Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations

BackgroundAdjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews.ObjectiveTo assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process.MethodsFour electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs.ResultsWe included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n = 9), joint posture procedures (JPPs, n = 11), and active ATs (n = 14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score = 7 [6–8]) but moderate (n = 2) or poor (n = 2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (> 3 months after botulinum toxin injections), particularly when performed at a high-intensity (> 3 h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended.ConclusionsJPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life.Review RegistrationPROSPERO (CRD42018105856).     

基于糖脂代谢研究筋疽（糖尿病足非缺血性坏疽）湿热毒盛证

[目的]通过现代检验技术研究筋疽(糖尿病足非缺血性坏疽)湿热毒盛证的糖脂代谢指标。[方法]收集136例筋疽(糖尿病足非缺血性坏疽)患者进行不同证型间指标的比较。[结果]湿热毒盛证患者空腹血糖(FBG)、糖化血红蛋白(HbA1c)、餐后2 h血糖(2 hPBG)、晚期糖基化终末产物(AGEs)、白蛋白(ALB)、总胆固醇(TC)、高密度脂蛋白(HDL-C)与其他证型比较存在统计学差异(P<0.05)。湿热毒盛证患者C-反应蛋白(CRP)、人可溶性血管细胞黏附分子1(sVCAM-1)与其他证型组间比较存在统计学差异(P<0.01)。[结论]筋疽(糖尿病足非缺血性坏疽)湿热毒盛证形成的原因与低营养状态下糖脂代谢紊乱引起的高血糖及持续炎症反应相关。     

基于胶质淋巴系统探讨“毒损脑络”

络脉是经脉系统的分支,具有沟通表里上下、联系脏腑的作用,在支持气血运行方面呈现双向流动的特性,具有物质交换和新陈代谢的功能。脑为诸阳之会,脑络纵横交错,脑络渗灌气血以充实脑髓并敷布阳气以温煦脑神,为"脑主神明"提供物质基础和源动力。病理情况下脑络不通,毒邪内生,而致"毒损脑络"。"毒损脑络"病机学说不仅应用于中风病机研究中,而且拓展到痴呆等其他脑病中,推动了中医脑病病机理论的发展。新近发现脑内存在"胶质淋巴系统",是星形胶质细胞介导的脑脊液-脑间质液的交换流动系统。胶质淋巴系统把脑脊液中的葡萄糖、脂质、电解质和载脂蛋白E等营养物质和神经活性物质运送到脑组织,也能清除脑内代谢产物(如乳酸)、可溶性蛋白(如β-淀粉样蛋白和Tau蛋白)和异物,这是维持脑内环境稳态的重要液体流动系统。胶质淋巴系统的发现为神经系统疾病病理机制的研究提供了新视角,可能成为脑血管疾病、神经退行性疾病等神经精神系统疾病干预的新靶点。作为脑内广泛分布的代谢废物排出途径和物质运送系统的胶质淋巴系统可能是"脑络"病变的生物学基础,是中西医对"毒损脑络"认识的交叉点,从胶质淋巴系统探析"毒损脑络",有可能为揭示"毒损脑络"的现代内涵提供新的靶点。     

Postmenopausal craniofacial hyperhidrosis treated with botulinum toxin type B

Hyperhidrosis can seriously impair patients’ quality of life. Medical history, including heredity and hyperhidrosis during youth, as well as current age and time elapsed since menopause, is important to consider when distinguishing between postmenopausal hyperhidrosis and vasomotor symptoms to enable adequate treatment. This report concerns a subgroup of eight postmenopausal patients participating in a randomized controlled trial regarding botulinum toxin (Btx) type B treatment in craniofacial hyperhidrosis. Even though the sample size is small and the enrolment is not yet completed, the promising data collected hitherto are interesting to present in advance because this subtype of craniofacial hyperhidrosis is often underrecognized and challenging to treat. Patients were randomized to receive Btx type B or placebo. Measurements were performed before treatment and 3 ± 1 weeks after. The Dermatology Life Quality Index (DLQI) score was improved for all patients after Btx type B treatment (n = 3) with a median decrease of 9 points (90% median improvement). The placebo group (n = 5) had a median increase of 2 points (–18% median decline). When the same group (n = 5) received Btx type B (open) the DLQI score decreased with a median of 7 points compared with baseline (91% median improvement). Treatment‐related adverse events were temporary and did not prevent improvement of life quality. Furthermore, background data evaluation uncovered interesting findings regarding vasomotor symptoms in relation to postmenopausal hyperhidrosis. In conclusion, the results indicated that Btx type B seems to be a safe and effective treatment in postmenopausal craniofacial hyperhidrosis. Further research is encouraged.     

肉毒毒素注射引起的不良反应

肉毒毒素注射引起的不良反应,是药物本身的组成成分引起的与用药目的无关的有害反应,与医生注射方式和注射技术无关。尽管肉毒毒素生产厂家的药品说明书上也有提示,但其所提供的信息不够全面,也未必能引起医生的足够重视。目前文献上多为散发病例。为此作者对过去20年有关肉毒毒素注射引起的过敏反应、肉瘤样肉芽肿、眼睑水肿、流感样症状等相关不良反应的临床表现、发病机制与治疗方法进行综述。     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

A型肉毒素在皮肤科疾病治疗中的进展

A型肉毒素是肉毒梭状芽孢杆菌在繁殖过程中分泌的A型毒性蛋白质,具有很强的神经毒性。其在皮肤美容方面的疗效显著而被熟知。除皮肤美容外,临床实践和前期研究均证实A型肉毒素在治疗皮肤病方面亦有明显疗效,且部分疾病经治疗预后明显优于传统治疗,如瘢痕与多汗症等。     

花宝金运用抗癌解毒药对治疗肿瘤经验探析

导师花宝金教授长期从事中西医结合肿瘤的临床与基础研究。认为"正气内虚"是肿瘤发生的根本,"癌毒"是肿瘤发生的必要条件。收集导师多年临床组方,归纳、总结后发现清热解毒或攻毒散结之法常贯穿于始终。结合现代药物理论及导师多年临床经验,总结出临床常用七组抗癌解毒药对:(1)夏枯草、半枝莲;(2)石见穿、猫爪草;(3)金荞麦、蒲公英;(4)龙葵、白英、白花蛇舌草;(5)山慈菇、浙贝母;(6)藤梨根、蛇莓;(7)全蝎、蜈蚣。通过整体与局部的辨病与辨证、根据肿瘤的不同类型及发病阶段,结合癌毒的病机特点,灵活运用抗癌解毒药对,临床疗效确切。     

Adjunct therapies to improve outcomes after botulinum toxin injection in children: A systematic review

BackgroundBotulinum toxin (BTX) injection alone is not sufficient to treat spasticity in children, notably those with cerebral palsy; thus, there is an emerging trend for adjunct therapies to offer greater outcomes than BTX alone.ObjectiveThe aim of this systematic review was to evaluate the general effectiveness of adjunct therapies regardless of their nature in children with spasticity.MethodsMedline, Cochrane and Embase databases were searched from January 1980 to March 15, 2018 for reports of parallel-group trials (randomized controlled trials [RCTs] and non-RCTs) assessing adjunct therapies after BTX injection for treating spasticity in children. Two independent reviewers extracted data and assessed the risk of bias by using the PEDro scale for RCTs and Downs and Black scale (D&B) for non-RCTs.ResultsOverall, 20 articles involving 662 participants met the inclusion criteria. The average quality was good for the 16 RCTs (mean PEDro score 7.4 [SD 1.6]) and poor to moderate for the 4 non-RCTs (D&B score 9 to 17). Adjunct therapies consisted of casting/posture, electrical stimulation, resistance training and rehabilitation programmes. Casting associated with BTX injection improved the range of passive and active motion and reduced spasticity better than did BTX alone (9 studies), with a follow-up of 1 year. Resistance training enhanced the quality and performance of muscles without increasing spasticity. Only 3 rehabilitation programmes were studied, with encouraging results for activities.ConclusionLower-limb posture with casting in children has a high level of evidence, but the long-term efficacy of short-leg casting needs to be evaluated. A comparison between the different modalities of casting is missing, and studies specifically devoted to testing the different kinds of casting are needed. Moreover, the delay to casting after BTX injection is not clear. Data on electrical stimulation are not conclusive. Despite the small number of studies, resistance training could be an interesting adjunct therapy notably to avoid loss of strength after BTX injection. Rehabilitation programmes after BTX injection still need to be evaluated.     

Efficacy of single-photon emission computed tomography aided botulinum toxin injection in cervical dystonia: A double-blind,randomized study

BackgroundAlthough single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD.MethodsPatients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2.ResultsA total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: β, −4.86 [95%CI -9.40 to −0.32; P = 0.036]; Tsui: β, −1.65 [95%CI -2.77 to −0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: β, −6.33 [95%CI -10.17 to −2.49; P = 0.001]; Tsui: β, −1.42 [95%CI -2.48 to −0.37; P = 0.008]) and T3 (TWSTRS: β, −6.05 [95%CI -11.09 to −1.01; P = 0.019]; Tsui: β, −1.24 [95%CI -2.40 to −0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 ± 28.6 versus 141.8 ± 51.0 days, P = 0.032).ConclusionsSPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.