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.
Deep Brain Stimulation , Dystonia , Dystonic Disorders , Subthalamic Nucleus , Humans , Dystonia/therapy , Dystonia/complications , Subthalamic Nucleus/physiology , Subthalamic Nucleus/surgery , Globus Pallidus , Treatment Outcome , Severity of Illness Index , Dystonic Disorders/therapy , Dystonic Disorders/etiology
Abstract 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.
Resumo 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 (62,00-98,00) e 20,60 ± 7,80 (13,00-32,00), 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.
Introduction: Deep brain stimulation (DBS) is a treatment option for refractory dystonia's motor symptoms, while its non-motor symptoms (NMS) have been less systematically assessed. We aimed to describe the effects of DBS on NMS in refractory generalized inherited/idiopathic dystonia prospectively. Methods: We evaluated patients before and 1 year after DBS surgery and applied the following scales: Burke-Fahn-Marsden Rating Scale (BFMRS), NMS Scale for Parkinson's Disease (NMSS-PD), Parkinson's Disease Questionnaire-8, short-form Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI), and short-form McGill Pain Questionnaire (MPQ). Results: Eleven patients (38.35 ± 11.30 years) underwent surgery, all with generalized dystonia. Motor BFMRS subscore was 64.36 ± 22.94 at baseline and 33.55 ± 17.44 1 year after DBS surgery (47.9% improvement, p = 0.003). NMSS-PD had a significant change 12 months after DBS, from 70.91 ± 59.07 to 37.18 ± 55.05 (47.5% improvement, p = 0.013). NMS changes were mainly driven by changes in the gastrointestinal (p = 0.041) and miscellaneous domains (p = 0.012). Seven patients reported chronic pain before DBS and four after it. BPI's severity and interference scores were 4.61 ± 2.84 and 4.12 ± 2.67, respectively, before surgery, and 2.79 ± 2.31 (0.00-6.25) and 1.12 ± 1.32 (0.00-3.00) after, reflecting a significant improvement (p = 0.043 and p = 0.028, respectively). NPSI score was 15.29 ± 13.94 before, while it was reduced to 2.29 ± 2.98 afterward (p = 0.028). MPQ's total score was 9.00 ± 3.32 before DBS, achieving 2.71 ± 2.93 after (p = 0.028). Conclusions: DBS improves NMS in generalized inherited/idiopathic dystonia, including chronic pain.
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.
Deep Brain Stimulation , Dystonia , Dystonic Disorders , Adult , Cross-Over Studies , Double-Blind Method , Dystonia/therapy , Dystonic Disorders/therapy , Globus Pallidus , Humans , Middle Aged , Sensory Thresholds , Treatment Outcome
