A型肉毒毒素治疗偏侧面肌痉挛的临床观察

目的探讨A型肉毒毒素治疗偏侧面肌痉挛的临床疗效。方法采用A型肉毒毒素局部多点注射治疗偏侧面肌痉挛142例,对治疗前后的病情随访并进行分级比较。结果症状完全缓解占54%,明显缓解占42%,部分缓解占4%,疗效平均持续约3~6个月,个别持续10个月左右,复发者重复注射仍有效,局部不良反应轻微短暂。结论局部注射A型肉毒毒素是治疗偏侧面肌痉挛一种安全有效且简便易行的手段。     

Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post-traumatic neuralgia, phantom limb, and complex regional pain syndrome with focal dystonia. The use of BTX-A could represent a novel therapeutic strategy in caring for neuropathic pain whenever common pharmacological tools have been ineffective. However, large and well-designed clinical trials are needed to recommend BTX-A use in the relief of neuropathic pain.     

Skeletal Muscle Atrophy Induced by Intramuscular Repeated Dose of Botulinum Toxin Type A in Rats

Botulinum toxin type A was intramuscularly administered to Sprague–Dawley rats once a day for 28 days at doses of 1, 3, and 9 ng kg^?1 day^?1 to investigate the possibility of unanticipated toxicity of repeated dose. A dose-related decrease in body weight gain was noted and lasted throughout the 4-week recovery period. Paralytic gait was a common clinical sign observed in the animals dosed at ≥3 ng kg^?1 day^?1 and muscle atrophy at 9 ng kg^?1 day^?1. Decreased creatinine was monitored in both males and females treated at 9 ng kg^?1 day^?1. Microscopic examination of the quadriceps femoris muscle, the test article application site, confirmed the muscle atrophy with a decrease in myofiber diameter and an increase of myofiber nuclei and intermyofiber connective tissue. Although antibody against botulinum toxin type A was detected in the sera from both males and females at 9 ng kg^?1 day^?1, no immunogenicity-related changes or lesions were noted. In conclusion, no other side effects of the botulinum toxin type A injection except the decrease in body weight gain and the muscle atrophy at the administration site were noted in the 28-day intramuscular repeated dose study.     

局部注射A型肉毒杆菌毒素治疗贲门失弛缓症临床疗效观察

目的:探讨局部注射A型肉毒杆菌毒素(BTA)治疗贲门失弛缓症的近期和远期临床疗效。方法:选择原发性贲门失弛缓症(PA)患者248例和假性贲门失弛缓症(SA)患者11例,内镜下在食管痉挛处注射BTA20IU,根据治疗前、后的临床症状缓解情况判定其疗效。结果:治疗1周后,所有PA患者的临床症状均有明显的缓解(100.0%),显著高于SA患者(18.2%)(P<0.001);PA患者治疗1、3、6个月的临床症状缓解总有效率达到91.5%、87.2%、77.0%,但治疗1、3、5、10年后总有效率只有51.1%、56.3%、49.0%、44.1%,长期疗效显著低于短期疗效(P<0.01)。结论:局部注射BTA治疗贲门失弛缓症的近期疗效较好,对PA和SA的鉴别也有一定价值。     

小剂量A型肉毒毒素治疗痉挛型脑瘫

目的 观察小剂量A型肉毒毒素（BTX—A）治疗痉挛型脑瘫的疗效。方法 选择65例痉挛型脑瘫患儿，进行小剂量A型肉毒毒素注射．再进行家庭康复治疗及配带矫形器进行步态训练治疗3—6个月，并设对照组对比观察。结果 经BTX—A注射后患儿肌张力降低，关节活动度扩大，继续康复治疗及配带足踝矫形器训练，肌张力、关节活动度、步态得到进一步改善。BTX—A组显效41侧，有效16例，无效8例，总有效率87．69％。对照组显效12例，有效8例，无效35例，总有效率46.16％。两组对比差异有显著性（P〈0．001）。结论 小剂量BTX—A神经阻滞术治疗痉挛型脑瘫具有解痉快，不良反应小，操作方便。安全可靠，费用低等优点．     

A型肉毒毒素治疗慢性偏头痛的临床疗效和安全性观察

目的：观察A型肉毒毒素( BTX-A)治疗慢性偏头痛的有效性和安全性。方法选取2012年9月—2014年9月慢性偏头痛患者39例,对每例患者给予BTX-A治疗,随访记录各时段(治疗前、治疗后1、2、3、6个月)各项观察指标的结果与评分,进行统计学分析。同时记录相关不良反应,来评价该药物的安全性。结果每月偏头痛发作频率、头痛发作持续时间、疼痛视觉模拟量表( VAS)评分、头痛强度、各等级头痛人数在治疗后各时段较治疗前均有改善(P<0．01)。 VAS评分在治疗后2个月时最低,重度头痛的人数变化最明显,疼痛缓解程度在治疗后2个月最明显。本实验共发生4例不良反应,未影响日常生活,轻度可逆。结论 BTX-A治疗慢性偏头痛效果显著,在临床应用中较安全。     

Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model

Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain in the orofacial region, its exact mechanism of transport remains unclear. In this study, we investigated the effects of BoNT/A in managing neuropathic pain in two different animal models and its transport mechanism in the trigeminal nerve. Intraperitoneal administration of cisplatin induced bilateral neuropathic pain in the orofacial region, reducing the head withdrawal threshold to mechanical stimulation. Unilateral infraorbital nerve constriction (IONC) also reduced the ipsilateral head withdrawal threshold to mechanical stimulation. Unilateral peripheral administration of BoNT/A to the rat whisker pad attenuated cisplatin-induced pain behavior bilaterally. Furthermore, contralateral peripheral administration of BoNT/A attenuated neuropathy-induced behavior caused by IONC. We also noted the presence of BoNT/A in the blood using the mouse bioassay. In addition, the Alexa Fluor-488-labeled C-terminal half of the heavy chain of BoNT/A (BoNT/A-Hc) was localized in the neurons of the bilateral trigeminal ganglia following its unilateral administration. These findings suggest that axonal and hematogenous transport are involved in the therapeutic effects of peripherally administered BoNT/A in the orofacial region.     

A型肉毒毒素在上面部除皱中的应用分析

目的:探讨A型肉毒毒素在上面部除皱治疗的应用方法。方法:用生理盐水将A型肉毒毒素稀释成25 u·mL-1分点注射,额横纹:10～14个注射点;鱼尾纹:3～4个注射点;眉间纹:4～5个注射点。结果:338例患者,注射后1～3 d可见皱纹减轻或消失,1～2周后出现最佳效果,可维持4～8个月,有效率达100%。1例发生休克,对症处理后好转;出现局部轻度水肿4例,局部瘀斑7例,眉型改变、眉下垂5例,以上并发症未做特殊处理,2～4周左右好转。结论:A型肉毒毒素注射除皱,虽然只能维持一定时间,但因有可逆性所以相对安全,是减少上面部动力性皱纹的有效方法。     

Potential of Botulinum toxin A to treat upper extremity spasticity in children with cerebral palsy

Abstract

Botulinum toxin type A has been used extensively to treat spasticity in children with cerebral palsy. Although the effectiveness of the toxin in the lower limbs is well established, its effectiveness in upper limbs has not been proved yet. Many studies published so far report conflicting results in terms of spasticity, function, activity and participation improvement. The scope of this review is to present the evidence from published studies, focusing on the effectiveness and the safety of botulinum toxin A.     

The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain

Anterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional “denervation” which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.     

Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.     

Efficacy and Optimal Dose of Botulinum Toxin A in Post-Stroke Lower Extremity Spasticity: A Systematic Review and Meta-Analysis

Post-stroke spasticity impedes patients’ rehabilitation progress. Contradictory evidence has been reported in using Botulinum Neurotoxin type A (BoNT-A) to manage post-stroke lower extremity spasticity (PLES); furthermore, an optimum dose of BoNT-A for PLES has not yet been established. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to identify the efficacy and optimal dose of BoNT-A on PLES. "Meta" and "Metafor" packages in R were used to analyze the data. Hedges’ g statistic and random effect model were used to calculate and pool effect sizes. Twelve RCTs met the eligibility criteria. Muscle tone significantly improved in week four, week eight, and maintained to week twelve after BoNT-A injection. Improvements in functional outcomes were found, some inconsistencies among included studies were noticed. Dosage analysis from eight studies using Botox® and three studies using Dysport® indicated that the optimum dose for the commonest pattern of PLES (spastic plantar flexors) is medium-dose (approximately 300U Botox® or 1000 U Dysport®). BoNT-A should be regarded as part of a rehabilitation program for PLES. Furthermore, an optimal rehabilitation program combined with BoNT-A management needs to be established. Further studies should also focus on functional improvement by BoNT-A management in the early stage of stroke.     

A型肉毒毒素对三叉神经痛患者心理状况及生活质量的影响

目的 探讨A型肉毒毒素对三叉神经痛患者心理状况以及生活质量的影响.方法 将2014年12月—2015年12月上海市杨浦区市东医院治疗的三叉神经痛患者100例根据不同的治疗方法分为观察组(52例)与对照组(48例).其中观察组接受A型肉毒毒素治疗,对照组接受卡马西平治疗.治疗8周后,观察并比较两组治疗效果及不良反应发生率.结果 治疗前,两组焦虑、抑郁、睡眠干扰、疼痛评分比较差异无统计学意义(P>0.05);治疗后,观察组上述指标较对照组改善更明显(P<0.05),有效率也明显高于对照组(P<0.05),两组不良反应发生率比较差异无统计学意义(P>0.05).结论 A型肉毒毒素治疗三叉神经痛,能显著改善患者心理状况与生活质量,且治疗有效、安全,具有推广价值.     

Effects of Botulinum Toxin Type A on Pain among Trigeminal Neuralgia,Myofascial Temporomandibular Disorders,and Oromandibular Dystonia

The differences in analgesic effects of botulinum toxin type A were compared in 28 patients with trigeminal neuralgia, 53 patients with myofascial temporomandibular disorders, and 89 patients with the jaw closing oromandibular dystonia. The patients were treated by injection of botulinum toxin type A into the masseter, temporalis, medial pterygoid, and other muscles based on the symptoms of each patient. The pain severity was evaluated using the visual analog scale, pain frequency, and pain scale of the oromandibular dystonia rating scale. Botulinum toxin injection was performed 1068 times in all patients without significant adverse effects. The visual analog, pain frequency, and pain scales at baseline were reduced (p < 0.001) after two, four, eight, and 12 weeks after the first botulinum toxin therapy and at the endpoint. The effects differed significantly (p < 0.001) among the groups (repeated-measures analysis of variance). The mean improvement (0%, no effect; 100%, complete recovery) at the endpoint was 86.8% for trigeminal neuralgia, 80.8% for myofascial pain, and 75.4% for oromandibular dystonia. Injection of the botulinum toxin can be a highly effective and safe method to treat trigeminal neuralgia, myofascial pain, and oromandibular dystonia.     

A型肉毒毒素联合透明质酸注射治疗面部老化临床疗效观察

目的：探讨A型肉毒毒素、透明质酸注射联合治疗面部皮肤老化疗效及安全性。方法：对45例患者面部老化问题,采用A型肉毒毒素联合透明质酸注射治疗,观察治疗效果。结果：患者面部老化问题得到不同程度的改善,治疗有效率83.11%,术后不良反应轻且都是暂时性,恢复良好。结论：A型肉毒毒素联合透明质酸注射治疗面部皮肤老化疗效好,患者满意度高,安全有效。     

A型肉毒毒素对神经病理性疼痛大鼠镇痛作用及作用途径的研究

目的：观察A型肉毒毒素（BTX—A）对L5前根切断（L5 VRT）神经病理性疼痛模型大鼠的镇痛作用并探讨其最佳给药途径。方法：雄性SD大鼠108只,随机分为3组（n=36）,皮下注射给药组、坐骨神经表面给药组、坐骨神经注射给药组,制备L5 VRT模型,各组又分为术后4d给药组、术后8d给药组、术后16d给药组且同时各设0．9％氯化钠注射液对照组（n=6）,于术前、术后及术后不同给药时间测定50％撤足阈值（PWT）。结果：①皮下给药组能明显的改善机械痛敏,坐骨神经表面及坐骨神经注射给药组机械痛敏改善不明显。②皮下给药组术后各不同时间给药小组,均能明显的改善机械痛敏,与对照组相比有统计学意义（P〈0．05）;给药后第15天效果最明显;这种镇痛作用持续至少20余天。③坐骨神经表面及坐骨神经注射给药组动物的机械痛敏改善不明显,与对照组相比无统计学意义（P〉0．05）。结论：皮下注射BTX—A,能改善L5VRT模型大鼠的机械痛敏,有镇痛作用,且为最佳给药途径。     

A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent.     

Multidimensional Effectiveness of Botulinum Toxin in Neuropathic Pain: A Systematic Review of Randomized Clinical Trials

Although botulinum toxin (BoNT) has been suggested as a treatment to counter neuropathic pain, no previous systematic reviews investigated the multidimensional effects of BoNT on pain relief and Health-Related Quality of Life (HR-QoL). The aim of this systematic review is to summarize the current evidence on the effectiveness of BoNT treatment for neuropathic pain, and to characterize its multidimensional effectiveness in order to guide physicians in clinical practice. Five databases were systematically searched up to 4 April 2022, to identify randomized controlled trials satisfying the following criteria: adults suffering from neuropathic pain, BoNT administration, any comparator, multidimensional assessment of pain as primary outcome, HR-QoL, physical function, anxiety and depression, and sleep quality as secondary outcomes. Twelve studies were included. The multidimensional pain scales used were short-form McGill Pain Questionnaire, Neuropathic pain scale, Neuropathic Pain Symptom Inventory, International SCI Pain Basic Data Set, West Haven-Yale Multidimensional Pain Inventory, Brief Pain Inventory, and Douleur Neuropathique 4. These scales highlighted the positive effects of BoNT administration. According to the Jadad scale, all the RCTs included were high-quality studies. BoNT administration might be effectively introduced in the comprehensive management of neuropathic pain. Further research should focus on optimal and cost-effective therapeutic protocols.     

Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.     

Pain in Patients with Post Paralytic Hemifacial Spasm: Before,during and after Botulinum Toxin Injections

It is well-established that botulinum toxin (BT) injections improve quality of life in patients with postparalytic hemifacial spasm. Nevertheless, injection-related pain and contracture-related pain have not yet been studied. The primary objective of our study was to evaluate injection-related pain in patients with facial palsy sequelae, and to compare the standard technique (syringe) with the Juvapen device. The secondary objective was to evaluate the improvement of contracture-related pain one month after BT injection. Methods: We conducted an observational, prospective, monocentric study based on 60 patients with facial palsy sequelae who received BT injections in our university ENT (ear, nose throat) department. There were 30 patients in the Juvapen group (J) and 30 in the standard technique group (ST). All patients completed Numerical Rating Scale (NRS) questionnaires immediately after the injections and one month later. Results: The average NRS score was 1.33/10 with Juvapen and 2.24/10 with the standard technique (p = 0.0058; Z = 2.75). In patients with contracture-related pain, the average NRS score was 3.53 before BT injection, and 0.41 one month after BT injection (p = 0.0001). Conclusions: Juvapen is a less-painful injection technique than the standard one. BT reduces contracture-related pain one month after injection.