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.     

Sympathetic block with botulinum toxin to treat complex regional pain syndrome

Complex regional pain syndrome is a refractory pain condition with few tested therapies. We hypothesized that botulinum toxin A (BTA) would prolong analgesia after sympathetic blocks in patients with complex regional pain syndrome. We compared the duration of standard lumbar sympathetic block (LSB) with bupivacaine to LSB with bupivacaine and BTA in nine patients with refractory complex regional pain syndrome. Median time to analgesic failure was 71 (95% confidence interval, 12–253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0–12) after standard LSB (log‐rank, p < 0.02). BTA profoundly prolonged the analgesia from sympathetic block in this preliminary study. Ann Neurol 2009;65:348–351     

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.     

Psychological features of patients with complex regional pain syndrome type I related dystonia

The objective of this study was to evaluate psychological features in severely affected patients with complex regional pain syndrome type I‐ (CRPS‐I) related dystonia. Personality traits, psychopathology, dissociative experiences, the number of traumatic experiences, and quality of life were studied in 46 patients. Findings were compared with two historical psychiatric control groups [54 patients with conversion disorder (CD) and 50 patients with affective disorders (AD)] and normative population data. The CRPS‐I patients showed elevated scores on the measures for somatoform dissociation, traumatic experiences, general psychopathology, and lower scores on quality of life compared with general population data, but had significantly lower total scores on the measures for personality traits, recent life events, and general psychopathology compared with the CD and AD patients. Rates of early traumatic experiences were comparable with the CD and AD patients, and the level of somatoform dissociation was comparable to the CD patients, but was elevated in comparison to the AD patients. Early traumatic experiences were reported in 87% of the CRPS‐I patients and were found to be moderately related to somatoform dissociative experiences, indicating that early traumatic experiences might be a predisposing, although not a necessary factor for the development of CRPS‐I‐related dystonia. Although the psychological profile of the patients with CRPS‐I‐related dystonia shows some elevations, there does not seem to be a unique disturbed psychological profile on a group level. © 2008 Movement Disorder Society     

A型肉毒毒素治疗口下颌肌张力障碍

目的观察A型肉毒毒素治疗口下颌肌张力障碍(OMD)患者的临床效果。方法对19例口下颌肌张力障碍患者进行临床分析,依据患者临床特点,将A型肉毒毒素注射到患者一侧或双侧咀嚼肌、颞肌及翼外肌,并根据肌肉收缩力量大小、肌肉体积及患者体重调整剂量。结果 68.4%的患者功能改善评分≥3分,疗效平均维持8～12周(有效范围2～28周)。4例患者注射后有轻度咀嚼无力,2～3周恢复。1例混合型患者注射后出现轻度鼻音,持续13天后症状消失。所有患者未出现其它严重副作用。结论 A型肉毒毒素对于口下颌肌张力障碍的治疗是有效、安全的。熟悉本病的临床特点及分型,选择正确的靶肌肉及注射适宜剂量的肉毒毒素是治疗本病的关键。     

Treatment of complex cervical dystonia with botulinum toxin: involvement of deep-cervical muscles may contribute to suboptimal responses

Complex cervical dystonia is a subgroup of cervical dystonia (CD) characterised by a combination of head deviations in more than one plane. In addition to superficial neck muscles, deep-cervical muscles contribute to a broad range of neck movements. These deep muscles include prevertebral muscles for primary neck flexion, lateral vertebral muscles for shoulder elevation and head tilt and a posterior group of muscles for neck extension. The authors describe three cases of complex deviations of the neck including anterocollis, retrocollis and lateral or sagittal shifts with involvement of deep-cervical muscles, which are not easily accessible by routine botulinum toxin (BoNT) therapy. Incomplete muscle selection may be one of the causes of treatment failures with BoNT in patients with complex CD, and targeting of deep-cervical muscles should be considered when patients exhibit complex deviations involving anterocollis, retrocollis, lateral or sagittal shifts.     

Jaw-opening oromandibular dystonia secondary to Wilson's disease treated with botulinum toxin type A

We have reported a case series of five patients with jaw-opening oromandibular dystonia secondary to Wilson's disease (WD), in which the patients were treated with botulinum toxin type A (BTX-A). In all cases, dystonia score was partially reduced three weeks after injections. The most common side effect was transient mild dysphagia. This preliminary study showed that jaw-opening oromandibular dystonia in WD may be partially responsive to the use of BTX-A.     

The complex relationship between antibody titers and clinical outcome in botulinum toxin type A long-term treated patients with cervical dystonia

Journal of Neurology - Repeated injections with abo- or onabotulinumtoxin type A (aboBoNT/A, onaBoNT/A) may lead to induction of neutralizing antibodies (NABs) and/or a secondary treatment failure...     

Thermal hypesthesia in patients with complex regional pain syndrome related dystonia

The quantitative thermal test showed cold and warmth hypesthesia without increased heat pain sensitivity in the affected limbs of complex regional pain syndrome (CRPS) patients with tonic dystonia (n = 44) in comparison with healthy controls with a similar age and sex distribution (n = 35). The degrees of cold and warmth hypesthesia were strongly correlated. We conclude that dysfunction in small nerve fiber (i.e., C and Aδ) processing is present in patients with CRPS-related dystonia.     

注射用A型肉毒毒素缓解脊髓损伤患者神经病理性疼痛的可行性

目的评价注射用 A型肉毒毒素缓解脊髓损伤（SCI）患者神经病理性疼痛（NP）的可行性。方法选择 2013年 4月 ~2016年 1月在荆州市第二人民医院就诊的SCI伴 NP患者 47例,随机分为试验组 24例和对照组 23例,分别给予注射用 A型肉毒毒素 200 U和生理盐水皮下注射,疗程 8周,评价治疗前和治疗 4周、8周后疼痛视觉模拟评分（VAS）、疼痛性质和生存质量。结果所有患者均顺利完成治疗。混合效应模型分析显示,试验组和对照组治疗前后不同时点 VAS评分、 VAS评分下降百分比、疼痛感觉、疼痛情感和总分差异均有统计学意义（P＜ 0.05）。重复测量效应分析显示,两组治疗前后各指标差异仍有统计学意义（P＜ 0.05）。分组与测量时点交互效应分析显示,两组各指标随时间变化趋势不同（P＜ 0.05）。以治疗前 WHO生存质量评估量表（WHOQOL）评分为协变量,治疗后第 8周试验组的生理领域、心理领域、环境领域评分高于对照组,差异有统计学意义（P＜ 0.05）社会关系领域组间比较差异无统计学意义（P＞ 0.05）。结论 A型肉毒毒素皮下注射能有效缓解 SCI患NP症状,镇痛效果优于安慰剂。     

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.     

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.     

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.     

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.     

Multifocal or generalized tonic dystonia of complex regional pain syndrome: a distinct clinical entity associated with HLA-DR13

We report on 26 patients with a distinct phenotype of complex regional pain syndrome that progressed toward a multifocal or generalized tonic dystonia. The dystonia initiated distally, involved mainly flexor muscles, and was associated with sensory and autonomic symptoms. Dryness of the eyes or mouth and bladder and bowel disturbances were frequently reported. There was no increase in the familial prevalence of autoimmune-mediated diseases. Compared with controls, a significant elevation of HLA-DR13 was found in the patients. Thus, HLA-DR13 may be a factor indicating susceptibility to this distinct phenotype of complex regional pain syndrome.