Botulinum toxin type A treatment in neurogenetic syndromes

Purpose: To review the use of therapeutic botulinum toxin type A (BoNT-A) treatments in uncommon neurogenetic syndromes.

Method: A retrospective questionnaire and interview study of a selected case series to assess the efficacy and safety following initial BoNT-A treatment (50–400 units per subject) was conducted to determine the response of families to treatment. Twelve male and six female subjects with ages from 2–19 years were included. The reasons for treatments were based on both patient-related and caregiver-related objectives. Satisfaction with achievement of stated goals was assessed by follow-up interviews.

Results: Beneficial effects were reported in 56%, some effects in 22% and no to minimal effects in 22%. The duration of effect ranged from 10 days to 12 months with an average of 3.16 months. Ten families would repeat the injections as needed, four would not and four were not sure. Unanticipated effects of BoNT-A treatments were reported by some families. Adverse effects did not occur with the doses that were used.

Conclusions: The results suggest that obtaining family input may be useful when treating spasticity in unusual circumstances. The use of BTX-A in uncommon neurogenetic syndromes was supported by the majority of families interviewed.     

Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.     

Botulinum injection for the management of myofascial pain in the masticatory muscles. A prospective outcome study

We prospectively analysed the outcome after botulinum injection in patients who did not recover after conservative measures to manage masticatory myofascial pain, and who were not willing to take low dose tricyclic antidepressants as a muscle relaxant. We prospectively 62 patients were assessed with visual analogue scores (VAS) for pain on the affected side before, and 6 weeks after botulinum injection(s) (50 units Dysport^® in up to 3 sites), and measured mouth opening in mm. Of those treated 49 (79%) showed at least some improvement (pain reduced by more than 25%). Patients reported more than a 90% reduction in the VAS for 25 (30%) of the 84 sides of the face treated. Only 22 of the 62 patients had more than one course of treatment to the same side. Interincisal distance improved by a mean/median of 0.9 mm (p < 0.03) after treatment. Side effects included 3 cases of temporary weakness of a facial muscle. Ranking the VAS pain scores using the Wilcoxon test before and after injection showed a significant reduction in pain (median change −29.5, interquartile range −53 to −16, p < 0.0001). The treatment significantly improved patients’ pain scores and the overall mean/median reduction in pain was 57%. Botulinum injection does not guarantee complete resolution of myofascial pain, but it usually has some beneficial effect in improving the symptoms, and should be considered as an alternate treatment for masticatory myofascial pain if conservative methods have failed.     

Ultrasound-guided injection of botulinum toxin A into the submandibular gland in children and young adults with sialorrhoea

Hypersalivation is a common and distressing complaint in children with neuromuscular disorders such as cerebral palsy. Complications associated with severe drooling include daily changes of clothing, perioral dermatitis, dental problems, dehydration, and aspiration pneumonia, which potentially have a detrimental effect on the quality of life of the patient and carer. In this paper we update our previous work to show the potential benefits of ultrasound-guided injection of botulinum toxin A (BTX-A) into the submandibular gland and report on new patients and follow-up data on the existing group.     

Intramural injection with botulinum toxin significantly elongates the pig esophagus

Background/Purpose

Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We hypothesized that intramural injections with BTX-A into the esophageal wall of piglets would significantly elongate the tissue upon stretch.

Methods

Twenty-four piglets were randomized to receive BTX-A of placebo (saline). After one hour, the esophagus was removed en bloc and tested in a stretch-tension device.

Results

The mean esophageal elongation was 84% (range 83–101) in the BTX-A-group and 65% (50–78) in the control group. The mean difference between the two groups was 18%, which was significant (p < 0.001).

Conclusion

Intramural injections with botulinum toxin type A elongate the esophagus significantly. Clinically, this could be a potential method to achieve primary anastomosis in LGEA. Additional clinical studies are necessary to evaluate the method before it can be generally recommended.     

不同剂量A型肉毒毒素皮内注射治疗腋部多汗症效果观察

目的 评估不同剂量A型肉毒毒素治疗腋部多汗症的时效.方法 腋部多汗症患者86例,患者左右侧腋窝自身对照:左侧为小剂量A型肉毒毒素注射组,皮内注射生理盐水稀释的A型肉毒毒素50U;右侧为大剂量A型肉毒毒素注射组,皮内注射生理盐水稀释的A型肉毒毒素200U;随访3～29个月,观察两组并发症,并建立两组等级资料,行x2检验,评价患者两侧腋窝维持疗效的时间差异.结果 两组疗效进行对比,大剂量与小剂量的A型肉毒毒素的疗效维持时间的差异有统计学意义(P＜0.05).结论 大剂量A型肉毒毒素能够显著延长腋部多汗症疗效时间.     

The effects of botulinum toxin injection frequency on calf muscle growth in young children with spastic cerebral palsy: a 12-month prospective study

Purpose

This study was a 12-month prospective investigation of changes in the medial gastrocnemius (MG) muscle morphology in children aged 2–5 years with spastic cerebral palsy (CP) who had received no previous intramuscular injections of botulinum neurotoxin type-A (BoNT-A) and were randomised to receive either single or multiple (three) BoNT-A injections to the gastrocsoleus. MG morphological changes were compared to age-matched typically developing (TD) peers.

Methods

Thirteen children with spastic CP with a mean age of 45 (15) months and 18 TD children with a mean age of 48 (14) months participated in the study. The principal outcome measures were MG muscle volume, fascicle length, pennation angle and physiological cross-sectional area (PCSA), which were obtained using 2D and 3D ultrasound.

Results

The single and multiple injection frequency groups significantly increased MG muscle volume at 12 months relative to the baseline by 13 and 15 %, respectively. There were no significant differences in the MG muscle volume 28.5 (12.3) versus 30.3 (3.8) ml, fascicle length 48.0 (10.4) versus 44.8 (1.2) mm or PCSA 7.0 (1.2) versus 6.6 (1.7) cm² between the single and multiple injection groups, respectively, at 12 months follow-up. The change in MG muscle volume in the single and multiple injection groups was significantly lower than the TD peers by 66 and 60 %, respectively.

Interpretation

In young children with spastic CP, naive to BoNT-A treatment, MG muscle growth over 12 months does not appear to be influenced by intramuscular BoNT-A injection frequency. However, MG muscle growth in the spastic CP groups was significantly lower than the age-matched TD peers. It is unclear whether this is an effect of intramuscular BoNT-A injections or reduced growth rates in children with spastic CP in general. Controlled investigations and longitudinal studies with multiple measurement time points are required in order to determine the influence of BoNT-A treatment on muscle physiological and mechanical growth factors in young children with spastic CP.     

A型肉毒毒素膀胱内不同部位注射治疗女性膀胱疼痛综合征/间质性膀胱炎的临床研究

目的 比较A型肉毒毒素膀胱内逼尿肌注射以及逼尿肌联合三角区注射两种不同注射方法治疗女性膀胱疼痛综合征/间质性膀胱炎的疗效以及安全性.方法 60例入选病例,随机分为两组:逼尿肌注射组(A组)、逼尿肌联合三角区注射组(B组),评估两组患者治疗前及治疗后8周的平均每日排尿次数、最大排尿量、残余尿量、PUF评分、QOL评分.结果 A组及B组治疗后平均每日排尿次数减少,最大排尿量增加,PUF及QOL评分降低,残余尿量无明显增加,B组治疗后与A组治疗后相比,平均每日排尿次数、最大排尿量及PUF评分改善更明显,残余尿量与QOL评分无明显区别.结论 A型肉毒毒素膀胱内注射治疗女性膀胱疼痛综合征/间质性膀胱炎疗效好,生活质量提高,采用逼尿肌联合三角区部位的注射,症状缓解更为明显,副作用无明显增加,值得进一步研究及推广.     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000 U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500 U and the peak improvement was at week 8 after injection. A dose of 1000 U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500 U.     

局部注射A型肉毒毒素后远隔部位F波的改变

目的探讨局部注射A型肉毒毒素(BTX-A)后其远隔部位F波的改变及其可能机制。方法对19例偏侧面肌痉挛(HFS)患者、5例Meige综合征患者及2例痉挛性斜颈(TS)患者行BTX-A注射，并在注射前、注射后1周及注射后12～24周时分别检测其尺神经及胫神经F波的各项参数变化。结果①注射后1周，有3例患者共5条尺神经未引出肯定波形。②与注射前比较，尺、胫神经F波平均潜伏期以及尺神经F波时限在注射1周后显著延长，且这种改变与注射剂量无明显相关性；注射12～24周时，上述两参数与注射前比较，差异均无显著性意义。结论F波平均潜伏期和时限是评价BTX-A远隔效应的敏感指标；BTX-A的远隔效应似与检查部位和注射部位间的距离有关，而与注射剂量无明显相关性。