内镜下注射肉毒毒素治疗贲门失弛缓症的研究

将48例贲门失弛缓症患者随机分为两组，A组注射肉毒毒素治疗，B组用小气囊扩张治疗。分别于治疗后1周、3个月和1年比较两组患者的临床症状积分、下食管插约肌的压力（LESP）、松弛率（LESRR）。结果：治疗后1周、3个月和1年的有效率及治疗前后LESP、LESRR的差值，注射肉毒毒素组均高于小气囊扩张组；两组均无并发症发生。认为内镜下食管下括约肌内注射肉毒毒素治疗贲门失弛缓症的近期疗效高，且患者痛苦小。     

A型肉毒毒素对面部三叉神经痛大鼠疼痛的改善作用及对炎性介质IL-6、TNF-α表达的影响

目的 探讨A型肉毒毒素（BTA）对面部三叉神经痛（TN）大鼠疼痛的改善作用及对炎性介质IL-6、TNF-α表达的影响。方法 从50只大鼠中随机取10只为对照组,剩余大鼠用结扎眶下神经的方法建立TN模型,分为模型组、BTA低剂量组（BTA-L组）、BTA高剂量组（BTA-H组）和卡马西平组,每组各10只。BTA-L组、BTA-H组分别以9、18 μL/kg BTA溶液于手术同侧面部须垫处注射,对照组及模型组给予等量生理盐水,卡马西平组以5 mg/kg卡马西平灌胃。检测大鼠疼痛阈值,ELISA法检测血清中IL-6、TNF-α水平,HE染色观察眶下神经组织病理变化;蛋白免疫印迹法检测三叉神经节中核因子κB（NF-κB）p65、磷酸化型NF-κB p65（p-NF-κB p65）、p38丝裂原活化蛋白激酶（p38MAPK）、磷酸化型p38MAPK（p-p38MAPK）蛋白相对表达量。结果 与对照组比较,模型组注射1、2、3周时疼痛阈值降低（P均 < 0.05）;与模型组比较,BTA-L组、BTA-H组、卡马西平组注射1、2、3周时疼痛阈值升高,且BTA-L组 < BTA-H组 < 卡马西平组（P均 < 0.05）;与对照组比较,模型组血清中IL-6、TNF-α水平及p-NF-κB p65、p-p38MAPK蛋白相对表达量升高（P均< 0.05）;与模型组比较,BTA-L组、BTA-H组、卡马西平组血清中IL-6、TNF-α水平及三叉神经节中p-NF-κB p65、p-p38MAPK蛋白相对表达量降低,且卡马西平组 < BTA-H组 < BTA-L组（P均< 0.05）;HE染色显示,与模型组比较,BTA-L组、BTA-H组、卡马西平组神经纤维肿胀、排列、炎性细胞浸润等异常改变减轻,其中卡马西平组减轻更显著。结论 BTA可降低炎性介质IL-6、TNF-α水平,减轻炎症反应,改善面部疼痛,可能通过抑制NF-κB、p38MAPK信号通路发挥作用。     

Self-rehabilitation combined with botulinum toxin to improve arm function in people with chronic stroke. A randomized controlled trial

BackgroundBotulinum toxin injection (BTI) reduces muscle hyperactivity, but its effect on active upper-limb function is limited. Intensive rehabilitation could optimize the effects; however, outpatient post-stroke rehabilitation is usually not intensive. One solution could be self-rehabilitation.ObjectivesThe aim of this randomized controlled trial was to determine the effect of a self-rehabilitation program combined with BTI on upper-limb function in individuals with chronic hemiparesis.MethodsIn total, 33 outpatients were randomly allocated to receive BTI + self-rehabilitation (R group: n = 17) or BTI alone (C group: n = 16). Outcomes evaluated just before the BTI and 4 weeks later included the Wolf Motor Function Test (WMFT time: primary outcome), Action Research Arm Test, fatigue and quality of life.ResultsChange in WMFT did not differ between groups at 4 weeks (WMFT time: ?14% for R group, ?4% for C group. WFMT score: +12% for R group, 0% in C group). WFMT time and score improved significantly in the R group only (?14%, P = 0.01, and +12%, P = 0.02). In addition, the proportion of patients with improved WMFT time and score was higher in the R than C group (R group: 71% improved score, 77% improved time; C group: 43% improved score, 50% improved time). Also, passive range of shoulder flexion (P = 0.03) and wrist extension (P = 0.01) improved only in the R group. No other variables changed significantly. Compliance was excellent; average daily training time was greater than that prescribed.ConclusionsThe addition of a self-rehabilitation program to BTI did not significantly improve functional outcomes more than BTI alone; however, movement quality and speed improved only in the self-rehabilitation group. Participants in the self-rehabilitation group trained more than they were asked to, which suggests that they found the program worthwhile. These clinically relevant findings justify larger-scale studies of the effects of self-rehabilitation to enhance the effects of BTI. Clinical trial: NCT02699762.     

Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

ObjectivesIn this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated.MethodsMale C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2^−/− mice.ResultsWe found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice.ConclusionThese results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.     

Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients

BACKGROUND: Intraparietal gastric administration of Botulinum Toxin A has been studied in open trials to induce satiety and increase weight loss of obese patients with contradictory results. In previous studies only the antrum was the target for Botulinum Toxin A, whereas the fundus, which exerts important activity on gastric accommodation, was excluded. In this study we report the effects of injection into both gastric regions on solid gastric capacity and emptying of the stomach. MATERIALS AND METHODS: In this study we extended our previous investigations to include 30 obese patients who received Botulinum Toxin A (120 U into the antrum and 80 U into the fundus) or saline by intraparietal endoscopic injection. The two groups were homogeneous for age, gender, body weight and body mass index. Body weight and body mass index, solid gastric emptying (T(1/2) and T(lag) at the octanoic acid breath test) and maximal gastric capacity for solids (kcal) were determined before injection and 2 months later. The results were expressed as mean values (S.E.M.). t-Test or Wilcoxon test was used for statistical analysis, p<0.05 being considered significant. RESULTS: Both treatments induced a significant reduction of body weight and body mass index but Botulinum Toxin A exerted a significantly greater effect (body weight -11.8+/-0.9 kg vs. -5.5+/-1.1 kg, p<0.0002; body mass index -4.1+/-0.2 vs. -2.2+/-0.4, p<0.001). The maximal gastric capacity for solids was also reduced by both Botulinum Toxin A and placebo, the former being significantly more effective (679+/-114 kcal vs. 237+/-94 kcal, p<0.008). Botulinum Toxin A also significantly increased T(1/2) from 83.4+/-3.9 to 101.6+/-9.9 min, p<0.03) but T(lag) was unchanged. Placebo had no effect on either of these parameters. CONCLUSIONS: Our results demonstrated that Botulinum Toxin A makes weight loss easier in obese patients. It acts by increasing the solid gastric emptying time and reducing the solid eating capacity of the stomach.     

偏侧咀嚼肌痉挛3例报告并文献复习

目的 加强对偏侧咀嚼肌痉挛这一罕见疾病的认识.方法 对我科收治的3例偏侧咀嚼肌痉挛患者的临床资料进行回顾分析,并对相关文献进行复习.结果 3例青年患者,病程长,反复发作性一侧咀嚼肌痉挛,累及咀嚼肌和颞肌,发作时不能张口,病初发作程度较轻,随病程发展,痉挛发作的持续时间及频率加重.诱发痉挛发作的常见因素有咀嚼、咬牙以及说话等.短暂的痉挛通常不伴有肌肉疼痛,严重时可以伴有疼痛.1例患者伴有痉挛侧面部肌肉肥大,2例伴有痉挛侧面部萎缩,无其他神经系统阳性体征.肌电图显示痉挛的咀嚼肌运动单位电位持续发放.2例患者经肉毒毒素局部注射治疗效果显著.结论 对于偏侧咀嚼肌痉挛,肉毒毒素局部注射治疗通常能够获得满意疗效.     

肌电分析在TMD临床疗效评价中的应用

目的:探讨3种不同方法治疗伴有磨牙症TMD的咀嚼肌肌电特征差异,评价3种治疗方法的效果.方法:30例伴有磨牙症的TMD患者被随机分为3组,每组10例.A组进行内毒杆菌毒素A(BTX-A)双侧咬肌肌内注射治疗,B组进行功能训练治疗,C组进行弹性颌垫治疗.对3组研究对象在治疗前、治疗1、3、6个月分别采集双侧咬肌(MM)和颞肌前束(TA)在下颌姿势位(MPP)以及牙尖交错位(ICP)最大紧咬牙时的肌电图(EMG),采用SAS 5.0统计学软件分析比较3组的峰值电位(Amp)之间是否存在统计学差异.结果:横向比较中各个治疗时间段A组患者疼痛视觉模拟评分(VAS)显著低于B组和C组(P＜0.05),肌电显示MPP中A组在治疗过程中能显著降低双侧咬肌肌力(P＜0.05),ICP时A组在1、3个月时显著降低双侧咬肌肌力(P＜0.05),同时双侧颞肌肌力显著增强(P＜0.05).纵向比较中3组在治疗过程中均能明显降低疼痛(P＜0.05),但3组时间点不同,A组缓解疼痛时间较长,肌电图显示3组均可显著降低咬肌MPP肌力(P＜0.05),A、C组可降低ICP咬肌肌力(P＜0.05),A组双侧颞肌肌力可代偿增强(P＜0.05),B、C组颞肌肌力治疗前后均无统计学差异(P＞0.05).结论:临床症状与肌电图的结合使用能够对口颌系统行使功能过程中咀嚼肌的表现进行很好地观测,对TMD患者的咀嚼肌生物力学和结构方面有很好地理解.BTX-A肌内注射方法治疗伴有磨牙症的TMD可显著缓解患者疼痛,疗效持续时间较长.BTX-A肌内注射可显著降低咀嚼肌力,使目标肌肉(咬肌)疲劳得到缓解,促进咀嚼肌力平衡重建,较传统方式存在潜在优势.