Brain Stimulation For Cervical Dystonia Research Articles

Directional deep brain stimulation for cervical dystonia: Outcomes, challenges and future directions

Directional deep brain stimulation for cervical dystonia: Outcomes, challenges and future directions

Bilateral globus pallidus internus (GPi) deep brain stimulation for cervical dystonia: Effects on motor and non-motor symptoms within 5 years follow

Cervical Dystonia ("CD") is a movement disorder characterised by sustained muscle contractions in the neck, causing involuntary posturing. Deep brain stimulation ("DBS") of the globus pallidal internus (GPi) is advanced treatment for pharmaco-refractory patients. As CD is a rare disease, cohort studies are often limited to patients of heterogenous disease profile, small sample size or short follow-up. This study firstly aimed to measure the efficacy of GPi-DBS on motor and non-motor symptoms of CD. A secondary aim was to evaluate if clinical factors - such as age, disease duration and baseline disease severity - influence variability of motor outcomes. 37 idiopathic CD patients were recruited from movement disorders clinics at The Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and 1year, 3years and 5years post-operatively with the following clinical scales: Toronto Western Spasmodic Torticollis Rating Scale ("TWSTRS"), Hospital Anxiety and Depression Scale and EuroQuol-5D. GPI-DBS significantly improved overall TWSTRS scores by 57% from baseline to 5Y FU (p<0.001). It also significantly improved TWSTRS severity, disability, and pain sub-scores by 72%, 59% and 46% respectively. We did not find a significant improvement in mood or quality of life scores at 5years. Similarly, clinical factors at baseline did not correlate with variability in motor outcome. We concluded that GPi-DBS is an effective treatment for motor symptoms and pain in CD. There was limited effect on mood and QoL, and no clinical predictive factors of outcome were identified.

Does Pallidal Physiology Determine the Success of Unilateral Deep Brain Stimulation in Cervical Dystonia?

Pallidal deep brain stimulation is a well-known surgical treatment for cervical dystonia. The resolution of dystonia typically requires bilateral pallidal stimulation, but in some instances, unilateral stimulation has been successful. In such instances, generally, the stimulated hemisphere was contralateral to the dystonic sternocleidomastoid, but rarely it was ipsilateral. We sought for the physiological features that determine the basis for success and laterality of deep brain stimulation for cervical dystonia with prominent torticollis. We found that pallidal physiology such as high burst to tonic ratio and significant interhemispheric differences in the neuronal firing rate and regularity are critical determinants of successful treatment with unilateral deep brain stimulation. We also found that higher lateralized differences in pallidal physiological parameters predict more robust improvement. In three out of four patients, the stimulation of the hemisphere ipsilateral to the dystonic sternocleidomastoid muscle was effective. These patients did not have any structural brain abnormalities on clinically available imaging studies. One patient responded to the unilateral deep brain stimulation in the hemisphere contralateral to the dystonic sternocleidomastoid. This patient had a structural putamen lesion on brain MRI. These results provide objective parameters determining the success of pallidal deep brain stimulation for treatment of cervical dystonia. The results also depict differences in the pallidal physiology in patients where ipsilateral versus contralateral deep brain stimulation was effective.

Neural Correlates of Optimal Deep Brain Stimulation for Cervical Dystonia.

A total of 15 individuals with cervical dystonia and good outcome after pallidal deep brain stimulation underwent resting-state functional magnetic resonance imaging under three conditions: stimulation using a priori clinically determined optimal settings (ON-Op), non-optimal settings (ON-NOp), and stimulation off (OFF). ON-Op > OFF and ON-Op > ON-NOp were both associated with significant deactivation within sensorimotor cortex (changes not seen with ON-NOp > OFF). Brain responses to stimulation were related to individual long-term clinical improvement (R = 0.73, R2 = 0.53, p = 0.001). The relationship was consistent when this model included four additional patients with generalized or truncal dystonia. These findings highlight the potential for immediate imaging-based biomarkers of clinical efficacy. ANN NEUROL 2022;92:418-424.

Vim-Thalamic Deep Brain Stimulation for Cervical Dystonia and Upper-Limb Tremor: Quantification by Markerless-3D Kinematics and Accelerometry.

Background:Deep Brain Stimulation (DBS) for dystonia is usually targeted to the globus pallidus internus (GPi), though stimulation of the ventral-intermediate nucleus of the thalamus (Vim) can be an effective treatment for phasic components of dystonia including tremor. We report on a patient who developed a syndrome of bilateral upper limb postural and action tremor and progressive cervical dystonia with both phasic and tonic components which were responsive to Vim DBS. We characterize and quantify this effect using markerless-3D-kinematics combined with accelerometry.Methods:Stereo videography was used to record our subject in 3D. The DeepBehavior toolbox was applied to obtain timeseries of joint position for kinematic analysis [1]. Accelerometry was performed simultaneously for comparison with prior literature.Results:Bilateral Vim DBS improved both dystonic tremor magnitude and tonic posturing. DBS of the hemisphere contralateral to the direction of dystonic head rotation (left Vim) had greater efficacy. Assessment of tremor magnitude by 3D-kinematics was concordant with accelerometry and was able to quantify tonic dystonic posturing.Discussion:In this case, Vim DBS treated both cervical dystonic tremor and dystonic posturing. Markerless-3D-kinematics should be further studied as a method of quantifying and characterizing tremor and dystonia.

Pallidal neuron activity determines responsiveness to deep brain stimulation in cervical dystonia

In patients with cervical dystonia we sought for the differences in neuronal behavior of pallidal regions where deep brain stimulation resulted in favorable therapeutic response compared to those where the response was absent. We compared single-unit activity of 564 neurons recorded from deep brain stimulation sensitive and non-sensitive regions in 17 cervical dystonia patients. Globus pallidus internus regions responsive to the deep brain stimulation had lower firing rates and bursting compared to non-responsive areas. The differences were robust in locations where neuronal responses correlated with neck movements. Per the effects of deep brain stimulation, the pallidal regions were classified in weak, intermediate, and excellent responsive. Pallidal regions with weak response to deep brain stimulation had fewer burst neurons and higher firing rate compared to neurons in areas with excellent response. The burst index was significantly decreased in excellent response regions. There was a significant decrease in the alpha band oscillation score but a substantial increase in the gamma band in excellent response neurons. The pallidal region that would be responsive to deep brain stimulation has distinct physiology compared to the non-responsive region. These results provide novel insights into globus pallidus interna neurons' physiology in cervical dystonia.

Embedded adaptive deep brain stimulation for cervical dystonia controlled by motor cortex theta oscillations

Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity. We confirmed the presence of theta (3-7Hz) oscillatory activity, which was coherent throughout the cortico-subthalamic circuit and specifically suppressed by high-frequency stimulation. Stimulation also reduced the duration, rate and height of theta bursts. These findings motivated a proof-of-principle trial of a new form of adaptive deep brain stimulation - triggered by theta-burst activity recorded from the motor cortex. This facilitated increased peak stimulation amplitudes without induction of dyskinesias and demonstrated improved blinded clinical ratings compared to continuous DBS, despite reduced total electrical energy delivered. These results further strengthen the pathophysiological role of low frequency (theta) oscillations in dystonia and demonstrate the potential for novel adaptive stimulation strategies linked to cortico-basal theta bursts.

Pallido-putaminal connectivity predicts outcomes of deep brain stimulation for cervical dystonia.

Cervical dystonia is a non-degenerative movement disorder characterized by dysfunction of both motor and sensory cortico-basal ganglia networks. Deep brain stimulation targeted to the internal pallidum is an established treatment, but its specific mechanisms remain elusive, and response to therapy is highly variable. Modulation of key dysfunctional networks via axonal connections is likely important.Fifteen patients underwent preoperative diffusion-MRI acquisitions and then progressed to bilateral deep brain stimulation targeting the posterior internal pallidum. Severity of disease was assessed preoperatively and later at follow-up. Scans were used to generate tractography-derived connectivity estimates between the bilateral regions of stimulation and relevant structures.Connectivity to the putamen correlated with clinical improvement, and a series of cortical connectivity-based putaminal parcellations identified the primary motor putamen as the key node (r = 0.70, P = 0.004). A regression model with this connectivity and electrode coordinates explained 68% of the variance in outcomes (r = 0.83, P = 0.001), with both as significant explanatory variables.We conclude that modulation of the primary motor putamen–posterior internal pallidum limb of the cortico-basal ganglia loop is characteristic of successful deep brain stimulation treatment of cervical dystonia. Preoperative diffusion imaging contains additional information that predicts outcomes, implying utility for patient selection and/or individualized targeting.

Improvement of head and neck range of motion induced by chronic pallidal deep brain stimulation for cervical dystonia.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an accepted treatment for severe cervical dystonia (CD). Assessment of therapeutic efficacy of DBS mostly focused on head position at rest but hardly on limitations of head and neck mobility, which represent a functionally important impairment in CD. We aimed to determine prospectively head and neck range of motion (ROM) preoperatively and during chronic bilateral GPi DBS in a series of 11 patients with idiopathic CD or segmental dystonia with prominent CD using a computerized motion analysis. Maximum horizontal rotation of the head in the transverse plane and lateral inclination in the frontal plane were measured preoperatively and at a median of 7months of chronic GPi DBS, using an ultrasound-based three-dimensional measuring system combined with surface electromyography of cervical muscles. Horizontal rotation of the head increased from 78.8° ± 31.5° (mean ± SD) preoperatively to 100.7° ± 24.7° with GPi DBS (p < 0.01), thereby improvement of head rotation to the anti-dystonic side (+ 14,2° ± 12,2°) was greater than to the pro-dystonic side (+ 7,8° ± 9,2°; p < 0.05). Movement-related agonistic-antagonistic EMG modulation during head rotation was enhanced with GPi DBS in both sternocleidomastoid (modulation index (MI) 35.8% ± 26.7% preoperatively vs. 67.3% ± 16.9% with GPi DBS, p < 0.01), and splenius capitis muscles (MI 1.9% ± 24.5% preoperatively vs. 44.8% ± 11.6% with GPi DBS, p < 0.01). Chronic bilateral GPi DBS significantly improves head ROM in CD, likely due to enhanced agonist-antagonist EMG activity with reduced co-contraction. Computerized motion analysis provides an objective measurement to assess the improvement of head and neck mobility in CD.

Predictive factors for outcome of pallidal deep brain stimulation in cervical dystonia

Primary cervical dystonia (CD) is characterized by abnormal contractions of neck muscles. Globus pallidus internus deep brain stimulation (GPi-DBS) is recognized as an effective therapy for patients with refractory CD, but the prognostic factors need further research. Our study investigated the predictive factors of clinical outcomes in CD patients who underwent GPi-DBS. Patients (n = 23) who underwent GPi-DBS at Chinese PLA General Hospital from March 2012 to April 2018 were included in our analysis. Their scores of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui were acquired at baseline and at the last follow-up visit. Percent improvement in these scores were compared between the categorical variables. Correlations between outcomes and continuous demographic and clinical variables were calculated. Patients showed significant improvement in TWSTRS total (55.71 %), severity (48.75 %), disability (57.05 %), pain (63.67 %) scores and total Tsui score (46.07 %, all P ﹤0.001). Follow-up duration was positively correlated with percent improvement in TWSTRS total (rho = 0.594, P = 0.003), severity (rho = 0.581, P = 0.004) and disability (rho = 0.470, P = 0.023) scores. No significant differences in the outcomes were found between any pair of the categorical variables. Follow-up duration was the only independent factor correlated to the outcomes of GPi-DBS for CD patients. However, follow-up duration is an indefinite factor prior to surgery, thus further studies are needed before the final conclusions of prognostic factors are established.

Motor Cortical Plasticity Relates to Symptom Severity and Clinical Benefit From Deep Brain Stimulation in Cervical Dystonia

To investigate the relationship between motor cortical plasticity, intracortical inhibition, and clinical response to pallidal deep brain stimulation (DBS) in patients with cervical dystonia (CD). Response to paired associative stimulation (PAS) and short interval intracortical inhibition (SICI) were assessed in patients with CD before and after three months of DBS and correlated with severity of dystonic symptoms as assessed by Toronto-Western-Spasmodic Torticollis Rating Scale (TWSTRS) severity score. Relations of electrophysiological parameters with clinical improvement were explored with correlation analysis. Patients with higher levels of plasticity before surgery showed higher symptom severity (R = 0.83, p = 0.008) but had also the larger clinical benefit following DBS (R = 0.88, p = 0.003). This correlation was independent from preoperative (preOP) TWSTRS motor score as revealed by partial correlation analysis. Intracortical inhibition was not altered in CD and not related to clinical outcome after DBS. Our findings indicate that a high degree of preOP plasticity is associated with higher symptom severity, underlining the role of abnormal plasticity in the pathophysiology of dystonia. At the same time individual degree of plasticity may drive reestablishment of normal motor programs, leading to better clinical outcome with DBS. The latter suggests that individual PAS-response may indicate the susceptibility for neuromodulatory processes as an important factor for clinical DBS effects. It might therefore serve as a neurophysiological marker to predict outcome and guide patient selection.

Electrode extension fracture in deep brain stimulation for cervical dystonia: case report and literature review.

La estimulación cerebral profunda (ECP) es utilizada como un método eficaz, adaptable y reversible para el tratamiento de diversas condiciones neurológicas. A pesar de su concepto mínimamente invasivo, estos procedimientos no se encuentran exentos de complicaciones. En este trabajo presentamos el caso de un paciente portador distonía cervical secundaria al uso de neurolépticos asociada a trastorno obsesivo compulsivo, quien recibió implante de electrodos cerebrales profundos en ambos globos pálidos internos. Evolucionó con brusca reaparición de los síntomas por la rotura de los cables extensores en dos oportunidades. Describimos la resolución del caso mediante la colocación de extensores expandibles y la reubicación del generador en el espacio interescapular, así como una revisión actualizada de la literatura.

EPV 7. PAS-induced plasticity relates to symptom severity and benefit from deep brain stimulation in cervical dystonia

Deep brain stimulation (DBS) of the globus pallidus internus (GPi-DBS) is an established treatment for patients with medication-refractory cervical dystonia ( Volkmann et al., 2014 ), but individual response to DBS is highly variable and predictive factors for the clinical outcome have not been identified yet. Cortical plasticity induced by paired associative stimulation is modulated by DBS in patients with generalized dystonia and has been related to the stability of the DBS effect after switching off stimulation ( Ruge et al., 2011 ). Here, we investigated DBS-induced changes in cortical plasticity over time in patients with cervical dystonia and explored whether differences in response to DBS might be explained by individual variability of neurophysiological markers of plasticity. Methods PAS25 was applied using transcranial magnetic stimulation (TMS) to investigate cortical plasticity in 9 patients with cervical dystonia preoperatively and 3 months after activation of pallidal DBS. PAS response was calculated as mean MEP response at timepoints 0, 15 and 30 min after PAS and expressed as percentage of pre-PAS MEP. Clinical changes were assessed using the TWSTRS severity subscore. Spearman’s correlation coefficient was calculated to evaluate the relationship between neurophysiological measures and clinical scores. Three out of 9 patients were lost to neurophysiological follow up due to intra- and postoperative complications or incompatibility of the neurostimulator for TMS. Results Mean TWSTRS pre OP (17.4 ± 2.1) was reduced with pallidal DBS by 49.5% (post OP TWSTRS: 8.8 ± 2.8; Wilcoxon signed rank test: p = 0.0078; n = 9). Mean PAS response post OP (125.0% ±24.7; n = 6) was smaller compared to pre OP (165.1 ± 26.3) but did not reach significance. Individual courses of both clinical and neurophysiological changes were highly variable across subjects. Preoperative TWSTRS correlated significantly with pre-operative PAS-response ( n = 9; R = 0.78; p = 0.018). In the 6 patients that could be followed up by TMS, the decrease in PAS-response correlated with the decrease in TWSTRS score absolute values at timepoint 6 months after DBS ( n = 6; p = 0.028; R = 0.89). Conclusions Maladaptive plasticity has been discussed to play a major role in the pathophysiology of dystonia ( Quartarone et al., 2003 ). On the other hand, increased cortical plasticity might also imply a greater capability for neuromodulation ( Ruge et al., 2011 ). We found a significant correlation between symptom severity and PAS-induced cortical plasticity as well as a relation of both clinical benefit and neurophysiological change during DBS in patients with cervical dystonia. The individual susceptibility for plastic changes may partially explain the broad range of clinical benefit from DBS in dystonia. Furthermore, the correlation of plasticity with clinical benefit might indicate PAS-induced plasticity as a potential predictive factor for DBS outcome that should be explored in larger studies.

Postoperative MRI localisation of electrodes and clinical efficacy of pallidal deep brain stimulation in cervical dystonia

IntroductionPallidal deep brain stimulation (DBS) has been shown to be effective in cervical dystonia (CD) with an improvement of about 50–60% in the Toronto Western Spasmodic Torticollis Rating (TWSTR) Scale....

Should We Consider Deep Brain Stimulation for Cervical Dystonia

A growing number of cases of cervical dystonia resistant to medications and botulinum toxin are presenting to clinicians for advanced management. This study was a randomized, sham-controlled, manufacturer-funded trial of bilateral globus pallidus deep brain stimulation (DBS) in this population (an investigational use not specifically approved by the FDA). Participants had to have at least a 3-year disease duration and a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score of ≥15 and be free …

Deep brain stimulation for cervical dystonia

Deep brain stimulation for cervical dystonia

Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery

There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-Fahn-Marsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P < .05) and by a mean of 69.5% according to the Burke-Fahn-Marsden dystonia rating scale (P < .05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P < .05) at long-term follow-up (mean, 41.5 months). Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients.

P161 Localization of deep brain electrodes correlates with clinical efficacy of pallidal deep brain stimulation in cervical dystonia

P161 Localization of deep brain electrodes correlates with clinical efficacy of pallidal deep brain stimulation in cervical dystonia

Bilateral Deep Brain Stimulation for Cervical Dystonia: Long-term Outcome in a Series of 10 Patients

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was shown to be effective in cervical dystonia refractory to medical treatment in several small short-term and 1 long-term follow-up series. Optimal stimulation parameters and their repercussions on the cost/benefit ratio still need to be established. To report our long-term outcome with bilateral GPi deep brain stimulation in cervical dystonia. The Toronto Western Spasmodic Torticollis Rating Scale was evaluated in 10 consecutive patients preoperatively and at last follow-up. The relationship of improvement in postural severity and pain was analyzed and stimulation parameters noted and compared with those in a similar series in the literature. The mean (standard deviation) follow-up was 37.6 (16.9) months. Improvement in the total Toronto Western Spasmodic Torticollis Rating Scale score as evaluated at latest follow-up was 68.1% (95% confidence interval: 51.5-84.6). In 4 patients, there was dissociation between posture severity and pain improvement. Prevalently bipolar stimulation settings and high pulse widths and amplitudes led to excellent results at the expense of battery life. Improvement in all 3 subscale scores of the Toronto Western Spasmodic Torticollis Rating Scale with bilateral GPi deep brain stimulation seems to be the rule. Refinement of stimulation parameters might have a significant impact on the cost/benefit ratio of the treatment. The dissociation of improvement in posture severity and pain provides tangible evidence of the complex nature of cervical dystonia and offers interesting insight into the complex functional organization of the GPi.

The Canadian multicentre study of deep brain stimulation for cervical dystonia

Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment for generalized dystonia. Its role in the management of other types of dystonia is uncertain. Therefore we performed a prospective, single-blind, multicentre study assessing the efficacy and safety of bilateral GPi-DBS in 10 patients with severe, chronic, medication-resistant cervical dystonia. Two blinded neurologists assessed patients before surgery and at 6 and 12 months post-operatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The primary outcome measure was the severity subscore (range 0-30, higher scores indicating greater impairment). Secondary outcomes included disability (0 to 30), pain (0 to 40) subscores and total scores of the TWSTRS, Short Form-36 and Beck depression inventory. Swallowing and neuropsychological assessment were also performed at baseline and 12 months. One-way repeated measures analysis of variance was used to analyse the data. The TWSTRS severity score improved from a mean (SD) of 14.7 (4.2) before surgery to 8.4 (4.4) at 12 months post-operatively (P = 0.003). The disability and pain scores improved from 14.9 (3.8) and 26.6 (3.6) before surgery, to 5.4 (7.0) and 9.2 (13.1) at 12 months, respectively (both P < 0.001). General health and physical functioning as well as depression scores improved significantly. Complications were mild and reversible in four patients. Some changes in neuropsychological tests were observed, although these did not impact daily life or employment. Our results support the efficacy and safety of GPi-DBS for the treatment of patients with severe and prolonged cervical dystonia who have failed medical management.