A型肉毒毒素注射治疗慢性紧张型头痛的临床对照研究

目的 对A型肉毒毒素注射治疗慢性紧张型头痛的疗效及安全性进行临床观察和研究.方法 纳入慢性紧张型头痛病人共50例,分为A型肉毒毒素注射治疗组和传统药物治疗对照组,每组各25例,对两组疗效进行比较研究,并对A型肉毒毒素注射治疗的安全性进行观察.结果 肉毒毒素注射治疗组较传统药物治疗对照组在治疗后1、2及3个月各项指标(头痛发作天数、发作时头痛严重程度、头痛发作持续时间、需临时口服止痛药的天数)的改善均更加显著(P<0.05).肉毒毒素注射治疗组约72%的病例感颈部乏力,约在1周~1月内消失,无其他明显不良反应.结论 A型肉毒毒素注射治疗慢性紧张型头痛方法简便、起效快、效果显著、副反应小、药效维持时间长.     

A型肉毒杆菌毒素

肉毒杆菌毒素是肉毒杆菌分泌的一种生物毒性蛋白质,其药理机制是与胆碱能神经末稍SNAP-25等蛋白产生作用,抑制乙酰胆碱释放,减少肌肉收缩和痉挛.目前,A型肉毒杆菌毒素获准用于治疗皱纹,其疗效平均持续4～6月,可以反复注射治疗.本文系统的回顾了A型肉毒杆菌毒的作用机制、临床试验、临床应用及不良反应.大量研究和病例分析已证明肉毒杆菌毒素注射术对于治疗面部各部位的皱纹是安全有效的.     

A型肉毒毒素作用于神经胶质细胞缓解神经病理性疼痛机制的研究进展

神经病理性疼痛是一个重要的临床问题,常规药物治疗效果不佳。A型肉毒毒素可缓解多种疼痛,其镇痛作用被认为与神经胶质细胞相关。本文概要介绍A型肉毒毒素作用于神经胶质细胞缓解神经病理性疼痛机制的研究进展,进一步探究A型肉毒毒素在神经病理性疼痛治疗上的临床潜力。     

A型肉毒毒素治疗紧张型头痛合并面肌痉挛的疗效观察

目的观察紧张型头痛合并面肌痉挛患者选择A型肉毒毒素治疗的临床效果。方法 52例紧张型头痛合并面肌痉挛患者,采用随机单盲法分为对照组和观察组,每组26例。对照组患者采用常规治疗,观察组患者采用A型肉毒毒素治疗。比较两组患者治疗效果、不良反应发生情况及疼痛评分。结果观察组患者的治疗总有效率100.00%明显高于对照组的80.77%,差异有统计学意义(P<0.05)。观察组不良反应发生率11.54%(3/26)和对照组的7.69%(2/26)比较差异无统计学意义(χ²=0.221, P=0.638>0.05)。治疗后,观察组患者的疼痛评分(4.1±0.6)分低于对照组的(4.9±0.9)分,差异具有统计学意义(t=3.771, P=0.000<0.05)。结论 A型肉毒毒素治疗紧张型头痛合并面肌痉挛的效果显著,安全度高,能减轻疼痛感受程度,应在临床治疗中引起关注。     

A型肉毒杆菌毒素治疗61例面肌痉挛的临床分析

目的探讨A型肉毒杆菌毒素对面肌痉挛的疗效及副作用。方法对61例面肌痉挛患者进行面部多点注射A型肉毒毒素,对其疗效进行电话随访。结果 A型肉毒毒素治疗总有效率为95%,副作用主要为短期上睑下垂、患侧眼流泪、复视。其疗效与病程长短和病情严重程度有关,病情越长,有效时间越短。结论局部注射A型肉毒毒素是治疗面肌痉挛的一种有效手段,方法简便易行,可作为治疗的首选药物。     

曲安奈德颈部注射治疗颈源性头痛的疗效观察

目的通过颈部注射曲安奈德治疗颈性头痛的临床观察,探讨其作用机制及临床治疗。方法随机将40位颈性头痛患者分为二组,分别给予颈部注射曲安奈德治疗和口服非甾体类药物和肌松药物治疗,观察其治疗后效果。结果治疗1个疗程后,治疗组治愈率为60%,对照组治愈率为30%,P<0.05,治疗组总有效率为90%,对照组的总有效率为50%,P<0.01。结论颈部注射曲安奈德是治疗颈源性头痛的有效方法之一,颈源性头痛的病因多数是由于颈部的软组损害引起。     

A型肉毒毒素注射治疗雄激素源性脱发的机制及研究进展

雄激素源性脱发作为常见的毛发疾病，其发病因素多元，且治疗周期性较长。明确其发病机制及治疗方法尤为重要。A型肉毒毒素注射治疗作为主流的治疗方式，取得了良好的效果。本文以此为背景，结合诸多研究结果及文献，综合性分析A型肉毒毒素注射治疗雄激素源性脱发的机制，治疗效果以及目前的研究进展，以期为后续的治疗奠定理论基础。     

A型肉毒毒素的临床拓展应用及认识

A型肉毒毒素[BTX-A]局部肌肉注射在神经科、整形美容科已普遍使用。目前也已在临床上许多学科常见病中拓展应用。作为一种新的微创治疗方法 ,其开辟了治疗某些疾病的新的有效途径。临床应用有许多优点,同时也存在缺点及副作用。应通过不断的临床实践、探讨、总结,更好的认识、使用和开发A型肉毒毒素。     

A型肉毒毒素局部注射注意事项

A型肉毒毒素通过阻断神经肌肉的传导的毒性作用，在特定条件下控制肌肉痉挛和缓解局灶性肌张力障碍，治疗人类疾病而被广泛应用于临床。目前在神经科领域，A型肉毒毒素可用于眼睑痉挛，面肌痉挛，痉挛性斜颈Meige综合征、构音障碍、书写痉挛、咬肌痉挛、胸瘫后遗症及其他一些疾病的治疗，现就我们注射A型肉毒毒素治疗面肌眼肌痉挛的一些注意事项总结如下：     

A型肉毒毒素抑制乙酰胆碱诱发的大鼠离体幽门平滑肌的收缩

目的：观察A型肉毒毒素对内、外源性乙酰胆碱诱发的大鼠离体幽门平滑肌收缩的作用,并探讨其可能作用机制。方法：利用电场刺激诱发大鼠离体幽门平滑肌释放乙酰胆碱或加入外源性乙酰胆碱诱发肌条收缩,比较A型肉毒毒素与阿托品对该诱发收缩的作用。结果：A型肉毒毒素抑制电场刺激诱发的大鼠离体胃幽门平滑肌的收缩（P〈0.001）。阿托品和A型肉毒毒素均抑制乙酰胆碱诱发的大鼠离体胃幽门平滑肌的收缩（P〈0.001）,但A型肉毒毒素对乙酰胆碱诱发的收缩表现为不完全抑制。结论：A型肉毒毒素抑制电场刺激诱发内源性乙酰胆碱释放所产生的收缩作用,可能其裂解突触前膜上的SNAP-25蛋白而致;A型肉毒毒素抑制外源性乙酰胆碱诱发的肌条收缩作用类似阿托品,但机制尚不明,可能A型肉毒毒素作用于突触后膜受体或者平滑肌上的SNAP-25蛋白,而抑制肌条的收缩。     

Investigating prophylactic botulinum toxin type A for chronic headache disorders

There is an increasing number of studies on botulinum toxin A in the treatment of idiopathic and symptomatic headache; however, many studies can hardly be compared with each other because of different end points and different trial designs. For the prophylactic treatment of tension-type headache, migraine and cervicogenic headache, no sufficient positive evidence for a successful treatment can be obtained from the randomised, double-blind and placebo-controlled trials performed so far. For the treatment of chronic daily headache (including medication-overuse headache), there is inconsistent positive evidence for subgroups (e.g., patients without other prophylactic treatment). This means that most of the double-blind and placebo-controlled studies do not confirm the assumption that botulinum toxin A is efficacious in the treatment of idiopathic headache disorders; however, it is possible that some subgroups of patients with chronic migraine benefit from a long-term treatment for ≥ 6 months.     

Cervicogenic headache: practical approaches to therapy

Cervicogenic headache is a relatively common and still controversial form of headache arising from structures in the neck. The estimated prevalence of the disorder varies considerably, ranging from 0.7% to 13.8%. Cervicogenic headache is a 'side-locked' or unilateral fixed headache characterised by a non-throbbing pain that starts in the neck and spreads to the ipsilateral oculo-fronto-temporal area. In patients with this disorder, attacks or chronic fluctuating periods of neck/head pain may be provoked/worsened by sustained neck movements or stimulation of ipsilateral tender points. The pathophysiology of cervicogenic headache probably depends on the effects of various local pain-producing or eliciting factors, such as intervertebral dysfunction, cytokines and nitric oxide. Frequent coexistence of a history of head traumas suggests these also play an important role. A reliable diagnosis of cervicogenic headache can be made based on the criteria established in 1998 by the Cervicogenic Headache International Study Group. Positive response after an appropriate nerve block is an essential diagnostic feature of the disorder. Differential diagnoses of cervicogenic headache include hemicrania continua, chronic paroxysmal hemicrania, occipital neuralgia, migraine and tension headache. Various therapies have been used in the management of cervicogenic headache. These range from lowly invasive, drug-based therapies to highly invasive, surgical-based therapies. This review evaluates use of drug therapy with paracetamol and NSAIDs, infliximab and botulinum toxin type A; manual modalities and transcutaneous electrical nerve stimulation therapy; local injection of anaesthetic or corticosteroids; and invasive surgical therapies for the treatment of cervicogenic headache. A curative therapy for cervicogenic headache will not be developed until increased knowledge of the aetiology and pathophysiology of the condition becomes available. In the meantime, limited evidence suggests that therapy with repeated injections of botulinum toxin type A may be the most safe and efficacious approach. The surgical approach, which includes decompression and radiofrequency lesions of the involved nerve structures, may also provide physicians with further options for refractory cervicogenic headache patients. Unfortunately, the paucity of experimental models for cervicogenic headache and the relative lack of biomolecular markers for the condition mean much is still unclear about cervicogenic headache and the disorder remains inadequately treated.     

Botulinum toxin type A for migraine. First, do no harm

Headache prevention in adults with chronic migraine is based first on oral drug therapy, preferably with propranolol, and on tapering off possible analgesic overuse. Botulinum toxin type A injections in head and neck muscles is now authorised for this purpose in the United Kingdom. It has been used off label for several years. Clinical evaluation in this indication is based on two placebo-controlled double-blind trials with identical designs. A total of 1384 patients underwent two sessions of intramuscular injections of botulinum toxin type A or placebo, 3 months apart, into at least 31 specific sites in the head and neck. Compared to baseline, patients who received botulinum toxin in one trial (but not in the other) experienced a statistically significant reduction in headache frequency at the end of the study, but the results are undermined by methodological issues. Botulinum toxin type A has not been compared with preventive oral therapy. An inherently unreliable indirect comparison suggests that botulinum toxin type A is clearly less effective than oral propranolol. In its other approved indications, botulinum toxin type A has been linked to deaths and muscle paralysis distant from the injection site, leading to swallowing difficulties and respiratory disorders. Some patients enrolled in clinical trials of botulinum toxin type A experienced transient worsening of their migraine and headache (9.3%, versus 5.8% of patients receiving placebo injections), exaggerated paralytic effects, and muscle pain and stiffness. In practice, given its uncertain efficacy, at best only modest, botulinum toxin type A is simply too risky a treatment for migraine. It is better to focus on fine tuning of standard prophylaxis.     

Investigating prophylactic botulinum toxin type A for chronic headache disorders

There is an increasing number of studies on botulinum toxin A in the treatment of idiopathic and symptomatic headache; however, many studies can hardly be compared with each other because of different end points and different trial designs. For the prophylactic treatment of tension-type headache, migraine and cervicogenic headache, no sufficient positive evidence for a successful treatment can be obtained from the randomised, double-blind and placebo-controlled trials performed so far. For the treatment of chronic daily headache (including medication-overuse headache), there is inconsistent positive evidence for subgroups (e.g., patients without other prophylactic treatment). This means that most of the double-blind and placebo-controlled studies do not confirm the assumption that botulinum toxin A is efficacious in the treatment of idiopathic headache disorders; however, it is possible that some subgroups of patients with chronic migraine benefit from a long-term treatment for > or = 6 months.     

Clinical profile of botulinum toxin A in patients with chronic headaches and cervical dystonia: a prospective, open-label, longitudinal study conducted in a naturalistic clinical practice setting

BACKGROUND AND OBJECTIVES: Some evidence for the efficacy of botulinum toxin A as a preventive treatment for chronic primary headaches has been reported in randomized, controlled clinical studies. This study investigated the clinical profile of botulinum toxin A in a naturalistic clinical practice setting in a population of patients with cervical dystonia associated with chronic headache and a history of migraine. METHODS: This was a prospective, open-label, longitudinal study. Following a prospective run-in period, eligible patients were given three sets of botulinum toxin A injections at 8- to 12-week intervals over a 16- to 24-week period and were monitored for 3 months after the final injections. Efficacy was assessed in terms of headache-related disability (using the Migraine Disability Assessment [MIDAS] questionnaire), pain and emotional function (using the Short Pain Inventory [SPI]), quality of life (QOL, using the Short-Form-36 [SF-36] questionnaire) and patient-assessed headache frequency and severity, and medication use and its effectiveness. Safety was assessed as adverse events. The primary endpoint was the change in MIDAS score from baseline following treatment with botulinum toxin A. RESULTS: Twenty-four patients took part in the study and 17 (71%) completed the study. There were significant improvements in headache-related disability (MIDAS score), pain and emotional function (SPI), QOL (SF-36), headache frequency and medication use following treatment with botulinum toxin A (p < 0.05 for all endpoints). An efficacy response occurred within 8 weeks of treatment initiation and was maintained throughout the study duration. Botulinum toxin A was generally well tolerated. CONCLUSIONS: This study demonstrated that botulinum toxin A is an effective and well tolerated preventive treatment for chronic headache in patients with cervical dystonia and a history of migraine. These results warrant further investigation in a large, randomized, controlled study.     

Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects

Botulinum toxin (BTX) injections are a well-recognised therapeutic modality for the treatment of regional involuntary muscle disorders and recently BTX has been used for treatment of pain and inflammatory disorders. The primary purpose of this review is to discuss the mechanism of action of therapeutic BTX in light of both the traditional understanding of BTX pharmacological effects as well as new observations. The review will deal with clinical observations and relevant animal experimentation. The data and hypotheses presented are not only relevant to botulinum toxin technology but will certainly prove important in the basic mechanisms of some of the diseases where botulinum toxin has been successfully applied. BTX used clinically comprises botulinum neurotoxin (BoNT) complexed with non-toxic proteins. The non-toxic components of the BTX complexes stabilise the labile BoNT during purification and formulation as a therapeutic. The complex proteins may also have unrecognised clinical significance such as slowing diffusion in tissues or imparting stability. The mechanisms of BTX formulations acting on SNARE proteins are briefly reviewed providing a basis for BTX clinical applications. The potential for design of improved botulinum toxins and formulations is addressed.     

Botulinum toxin type A for the treatment of migraine

Migraine is a common and debilitating disorder that often requires prophylactic therapy, particularly for those migraine patients who meet the diagnostic criteria for chronic daily headache (chronic migraine). Existing prophylactic treatments for migraine are inadequate for many patients due to their modest efficacy and/or systemic side effects. Alternative treatment strategies are needed, particularly in those with chronic migraine. Botulinum toxin type A is a locally injected protein complex that has been investigated as a treatment for episodic migraine and chronic daily headache. A systematic series of controlled trials has led to the identification of a subset of migraineurs with chronic daily headache who obtain demonstrated benefits of botulinum toxin type A over placebo that is maintained with repeated treatments.     

Botulinum Toxin in the Treatment of Headache

Botulinum toxin type A has been used in the treatment of chronic migraine for over a decade and has become established as a well-tolerated option for the preventive therapy of chronic migraine. Ongoing research is gradually shedding light on its mechanism of action in migraine prevention. Given that its mechanism of action is quite different from that of the new monoclonal antibodies directed against calcitonin gene-related peptide (CGRP) or its receptor, it is unlikely to be displaced to any major extent by them. Both will likely remain as important tools for patients with chronic migraine and the clinicians assisting them. New types of botulinum toxin selective for sensory pain neurons may well be discovered or produced by recombinant DNA techniques in the coming decade, and this may greatly enhance its therapeutic usefulness. This review summarizes the evolution of botulinum toxin use in headache management over the past several decades and its role in the preventive treatment of chronic migraine and other headache disorders.     

Botulinum toxin B: a review of its therapeutic potential in the management of cervical dystonia

Botulinum toxins are well known as the causative agents of human botulism food poisoning. However, in the past two decades they have become an important therapeutic mainstay in the treatment of dystonias including cervical dystonia, a neurological disorder characterised by involuntary contractions of the cervical and/or shoulder muscles. The toxins inhibit acetylcholine release from neuromuscular junctions, producing muscle weakness when injected into dystonic muscles. Data from three double-blind, randomised, placebo-controlled trials demonstrate that botulinum toxin B effectively reduces the severity, disability and pain of cervical dystonia. In two of the trials, mean Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 (primary efficacy measure) after botulinum toxin B 10 000U was reduced by 11.7 (25%) or 11 (21%) compared with baseline. These changes were significantly greater than those obtained with placebo [4.3 (10%) or 2 (4%)] and were generally similar in patients who were responsive or resistant to botulinum toxin A. Statistically significant benefits compared with placebo were also evident for a range of other efficacy parameters including TWSTRS-Severity, -Pain and -Disability subscales, patient- assessed pain and patient-/physician-assessed global improvement ratings. In another trial, the percentage of patients with botulinum toxin A-resistant or -responsive cervical dystonia who had a > or =20% improvement in the TWSTRS-Total score between baseline and week 4 was significantly higher with botulinum toxin B 2500 to 10 000U (58 to 77%) than with placebo (27%). Overall, botulinum toxin B was generally well tolerated. The most frequently reported treatment-related adverse events were dry mouth and dysphagia. Most adverse events in patients receiving botulinum toxin B were mild or moderate; no serious adverse events or laboratory abnormalities were associated with the use of botulinum toxin B and, where reported, no patients discontinued from any of the clinical trials as a result of adverse events. CONCLUSIONS: Botulinum toxin B has shown clinical efficacy in patients with cervical dystonia at doses up to 10 000U and is generally well tolerated. Its efficacy extends to patients who are resistant to botulinum toxin A. Although the potential for secondary resistance to botulinum toxin B remains unclear, it may occur less than with botulinum toxin A because methods for manufacturing commercially available botulinum toxin B do not include lyophilisation and the product does not require reconstitution before use. As injection with botulinum toxin is generally considered the treatment of choice for patients with cervical dystonia, botulinum toxin B should be considered a potential treatment option in this setting.