Posturographic findings in patients with idiopathic cervical dystonia before and after local injections with botulinum toxin.

In this posturographic study, whole-body postural control was impaired in more than 75% of patients with idiopathic cervical dystonia (ICD) before local injections with botulinum toxin type A (BTX-A) and the impairment was independent of the direction of the torticollis. Six weeks after therapy with BTX-A, the number of pathological posturographic parameters had decreased by almost 30%, and the improvement reached statistical significance for sway path, sway area and anteroposterior sway during stance on foam with eyes closed. From a pathophysiological point of view, this improvement may be explained - at least in part - by a reduction of abnormal proprioceptive input from the neck. Accordingly, it seems possible that neck proprioceptive input plays a role in whole-body postural control in ICD patients, even though previous studies suggested that the neck input is relatively ignored in these patients.     

Long-term follow-up of cervical dystonia patients treated with botulinum toxin A.

We followed the course in 100 consecutive patients with cervical dystonia (CD) after they were initially treated with botulinum toxin (BTX) in the form of Dysport 10 to 12 years ago. A total of 4 patients had died, and 6 were lost to follow-up. Of the remaining 90 patients, 57 (63%) were still treated with BTX. In the patients treated at one centre over the whole period with Dysport, mean dose used during each treatment session was 833 (SD +/- 339) units Dysport with a cumulative dose of 20,943 (SD +/- 9462) units Dysport over a mean of 26.8 (SD +/- 8.6) treatment cycles. Secondary nonresponse was detected in 3 of the 90 patients. During follow-up, 12 patients developed blepharospasm, 13 oromandibular dystonia, and 17 patients writer's cramp. We conclude that BTX remains effective and safe for approximately 60% of CD patients for more than 10 years.     

The impact of blepharospasm and cervical dystonia on health-related quality of life and depression

The aim of the study was to evaluate and compare health-related quality of life (HR-QoL) and depression in essential blepharospasm (BSP) and idiopathic cervical dystonia (CD), to identify the clinical and demographic factors associated with poor HR-QoL in both disorders and to analyse the effect of Botulinum Toxin A (BtxA) therapy. Two hundred-twenty consecutive patients with BSP (N = 89, 62 % women, mean age 64 years, mean disease duration 7 years) and CD (N = 131, 64 % women, mean age 53 years, mean disease duration 8 years) recruited from routine referrals to eight Austrian dystonia clinics were included. HR-QoL was measured by the Short Form 36 (SF-36) and depression by the Beck Depression Inventory (BDI). At baseline, patients with CD and BSP scored significantly worse in all eight SF-36 domains compared with an age-matched community sample. In addition, 47 % of patients with CD and 37 % of those with BSP were depressed. Women with BSP scored significantly lower in all SF-36 domains and were more depressed than male patients. In contrast, there was no significant effect of gender on HR-QoL and depression in CD. Neck pain had a significant impact on all SF-36 domains and represented the main determinant of depression in CD. Although BtxA therapy resulted in a significant improvement of clinical symptoms in BSP and CD, HR-QoL did not improve in BSP and only two of the eight SF-36 domains improved significantly in patients with CD. The present study for the first time demonstrated that BSP has a substantial impact on health status emphasizing the need for psychological support with interventions aimed at treating depression in these patients. Our results provide further evidence for the profound impact of CD on HR-QoL and indicate the importance of an adequate management of neck pain in addition to reducing the severity of dystonia in CD. The mismatch between objective BtxA derived improvement of dystonia and lack of change of HR-QoL as determined by the SF-36 illustrates the need for optimized disease specific quality of life rating scales in patients with craniocervical dystonia.     

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.     

Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia

Neutralization of antibodies poses a problem for a substantial number of cervical dystonia (CD) patients treated with botulinum toxin type A (BoNT/A). Presence of these antibodies may lead to a secondary nonresponse to BoNT/A treatment. In this study, we compared 6 antibody-positive (Ab+) with 12 antibody- negative (Ab-) CD patients treated with BoNT/A (Dysport) and matched for du- ration of treatment, number of BoNT/A injections, and severity of clinical symptoms. The two groups differed in cumulative BoNT/A dose (Ab+, 5984 mouse units [MU ], SD = 3151 MU; Ab-, 3143 MU, SD =1294 MU; P <.05), in addition, ab+ patients were significantly younger (ab+ mean age = 41.3 y, sd =5.9 y; ab - mean age = 56.8 y, sd = 15.3 y; p <.05), in or- der to avoid formation of neutralizing antibodies, doses of bont/a should be kept as low as possible, the risk of antibody formation seems to be higher in younger patients.     

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.     

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     

Factors affecting health-related quality of life amongst Asian patients with Parkinson's disease

Background and purpose:  This cross-sectional study was carried out to identify factors predicting health-related quality of life (HRQoL) amongst Asian patients with Parkinson's disease (PD).
Methods:  A total of 183 PD patients (mean age: 61 years, male: 68.9%) attending a tertiary neuroscience clinic in Singapore completed the English or Chinese version of the 8-item Parkinson's Disease Questionnaire (PDQ-8). Patients' socio-demographic characteristics and their clinical variables were analysed to identify factors influencing the PDQ-8 Summary Index and responses to its eight dimensions.
Results:  In the multiple linear regression model, the use of Chinese survey, higher motor score and longer duration of PD were associated with poorer overall HRQoL. The multiple logistic regression analyses showed that female patients and patients with higher Hoehn and Yahr stage were more probably to report worse emotional well-being; patients who completed Chinese survey reported more problems with mobility, cognition and stigma; patients with higher motor scores were more probably to report problems with activities of daily living; patients with longer duration of PD were more probably to report problems with mobility, social support, communication and stigma.
Conclusion:  Both socio-demographic factors and disease-specific variables influence HRQoL in PD patients; the effects of culture-related factors on HRQoL should not be overlooked when assessing HRQoL in multi-cultural settings.     

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.     

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.     

Effects of botulinum toxin type A on intracortical inhibition in patients with dystonia

To find out whether botulinum toxin alters the excitability of cortical motor areas, we studied intracortical inhibition with transcranial magnetic stimulation in patients with upper limb dystonia before, 1 month after, and 3 months after the injection of botulinum toxin type A in the affected muscles. Eleven normal subjects and 12 patients with dystonia involving the upper limbs (7 with generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were studied. Patients were assessed clinically with the Dystonia Movement Scale. Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators connected through a Bistim module to a figure-of-eight coil placed over the motor area of the forearm muscles. Paired stimulation was given at rest. A subthreshold (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before the suprathreshold (120% of motor threshold) test stimulus. Electromyographic signals were recorded over the flexor or extensor muscles of the forearm on the affected side. We measured the amplitude of the test motor evoked potential (expressed as a percentage of the unconditioned motor evoked potential). All results were compared using ANOVA. In all patients, a botulinum toxin type A injection (50-100 mouse units) reduced dystonic movements in the arm. In normal subjects, electromyographic recordings showed significant inhibition of the test response. Before botulinum toxin injection, patients had less test response inhibition than normal subjects. One month after injection, patients had test response inhibition similar to that of normal subjects. At 3 months after injection, they again had less inhibition than normal subjects or patients at 1 month after injection. In conclusion, our data suggest that botulinum toxin can transiently alter the excitability of the cortical motor areas by reorganizing the inhibitory and excitatory intracortical circuits. The cortical changes probably originate through peripheral mechanisms.     

颈部肌张力障碍临床分型及肉毒毒素疗效

目的根据颈部肌张力障碍患者的不同临床特点进行临床分型并观察不同类型患者A型肉毒毒素治疗效果。方法分析186例颈部肌张力障碍患者头颈部的异常姿势，进行临床分型，并对152例患者采用A型肉毒毒素肌肉注射治疗。结果186例颈部肌张力障碍患者头颈部异常姿势中，单纯扭转型88例（47．3％），侧倾型10例（5．4％），前屈型1例（0．5％），后仰型12例（6．5％），单纯震颤型5例（2．7％），旋转前屈型26例（14．0％），旋转后仰I型13例（7．0％），旋转后仰Ⅱ型3l例（16．7％）。有152例局部注射A型肉毒毒素治疗颈部肌张力障碍，其中10例资料不完整者剔除。临床症状显著缓解121例（85．2％），其中单纯扭转型缓解率最高，为93．4％（71／76），旋转后仰Ⅱ型缓解率最低（43．8％，7／16）。最常见的副作用是注射局部的肌肉疼痛和颈肌无力。结论熟悉颈部肌张力障碍的临床分型，精确定位受累肌肉及注射适宜剂量的肉毒毒素是有效治疗的关键。     

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.

     

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.     

CDIP-58 can measure the impact of botulinum toxin treatment in cervical dystonia

We compared the responsiveness of the Cervical Dystonia Impact Profile (CDIP-58), Medical Outcome Study Short Form-Health Survey (SF-36), Functional Disability Questionnaire (FDQ), and Pain and Activities of Daily Living subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in participants with cervical dystonia treated with botulinum toxin A. Subscales of CDIP-58 were more sensitive in detecting statistical and clinical change than comparable subscales of the SF-36, FDQ, and TWSTRS.     

肌电图下局部注射A型肉毒毒素治疗痉挛性斜颈临床观察

目的探讨肌电图引导下局部注射A型肉毒毒素治疗痉挛性斜颈的疗效。方法在肌电图引导下采用A型肉毒毒素局部多点注射治疗痉挛性斜颈42例,治疗前后的病情采用Tsui量表进行评分比较。结果症状基本缓解20例,占47.62%,明显缓解18例,占42.86%,部分缓解4例,占9.52%,无效0例,有效率90.48%。疗效平均持续约6月左右,最长达1~3年。复发者重复注射仍有效且剂量无增加,局部不良反应轻微短暂。结论肌电图引导下局部注射A型肉毒毒素治疗痉挛性斜颈是一种安全有效且简便易行的方法,可重复注射。     

A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia

A new botulinum toxin type A free of complexing proteins (NT 201) was compared with BOTOX in patients with cervical dystonia by means of a double-blind noninferiority trial. Four hundred sixty-three patients received IM injections of 70 to 300 U of NT 201 or BOTOX and were followed up over 16 weeks. The study clearly shows that NT 201 is at least as effective and safe as BOTOX.     

Patients' perception of stopping or continuing treatment of cervical dystonia with botulinum toxin type A.

Despite widespread commercial acceptance of botulinum toxin (BTX) for idiopathic cervical dystonia (ICD), no follow up has been performed to determine when and why some patients stop therapy. It has been suggested that some patients who stop BTX treatment may do so because of permanent improvement. We surveyed 155 patients with ICD who were treated over 6 years with BTX to determine when and why patients stopped treatment with BTX, and what adverse events and changes in dose and/or frequency of treatments occurred in those who continued treatment. Of the 133 (86.6%) individuals returning the surveys, 104 continued on BTX treatment and 29 had stopped therapy. Of the 29 subjects no longer receiving BTX, 11 individuals had only received one or two injections. Prior surgical treatment for ICD did not influence their decision to stop therapy. Of those 104 of 133 continuing on BTX treatments, two thirds of the subjects reported the injections always help, whereas one quarter estimated one set of injections did not help. One third of those continuing treatment reported the first injection was most helpful, whereas another one third felt all injections were similarly effective. After an initial adjustment, BTX dosages and frequency of treatment remained stable in this group.