肉毒毒素中毒

肉毒毒素是肉毒梭(杆)菌产生的外毒素. 肉毒杆菌厌氧生长,能长久在土壤、泥土中生存.在一些草食动物肠道中生存,仅在特定情况下在肠道大量繁殖.菌体在不良环境下生成芽孢,芽孢对环境的适应力极强,耐热、耐干燥,一般的灭菌方法,如煮沸、紫外线照射等均不能杀灭.     

肉毒梭菌及其毒素分型方法概述

自1897年van Ermengem分离并报道了可形成孢子的肉毒梭菌导致人类中毒以来,研究人员通过血清中和方法发现自然界中存在7种不同型别的肉毒梭菌。 随后,再次应用血清学方法又发现了可产生双价毒素Ab、Ba、AB、Af和Bf等肉毒梭菌。 随着基因测序技术的逐渐成熟和完善,通过提取肉毒梭菌基因进行全基因组测序,不仅可识别不同血清型肉毒毒素的基因组成,也可开展核酸或蛋白质分子水平的分型研究。 相比血清中和分型方法,这些新涌现的分型技术和方法不仅可解开血清学分类中遇到的难题,更可快速准确地鉴别肉毒梭菌导致的食物或药物中毒,并追踪源头及应用相应药物治疗。 此外,不同分型方法对于肉毒梭菌菌种鉴定和使用,新型毒素的研发都提供了新的工具和思路。     

肉毒杆菌毒素在眼科的应用进展

肉毒杆菌毒素是由肉毒杆菌在繁殖过程中所产生的一种神经毒素蛋白,其作用机制是阻断乙酰胆碱在胆碱能神经的神经肌肉接头释放而阻断传导冲动。在眼科诊疗中,它已被常规用于眼睑痉挛、斜视、眼周除皱、上睑挛缩等眼部疾病的治疗,其疗效确切。本文综述了肉毒杆菌毒素在眼科的相关应用进展。     

肉毒毒素在康复医学中的应用

肉毒毒素（botulinum toxins, BTXs）是从肉毒杆菌属中获得的嗜神经毒素.依其毒性和抗原性的不同,分为A～G 7型.其中毒力最强的是A型肉毒杆菌毒素（BTXA）,它是最早被提纯为结晶,生产工艺最成熟,最早应用于实验研究,也是目前临床最常用的.现就其作用机制、在康复医学中的应用和应用要点综述如下.     

肉毒毒素的结构和功能

内毒杆菌可产生A～G型7种独特的神经毒素，抑规神经肌肉接头处及实问乙酸胆陆的释放，引起人和动物的内毒中毒．各型神经毒素的分子量约150KDa，与非毒性成分结合，形成300～900KDa的原始毒素．目前，A～G型神经毒素的基因巴克隆化，并确定了氨基酸序列．该毒素是一种锌结合蛋白，具蛋白两活性．1神经写囊的结构和功能A～G型神经毒素首先以单链形式台成（约150KDa），然后被蛋白酶在N端1／3处分割为由二疏因连接的两条单键（轻键50IClk，重键100KDa），重键的50KDaC末端参与神经特异性结合，其余部分作为介导轻铸进人胞液的通道．由…     

注射用A型肉毒毒素在眼睑与面肌痉挛中的应用

目的 提高应用肉毒毒素治疗眼睑与面肌痉挛的安全性.方法 采用注射用A型肉毒毒素对眼睑、面肌痉挛患者进行局部肌肉多点注射法.结果 21例眼睑、面肌痉挛经注射肉毒毒素,大部分完全缓解或明显缓解,仅少部分为部分缓解,有效率达100%.全部病例均未出现全身毒副作用,局部并发症有轻微上睑下垂、眼睑闭合不全、瞬目减少,轻度面瘫,均于治疗后3～4周自然恢复.结论 肉毒毒素局部注射为眼睑、面肌痉挛患者提供了一个安全、有效、可靠的治疗方法,值得临床推广使用.     

A型肉毒毒素在慢性疼痛中的应用进展

A型肉毒毒素因松弛麻痹肌肉的药理作用,曾广泛应用于神经肌肉过度活跃性疾病。近年来随着人们发现其在外周和中枢神经系统的去敏化作用,其临床应用范畴已由肌痉挛相关性疼痛逐步扩展到慢性偏头痛乃至神经病理性疼痛。但目前A型肉毒毒素镇痛机制尚需进一步完善,临床应用仍处起步阶段,其镇痛适应证、剂量、注射部位、治疗时机和远期疗效等仍需探索。本文就A型肉毒毒素治疗慢性疼痛的镇痛机制和应用进展进行综述。     

肉毒毒素临床应用进展及适应症审批的意义

肉毒毒素是肉毒梭菌增殖过程中产生的一种细菌外毒素,其可作用于周围神经末梢的神经肌肉接头处抑制突触前神经递质乙酰胆碱的释放,实现肌肉化学性去神经支配、镇痛、调节自主神经紊乱等效应.本文重点概述肉毒毒素的治疗效应,以及肉毒毒素临床应用进展和肉毒毒素适应症开发的临床价值.     

A型肉毒毒素治疗三叉神经痛

目的:观察A型肉毒毒素治疗三叉神经痛(TN)的临床疗效。方法:选取57例TN患者,随机分为A、B 2组。A组28例患者口服卡马西平片治疗;B组29例在疼痛部位及板机点周围皮下注射肉毒素治疗。治疗后1,3及6个月时随访,行简式McGill疼痛问卷表(SF-MPQ)及生活质量评价量表(SF-36)评分,并观察不良反应。结果:治疗中脱失7例,A组3例,B组4例。与治疗前3个月SF-MPQ及SF-36平均分作为基础水平比较,治疗1,3及6个月后2组SF-MPQ评分明显下降,SF-36明显上升(P<0.01),B组表明更明显(P<0.05,P<0.01)。治疗过程中,A组出现不适患者多于B组。结论:A型肉毒毒素疼痛点皮下注射治疗TN发作作用高峰1～3个月,维持时间6个月,且临床疗效显著,不良反应轻微。     

肉毒毒素注射为主治疗偏瘫肩痛

2011年3～5月我科住院的脑卒中后偏瘫肩痛患者3例,均符合第四届脑血管病会议制定的诊断标准,且偏瘫侧肩呈自发性疼痛,活动受限,被动活动时加剧,男2例,女1例;年龄50～70岁,病程3～7个月。     

尿道镜下外括约肌注射A 型肉毒毒素治疗62例排尿障碍患者的疗效观察

目的 评价A型肉毒毒素（BTX-A）尿道外括约肌注射治疗多种因外括约肌痉挛所致的排尿障碍的疗效。方法　选取2005年5月至2007年6月多种因外括约肌痉挛所致的排尿障碍的患者62例，其中男43例，女19例，中位年龄37岁（15～78岁）。临床表现为尿潴留、排尿困难，需腹肌用力协助排尿，尿频，尿失禁等。将BTX-A200 U溶解于8 ml生理盐水，尿道镜下使用注射针分8点二平面注射于尿道外括约肌处，1 ml/ 点，25U/点。记录治疗前后排尿症状，尿动力学检查，并观察毒副作用。记录患者注射前后排尿前和排尿时EMG振幅值（T、L值），我们将排尿前EMG振幅值T与排尿中L值的比值之常用对数定义为TL值，用以反映外括约肌协调程度。统计学处理采用治疗前后指标配对t检验方法，检验水准ɑ＝0.05。结果　所有患者均随访到排尿症状改善情况，其中明显改善14例，中度改善20例，轻微改善19例，无改善9例。42例在治疗前后均进行了尿动力学检查。MUCP平均降低9.3cmH2O（4-29cmH2O）。患者在BTX-A注射后，TL值平均增高0.44（P＜0.05），其中34例TL值增高，8例下降。另20例进行电话随访，其中1例因全身疾病死亡。注射后未出现与BTX-A相关的全身及局部并发症。结论 BTX-A尿道外括约肌注射是一种治疗各种病因引起尿道外括约肌痉挛的有效方法，短期内对部分患者能够显著改善排尿症状，提高生活质量。TL值是反映外括约肌功能状态较准确的指标。     

书写痉挛责任肌群的认定及肉毒毒素治疗的疗效观察

目的　寻找引起患者书写痉挛 (writer scramp)并导致字迹抖动不清的主要责任肌群 ,并同时观察局部注射肉毒毒素 A (botulinumtoxin A ,BTX A)对书写痉挛病症的治疗效果及副反应发生情况。方法　通过对前臂肌群的选择性运动 ,判断各肌群对书写痉挛症状的影响 ,并初步认定责任肌群 ,然后用维库溴铵对初步确定的责任肌群进行选择性注射 ,以进一步确定引起书写痉挛的主要责任肌群 ,最后对已确定的主要责任肌群进行BTX A多点注射 ,观察其疗效及副反应发生情况。结果　本研究发现 ,当前臂旋转肌群运动时会加重书写痉挛症状 ,对该群肌肉注射维库溴铵后可消除痉挛症状。当对旋转肌群进行BTX A注射后 ,受试的 3例患者 (共 5侧患肢 )症状全部得到改善 ,无一例发生可察觉的握力减退及垂腕等副反应。结论　前臂旋转肌群是导致书写痉挛并致使字迹抖动不清的主要责任肌群 ,对其进行BTX A选择性多点注射可获得满意疗效 ,同时还可避免握力减退及垂腕等副反应的发生。     

Botulinum toxin injection to facilitate rehabilitation of muscle imbalance syndromes in sports medicine

Intramuscular injection of Botulinum toxin to produce reduction of focal muscle overactivity, and localized muscle spasm, has been utilized therapeutically for almost two decades. Muscle overactivity in neurologically normal muscle, where an imbalance exists between a relatively overactive muscle and its less active synergist or antagonist, can inhibit control of the antagonist producing a functional muscle imbalance. This brief review provides an overview of the role of muscle imbalance in sports-related pain and dysfunction, and outlines the potential for intramuscular injection of Botulinum toxin to be used as an adjunct to specific muscle re-education and functional rehabilitation in this patient group. A comprehensive understanding of normal movement and the requirements of the sporting activity are essential to allow accurate diagnosis of abnormal motor patterns and to re-educate more appropriate movement strategies. Therapeutic management of co-impairments may include stretching of tight soft tissues, specific re-education aimed at isolation of the non-dominant weak muscles and improvement in their activation, ‘unlearning’ of faulty motor patterns, and eventual progression onto functional exercises to anticipate gradual return to sporting activity. Intramuscular injection of Botulinum toxin, in carefully selected cases, provides short term reduction of focal muscle overactivity, and may facilitate activation of relatively ‘inhibited’ muscles and assist the restoration of more appropriate motor patterns.     

Botulinum toxin treatment of axial and cervical dystonia

Axial truncal dystonia is characterized by an abnormal trunk posture often superimposed by myoclonic motor activities. Cervical dystonia is a motor syndrome characterized by abnormal head and neck posture due to tonic involuntary contractions in a certain set of muscles often superimposed by myoclonic or tremolous movements. Intramuscular injection of botulinum toxin is the first line treatment in cervical dystonia, in axial truncal dystonias botulinum toxin therapy is used only in mild forms. In this review the theoretical background, practical aspects and efficacy results especially in cervical dystonia are presented. Treatment of axial trunk dystonia is only briefly discussed at the beginning of this review.     

Botulinum toxin injection for management of thoracic outlet syndrome: a double-blind, randomized, controlled trial

We studied the effect of botulinum toxin type A (BTX-A) injections to the scalene muscles on pain in subjects with thoracic outlet syndrome (TOS) in this double-blind, randomized, parallel group trial with follow-up at 6 weeks, 3 months, and 6 months. Thirty-eight patients referred to physiatrists for management of TOS with BTX-A injection were included. One subject was lost to follow-up and all other subjects completed the trial. A 75-unit dose of BTX-A reconstituted with 0.75 cc of normal saline was injected to the anterior scalene (37.5 units) and middle scalene (37.5 units) muscles using electromyographic guidance. The primary outcome measure was pain as measured on a horizontal visual analog scale (VAS) 6 weeks-post-injection. Secondary outcomes were paresthesias measured on a VAS and function measured with the Disabilities of the Arm, Shoulder and Hand (DASH) and Short-form 36 (SF-36) questionnaires. For the primary outcome measure of VAS scores for pain at 6 weeks, the difference in the means adjusted for baseline VAS scores between placebo and BTX-A was 5.03 mm in favor of BTX-A (95% confidence interval −15.7 to 5.7, P = .36). Changes in secondary outcome measures were also not statistically significant. We conclude that BTX-A injections to the scalene muscles did not result in clinically or statistically significant improvements in pain, paresthesias, or function in this population of subjects with TOS.     

Botulinum toxin injections for the treatment of frontal tension headache

Abstract We performed a randomized, double-blind, placebo-controlled trial to determine the efficacy of botulinum toxin type A (BOTOX; Allergan) in treating frontal tension-type headache (TTH). A total of 40 patients attending a headache treatment center were randomized to receive 50 U botulinum toxin type A or saline, injected at 10 sites of the forehead. Frequency and severity of headaches before and after injection were compared. The intensity of headaches in the botulinum toxin type A group, but not the placebo group, fell significantly from an average score of 5.19 to 4.65 (p<0.0001). Botulinum toxin type A patients and placebo patients experienced an average reduction in the number of headaches per month, but these reductions were not significantly different between groups. Botulinum toxin type A was well tolerated, with no significant adverse events. Botulinum toxin type A injections in the management of frontal TTH has been shown by this study to be both effective and well tolerated. It should be noted that the effect of botulinum toxin on intensity of headache, although statistically significant, was relatively small.     

Botulinum toxin A for myofascial trigger point injection: a qualitative systematic review.

Botulinum toxin injection is used to treat various pain conditions including muscle spasticity, dystonia, headache and myofascial pain. Results are conflicting regarding the use of Botulinum toxin for trigger point injection in terms of improvement in pain. The aim of this study was to carry out a systematic review to assess the evidence for efficacy of Botulinum toxin A (BTA) compared with placebo for myofascial trigger point injection. Electronic databases on Medline, Cochrane Library, Scopus, CINAHL were queried using key words such as "botulinum toxin", "myofascial pain", "trigger point", "chronic pain" and "musculoskeletal pain". Relevant published randomized controlled trials that described the use of BTA as injection therapy for trigger points were considered for inclusion. The five-item 0-16 point Oxford Pain Validity Scale (OPVS) was used as a selection criteria for suitable clinical trials. Trials were also assessed based on quality using the Oxford Rating Scale. Data extracted from qualified trials included outcome measures such as pain intensity and pain pressure threshold. All studies were ranked according to the OPVS and the authors' conclusions were compared. Five clinical trials met the inclusion criteria. One trial concluded that BTA was effective, and four concluded that it was not effective for reducing pain arising from trigger points. OPVS scores ranged from 8 to 14 with the negative studies corresponding with higher validity scores. The current evidence does not support the use of BTA injection in trigger points for myofascial pain. The data is limited and clinically heterogeneous.     

A型肉毒毒素肌注后神经芽生的实验研究

目的 研究A型肉毒毒素肌注后神经芽牛的病理和电生理过程。方法 SD大鼠40只，随机分为肉毒毒素组和生理盐水组。在SD大鼠右侧腓肠肌肌注5U的A型肉毒毒素或同容积的生理盐水，于肌注后1，4，8，12周测定单纤维肌电图的运动电位平均连续波间差（MCD）和肌纤维密度，观察病理神经纤维数目。结果 运动单位MCD结果为1～4周显著延长，8周开始好转，12周恢复正常；提示肌注肉毒毒素后出现神经肌肉接头传导阻滞，并于12周恢复功能。肌纤维密度和神经纤维数目计数均增加，结果 提示肌注肉毒毒素后出现神经芽生。结论 大鼠肌注肉毒毒索后出现了神经芽生，神经肌肉接头功能在12周内恢复。     

Botulinum toxin type A for poststroke cricopharyngeal muscle dysfunction

OBJECTIVE: To evaluate the therapeutic effectiveness of botulinum toxin type A (BTX-A) in poststroke patients with cricopharyngeal muscle dysfunction. DESIGN: Before-after trial. SETTING: University hospital. PARTICIPANTS: Eight poststroke patients. INTERVENTION: BTX-A injection into the cricopharyngeal muscle under endoscope guidance for poststroke cricopharyngeal muscle dysfunction. MAIN OUTCOME MEASURES: Clinical symptom score, disability rating scale for swallowing impairment, videofluoroscopic swallowing study, and upper esophageal sphincter (UES) manometry. RESULTS: Clinical symptom score, disability rating scale for swallowing impairment, residue in piriform sinus, and UES pressure were all significantly improved at 2 weeks after BTX-A injection compared with evaluations before injection (P<.05). The effects on the clinical symptom score and disability rating scale for swallowing impairment continued to be significantly improved to 12 weeks after injection (P<.05). However, the residue in piriform sinus and the UES pressure at 12 weeks postinjection were reduced compared with before-injection evaluations; these results were not significant. The pharyngeal transit time was not changed after injection. There were no side effects observed in the patients studied. CONCLUSIONS: The results of the present study suggest that BTX-A injection may be an effective and safe treatment in patients with poststroke cricopharyngeal muscle dysfunction.     

Botulinum toxin injection for Cockayne syndrome with muscle spasticity over bilateral lower limbs: A case report

BACKGROUNDCockayne syndrome (CS) is a rare inherited disease characterized by progressive motor symptoms including muscle weakness, joint contracture, ataxia, and spasticity. Botulinum neurotoxin type A has been used for conditions such as dystonia and spasticity, but it has rarely been used in patients with CS.CASE SUMMARYWe report a 6-year-and-9-mo old girl diagnosed with CS who received an injection of botulinum neurotoxin type A to manage her difficulty with walking. A total dose of 210 units of botulinum neurotoxin type A was administered into the bilateral tibialis posterior and gastrocnemius muscles. To evaluate the treatment effects on spasticity, joint contracture, pain, and ataxia, measurement tools including the Modified Ashworth Scale, the passive range of motion, the Faces Pain Scale-Revised, and the Scale for the Assessment and Rating of Ataxia, were employed. The first week after the injection, the Modified Ashworth Scale score for the plantar flexors and foot invertors improved bilaterally, along with advancements in the passive range of motion of the bilateral ankles and a lower score for the Faces Pain Scale-Revised. These treatment effects persisted to the 8^th week post-injection, but returned to baseline values at the 12^th week post-injection, except for the pain scale.CONCLUSIONBotulinum toxin injection can thus be considered as a treatment option for lower extremity spasticity, joint contracture, and pain derived from CS.