Botulinum toxin for the treatment of pain syndromes

Although botulinum toxin (BoNT) is being used for therapeutic purposes for more than 20 years, the list of potential new indications continues to increase and includes various pain syndromes. The pain relief experienced by patients with dystonia and spasticity from intramuscular BoNT injections suggested that other chronic skeletal-muscles pain conditions may also benefit. BoNT inhibits the release of acetylcholine at the neuromuscular junction thereby reducing striatal muscle contractions and the proposed analgesic property was initially attributed to muscular relaxation. A specific analgesic BoNT effect is difficult to conclude from studies where pain is conditioned by other associated symptoms like dystonia, muscle contraction or spasticity. One alternative is to critically appraise clinical trials where BoNT was studied as the active intervention and pain evaluated as an outcome. From this analysis there is convincing evidence for the effectiveness of BoNT in the treatment of pain associated with cervical dystonia. For all other pain syndromes there have been relatively few, small sized, placebo-controlled studies (myofascial pain syndrome, chronic neck and low back pain, piriformis syndrome and fibromyalgia) and the results of these studies have been contradictory or non conclusive. To establish the analgesic properties of BoNT there is a need for appropriately designed, exploratory randomized controlled studies in well accepted human models of nociceptive or neuropathic pain. This does not exclude the subsequent need to conduct pragmatic trials to evaluate the effectiveness of BoNT in conditions where the improvement of pain or any associated clinical sign or symptom may be of clinical relevance.     

Botulinum toxin for oropharyngeal dysphagia: case report of flexible endoscope-guided injection

Botulinum toxin (BT) has been used in neurology, ophthalmology, otorhinolaryngology and gastroenterology. Twenty-four patients with oropharyngeal dysphagia treated with BT injection into the cricopharyngeal muscle were reported, with good results in up to 79% of the patients. Different techniques were used to inject BT: percutaneous (guided by electromyography, computed tomography or videofluoroscopy) or direct injection during esophagoscopy (with a rigid esophagoscope). We report the first case of oropharyngeal dysphagia treated by BT injection into the cricopharyngeal muscle using a flexible scope, with clinical, radiological and manometric improvement. A reduction in the disability score 4 to 2 and sustained capacity to maintain adequate oral caloric intake were observed. The patient was also able to have the tracheotomy orifice closed and the gastrostomy tube removed after 3 months. Manometry showed a 38% reduction in the upper esophageal sphincter pressure with the presence of pharyngeal waves that were previously absent. After 1 year of follow-up, the patient was in good condition with mild dysphagia for solid foods. This is another case of complex dysphagia and relative hyperfunction of the cricopharyngeal muscle successfully treated with BT injection.     

Botulinum toxin A for the treatment of chronic anal fissure

Since its introduction for the treatment of strabismus, botulinum toxin (BoNT) has been increasingly used in the treatment of several disorders with excessive or inappropriate muscle contractions. The therapeutic effects of BoNT occur through the temporary chemodenervation caused by the injection into the local target muscle or skin. Modulation of muscle relaxation may be achieved by varying the dose of BoNT solution injected; most adverse effects are transient. Indeed, botulinum neurotoxin has been used to selectively weaken the internal anal sphincter as a treatment for chronic anal fissure in several randomized, controlled trials and open-label studies. The use of botulinum neurotoxin seems to be an effective and safe approach for the treatment of chronic anal fissure, particularly in patients at high risk for incontinence.     

Botulinum toxin A for the treatment of delayed gastric emptying

BACKGROUND: Observational data suggest that intrapyloric injection of botulinum toxin A (BoTN/A) reduces symptoms and accelerates gastric emptying in idiopathic and diabetic gastroparesis. Our purpose was to determine whether botulinum toxin improves symptoms to a significantly greater extent than placebo. An additional objective was to determine whether there is an acceleration of gastric emptying after injection. METHODS: A single-institution, randomized, double-blind, placebo-controlled trial* was done. Eligible patients had a Gastroparesis Cardinal Symptom Index score > or = 27 with randomization to intrapyloric botulinum toxin, 200 U (units), or saline placebo. Reassessment of symptoms and repeat gastric emptying scan at 1-month follow-up were done. RESULTS: Thirty-two patients were randomized to botulinum toxin (N = 16) and placebo (N = 16). At 1-month follow-up, 37.5% randomized to botulinum toxin and 56.3% randomized to placebo achieved improvement as defined by this study. There were no identifiable clinical predictors of response. The botulinum toxin group demonstrated improvement in gastric emptying; however, this was not superior to placebo. No serious adverse events were attributable to botulinum toxin. CONCLUSIONS: Intrapyloric injection of botulinum toxin improves gastric emptying in patients with gastroparesis, although this benefit was not superior to placebo at 1 month. Also, in comparison to placebo, symptoms do not improve significantly by 1 month after injection. Overall, we are unable to recommend botulinum toxin therapy for widespread use in the treatment of delayed gastric emptying until more data are available.     

A型肉毒素治疗卒中后上肢痉挛疗效的Meta分析

目的系统评价A型肉毒素治疗卒中后上肢痉挛的临床疗效。方法计算机检索Pub Med、EMbase、Cochrane Library、CBM、中国知网(CNKI)和万方数据库。搜集A型肉毒素结合康复训练与常规康复治疗卒中后上肢痉挛疗效比较的随机对照试验或两组病例对照研究,检索时限均从建库至2016年9月1日。由至少2名评价员按纳入与排除标准进行文献筛查、资料提取和质量评价。利用Cochrane协作网提供的Rev-Man 5.3软件进行Meta分析。结果共检出相关文献356篇,最终11篇文献符合纳入标准,改良Jadad评分显示9篇文献在4分以上,属高质量文献。11篇文献共含614例患者,其中肉毒素治疗组316例,对照组298例。Meta分析结果显示,肉毒素治疗组在Fugl-Meyer评分[标准化均数差(SMD)=0.94,95%CI:0.75~1.12]、改良Ashworth评分(SMD=-1.59,95%CI:-1.78~-1.40)及改良Barthel指数(SMD=0.86,95%CI:0.65~1.08)方面均优于对照组,差异均有统计学意义(均P0.05),两组不良事件发生率(RR=1.06,95%CI:0.78~1.45)相似,差异无统计学意义(P0.05)。结论 A型肉毒素治疗卒中后上肢痉挛疗效确切,安全性高,配合适当的康复训练,能够有效地改善患者肢体运动功能、肌肉紧张状态及生活质量。     

Botulinum toxin for the treatment of secondary chronic anal fissure

Abstract. Background: Botulinum toxin A (BT-A) injection into internal or external anal sphincter causes relaxation of the anal sphincters, enhancing microcirculation at the fissure site and promoting fissure healing. There are no such observations in patients with secondary anal fissure. Methods: Six patients with fissures after surgical or nonsurgical treatment of hemorrhoids and four patients with ulcerative colitis received injections of BT-A on both edges of the fissure (total dose, 25 U Botox). Results: In the week following BTA injection, patients with fissure after hemorrhoids treatment had relief of fissure symptoms, but one month later the fissures still existed. They then received an additional 25 U Botox. One month after the second BT-A injection, all fissures were healed. The patients with ulcerative colitis had only symptomatic improvement after BT-A injection. Conclusion: BT-A therapy seems effective for the treatment of chronic anal fissure after surgical or nonsurgical treatment of hemorrhoids.     

Botulinum toxin in the treatment of overactive bladder

Clinical effectiveness of botulinum toxin (BTX) in the treatment of both neurogenic and idiopathic detrusor overactivity has been demonstrated in several studies. However, different protocols and techniques have been used by authors. METHODS. Literature review on intradetrusor injection of BTX for detrusor overactivity. RESULTS. The greatest clinical experience reports the use of 200 and 300 U Botox?. Available data suggest that clinical efficacy, duration, and the side effect profile is similar at these doses. Very few data, on the other hand, are available regarding the clinical outcomes using the Dysport? preparation; isolated reports support that efficacy is similar when using a dosing range of 500 to 1000 SU with increased risk of systemic side effects using 1000 SU. A variety of injection volumes was used, demonstrating similar efficacy and tolerability profile. Clinical effect duration extends six to ten months in the majority of studies. Data suggest that a repeated injection scheme proves successful in the vast majority of initial responders. CONCLUSIONS. Safety, effectiveness, specificity and reversibility make BTX a new attractive treatment modality for overactive bladder syndrome. However, more experience is needed to standardize the injection protocol with respect to therapeutic outcomes and adverse effects.     

Pyloric injection of botulinum toxin for treatment of diabetic gastroparesis

BACKGROUND: Diabetic gastroparesis is a common clinical problem. The pathophysiology includes prolonged pyloric contractions that may cause functional resistance to gastric outflow. Botulinum toxin was injected into the pyloric sphincter in an attempt to decrease pyloric resistance and improve gastric emptying. METHODS: Six patients with diabetic gastroparesis and an abnormal solid phase gastric emptying study underwent upper endoscopy during which 100 units of botulinum toxin were injected into the pyloric sphincter. Gastric emptying studies were obtained at 48 hours and 6 weeks after injection. Patients were questioned about symptoms of gastroparesis, and a symptom score was obtained at baseline and at 2 weeks and 6 weeks after injection. OBSERVATIONS: There was a mean improvement in the subjective symptom score at 2 weeks of 55% (range 14% to 80%). This improvement was maintained at 6 weeks. There was a 52% improvement in gastric emptying at 2 and 6 weeks. CONCLUSION: Pyloric injection of botulinum toxin can improve symptoms and gastric emptying in patients with diabetic gastroparesis. Further evaluation of pyloric injection of botulinum toxin as a treatment for diabetic gastroparesis is warranted.     

Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial

Background—Intrasphinctericinjection of botulinum toxin is a new treatment option for achalasia.
Aims—To compare the immediate andlong term efficacy of botulinum toxin with that of pneumatic dilatation.
Methods—Symptomatic patients withachalasia were randomised to botulinum toxin (22 patients, median age57 years) or pneumatic dilatation (20 patients, median age 56 years).Symptom scores were assessed initially, and at one, three, six, nine,and 12months after treatment. Objective assessment includedoesophageal manometry initially and at one month, and bariumoesophagram initially and at one, six, and 12 months post-treatment.
Results—Pneumatic dilatationresulted in a significantly (p=0.02) higher cumulative remission rate.At 12 months, 14/20 (70%) pneumatic dilatation and 7/22 (32%)botulinum toxin treated patients were in symptomatic remission(p=0.017). Failure rates were similar initially, but failure over timewas significantly (p=0.01) higher after botulinum toxin (50%) thanpneumatic dilatation (7%). Pneumatic dilatation resulted insignificant (p<0.001) reduction in symptom scores, and loweroesophageal sphincter pressure, oesophageal barium column height, andoesophageal diameter. Botulinum toxin produced significant reduction insymptom scores (p<0.001), but no reduction in objective parameters.
Conclusions—At one year pneumaticdilatation is more effective than botulinum toxin. Symptom improvementparallels objective oesophageal measurements after pneumatic dilatationbut not after botulinum toxin treatment for achalasia.

Keywords:achalasia; pneumatic dilatation; botulinum toxin; barium oesophagram

     

Botulinum toxin in the treatment of diffuse esophageal spasm

Diffuse esophageal spasm is a primary esophageal motility disorder. The prevalence is 3–10% in patients with dysphagia and treatment options are limited. This review summarizes the treatment of diffuse esophageal spasm, including pharmacotherapy, endoscopic treatment, and surgical treatment with a special focus on botulinum toxin injection. A PubMed search was performed to identify the literature using the search items diffuse esophageal spasm and treatment. Pharmacotherapy with smooth muscle relaxants, proton pump inhibitors, and antidepressants was suggested from small case series and uncontrolled clinical trials. Endoscopic injection of botulinum toxin is a well‐studied treatment option and results in good symptomatic benefit in patients with diffuse esophageal spasm. Surgical treatment was reported in patients with very severe symptoms refractory to pharmacologic treatment. This article summarizes the present knowledge on the treatment of diffuse esophageal spasm with a special emphasis on botulinum toxin injection. Endoscopic injection of botulinum toxin is presently the best studied treatment option but many questions remain unanswered.     

Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis

BACKGROUND: Botulinum toxin A injected into the pyloric sphincter has been reported in small case series to treat gastroparesis. This study reviews the use of this treatment in a large number of patients with gastroparesis. METHODS: Patients who underwent pyloric botulinum injection for treatment of gastroparesis were identified. Response was defined as improvement or resolution of the patient's major symptom and/or two minor symptoms for 4 weeks. RESULTS: Of 115 patients treated, 63 patients met the study criteria. There were 53 women, 10 men, mean age 42 years. Most patients (56%) had idiopathic gastroparesis. Twenty-seven of 63 (43%) patients experienced a symptomatic response to treatment. By stepwise logistic regression, male gender was associated with response to treatment (OR 3.27: 95% CI[1.31, 8.13], p = 0.01). Vomiting as a major symptom was associated with a lack of response (OR 0.16: 95% CI[0.04, 0.67], p = 0.01). Despite the association of male gender with response, the mean duration of response for those patients responding, with a minimum of 3 months' follow-up was 4.9 months (+/-2.7 months) for women and 3.5 months (+/-0.71 months) for men (p = 0.59). The corresponding medians and interquartile ranges (IQR) were 5 (IQR 3-6) for females and 3.5 (IQR 3-4) for males. CONCLUSIONS: Of the patients, 43% had a response to botulinum toxin treatment that lasted a mean of approximately 5 months. Male gender was associated with a response to this therapy; however, durability of response was unrelated to gender. Vomiting as a major symptom predicted no response.