Riluzole therapy in cervical dystonia.

We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment. The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002). In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale. These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies.     

Long-term outcome of bilateral pallidal deep brain stimulation for primary cervical dystonia

Ten patients with severe cervical dystonia (CD) unresponsive to medical treatment underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed for 31.9 +/- 20.9 months. At last follow-up, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score improved by 54.8%, the TWSTRS disability score improved by 59.1%, and the TWSTRS pain score improved by 50.4%. Bilateral GPi DBS is an effective long-term therapy in patients with CD.     

Efficacy of single-photon emission computed tomography aided botulinum toxin injection in cervical dystonia: A double-blind,randomized study

BackgroundAlthough single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD.MethodsPatients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2.ResultsA total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: β, −4.86 [95%CI -9.40 to −0.32; P = 0.036]; Tsui: β, −1.65 [95%CI -2.77 to −0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: β, −6.33 [95%CI -10.17 to −2.49; P = 0.001]; Tsui: β, −1.42 [95%CI -2.48 to −0.37; P = 0.008]) and T3 (TWSTRS: β, −6.05 [95%CI -11.09 to −1.01; P = 0.019]; Tsui: β, −1.24 [95%CI -2.40 to −0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 ± 28.6 versus 141.8 ± 51.0 days, P = 0.032).ConclusionsSPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.     

Hyper- and hypo-connectivity in sensorimotor network of drug-naïve patients with cervical dystonia

BackgroundCervical dystonia (CD) is the most common form of focal dystonia with involuntary movements and postures of the head. The pathogenesis and neural mechanisms underlying CD have not been fully elucidated.MethodsTwenty-seven newly drug-naïve patients with CD and 21 healthy controls (HCs) were recruited with clinical assessment and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Severity of CD was measured by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores. Whole-brain voxel-wise intrinsic connectivity (IC) and seed-based functional connectivity (FC) analyses were performed for detection of changes in the CD group relative to HCs, controlling for age, gender, and global time series correlation, followed by correlation analyses of IC, seed-based FC and clinically relevant features, respectively.ResultsIn comparison with HCs, CD patients showed significantly increased IC measurement in the anterior part of the left supramarginal gyrus and extended to the inferior left postcentral gyrus (AL-SMG/IL-PCG). With this cluster as a seed, decreased FC was found in the right precentral and postcentral gyrus. Moreover, the regional IC value in the AL-SMG/IL-PCG was significantly positively correlated with TWSTRS-1 (severity) score, and significantly negatively correlated with the associated seed-based FC strength.ConclusionsOur results showed signs of both hyper- and hypo-connectivity in bilateral regions of the sensorimotor network related to CD. The imbalance of functional connectivity (both hyper- and hypo-) may hint both overloading and disrupted somatosensory or sensorimotor integration dysfunction within the sensorimotor network underlying the pathophysiology of CD, thus providing a network target for future therapies.     

Bilateral pallidal stimulation improves cervical dystonia for more than a decade

IntroductionDeep brain stimulation (DBS) is an effective treatment in medically resistant cervical dystonia (CD) with a documented therapeutic effect. Long term outcome beyond a decade, however, has not been studied systematically.MethodsTo investigate the impact of pallidal DBS beyond 10 years in CD we followed a series of five consecutive patients with severe medication-resistant CD. Severity of head and neck deviation, disability, and pain related to dystonia were assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in the frame of a prospective study. The primary endpoint of this study was a change in the TWSTRS total score. Secondary endpoints were changes in the subscores of the TWSTRS.ResultsThe mean follow-up time was 11.5 years (range 10–12.8). Comparing baseline and the last follow-up, CD improved by 53% on the total TWSTRS score, by 54.1% on the severity score, and by 70.1% on the disability score, while pain did not improve significantly. Improvement was stable over time. Patients with a tonic pattern of CD responded less to DBS than patients with a phasic pattern. DBS had no significant effect on mood and cognition. Two patients underwent electrode revisions. One patient had an infection of the proximal cable two years after surgery.ConclusionsChronic bilateral pallidal stimulation improves severity of dystonia and disability over more than a decade in treatment resistant CD. Results may vary among individual patients.     

Pallidal stimulation in cervical dystonia: clinical implications of acute changes in stimulation parameters

Background and purpose:  Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is successful in dystonia, but the role of each electrical parameters of stimulation is unclear. We studied the clinical effects of acute changes of different parameters of GPi–DBS in cervical dystonia (CD).
Methods:  Eight CD patients with bilateral GPi–DBS at 28.6 ± 19.2 (mean ± SD) months after surgery were recruited. Mean improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score was 54.5% compared to before surgery. Ten settings, including a combination of a wide range of pulse widths (PWs), low and high frequencies and voltage, were administered in a randomized double blinded fashion. Clinical benefit was assessed by two raters using the TWSTRS and by the patients using an analogue rating scale.
Results:  The TWSTRS severity scores were reduced by 56.7% with stimulation at the best settings. Improvement was significantly associated with high frequency (≥60 Hz) and high voltage. Stimulation at 130 Hz showed the best clinical improvement. Increasing PWs (from 60 to 450 μs) did not result in a significant improvement.
Conclusion:  Frequency and amplitude appear to be the most important factors in the acute anti-dystonic effects in GPi–DBS patients with CD.     

Personalized botulinum toxin type A therapy for cervical dystonia based on kinematic guidance

Background

Botulinum toxin type A (BoNT-A) injections is the accepted first-line therapy for cervical dystonia (CD), however, numerous patients discontinue treatment early due to perceived sub-optimal relief. To improve BoNT-A therapy for CD, proper assessment of neck motion and selection of relevant muscles and dosing must be met. Kinematic technology may improve treatment outcomes by guiding physicians to better tailor muscle selection and BoNT-A dosing for CD therapy.

Methods

28 CD participants were placed into either group: expert injector determined injection patterns by visual assessment (“vb”) versus injection patterns based on kinematics interpreted by an expert injector (“kb”). Injections occurred at weeks 0, 16 and 32 with follow-ups at weeks 6, 22 and 38. Kinematics utilized four sensors to capture the severity of multiaxial, static neck posturing (e.g., torticollis) and dynamic, spasmodic/tremor movements while participants were seated. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score changes were evaluated over 38 weeks.

Results

For the “kb” participants, there was a significant 28.8% (? 11.25 points) reduction in TWSTRS total score at week 6, as well as significant reduction in severity and disability TWSTRS sub-scores (parts I and II) with maintained improvement at subsequent visits. As for the “vb” participants had a significant reduction in total TWSTRS score by 28.5% (? 9.84 points) after week 22. Disability score for the “vb” group trended towards improvement over 38 weeks.

Conclusion

Clinical judgement guided by kinematic analysis of CD biomechanics can result in faster optimal muscle selections and minimize use of higher BoNT-A doses as compared to visual determination, thereby achieving comparable and potentially better treatment outcomes.

     

How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective,long-term observational study

Background

Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice.

Methods

This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle.

Results

Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years.

Conclusions

Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

     

Pain incidence in cervical dystonia is determined by the disease phenotype

BackgroundCervical dystonia (CD) is a movement disorder caused by prolonged contractions of the head and neck muscles resulting in abnormal postures and repetitive movements. Depending on the direction of the head and neck deviation, CD phenotypes are divided into torti-, latero-, antero-, and retro- impairments assessed in commonly used TWSTRS classification, or -caput and -collis according to the novel Col-Cap concept. Cervical pain, which pathophysiology has not been fully elucidated, affects more than 60% of CD patients. To date, none of the studies have investigated the risk of pain associated with the particular disease phenotype.MethodsIn this observational study data collection was based on the survey completion by the participants, analysis of the medical records, and physical examination with the use of proper scales (TWSTRS, Col-Cap, Tsui). Extended pain profile questionnaire included detailed questions about pain localization, character, and intensity.ResultsWe examined 60 patients suffered from CD; 66,7% of them reported cervical pain. Latero- as the only TWSTRS phenotype was associated with increased risk of pain occurrence (OR = 3,95; p < 0,05). Interestingly, each of two Col-Cap phenotypes correlated with cervical pain: -caput positively (OR = 3,78; p < 0,05) and -collis negatively (OR = 0,29; p < 0,05).ConclusionsThe risk of dystonic pain was highly differentiated within the particular CD phenotypes. The enhanced risk of cervical pain was observed in latero- (TWSTRS) and -caput (Col-Cap) phenotypes; conversely, -collis type (Col-Cap) was characterized by the lowest risk of cervical pain.     

Erste Erfahrungen mit der klinischen Anwendung von Botulinum-Toxin Typ B

Recently, botulinum toxin type B (BT-B) was introduced for treatment of cervical dystonia (CD). We wish to report on experience with BT-B derived from registration studies and from our own preliminary clinical experience. Botulinum toxin type B can be used successfully in CD patients with antibody-induced failure of botulinum toxin type A therapy (antibody patients). In our own 15 antibody patients, 11835 +/- 2,039 mouse units of BT-B (NeuroBloc) reduced the Toronto Western spasmodic torticollis rating scale (TWSTRS) score from 20.5 +/- 3.6 to 13.1 +/- 5.4. BT-B can also be used successfully in CD patients not previously exposed to BT-A or BT-B (de novo patients). In our own nine de novo patients, 10436 +/- 3,320 mouse units of BT-B reduced the TWSTRS score from 18.4 +/- 5.4 to 9.2 +/- 4.8. Altogether, dryness of the mouth occurred in 21 CD patients (severe 10, moderate 7, mild 4), accommodation difficulties in seven, conjunctival irritation in five, reduced sweating in four, swallowing difficulties in three, heartburn in three, constipation in three, bladder voiding difficulties in two, and dryness of nasal mucosa, head instability, and thrush in one each. BT-B produces substantially more systemic autonomic side effects than BT-A. It can be considered the therapy of choice in antibody patients. For de novo patients and for BT-A-treated CD patients, BT-B cannot be recommended currently.     

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study

Background and purpose: Deep brain stimulation of the internal globus pallidus (GPi‐DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer‐blinded outcome assessment of long‐term GPi‐DBS, with 1‐year follow‐up. Methods: In this prospective, single‐centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi‐DBS for median (range) 30 (12–48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short‐Form Health Survey‐36 (SF‐36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow‐up. Results: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19–30) to 8 (4–23) (P = 0.028), thus a 70% (23–82) score reduction. In the open evaluation, median Severity score improvement at the last follow‐up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF‐36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. Conclusions: This single‐blinded study shows good long‐term efficacy of GPi‐DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.     

Psychiatric co-morbidity is highly prevalent in idiopathic cervical dystonia and significantly influences health-related quality of life: Results of a controlled study

IntroductionThe aim of this study was to systematically investigate the prevalence of psychiatric disorders and factors influencing health-related quality of life (HR-QoL) in cervical dystonia (CD) patients, in the context of objective dystonia motor severity.MethodsWe studied 50 CD patients and 50 matched healthy controls. Psychiatric assessment included the MINI–PLUS interview and quantitative questionnaires. Dystonia motor severity (based on video evaluation), pain and disability were determined with the TWSTRS rating scale. In addition, severity of tremor and jerks was evaluated with the 7-point CGI-S scale. HR-QoL was determined with the RAND-36 item Health Survey and predictors of HR-QoL were assessed using multiple regression analysis.ResultsIn CD patients, the MINI-PLUS revealed a significantly higher prevalence of psychiatric disorders (64% vs. 28%, p = 0.001), with substantially more depression (32% vs. 14%) and anxiety disorders (42% vs. 8%). This was confirmed by the quantitative rating scales. Disease characteristics did not differ between patients with and without a psychiatric diagnosis. HR-QoL in dystonia patients was significantly lowered. The most important predictors of HR-QoL appeared severity of depressive symptoms, pain and disability, but not severity of motor symptoms.ConclusionPsychiatric co-morbidity is highly prevalent and is an important predictor of HR-QoL in CD patients, rather than dystonia motor severity. Our findings support the theory of a shared neurobiology for motor and non-motor features and highlight the need for systematic research into psychiatric disorders in dystonia. Adequate treatment of psychiatric symptoms could significantly contribute to better overall quality of life of CD patients.     

Determinants and status of quality of life after long-term botulinum toxin therapy for cervical dystonia

The aim of this study was to assess health-related quality of life (HRQoL), using the Short Form Health Survey-36 (SF-36), in 70 cervical dystonia (CD) patients after long-term botulinum toxin (BTX) treatment (median 5.5 years), and to identify factors determining reduced HRQoL. We used combined patient-and physician-based measures to assess both CD severity [Toronto Western Spasmodic Torticollis Rating Scale, (TWSTRS)] and effect of long-term BTX treatment, and the Hospital Anxiety and Depression Scale (HAD) and General Health Questionnaire-30 to assess psychological distress. Mean SF-36 domain scores of the CD patients were reduced by <1 SD compared with age- and gender-matched population samples. High TWSTRS total scores and high HAD-depression (HAD-D) scores were the main factors associated with reduced scores in the physical and mental SF-36 domains, respectively. Patients evaluated to have a 'good effect' of long-term BTX treatment ( n  = 47), had significantly lower median TWSTRS total score, and a 3× lower frequency of high HAD-D scores, than those evaluated to an 'unsatisfactory effect' ( n  = 23). In conclusion, most CD patients enjoy a good HRQoL after long-term BTX therapy. Reduced HRQoL was associated with more severe disease and/or depressive symptoms.     

Botulinum toxin type A and cervical dystonia: a seven-year follow-up

Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6 ± 6.6 and 17.7 ± 4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD.     

Predictable variables for short- and long-term botulinum toxin treatment response in patients with cervical dystonia

We retrospectively evaluated 118 patients with cervical dystonia (CD) treated with botulinum toxin type A (BTX-A) for the following variables: gender, age at evaluation, age at symptom onset, disease duration, presence of head/neck pain and/or tremor, pattern of head deviation, disease progression (spreading of symptoms), etiology (primary vs. secondary), pretreatment with oral medication, and Tsui score. We investigated whether these parameters could predict the clinical outcome in a short- (<30 days) and long-term basis. On short-term treatment, there were no clinically significant differences between BTX-A responsive and non-responsive patients. On long-term treatment, however, intake of oral medication previously to BTX-A injection and higher Tsui scores were predictors of favorable response. These results suggest that the greater CD severity the more likely patients will respond to BTX-A.     

Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome).

Idiopathic cranial-cervical dystonia (ICCD) is an adult-onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.     

Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia

OBJECTIVES: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia. Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies. The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport. METHODS: A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed. The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four). The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed. RESULTS: Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox. The number of adverse events was higher with both Dysport treatments. The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients. No adverse event required withdrawal of therapy or specific management. CONCLUSIONS: Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects. This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia.     

Rating scales for states for anxiety, depression, mania and schizophrenia. A multiaxial approach

Rating scales are considered to be an efficient instrument in the assessment of treatment effect, and during the last 25 years a number of rating scales has been constructed for measuring states of anxiety, depression, mania and schizophrenia. The paper describes some of the most frequently used scales. Time has come to coordinate the existing rating scales and to agree upon common operational definitions in the judgement of psychopathological symptoms. Basic practical guidelines to be used in both clinical practice and research are given.     

Long Disease Duration Interferes With Therapeutic Effect of Globus Pallidus Internus Pallidal Stimulation in Primary Cervical Dystonia

Objectives: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). Materials and Methods: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. Results: At last follow‐up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed‐rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). Conclusions: Bilateral GPi‐DBS is an effective long‐term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.