Severity Of Cervical Dystonia Research Articles

Content overlap of 91 dystonia symptoms among the seven most commonly used cervical dystonia scales

IntroductionDystonia is a movement disorder characterized by sustained or intermittent muscle contractions. Cervical dystonia (CD) is the most common focal dystonia. There are several instruments assessing the symptoms of CD. However, different scales assess different features which may lead to poor patient evaluation.AimThe aim of the study was to evaluate the degree of overlap of most often used CD rating scales identified by the literature review.MethodsA thorough search of the Medline database was conducted in September 2021. Then the frequency of each scale was calculated, and 7 most common scales were included in the content overlap analysis using Jaccard index (0 – no overlap, 1 – full overlap).ResultsToronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui score, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Cervical Dystonia Impact Profile 58 (CDIP-58), Craniocervical Dystonia Questionnaire 24 (CDQ-24), Cervical Dystonia Severity Rating Scale (CDSS), Cervical Dystonia Severity Rating Scale (DDS) and The Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) were the most common scales. 91 CD symptoms were distinguished from 134 items used in the scales. The mean overlap among all scales was 0.17. 52 (62%) symptoms were examined by more than one scale. The CIDP-58 captured the highest number of symptoms (63.0%), while the CDSS captured the lowest number (8.0%). None of the symptoms were examined by seven instruments.ConclusionsThere was a very weak overlap among scales. High inconsistency between the scales may lead to highly different dystonia severity assessment in clinical practice. Thus, the instruments should be combined.

Assessing the Severity of Cervical Dystonia: Ask the Doctor or Ask the Patient?

Assessing disease severity can be performed using either clinician-rated scales (CRS) or patient-rated outcome (PRO) tools. These two measures frequently demonstrate poor correlations. To determine if the correlation between a CRS and PRO for motor features of cervical dystonia (CD) improves by accounting for non-motor features. Subjects with CD (N = 209) were evaluated using a CRS (Toronto Western Spasmodic Torticollis Rating Scale, TWSTRS) and a PRO (Cervical Dystonia Impact Profile, CDIP-58). Linear regression revealed a weak correlation between the two measures, even when considering only the motor subscales of each. The strength of this relationship improved with a regression model that included non-motor symptoms of pain, depression, and disability. These results argue that the results of motor assessments in a PRO for CD cannot be fully appreciated without simultaneous assessment of non-motor co-morbidities. This conclusion might apply to other disorders, especially those with frequent non-motor co-morbidities.

Lessons about Botulinum Toxin A Therapy from Cervical Dystonia Patients Drawing the Course of Disease: A Pilot Study.

To compare the course of severity of cervical dystonia (CD) before and after long-term botulinum toxin (BoNT) therapy to detect indicators for a good or poor clinical outcome. A total of 74 outpatients with idiopathic CD who were continuously treated with BoNT and who had received at least three injections were consecutively recruited. Patients had to draw the course of severity of CD from the onset of symptoms until the onset of BoNT therapy (CoDB graph), and from the onset of BoNT therapy until the day of recruitment (CoDA graph) when they received their last BoNT injection. Mean duration of treatment was 9.6 years. Three main types of CoDB and four main types of CoDA graphs could be distinguished. The demographic and treatment-related data of the patients were extracted from the patients' charts. The best outcome was observed in those patients who had experienced a clear, rapid response in the beginning. These patients had been treated with the lowest doses and with a low number of BoNT preparation switches. The worst outcome was observed in those 17 patients who had drawn a good initial improvement, followed by a secondary worsening. These secondary nonresponders had been treated with the highest initial and actual doses and with frequent BoNT preparation switches. A total of 12 patients were primary nonresponders and did not experience any improvement at all. No relation between the CoDB and CoDA graphs could be detected. Primary and secondary nonresponses were observed for all three CoDB types. The use of initial high doses as a relevant risk factor for the later development of a secondary nonresponse was confirmed. Patients' drawings of their course of disease severity helps to easily detect "difficult to treat" primary and secondary nonresponders to BoNT on the one hand, but also to detect "golden responders" on the other hand.

Clinical significance of indicators of energy metabolism in muscles involved in dystonic hyperkinesis in patients with idiopathic muscular dystonia

Introduction. Dystonia is a syndrome with location of pathological mechanisms in the central nervous system. The clinical manifestation of the syndrome is dystonic hyperkinesis with the formation of increased muscle tone, which may be associated with changes in cellular metabolism. Aim is to evaluate the indicators of energy metabolism in the muscles involved in dystonic hyperkinesis and compare with the severity of dystonia in patients with idiopathic muscular dystonia.
 Materials and methods. There were examined eighty four patients diagnosed with idiopathic muscular dystonia, including 17 men (20.2%) and 67 women (79.8%). In 38 cases there was cervical muscular dystonia, 36 and 10 cases showed segmental and generalized forms of dystonia with predominance of cervical dystonia syndrome, respectively. The average age of patients was 46 ± 11 among men and 52 ± 11 among women. The control group included 10 conditionally healthy individuals with an average age of 53.0 ± 13.4 years. The severity of cervical dystonia was assessed by the TWSTRS and Tsui scales. All participants of the study underwent biopsy sampling from the trapezius muscle, followed by determination of the level of ATP (adenosine triphosphoric acid), lactate and 2,3 DPH (2,3-diphosphoglyceric acid).
 Results. The results of the study revealed changes in the bioenergetics of muscle tissue in the form of a decrease in ATP and 2,3-DPH and an increase in lactate levels that did not correlate with the severity of dystonia on the TWSTRS and Tsui scales.
 Conclusion. Thus, bioenergetic changes in muscle tissue are not associated with the severity of dystonia and probably reflect general changes in the organization of intracellular energy metabolism in muscles in a hypertonic state.

The effectiveness of rhythmic transcranial magnetic stimulation in relation to the severity of cervical dystonia, quality of life, levels of anxiety and depression

The effectiveness of rhythmic transcranial magnetic stimulation in relation to the severity of cervical dystonia, quality of life, levels of anxiety and depression

Botulinum Toxin in the Treatment of Cervical Dystonia: Evidence-Based Review

Cervical dystonia is the most common form of dystonia encountered in a movement disorders clinic. Botulinum toxin has been a long-established first line therapy. Several studies, including nearly two dozen randomized clinical trials, have shown that botulinum toxin is safe and effective in reducing the clinical severity of cervical dystonia. Longitudinal data have demonstrated decades of sustained benefit and safety. Although there is a potential for the development of botulinum toxin immunoresistance, this is quite rare, and partly determined by frequency of administration, cumulative dosage, and properties of the injected product. When immunoresistance does occur, switching to an alternative type of botulinum toxin (e.g., from type A to type B) usually restores the efficacy. In this evidence-based review we highlight the results of published double blind, placebo-controlled studies. We also briefly discuss injection techniques and some unmet needs, such as the development of practical assays to detect immunoresistance and longer-acting formulations of botulinum toxin.

P.0125 Impact of anxiety and depression on the severity of cervical dystonia

P.0125 Impact of anxiety and depression on the severity of cervical dystonia

Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

Botulinum toxin type A versus anticholinergics for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment. To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia. We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020. Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness). We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.

A new approach to study the influence of the course of cervical dystonia severity before botulinum toxin on long-term outcome after botulinum toxin therapy

A new approach to study the influence of the course of cervical dystonia severity before botulinum toxin on long-term outcome after botulinum toxin therapy

Improvement in Quality of Life with OnabotulinumtoxinA for Cervical Dystonia: POSTURe.

Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments. This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded. Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (-31.0) and psychosocial functioning (-28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from -0.5 post-treatment 1 to -2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use. These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

Deep Brain Stimulation Versus Peripheral Denervation for Cervical Dystonia: A Systematic Review and Meta-Analysis

Cervical dystonia is a disabling medical condition that drastically decreases quality of life. Surgical treatment consists of peripheral nerve denervation procedures with or without myectomies or deep brain stimulation (DBS). The current objective was to compare the efficacy of peripheral denervation versus DBS in improving the severity of cervical dystonia through a systematic review and meta-analysis. A search of PubMed, MEDLINE, EMBASE, and Web of Science electronic databases was conducted in accordance with PRISMA guidelines. Preoperative and postoperative Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores were used to generate standardized mean differences and 95% confidence intervals (CIs), which were combined in a random-effects model. Both mean percentage and absolute reduction in TWSTRS scores were calculated. Absolute reduction was used for forest plots. Eighteen studies met the inclusion criteria, comprising 870 patients with 180 (21%) undergoing DBS and 690 (79%) undergoing peripheral denervation procedures. The mean follow-up time was 31.5 months (range, 12-38 months). In assessing the efficacy of each intervention, forest plots revealed significant absolute reduction in total postoperative TWSTRS scores for both peripheral denervation (standardized mean difference 1.54; 95% CI 1.42-1.66) and DBS (standardized mean difference 2.07; 95% CI 1.43-2.71). On subgroup analysis, DBS therapy was significantly associated with improvement in postoperative TWSTRS severity (standardized mean difference 2.08; 95% CI 1.66-2.50) and disability (standardized mean difference 2.12; 95% CI 1.57-2.68) but not pain (standardized mean difference 1.18; 95% CI 0.80-1.55). Both peripheral denervation and DBS are associated with a significant reduction in absolute TWSTRS total score, with no significant difference in the magnitude of reduction observed between the 2 treatments. Further comparative data are needed to better evaluate the long-term results of both interventions.

Selective Cervical Denervation for Cervical Dystonia: Modification of the Bertrand Procedure.

Cervical dystonia, commonly referred to as spasmodic torticollis, is a neurological disorder characterized by aberrant, involuntary contraction of the muscles of the neck and shoulders. One surgical option that can be considered is selective cervical denervation. To report our modification of the Bertrand procedure for selective cervical denervation. Our modification of the Bertrand procedure for selective cervical denervation is reported with intraoperative photographs and schematic depictions of the operative steps. We report our modification of the Bertrand procedure for selective cervical denervation, which consists of a combination of C2-6 denervation, myectomy of the splenius capitis and/or semispinalis capitis, myotomy of the levator scapulae when indicated, and myotomy and selection denervation of the sternocleidomastoid. The combination of techniques utilized depends on the subtype and severity of cervical dystonia. Our modification of the original Bertrand procedure for selective cervical denervation represents an alternative surgical strategy for the treatment of cervical dystonia, with the potential advantages and disadvantages discussed.

Impact of Cervical Dystonia on Work Productivity: An Analysis From a Patient Registry.

BackgroundCervical dystonia is thought to result in high disease burden, but limited information exists on its impact on employment and work productivity. We utilized data from the Cervical Dystonia Patient Registry for the Observation of OnabotulinumtoxinA Efficacy (ClinicalTrials.gov identifier: NCT00836017) to assess the impact of cervical dystonia on employment and work productivity and examine the effect of onabotulinumtoxinA treatments on work productivity.MethodsSubjects completed a questionnaire on employment status and work productivity at baseline and final visit. Baseline data were examined by severity of cervical dystonia, predominant subtype, presence of pain, prior exposure to botulinum toxin, and/or utility of a sensory trick. Work productivity results at baseline and final visit were compared in subjects who were toxin‐naïve at baseline and received three onabotulinumtoxinA treatments.ResultsOf 1,038 subjects, 42.8% were employed full‐ or part‐time, 6.1% unemployed, 32.7% retired, and 11.8% disabled. Of those currently employed, cervical dystonia affected work status of 26.0%, caused 29.8% to miss work in the past month (mean, 5.1 ± 6.4 days), and 57.8% reported decreased productivity. Half of those unemployed were employed when symptoms began, and 38.5% attributed lost employment to cervical dystonia. Pain, increasing severity, and anterocollis/retrocollis had the largest effects on work status/productivity. Preliminary analyses showed that absenteeism and presenteeism were significantly decreased following onabotulinumtoxinA treatments in the subpopulation that was toxin‐naïve at baseline.ConclusionsThis analysis confirms the substantial negative impact of cervical dystonia on employment, with cervical dystonia‐associated pain being a particularly important driver. OnabotulinumtoxinA treatment appears to improve work productivity.

Threshold of Clinical Severity of Cervical Dystonia for Positive18F-FDG PET/CT

ObjectiveTo examine whether the clinical severity of cervical dystonia (CD) significantly correlates with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings as well as to determine the threshold of the clinical severity of CD for positive 18F-FDG PET/CT study findings.MethodsForty-seven subjects with torticollis as one of the symptoms of CD were included. The clinical severity of CD was evaluated with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at the time of 18F-FDG PET/CT. The correlation between the clinical severity of CD and the highest SUVmax was examined. The threshold of the clinical severity of CD necessary for positive 18F-FDG PET/CT findings was determined using receiver operating characteristics curve analysis.ResultsThirty-three of the 47 subjects (70.21%) showed positive 18F-FDG PET/CT findings. The ipsilateral splenius capitis/cervicis, oblique capitis inferior, and longus colli/capitis were the rotators most frequently involved. The highest SUVmax of 18F-FDG PET/CT was significant correlated with the TWSTRS. Subjects with a total TWSTRS exceeding 39 showed positive 18F-FDG PET/CT findings, with those having a total TWSTRS ≤22 showing negative 18F-FDG PET/CT results. The cutoff value of the total TWSTRS for positive 18F-FDG PET/CT findings was set at 27.5 with 90.9% sensitivity and 64.3% specificity.ConclusionA significant correlation was evident between the clinical severity of CD and 18F-FDG PET/CT findings, providing a threshold of the clinical severity of CD for acquisition of positive 18F-FDG PET/CT findings.

Poster 89 Severity of Cervical Dystonia: Baseline Characteristics from the Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE)

Poster 89 Severity of Cervical Dystonia: Baseline Characteristics from the Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE)

Efficacy, Tolerability, and Immunogenicity of OnabotulinumtoxinA in a Randomized, Double-Blind, Placebo-Controlled Trial for Cervical Dystonia

To evaluate the efficacy, tolerability, and neutralizing antibodies in the treatment of cervical dystonia with onabotulinumtoxinA (BOTOX). Subjects received onabotulinumtoxinA (containing original bulk toxin) treatment in a 10-week open-label period (period 1). Eligible subjects who completed this period were randomized to onabotulinumtoxinA or placebo in a 10-week double-blind period (period 2). The primary outcome measures were the Cervical Dystonia Severity Scale and the physician Global Assessment Scale at week 6 in period 2. Serum samples for immunogenicity tests were taken at baseline and study exit. The potential impact of preexisting neutralizing antibodies (nAbs) was examined across subgroups for period 1 and by analysis of covariance for period 2. Of 214 subjects enrolled in period 1, 170 enrolled in period 2 and received placebo (n = 82) or onabotulinumtoxinA (n = 88). In period 1, subjects with preexisting nAbs responded similarly to those without preexisting nAbs. In period 2, onabotulinumtoxinA produced significantly greater improvements than placebo on the Cervical Dystonia Severity Scale (-1.81 vs -0.31 points; P = 0.012) and physician Global Assessment Scale (61.7% vs. 41.6% improved; P = 0.022) at the primary time point week 6, using baseline severity and neutralizing antibody (nAb) status at study entry as covariates. Two subjects seroconverted from nAb negative at baseline to nAb positive at study exit but remained responsive to onabotulinumtoxinA during both the open and blinded treatment periods. Rhinitis and treatment-related dysphagia were reported significantly more frequently with onabotulinumtoxinA than placebo. OnabotulinumtoxinA was well tolerated and more effective than placebo for the treatment of cervical dystonia. Subject nAb status at baseline was not a clear predictor of response to onabotulinumtoxinA.

CT-guided intramuscular botulinum toxin A injections into the deep anterior neck muscles in patients with pure antecaput or antecollis

Aim of the studyTo demonstrate the influence of botulinum toxin (BTX) type A injections into the deep anterior neck muscles (aDNMs) on the severity of cervical dystonia (CD) in severely affected CD-patients with pure antecaput and/or antecollis. MethodsRetrospective analysis of our (Access) data bank and the CT-scans performed during injections.In eight patients CT-guided injections were performed. Outcome was measured by means of the TSUI-score and a 4 point global assessment scale (GAS) to score efficacy, tolerability and pain relief of BTX-A injections into the aDNMs. Patients were asked for side effects of the injections. ResultsRetrospective analysis reveals that CT-guided intramuscular injections of BTX-A into the aDNMs improve antecollis better than antecaput and reduce pain, but are tolerated barely. The most frequent side-effects were dysphagia and anxiety. The majority of patients wanted to be reinjected. ConclusionFor the special subgroup of CD-patients with a severe antecollis CT-guided injections of the aDNMs are a relevant treatment option for intermittent but not continuous intervention.

Stress Levels Correlate with Severity of Cervical Dystonia (P01.234)

Stress Levels Correlate with Severity of Cervical Dystonia (P01.234)

Severity of Cervical Dystonia: Baseline Characteristics from the Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD-PROBE) (P01.231)

Severity of Cervical Dystonia: Baseline Characteristics from the Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD-PROBE) (P01.231)