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。     

A型肉毒毒素在整形美容方面及其临床拓展应用的进展

近年来,随着对A型肉毒毒素基础研究和临床研究的深入,其在临床上应用范围也越来越广泛。A型肉毒毒素在医学美容整形方面应用最为广泛,此外,国内外还将A型肉毒毒素用于涉及皮肤科疾病、雷诺现象、疼痛性疾病、泌尿系统疾病、眼科疾病以及脑血管系统疾病等50余种病症的治疗,被誉为“20世纪90年代神经药物的一大进展”。     

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。     

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 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.     

A型肉毒毒素治疗脊髓损伤痉挛状态的临床研究

目的 :研究A型肉毒毒素对脊髓损伤痉挛状态的治疗作用。方法 :选择 9例脊髓损伤痉挛状态患者的 76块对功能影响较大且改良Ashworth分级≥Ⅱ级的痉挛肌进行A型肉毒毒素多点注射 ,记录治疗前及治疗后 3天、1周、1个月、2个月、3个月痉挛肌改良Ashworth分级、痉挛性疼痛评分 (VAS)、夜间抽搐的频率、内收肌角、直腿抬高角及FIM运动分的变化。结果 :注射后 3天即有 72 .3 %靶肌的改良Ashworth分级下降 (P <0 .0 1 ) ,1个月时所有靶肌 (1 0 0 % )的改良Ashworth分级显著下降 (P <0 .0 1 ) ,60 %的靶肌疗效持续时间≥ 3个月。注射后痉挛性疼痛(VAS)、夜间抽搐的频率、内收肌角、直腿抬高角显著改善 (P <0 .0 1 ) ,FIM运动分注射 1个月后持续改善 (P <0 .0 1 )。结论 :A型肉毒毒素对脊髓损伤痉挛性疼痛、抽搐及痉挛性关节活动度障碍有明显疗效 ,辅以康复训练能有效改善脊髓损伤患者的运动能力     

肉毒毒素在痉挛型脑瘫治疗中的应用及研究进展

本文介绍了肉毒毒素由毒素到药物的演变过程以及其作用机理，综述了其在痉挛型脑瘫治疗中的应用剂量、治疗效果及副作用等方面的研究进展。     

Botulinum toxin A in the prophylactic treatment of migraine--a randomized, double-blind, placebo-controlled study

Botulinum toxin A has been suggested to be effective in the prophylactic treatment of migraine. However, only very few randomized, double-blind, placebo-controlled studies are available. We designed such a study with a specific focus on different injection sites. Sixty patients with a migraine according to the criteria of the International Headache Society were randomly assigned to receive either placebo in the frontal and neck muscles, or to receive 16 U botulinum toxin A in the frontal muscles and placebo in the neck muscles, or to receive in total 100 U botulinum toxin A in the frontal and neck muscles. The observation period was 3 months. In both treatment groups, 30% of patients showed a reduction of migraine frequency in month 3 by at least 50% compared with baseline, in the placebo group 25% of the patients showed such a reduction (P = 0.921). There were no significant differences between the three study groups with respect to reduction of migraine frequency, number of days with migraine, and the number of total single doses to treat a migraine attack. In the post hoc analysis, the reduction of all accompanying symptoms was significantly higher in the 16 U treatment group compared with the placebo group. In the 100 U treatment group significantly more adverse events occurred compared with the placebo group. All adverse events were mild and transient. Our study did not show any efficacy of botulinum toxin A in the prophylactic treatment of migraine. Only accompanying symptoms were significantly reduced in the 16 U but not in the 100 U treatment group. Future studies should focus on the efficacy of botulinum toxin A in specific subgroups of patients, on the efficacy of repetitive injections, and on other injection sites.     

Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study

Sixty patients with headaches of more than 15 days per month were recruited for this double-blind, placebo-controlled, parallel study of botulinum toxin type A (BTX) for chronic tension type and chronic migraine headaches. The primary efficacy point was the number of headache-free days as assessed by diary for 12 weeks after BTX injection. Secondary efficacy points included global impressions, the use of abortive headache medications, and palpation. After recruitment, subjects kept diaries for 4 weeks prior to randomization, at which time they received either 200 U of BTX or matching placebo and were followed. After the week-12 evaluation, patients were offered 200 U of BTX (open label), and were similarly followed for another 12 weeks. The mean days with headache of the 60 subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30. Both groups were demographically similar (58 completed). Over a 12-week period after injections, headache-free days had improved in the BTX group from week 8 to 12 (P < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23 vs. 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori significance criteria. The subject global impressions (P < 0.05), subject change in headache impressions (P < 0.005), and investigator global impressions (P < 0.001) all improved in the BTX group compared with placebo. Adverse events were mild and did not differ between groups. At week 24 (open label), headache-free days were less in the twice BTX injected group compared with the once injected group, 40 +/- 26 vs. 26 +/- 19 (P < 0.05). BTX may help chronic daily headache and appears to have a cumulative effect with subsequent injections. The treatment was very well tolerated.     

A型肉毒毒素加强法治疗面肌及眼睑痉挛的临床疗效

目的 观察A型肉毒毒素加强法治疗面肌及眼睑痉挛的疗效.方法 对36例面肌及眼睑痉挛患者应用A型肉毒毒素对痉挛肌肉多点注射,并在1周内追加注射（加强组）,随访12～24个月,与同期行1次性注射A型肉毒毒素的该病患者30例（常规组）进行疗效比较.结果 两组有效率均较高,而加强组治愈率明显高于常规组（P＜0.05）.结论 A型肉毒毒素加强法治疗面肌及眼睑痉挛,可提高其治愈率,且疗效维持时间较长.     

Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine

OBJECTIVE: To compare the efficacy and safety of botulinum toxin type A (BoNTA; BOTOX: Allergan, Inc.) and divalproex sodium (DVPX; DEPAKOTE: Abbott Laboratories) as prophylaxis in reducing disability and impact associated with migraine. BACKGROUND: There is a need for effective, well-tolerated prophylactic treatment of migraine. DESIGN/METHODS: This was a randomized, double-blind, single-center prospective study. Fifty-nine patients received either BoNTA 100 U/placebo-DVPX bid or placebo-BoNTA/DVPX 250 mg bid. BoNTA/placebo injections were given at Day 0 and at Month 3. Patients were evaluated at Months 1, 3, 6, and 9. RESULTS: Both treatments showed significant improvements in migraine disability scores and reductions in headache days and headache index. A trend to decreased headache severity was observed with BoNTA. A greater percentage of DVPX patients reported adverse events possibly related to treatment (DVPX 75.8% vs BoNTA 50%, P = .04) and discontinued because of adverse events (DVPX 27.6% vs BoNTA 3.3%, P = .012). CONCLUSIONS: Both BoNTA and DVPX significantly reduced disability associated with migraine; BoNTA had a favorable tolerability profile compared with DVPX.