Long-term botulinum toxin treatment increases employment rate in patients with cervical dystonia.

We examined the impact of cervical dystonia (CD) and long-term botulinum toxin (BTX) treatment on employment status. Data on employment status at onset of CD, at initiation of BTX treatment, and at evaluation of long-term treatment were obtained from 62 CD patients aged 31-66 years (median, 53 years; 61% females) who had been treated for a median of 5 years (range, 1.5-10 years). The employment rate fell from 84% at the onset of CD to 47% before initiation of BTX treatment. With long-term BTX treatment, 72% of those who worked at the initiation of treatment stayed employed, and 67% of those on sick leave returned to work. A younger age and a higher level of education increased the probability of being employed and avoiding disability benefits. Among those who were younger than 55 years at evaluation of BTX treatment (n = 40), the employment rate increased from 47% to 65% with treatment, and among the male patients, it reached the level of the general population (86%). About half of the 34% who received disability benefits did so already before the BTX treatment was initiated.     

Long-term follow-up by video of cervical dystonia treated with botulinum toxin

We have analysed video recordings of 21 patients with cervical dystonia treated with botulinum toxin. Fourteen patients have a record both of their response shortly after injections were commenced and between four years five months and six years seven months later. Our analysis shows that the long term outcome is often better than the initial response. We suggest that chronic treatment with botulinum toxin allows different muscles to those initially injected to be identified as contributors to the dystonia. Subsequent injection of these muscles leads to further improvement. It implies that cervical dystonia is a more widespread disorder of motor control, rather than simply limited to a few muscles.     

A型肉毒毒素治疗头颈部肌张力障碍的临床观察

目的观察A型肉毒毒素(BTXA)治疗偏侧面肌痉孪、睑痉孪、Meige’s综合征、痉孪性斜颈的疗效。方法治疗组(A组)用BTXA对86例患者进行头颈部肌肉多点注射,对照组(B组)50例根据诊断选用不同的药物或/和针灸、理疗、中医药治疗。观察两组疗效及副作用。结果A组治疗后当日至3d内开始见效,7～15d达高峰,疗效维持2～6月。总有效率为100%,疗效明显高于B组(P<0.001)。BTXA重复注射疗效无下降,1例HFS患者第三次注射产生耐药性,少数患者有轻微的局部副反应,未见全身副作用。B组62%(31例)的患者疗效维持5～15月后减退,需逐渐增加剂量,少数患者出现白细胞减少、肝功能损害、皮疹、共济失调等不良反应。结论A型肉毒毒素局部注射是治疗头颈部肌张力障碍的一种安全、有效、简便的方法。     

Somatosensory temporal discrimination tested in patients receiving botulinum toxin injection for cervical dystonia

We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow‐up in all CD patients. The lack of BTX‐induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation. © 2010 Movement Disorder Society     

Treatment of cervical dystonia with botulinum toxins

Botulinum toxin (BoNT) treatment has been used extensively for the treatment of cervical dystonia. In most studies, there is significant improvement following treatment for head posture and pain. The common side effects following treatment include dysphagia, dry mouth, and neck weakness. There are five brands and two serotypes of BoNT available. The dosing of each serotype and brand differs. Perhaps more importantly, each brand and serotype may differ in immunogenic potential and occurrence of secondary unresponsiveness, an issue that is currently under active investigation. Although many aspects of the technique of injection have not been adequately studied, general guidelines are available.     

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.     

Long-term botulinum toxin efficacy, safety, and immunogenicity.

To determine the long-term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow-up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 +/- 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0-to-4 scale (0 = no effect; 4 = marked improvement) was 3.7 +/- 0.6 and the mean total duration of response was 15.4 +/- 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab-negative patients, 16 resumed responsiveness after dose adjustments and 2 persisted as nonrespondents. Except for 1 patient, the 4 Ab-positive and the 2 clinical nonresponders are being treated with BTX-B. This longest reported follow-up of BTX injections confirms the long-term efficacy and safety of this treatment.     

Secondary nonresponsiveness to botulinum toxin type A in patients with oromandibular dystonia.

Intramuscular injection of botulinum toxin type A is the treatment of choice for most cases of oromandibular dystonia. We report on five patients with oromandibular dystonia that developed secondary nonresponsiveness to botulinum toxin type A following multiple injections over a 6-year period.     

Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy

The success of botulinum toxin (BT) injections for treatment of cervical dystonia depends on precise identification of dystonic muscles and on quantification of their dystonic involvement. Conventionally, this is attempted by clinical examination analysing the dystonic head position. In this presentation, a more systematic approach is sought by using an electromyography (EMG)-based evaluation procedure. In 10 consecutive patients with cervical dystonia not previously exposed to BT clinical examination, analysing the dystonic head position was performed to classify patients into four groups with similar dystonic head positions. Additionally, a 2-channel concentric needle EMG was used to measure the amplitudes of dystonic and maximal voluntary activities in sternocleidomastoid (SCM), splenius capitis (SC) and trapezius/semispinalis capitis (T/SS) muscles bilaterally. The ratio between both amplitudes, the dystonia ratio, was used to quantify dystonic muscle involvement. In all patients dystonia ratios could be calculated. In patients with similar head positions, EMG evaluation revealed different qualitative and quantitative dystonic involvement patterns. In six patients, there were discrepancies in identification of dystonic muscles between clinical examination and EMG evaluation. EMG evaluation excluded dystonic involvement in five patients. All excluded muscles were SCM. In one of these patients, additional T/SS involvement was detected by EMG evaluation. In one patient, SC involvement was revealed by EMG evaluation. All dystonic muscle involvement detected by EMG evaluation represented genuine dystonic muscle coactivation rather than compensatory muscle activity. The EMG evaluation presented allows quantitative and qualitative identification of dystonic muscle involvement which cannot be achieved by clinical examination. Both pieces of information may be helpful for optimization of BT therapy.     

Sustained attention in cranial dystonia patients treated with botulinum toxin

BACKGROUND: Primary cranial dystonia (PCD) is related to a functional disorder in basal ganglia usually accompanied by impaired executive function. AIM: To investigate symptom relief and neurocognitive change in response to treatment with botulinum toxin (BTX) in a group of patients with PCD. METHODS: We assessed nine patients with PCD and nine age- and educationally matched healthy individuals using tests of memory, sustained attention, span of auditory attention, and perceptual flexibility. RESULTS: Despite well-preserved intellectual skills relative to controls, we identified a sustained attention deficit in patients with PCD. After BTX treatment, there was an increase in the scores of the concentration endurance test (sustained attention) and the values did not differ significantly from control group patients' scores. CONCLUSION: The results support the view that executive dysfunction in PCD is secondary to the disrupting effects of the symptoms. Treatment with BTX alleviates the symptoms and, consequently, improves sustained attention.     

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     

Autonomic cardiovascular function and baroreflex sensitivity in patients with cervical dystonia receiving treatment with botulinum toxin type A

OBJECTIVE: To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A. METHODS: Short-term power spectral analysis of heart rate and systolic blood pressure variability, high-frequency and low-frequency oscillations of heart rate variability, low frequency/high frequency ratio and baroreflex sensitivity (alpha index) were measured in 12 patients with cervical dystonia before and 2-4 weeks after botulinum toxin type A injection and compared with normative data. RESULTS: Before treatment, at rest, patients had significantly lower high frequency power than healthy subjects (p < 0.01), whereas no differences were found in low frequency power. Botulinum toxin injection in patients induced no changes in either power frequency. In patients before treatment and healthy subjects the low frequency oscillatory components increased similarly from rest to tilt (p < 0.01), but tilt induced lower low frequency values in patients than in healthy subjects (p < 0.01). In patients before treatment, the high frequency variations from rest to tilt remained unchanged, whereas in healthy subjects they decreased significantly (p < 0.01). Botulinum toxin type A injection in patients induced no changes in low frequency or high frequency powers. In patients before treatment the low frequency/high frequency ratio increased slightly from rest to tilt, but in healthy subjects increased significantly (p < 0.01). Botulinum toxin type A left the pretreatment low frequency/high frequency ratio unchanged. The alpha-index measured at rest in patients before treatment was lower than in healthy subjects (p<0.05), whereas during tilt was similar in both groups. The alpha-index measured after botulinum toxin injection in patients remained unchanged at rest and during tilt. CONCLUSIONS: Patients with cervical dystonia receiving treatment with botulinum toxin type A have mild, subclinical abnormalities in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity. These changes do not worsen after acute botulinum toxin type A injection.     

Botulinum toxin type B vs. type A in toxin‐naïve patients with cervical dystonia: Randomized,double‐blind,noninferiority trial

The objective of this study was to compare efficacy, safety, and duration of botulinum toxin type A (BoNT‐A) and type B (BoNT‐B) in toxin‐naïve cervical dystonia (CD) subjects. BoNT‐naïve CD subjects were randomized to BoNT‐A or BoNT‐B and evaluated in a double‐blind trial at baseline and every 4‐weeks following one treatment. The primary measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) from baseline to week 4 post‐injection. Secondary measures included change in TWSTRS‐subscale scores, pain, global impressions, and duration of response and safety assessments. The study was designed as a noninferiority trial of BoNT‐B to BoNT‐A. 111 subjects were randomized (55 BoNT‐A; 56 BoNT‐B). Improvement in TWSTRS‐total scores 4 weeks after BoNT‐B was noninferior to BoNT‐A (adjusted means 11.0 (SE 1.2) and 8.8 (SE 1.2), respectively; per‐protocol‐population (PPP)). The median duration of effect of BoNT‐A and BoNT‐B was not different (13.1 vs. 13.7 weeks, respectively; P‐value = 0.833; PPP). There were no significant differences in the occurrence of injection site pain and dysphagia. Mild dry mouth was more frequent with BoNT‐B but there were no differences for moderate/severe dry mouth. In this study, both BoNT‐A and B were shown to be effective and safe for the treatment of toxin‐naive CD subjects. © 2007 Movement Disorder Society     

The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences.

The increasing use of botulinum toxin type-A, especially for focal dystonia and spasticity has highlighted the issue of secondary non-responsiveness. Within the last few years botulinum toxin type-B (Myobloc/Neurobloc) has become commercially available as an alternative to type-A. This paper discusses our initial experience of botulinum toxin type-B in a total of 63 individuals who attended our botulinum clinic. Thirty-six patients had cervical dystonia and a secondary non-response to type-A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type-A resistant. Seven of these show some continuing response to type-B, without unacceptable side effects. These findings demonstrate that botulinum toxin type-B has a place in the management of patients who have become non-responsive to type-A, but overall the responses to type-B toxin were disappointing.     

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.     

Treatment of cervical dystonia hand spasms and laryngeal dystonia with botulinum toxin

Summary One hundred and twenty-six patients with different forms of focal dystonia (89 with cervical dystonia, 12 with hand cramps and 25 with laryngeal dystonia) were treated with localised injections of botulinum toxin. Mean doses per muscle were 200 mouse units (m.u.) for treating cervical dystonia, 40–120 m.u. for forearm muscles in writers' cramp and 3.7 m. u. for the thyroarytenoid muscle in laryngeal dystonia. Responder rates have been above 80% in all patient groups and beneficial effects could be reproduced over follow-up periods of up to 4 years. The commonest side-effects were dysphagia after treatment of spasmodic torticollis, weakness of neighbouring muscles after injections for hand cramps and breathiness and hypophonia following laryngeal injections. All these were transient and generally well tolerated. It is concluded that botulinum toxin injections are a safe and effective treatment in all three types of focal dystonia.     

Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations

Amongst all regions of the body, the craniocervical region is the one most frequently affected by dystonia. Whilst blepharospasm – involuntary bilateral eye closure – is produced by spasmodic contractions of the orbicularis oculi muscles, oromandibular dystonia may cause jaw closure with trismus and bruxism, or involuntary jaw opening or deviation, interfering with speaking and chewing. Both forms of dystonia can be effectively treated with botulinum toxin injection. This article summarizes injection techniques in both forms of dystonia and compares doses, potency and efficacy of different commercially available toxins, including Botox®, Dysport®, Xeomin® and Myobloc®/NeuroBloc®.