had undergone bilateral pallidotomy came to our service seeking additional treatment because of dystonic symptom progression. Bilateral subthalamic nucleus DBS (B-STN-DBS) was the treatment of choice. The patients were evaluated with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Dystonia Rating Scale (UDRS) before and 2 years after surgery. RESULTS: All patients showed significant functional improvement, averaging 65.3% in BFMDRS (P = .014) and 69.2% in UDRS (P = .025). CONCLUSIONS: These results suggest that B-STN-DBS may be an interesting treatment option for generalized dystonia, even for patients who have already undergone bilateral pallidotomy.

Focal dystonia in musicians.

INTRODUCTION: A special group of focal dystonia is that known as occupational, which include dystonic disorders triggered by repetitive motor activity, closely associated with the professional activity of a specific task that the affected person performs. In this sense, musicians are a population particularly vulnerable to this disorder, which is presented during the execution of highly trained movements. OBJECTIVE: This article reviews the pathophysiology of focal dystonia and its therapeutic implications. DEVELOPMENT: The pathophysiological basis of focal dystonia in the musician is still not well established. However, due to the contribution of neurophysiological studies and functional neuroimaging, there is growing evidence of anomalies in the processing of sensory information, sensory-motor integration, cortical and subcortical inhibitory processes, which underline this disease. Clinically, it is characterised by the appearance of involuntary muscle contractions, and is associated with loss of motor control while practicing music. It is a gradual appearance and sometimes there may be a history of musculoskeletal injuries or non-physiological postures preceding the appearance of the symptoms. The neurological examination is usually normal, although subtle dystonic postures can develop spontaneously or with movements that involve the affected segments. The dystonia remains focal and is not generalised. CONCLUSIONS: Treatment is based on using multiple strategies for the management of the dystonia, with variable results. Although a specific therapy has not been defined, there are general principles that are combined in each situation looking for results. This includes, among others, pharmacological interventions, management with botulinum toxin, and sensory re-training techniques.

Pallidal surgery for the treatment of primary generalized dystonia: long-term follow-up.

OBJECTIVE: To describe the results and long-term follow-up after functional surgery of the internal segment of the globus pallidus (GPi) in 10 patients with primary generalized dystonia. PATIENTS AND METHODS: Nine of the 10 patients were positive for the DYT1 gene mutation. Bilateral deep brain stimulation (DBS) of the GPi was performed in three cases, bilateral pallidotomy in two, and combined surgery (unilateral GPi lesion with contralateral stimulation) in the remaining five. All patients were evaluated with the Burke-Fahn-Marsden dystonia scale (BFMDS) before, immediately after surgery, at 3 weeks, 3 and 6 months and then yearly. Follow up time ranged from 15 to 105 months (mean: 66.1 months) with six patients having more than 6 years follow up. RESULTS: All patients improved after surgery. All patients with unilateral or bilateral DBS experienced an immediate improvement before starting stimulation. The magnitude of this initial micro lesion effect did not predict the magnitude of the long-term benefit of DBS. The mean decrease in the in the BFMDS was 34%, 55%, and 65% in the movement scale; and 32%, 48%, and 49% in the disability scale for patients with bilateral pallidal DBS, combined unilateral DBS and contralateral pallidotomy, and bilateral pallidotomy, respectively. Worsening of dystonia after a plateau of sustained benefit was observed in three patients. Two patients required multiple pallidal surgeries. Adverse events included: permanent anarthria (1), misplacement of the electrode requiring further surgery (2), scalp infection (1), and hardware related problems (3). CONCLUSIONS: This long-term follow up study confirms the beneficial effect of pallidal DBS or pallidotomy in primary generalized dystonia. In addition, our results extent previous observations by showing that, in these patients, (1) the microlesion effect of DBS is not predictive of long-term benefit; (2) combined DBS with contralateral pallidotomy appears to be more effective than bilateral pallidal DBS; and (3) dystonia can reappear after an initial good response during long term follow up.