Muscle selection for treatment of cervical dystonia with botulinum toxin--a systematic review

RationaleCervical dystonia, also called spasmodic torticollis, is the most common form of (primary) dystonia. Intramuscular injections with botulinum toxin are the first line of treatment for cervical dystonia. To optimise the treatment response to botulinum toxin correct muscles should be selected. Clinical evaluation is important for muscle selection but the value of additional tests to identify dystonic muscles remains unclear.ObjectiveTo evaluate all relevant literature regarding the best approach to select dystonic muscles for treatment with botulinum toxin.MethodsWe conducted a systematic review of studies that had investigated methods of selecting muscles for treatment with botulinum toxin. In addition, we compared all prospective botulinum toxin trials using either clinical evaluation or polymyographic electromyography for muscle selection.ResultsForty relevant studies were included and polymyographic electromyography recordings were most often employed. In several studies, polymyographic electromyography revealed a different pattern of muscle involvement compared to that found during clinical evaluation. In one randomized controlled trial polymyographic electromyography significantly improved the outcome of botulinum toxin treatment. A limited number of studies used positron emission tomography – computed tomography imaging or frequency analysis of the electromyography signal to identify dystonic muscles but their effect on the outcome of treatment has never been studied.ConclusionPolymyographic electromyography may improve the outcome of botulinum toxin treatment in cervical dystonia, but evidence is limited and larger studies are needed.     

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.     

Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment

The muscular patterns of cervical dystonia were identified by polymyographic recordings in 76 patients before botulinum toxin treatment. The leading muscles were considered to be those which started dystonic movement and which showed constant and maximal activity during all dystonic movements. The dystonic muscles were repeatedly treated by local Injections of botulinum toxin. Sixteen patients showed (after repeated injections) loss of the benefit of local applications of botulinum toxin after various periods of time. Repeated polymyographic recordings were performed in these patients during the loss of the benefit of injected botulinum toxin. In four patients repeated polymyographic recordings showed an Identical pattern of cervical dystonia, but the activity of previously injected muscles was apparently decreased. In 12 patients only minimum or no activity was recorded in muscles which had previously been treated with botulinum toxin, but the pattern of cervical dystonia was changed. Different patterns of cervical dystonia with different leading muscles, but with identical directions of head deviation, were observed in six patients. In another six patients, the head deviation direction was to the opposite side and was accompanied by a change of the leading muscle and a change of the muscular pattern of dystonia. These results suggest either that dystonic activity from the cerebral generator changes to new effectors during the peripheral blockade of primary dystonic muscles, or that a change of generators at different levels of the CNS occurs. It may be neccessary to carry out repeated polymyographic recordings throughout the period of loss of benefit of previously successful local botulinum toxin injections.     

Fluoroscopic, EMG-guided injection of botulinum toxin into the longus colli for the treatment of anterocollis

BackgroundAnterocollis is a form of cervical dystonia characterized by forward neck flexion. While botulinum toxin is the treatment of choice for cervical dystonia, patients with anterocollis, who receive injections into the sternocleidomastoid and anterior scalene muscles, represent a disproportionate number of treatment failures. Deep cervical muscles such as the longus colli likely play an important role in neck flexion but are not routinely injected.ObjectiveTo describe a technique for longus colli injection in cases of anterocollis and to report the clinical outcomes of 10 such injections of botulinum toxin.MethodsThree patients were referred for evaluation and treatment of anterocollis. All had previous treatment failures with sternocleidomastoid/anterior scalene injections or no activity noted on needle EMG investigation of these muscles. All patients received injections of botulinum toxin into the longus colli under fluoroscopic and EMG guidance.ResultsAll patients experienced symptomatic improvement (eight of 10 injections). Two patients reported mild dysphagia without serious complications after dose increases in botulinum toxin.ConclusionsIncomplete muscle selection may be one cause of treatment failures in anterocollis. Deep cervical flexors such as the longus colli represent an under-recognized potential target for symptomatic treatment of anterocollis.     

Botulinum toxin in cervical dystonia: low dosage with electromyographic guidance

Sixty patients with idiopathic cervical dystonia were treated a total of 240 times with botulinum toxin type A (BTA). Selected muscles were injected with BTA under electromyographic (EMG) guidance. The clinical effect was measured on the Tsui scale and a 10-point anchored visual analogue scale. A dosage of 150–300 mouse units was used in 77% of the treatments (mean 204 mouse units). Based on the Tsui scale, 45% of 240 treatments were still effective at the moment of reinjection (median improvement 2 points). Based on the 10-point anchored visual analogue scale, 73% of treatments were successful (median improvement 3 points). Forty-eight patients (80%) responded favourably to the treatment. Side-effects were mild and transient. Dysphagia occurred in 9% of treatments. Antibody production was investigated in 41 patients and was negative in all. A striking difference from previous reports is the lower dosage used in this study. The clinical response, however, was similar to that of other studies. We conclude that a dosage of 200–400 mouse units BTA (Dysport) may also be effective in the treatment of cervical dystonia, but with fewer side effects. EMG guidance and application of BTA into deep cervical muscles may further improve the clinical effect.     

肌电图引导下A型肉毒毒素治疗不同类型痉挛性斜颈的临床研究

目的：探讨A型肉毒毒素（BTX-A）局部注射治疗不同类型原发性痉挛性斜颈的疗效。方法：在肌电图引导下,对24例痉挛性斜颈患者行BTX-A局部肌肉注射,按其临床类型分组比较疗效及不良反应。结果：全部患者治疗后Tsui量表评分均明显下降,混合型改善程度更明显。所有患者均未见严重不良反应。结论：肌电图引导下BTX-A治疗不同类型痉挛性斜颈均有效,且安全。     

A new treatment for cervical vertigo with botulinum toxin

A new and unique treatment for cervical vertigo with botulinum toxin is presented for a woman who sustained neck trauma from being hit by a wave. A diagnosis of cervical vertigo and cervical dystonia was confirmed by history, physical exam, dystonia on EMG exam, and a negative test for benign paroxysmal positional vertigo.She experienced consistent resolution of her vertigo symptoms and pain after each treatment for a total of 5 treatments with botulinum toxin to the upper cervical muscles. This report appears to be the first to demonstrate the missing link between vertigo and cervical dystonia with pain. Chemodenervation was effective in treating cervical vertigo and is likely to have altered the cervical proprioceptive input by relaxing the overactive muscles and/or by decompression of cervical nerves.     

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.

     

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.     

肌电图引导局部肌肉注射A型肉毒毒素治疗痉挛性斜颈的疗效观察

目的 观察肌电图(EMG)引导局部肌肉注射A型肉毒毒素(BTX-A)治疗痉挛性斜颈(CD)的疗效.方法 应用EMG检查19例CD患者头颈部152块肌肉,针对放松状态下出现的多频群放电位的114块靶肌肉进行BTX-A局部肌肉注射;治疗前后分别采用Tsui量表对病情和疗效进行评估;随访观察疗效持续时间以及不良反应.结果 治疗后EMG发现靶肌肉5块;根据Tsui量表评分,治疗后总有效率第1周为47.3%,第2周为78.9%,第3、4周均为94.7%;随访显示疗效平均保持10个月;不良反应轻微,均在4周内自行缓解.结论 EMG引导局部肌肉注射BTX-A治疗CD安全有效.     

Elimination of dysphagia using ultrasound guidance for botulinum toxin injections in cervical dystonia

Introduction: Dysphagia is a common side effect after botulinum toxin injections for cervical dystonia, with an incidence of 10–40%, depending upon the study and dose used. Methods: Our study consisted of 5 preselected women who met criteria for cervical dystonia and subsequent dysphagia after electromyography (EMG)‐guided injections. Injections were performed with ultrasound (US) imaging, and the effects on swallowing were examined. Separately, sternocleidomastoid (SCM) thickness in healthy controls and treated patients was measured. Results: There were 34 episodes of dysphagia over 98 injection sessions using EMG guidance for a cumulative rate of 34.7%. Using US plus EMG guidance, there was 0% dysphagia across 27 injection sessions. SCM thickness was <1.1 cm. Conclusion: US combined with EMG guidance eliminated recurrent dysphagia after botulinum toxin treatment, possibly by keeping the injectate within the SCM. Muscle Nerve 46: 535–539, 2012     

Electromyographic guidance of botulinum toxin treatment in cervical dystonia

We report the results of electromyographic (EMG) guidance in the treatment of cervical dystonia with botulinum toxin. Eight-four patients received a total of 225 injection sessions. Overall there was moderate objective improvement in 78.7%. The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean duration of maximum effect was 107 +/- 49 days. Complications included excessive neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions. We conclude that EMG guidance is a safe and effective method of administering botulinum toxin in the treatment of cervical dystonia.     

Prise en charge de la crampe de l’écrivain : 14 ans d’expérience de la toxine botulique

IntroductionWriter's cramp is a focal dystonia; treatment remains disappointing. We report our 14-year experience with a population of 119 patients aged between 18 and 85 years (average age 43 years).MethodsTreatment was based on botulinum toxin injections (Dysport^®) and physiotherapy. Patients were reviewed every four to six months with clinical and video evaluation by three different observers and subjective analysis of the treatment efficiency by the patient (score of 1 to 3). The post-injection deficit, if present, was also quantified.ResultsIn the group treated with toxin and physiotherapy, cramps improved (score 2 and 3) in 61.6% of patients; a majority of patients (n = 14) reported they were moderately satisfied (score 2). In the group treated with toxin alone, 37.9% of patients were improved (score 2 and 3) with a majority (n = 18) very satisfied reporting normal writing (score 3). Age was not a predictor of therapeutic response. Good results were obtained with injections of the flexor carpi radialis followed by flexor digitorum profundus II and III and the flexor pollicis longus. Seventy-one per cent of injections caused moderate muscle weakness, minimally disabling compared to the benefit of injections. Twenty-seven patients were followed for more than two years and three patients, who had achieved score 3 with excellent response, were followed for 14 years with very efficient repeated injections. If the injections were not effective the first time, we re-assessed the situation and adjusted the injections; we considered that toxin treatment was unsuccessful after three injections without benefit.ConclusionThe choice treatment for writer's cramp remains well-targeted injections of botulinum toxin. Physiotherapy is useful when the toxin injections are ineffective in completely improving writing. This requires close cooperation between the injector, the physiotherapist and the patient.     

Evidence-based medicine in botulinum toxin therapy for cervical dystonia

Early controlled studies of botulinum toxin (BTX) in cervical dystonia were unblinded and indicated that BTX injections are more successful than medication. In this article, the use of botulinum toxin (BTX) in cervical dystonia is reviewed according to evidence-based medicine. To document the efficacy of BTX, there have been a number of prospective, placebo-controlled studies of the use of BTX in cervical dystonia. Most were double-blind, some included videotapes to provide blinded objective assessments. The more recent studies of BTX in cervical dystonia focused on particular issues such as utility of EMG guidance, comparison to anticholinergic treatment, BTX serotype B in BTX type A resistant and non-resistant patients and different dosages. Despite the wealth of data generated with prospective placebo-controlled studies on the effectiveness of BTX in cervical dystonia, there is uncertainty on which outcome measures to use to express the efficacy of treatments for cervical dystonia. Disease specific instruments to measure quality of life in cervical dystonia have not been used so far. Data on the use of BTX for cervical dystonia have long been restricted to small series of patients reflecting exclusively the experience of individual specialized centers.

     

Trick maneuvers in cervical dystonia: investigation of movement- and touch-related changes in polymyographic activity.

Antagonistic gestures or trick maneuvers are well-known clinical features to reduce or abolish dystonic posturing in cervical dystonia (CD). The maneuvers typically consist of a finger touch to the facial skin but their physiology remains unknown. To determine the temporal profile of geste maneuver performance, 25 patients with idiopathic CD were studied by means of polymyography of six cervical muscles prior to any botulinum toxin treatment. Two piezoelectric elements fixed to a fingertip of the hand involved in the trick maneuver and to the facial target region, respectively, were used to relate the essential points of the trick maneuver time course (start of geste-arm movement, facial contact, end of contact, end of movement) to changes in polymyographic activity. Thirteen patients (52%) showed marked reductions of electromyographic (EMG) activity (> or =50% in at least one muscle) during arm movement, definitely prior to contact between fingers and facial target area; in the remaining 12 patients (48%), geste-related EMG effects were confined to facial-finger contact. These results might indicate different physiological mechanisms in clinically indistinguishable antagonistic gestures.     

Tremulous cervical dystonia is likely to be familial: Clinical characteristics of a large cohort

BackgroundPrimary cervical dystonia is the most common form of adult-onset focal dystonia. Although most frequently sporadic, 15–20% of patients report a positive family history, suggesting a possible genetic cause. Head tremor is often present in patients with cervical dystonia and may be a prominent symptom.ObjectiveTo describe the clinical characteristics of patients with tremulous cervical dystonia.MethodsPatients with primary cervical dystonia attending our botulinum toxin clinic were assessed with an interview and neurological examination and their notes reviewed. Patients were classified as having either tremulous or non-tremulous cervical dystonia, according to the presence or absence of head tremor on examination. Clinical and demographic data were compared between groups.ResultsFrom 273 patients included (190 females, 83 males), 125 (46%) were classified as tremulous and 148 (54%) as non-tremulous. Tremulous patients were more likely to have a segmental distribution (61% vs 25%), often involving the arms (48%), and had more frequently associated arm tremor (55% vs 10%). A positive family history of dystonia and/or tremor was more frequent in tremulous patients (50% vs 18%).ConclusionsPatients with cervical dystonia with associated head tremor are more likely to have a segmental distribution (with frequent arm involvement), associated arm tremor and a positive family history, suggesting a genetic etiology in this subgroup of patients.     

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.     

Utility of an EMG mapping study in treating cervical dystonia

Intramuscular injections of botulinum toxin are the cornerstone of treatment for cervical dystonia. Controversy exists regarding the necessity for EMG-guided injections. We compared the clinical examination of four movement disorder specialists to an electromyographic (EMG) mapping study. Clinical predictions of individual muscle involvement were only 59% sensitive and 75% specific. Muscle hypertrophy, shoulder elevation, and dominant head vector did not bolster clinical accuracy. An EMG mapping study facilitates identification of dystonic muscles in cervical dystonia, which may enhance botulinum toxin therapy.     

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

Journal of Neurology - The article How satisfied are cervical dystonia patients after 3&nbsp;years of botulinum toxin type A treatment?     

Long-term botulinum toxin treatment of cervical dystonia--EMG changes in injected and noninjected muscles.

OBJECTIVE: To evaluate changes in quantitative EMG of injected and noninjected sternocleidomastoid muscles following long-term unilateral botulinum toxin treatment of cervical dystonia. METHODS: We investigated 27 patients with cervical dystonia, who received repeated unilateral botulinum toxin injections of the sternocleidomastoid muscle, with quantitative EMG at rest and at maximal voluntary contraction. The patients had on the average 7.1 botulinum toxin treatments and the follow-up period was on the average 31 months (SD 16). RESULTS: After the first treatment, the injected sternocleidomastoid muscles showed a significant decrease in turns/s (mean 45%) and amplitude (mean 52%) at rest, and in amplitude at maximal flexion (mean 24%) and rotation (mean 39%). Except for a reduction in turns/s at rotation (mean 19%) no further reductions in EMG parameters were seen after long-term treatment. The contralateral noninjected sternocleidomastoid muscles showed no significant change in EMG activity after the first BT treatment, but after long-term treatment a significant reduction in turns/s and amplitude at both maximal flexion (turns: mean 28%; amplitude: mean 25%) and rotation (turns/s: mean 32%; amplitude: mean 25%) were seen as compared to pretreatment values. CONCLUSION: The results indicate that there seems to be no cumulative chemodenervation by repeated botulinum toxin injections of sternocleidomastoid muscles measured by quantitative EMG. Contralateral noninjected sternocleidomastoid muscles however, seem to be affected following long-term treatment. The mechanism behind this finding is unknown.