Botulinum toxin therapy of migraine and tension‐type headache: comparing different botulinum toxin preparations

Most of the initial reports on botulinum toxin in tension‐type headache (TTH) and in migraine were positive. Unfortunately, these results were not reproduced in well‐designed, randomized controlled trials. So far, doses from 20 U (Botox®) to 500 U (Dysport®) have been studied in patients with chronic TTH, and doses from 16 to 200 U (Botox®) in patients with migraine. Overall, there is no evidence for a beneficial effect of botulinum toxin, although trends favoring botulinum toxin were reported. Experience with botulinum toxin type B (Myobloc®/NeuroBloc®) is limited and similar to the experience with the type A. Thus, a widespread use of botulinum toxin therapy in headache can currently not be recommended.     

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.     

Beneficial effects of botulinum toxin type a for patients with painful tic convulsif

Botulinum toxin is a well-known therapy for patients with diverse movement disorders. Its application has been extended to other disorders. Here, we document the case of a 70-year-old man with hemifacial spasm associated to trigeminal neuralgia secondary to an ectatic basilar artery. He was treated with botulinum toxin type A, 2.5 mouse units over five sites at the orbicularis oculi and one over the buccinator muscle. After botulinum toxin injections, relief was gained not only from twitching but also from pain. When the effects of the toxin vanished, spasms and pain recurred. Further infiltrations were given every 12 weeks following the same response pattern. This observation further validates the increasing role of botulinum toxin in pain management.     

Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: an open-label, dose-escalation pilot study

Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of I or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.     

Treatment of hip adductor spasticity with botulinum toxin type B

For the treatment of focal spasticity using botulinum toxin, only studies using type A have been published.Botulinum toxin type B (Neurobloc) is registered for cervical dystonia, but there is increasing interest in ist effectiveness for treating other diseases. Four patients, each with seriously disabling hip adductor spasticity of different origins, were treated with botulinum toxin type B following the failure of other therapeutic options.Total doses of 10,000 IU to 22,000 IU were injected bilaterally into the hip adductor muscles. A reduction in muscle tone or painful spasms was observed in all patients within 2 weeks, leading to an improvement in gait and increased ease of nursing care. Therefore, botulinum toxin type B may be a more cost-effective treatment for hip adductor spasticity than botulinum toxin type A.     

Botulinum Toxin for the Treatment of Movement Disorders

After botulinum toxin was initially used to treat strabismus in the 1970s, others started using it to treat movement disorders including blepharospasm, hemifacial spasm, cervical dystonia, spasmodic dysphonia, and oromandibular dystonia. It was discovered that botulinum toxin can be an effective treatment for focal movement disorders with limited side effects. Over the past three decades, various formulations of botulinum toxin have been developed and the therapeutic use of these toxins has expanded in movement disorders and beyond. We review the history and mechanism of action of botulinum toxin, as well as describe different formulations available and their potential therapeutic uses in movement disorders.     

Quantitative reduction of saliva production with botulinum toxin type B injection into the salivary glands

Drooling is common in patients with neurological disorders. Recently, botulinum toxin type B has been shown to be effective in the treatment of drooling. The authors present a unique case of a 57-year-old man with a history of a brainstem stroke and severe drooling. The patient's parotid and submandibular glands were injected under ultra-sound guidance with botulinum toxin type B. Saliva was collected and quantified before and after the injections by 2 different collection methods: suctioning and dental rolls. Total saliva production decreased by 23.8% after injection of the parotid glands and by 85.8% after submandibular injection compared to the preinjection level. The 2 methods demonstrated similar results. In addition, the patient experienced less drooling and increased participation in therapies without any side effects. This case demonstrates that saliva secretion and drooling can effectively be treated by injections of botulinum toxin type B into the salivary glands.     

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.     

重复局部注射A型肉毒毒素治疗局限性肌张力障碍长期疗效观察

目的研究重复局部注射A型肉毒毒素治疗偏侧面肌痉挛、眼睑痉挛、Meige's综合征、痉挛性斜颈的长期疗效及维持时间,有无剂量增加趋势。方法用A型肉毒毒素对241例患者重复小剂量局部多点注射,随访治疗10年,将6轮次治疗疗效以及剂量、疗效维持时间、不良反应进行比较分析。结果各轮次总有效率分别为98.7%、98.9%、99.3%、100%、100%、100%。作用持续(20±3)周,平均剂量40U,各轮间疗效、平均剂量、作用持续时间均无显著差异(P>0.05)。结论重复局部注射治疗局限性肌张力障碍长期疗效稳定,作用持续时间相似,维持疗效无需增加剂量,局部不良反应轻微短暂。     

Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review

Over the last several years, botulinum toxin type A has gained widespread use for the management of focal spasticity in children with cerebral palsy. To assess the current patterns of botulinum toxin type A use in the clinical setting, the dose, muscles injected, age at injection, and interval between injections of botulinum toxin type A treatments were examined in a retrospective chart review of children with cerebral palsy (N = 270) over a 2-year period at three major treatment centers. The average dose of botulinum toxin type A across the three centers ranged from 7.7 to 10.8 U/kg body weight, and the average total amount of botulinum toxin type A injected at a single visit ranged from 154 to 205 U. The majority of botulinum toxin type A injections were to the muscles to the lower limbs. The average age at first injection was 6.2 years, and the average interval between injections ranged from 134 to 199 days.     

Safety of high-dose botulinum toxin type A therapy for the treatment of pediatric spasticity

This retrospective chart review examines the safety of high-dose (> or = 15 U/kg body weight or > or = 800 total units) botulinum toxin type A (BOTOX, Allergan Inc., Irvine, CA) in children and young adults with spasticity. Ninety-four children weighing < 45 kg received a mean total dose of 334.1 U or 19.1 U/kg. Fourteen young adults weighing > or = 45 kg received a mean total dose of 927.3 U or 15.2 U/kg. Adverse events were reported by 3 of the 108 patients (2.8%) and included single instances of rash and enuresis. The only serious adverse event consisted of mild, generalized botulism in a 13-year-old patient who received a 23 U/kg dose to the hamstrings and gastrocnemius/soleus bilaterally. No serious adverse events were noted in children weighing < 45 kg who received botulinum toxin type A doses of 15 to 22 U/kg of body weight or in young adults > or = 45 kg who received total doses of 800 to 1200 U in a single injection protocol. High-dose botulinum toxin type A is safe for the treatment of spasticity in children and young adults.     

Botulinum toxin B reduces sialorrhea in parkinsonism.

We report on our open-label experience with botulinum toxin B for the treatment of severe sialorrhea associated with parkinsonism. Nine adult patients with parkinsonism and medically intractable sialorrhea were treated with botulinum toxin B (1,000 units into each parotid gland using superficial landmarks). After treatment, patients experienced a 61% mean subjective improvement and a 42% mean reduction of quantitative saliva production. There were no adverse effects seen in any subjects. Mean peak benefit from injections lasted 14 weeks. We conclude that denervation of salivary glands with botulinum toxin B produces excellent reduction of excessive salivation associated with parkinsonism.     

Therapeutic interventions for tone abnormalities in cerebral palsy

Cerebral palsy (CP) is a common cause of movement disorders in children. The upper motor neuron syndrome of CP leads to several types of muscle overactivity, including spasticity. Reduction of muscle overactivity may be an important treatment goal, to improve comfort, care, and active function and to prevent future musculoskeletal complications. After a comprehensive team evaluation, a treatment plan is generated. Treatments may include physical and occupational therapy, oral medications, botulinum toxin and/or phenol injections, intrathecal baclofen, selective dorsal rhizotomy, and orthopedic surgery. Successful and early prevention of contracture may reduce the need for later corrective surgery.     

Botulinum toxin B increases mouth opening in patients with spastic trismus

Background: Severe generalized spastic movement disorders of various aetiologies often involve the jaw muscles and lead to a spastic trismus with masseter muscle hypertonia. We report a placebo‐controlled randomized study on patients with spastic trismus. Methods: Eleven patients with masseter hypertonia because of stroke, hypoxic encephalopathy or traumatic brain injury were allocated to either botulinum toxin serotype B (BoNT/B) injections into the masseter muscles or placebo treatment. The dental gap, the amount of saliva, salivation scales, and a clinical goal attainment were evaluated. Results: Three weeks after injection the BoNT/B group showed a significantly increased mouth opening compared with placebo treatment (P < 0.05). In addition to the muscle paralysing effect, a goal attainment scale demonstrated a clinical benefit for the BoNT/B group (P < 0.01). Conclusions: Botulinum toxin serotype B injections into the masseter muscles effectively reduce hypertonia and provide for better mouth opening, thereby contributing to a positive and desired clinical goal.     

Pharmacotherapy of spasticity in children with cerebral palsy

Spasticity is one of the most common symptoms presented by neurologic patients. Apart from surgical management, drug therapy is an important treatment of children suffering from spasticity. In this review, recent advances in the pharmacologic armamentarium are reported in detail. In particular, there are oral medications (benzodiazepines, baclofen, dantrolene sodium, alpha 2 adrenergic agonists) and parenteral medications (botulinum toxin type A and B, alcohol). Moreover, there is also baclofen that can be administered intrathecally. There are some reports supporting the use of intramuscular alcohol (45% and/or 5-7% phenol) to reduce spasticity without the loss of voluntary movement or loss of sensation. Among these drugs, intrathecal baclofen is one of the most effective substances that can reduce spasticity significantly in the upper and lower extremities. Finally, the effectiveness of therapy with botulinum toxin type A in the management of spasticity is analyzed. Botulinum toxin type A reduces hypertonia in the injected muscles for a period of 2 to 4 months without important side effects. The purpose of this article is to provide an overview of available oral and parenteral drugs for treatment of spasticity in cerebral palsy and to outline indications and contraindications.     

The use of botulinum toxin type A treatment in children with spasticity

The current modalities in managing spastic children have some limitations; thus, alternative therapeutic agents are in need. The purpose of this study is to investigate whether intramuscular botulinum toxin type A administration may be an alternative agent in the treatment of children with cerebral palsy. Eighteen children who were aged between 3 and 17 years and manifested cerebral palsy were administered intramuscular botulinum toxin type A with a total dose of 6 U/kg body weight. Outcome measurements were determined with four methods, including Ashworth Spasticity Scale, standardized videotape assessments, observational gait analysis, and walking velocity. Ashworth Spasticity Scale and videotape assessments were statistically significant before and after treatment in all muscles (P < 0.001). The best improvement in video gait analysis was evident at week 8. The botulinum toxin type A injections yielded an improved walking velocity at all visits. The observational gait analysis and walking velocity demonstrated an improvement after treatment in the gastrocnemius-injected group (P < 0.001). In conclusion, intramuscular botulinum toxin type A administration may be effective in children with cerebral palsy, especially at week 4 and when injected in gastrocnemius.     

Botulism type B presenting as pure autonomic dysfunction

Abstract. Botulism nowadays is a rare mostly food-borne disease caused by the toxin of Clostridium botulinum. On the other hand, botulinum toxin blocking cholinergic transmission has become a most powerful treatment option for many focal movement disorders and is increasingly used to treat autonomic disorders [2, 7, 8]. Although muscle weakness is the hallmark of botulism, autonomic dysfunction may be the leading clinical symptom in rare cases and should be included in the differential diagnosis of pure dysautonomia. Here, we describe a patient with autonomic dysfunction as the leading symptom of botulism type B.     

Botulinum toxin type A for treating voice tremor

BACKGROUND: Voice tremor, like spasmodic dysphonia and other tremor disorders, may respond to botulinum toxin type A injections. OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injections as treatment for voice tremor. DESIGN: A randomized study of 3 doses of botulinum toxin type A with 6 weeks of follow-up. SETTING: A single-site tertiary care center.Participants and METHODS: Thirteen subjects (11 women, 2 men; mean age, 73 years) with voice tremor and no spasmodic dysphonia or head, mouth, jaw, or facial tremor were entered into this study. Patients received 1.25 U (n = 5), 2.5 U (n = 5), or 3.75 U (n = 3) of botulinum toxin type A in each vocal cord. All patients were evaluated at baseline and postinjection at weeks 2, 4, and 6. MAIN OUTCOME MEASURES: The primary outcome measure was the patient tremor rating scale, with secondary measures including patient-rated functional disability, response rating scale, independent randomized tremor ratings, and acoustical measures. RESULTS: All patients at all dose levels noted an effect from the injection. The mean time to onset of effect was 2.3 days (range, 1-7 days). For all patients combined, mean tremor severity scale scores (rated by patients on a 5-point scale) improved 1.4 points at week 2, 1.6 points at week 4, and 1.7 points at week 6. Measures of functional disability, measures of the effect of injection, independent ratings of videotaped speech, and acoustic measures of tremor also showed improvement. The main adverse effects at all doses were breathiness and dysphagia. CONCLUSION: Voice tremor improves following injections of botulinum toxin type A.     

Botulinum toxin A as a treatment for excessive drooling in children

Drooling is problematic for some neurologically impaired children. Botulinum toxin A injection to salivary glands has effectively reduced drooling in adults but has only recently been used to treat children. This was a preliminary study to determine the efficacy and safety of botulinum toxin in children. Children identified as having severe daily drooling were enrolled. The preinjection assessment included measurement of the amount and frequency of drool. Each parotid gland was injected with 5 U of botulinum toxin A. Follow-up was for a minimum of 16 weeks. Nine children were enrolled, 4-17 years of age. All children had moderate or severe mental retardation. At week 4, all patients had a reduced drooling frequency and eight of nine patients had a reduction in the weight of saliva. Overall, five of nine parents (55%) deemed the treatment successful. This preliminary study demonstrates that botulinum toxin A is a relatively effective treatment for some children with significant drooling without serious side effects.     

Evaluation of botulinum toxin A therapy in children with adductor spasm by gross motor function measure

Intramuscular injection of botulinum neurotoxin A is a relatively new method for treating spastic movement disorders in children. One major goal of any therapy for patients with movement disorders is to improve gross motor function. In this study, 18 patients with adductor spasm were treated with botulinum neurotoxin A. Treatment effect was determined with the Gross Motor Function Measure, a standardized, validated instrument designed to assist in assessment of gross motor function. Spastic muscle hyperactivity and joint mobility were evaluated by the modified Ashworth Scale and by range of motion, respectively. Compared to pretreatment values, significant improvement in gross motor function (P < .010), decrease in the modified Ashworth Scale, and increase in the range of motion (P < .010) were achieved. Patients with moderate impairment of gross motor function (classed at level III and level IV in the Gross Motor Function Classification System) benefited most from treatment. In patients with severe handicap (level V), only one of five treated patients showed improvement in gross motor function. Nevertheless, all patients in this subgroup benefited from improved ease in hygienic care. In conclusion, we have demonstrated that for most children with moderate functional impairment, the Gross Motor Function Measure is a useful instrument for objective documentation of improvements of gross motor function following treatment with botulinum neurotoxin A.