Failure of fixed-dose, fixed muscle injection of botulinum toxin in torticollis

We studied the effect of botulinum toxin injection in 30 patients with torticollis in a double-blind, placebo-controlled, crossover study. A fixed dose of toxin was injected into the contralateral sternocleidomastoid and both trapezius muscles. Clinical improvement was assessed by a rating scale and by patient self-evaluation. Subjective rating noted improvement in some patients, but there was no change in objective measures. The use of larger doses and injection of additional muscles may be necessary to achieve increased efficacy of botulinum toxin in the treatment of torticollis.     

Experience with botulinum toxin type A in medically intractable pediatric chronic daily headache

In adults, botulinum toxin type A has been studied as a potentially effective treatment for chronic daily headache. For pediatric chronic daily headache, the literature evaluating efficacy of botulinum toxin type A is sparse, with no studies assessing tolerability. The purpose of this retrospective case series study was to assess tolerability and efficacy of botulinum toxin type A in the treatment of pediatric chronic daily headache. The series comprises 10 patients (ages 11-17 years) who received a standard 100-unit dose of onabotulinumtoxinA (trade name, Botox) for refractory chronic daily headache. Attention was given to therapeutic history, efficacy, and tolerability. The patients had attempted an average of 8.0 ± 2.40 S.D. therapies prior to botulinum toxin type A. Most patients reported adverse events from at least one of these prior medications. With botulinum toxin type A, four patients (40%) reported subjective but clinically meaningful relief, consisting of a decrease in headache intensity, and two patients additionally noted a decrease in headache frequency. The four responders noted improvements in quality of life. Three patients experienced minor adverse events from botulinum toxin type A. This case series suggests that botulinum toxin type A can be well tolerated and may be a useful therapeutic in pediatric patients with highly medically intractable chronic daily headache.     

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.     

Evaluating the role of botulinum toxin in the management of focal hypertonia in adults

OBJECTIVES: To investigate the effects of EMG guided botulinum toxin (BTX-A) on impairment and focal disability in adults presenting with focal hypertonia. METHODS: A prospective, randomised, double blind, placebo controlled, parallel group trial was carried out with standardised assessment before and at 3 week intervals until 12 weeks after injection, in patients with focal hypertonia affecting upper or lower limbs. Botulinum toxin or placebo was injected with EMG guidance after multidisciplinary assessment. The modified Ashworth scale of spasticity, percentage passive range of joint motion, subjective rating of problem severity, the Rivermead motor assessment scale, a timed 10 metre walk (lower limb patients), nine hole peg test (upper limb patients), and a modified goal attainment scale were used as outcome measures. The patients were 52 adults; 34 male, 18 female; mean age 40.31, range 16-79 years; mean duration of symptoms 35 months (range 3 months to 22 years). Diagnoses included cerebrovascular accidents (23), head injury (12), incomplete spinal cord injury (six), tumour (five), cerebral palsy (three), and anoxic episodes (three). RESULTS: For each variable an overall score for the treatment period was computed by summing the scores from the 3, 6, 9, and 12 week assessments. These overall scores were significantly better in the treated group for the Ashworth scale, percentage passive range of movement, Rivermead lower limb, and subjective rating of problem severity. The significant treatment effect on the Ashworth scale was seen on analysis of variance (ANOVA) at 3 weeks and the subjective rating of problem severity at 3 and 6 weeks. The goal attainment scale score in both groups was similar at 12 weeks. CONCLUSION: Selective use of botulinum toxin to weaken muscles can lead to a reduction in resistance to passive movement about a distal limb joint. This allows for improvements in passive range of movement and focal disability, particularly in patients presenting with focal spasticity of the lower limb.     

Controlled trial of botulinum toxin injections in the treatment of spasmodic torticollis

We administered local injections of botulinum toxin to 20 patients with torticollis in a blinded, placebo-controlled study. Each patient received four sets of injections: three different doses of botulinum toxin and one placebo. The order of the sessions was random and unknown to the patients. Sixteen of the patients (80%) reported subjective improvement to at least one dose of botulinum toxin; 11 (55%) reported substantial improvement. No objective benefit was documented. Side effects were minor and transient, although dysphagia occurred in four. Some patients reported that the effect waned despite persistent relaxation or even flaccidity of previously overactive muscles, suggesting a change in the pattern of muscle activity after botulinum toxin injections.     

Treatment of spasticity with botulinum toxin]

Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition.     

High doses of botulinum toxin effectively treat disabling up-going toe

Involuntary up-going toe can be a disabling consequence of dystonia or spasticity. In this study, we treated eight patients with botulinum toxin (BTx) in the extensor hallucis longus (EHL) and applied objective and subjective outcome measures to determine treatment efficacy. Using 100% higher doses than generally reported, patients noted 62+/-20% mean benefit and scores on a modified Fahn-Marsden Dystonia Scale decreased significantly by 1.8+/-0.6 (p=0.010). High doses (up to 160 BTx A units) into the EHL were safe and dosage correlated highly and significantly with treatment efficacy (rho=0.859, p=0.006).     

Treatment of childhood myoclonus with botulinum toxin type A

Because of inadequate response to or intolerable side effects of oral medication, nine patients with segmental, generalized, and focal myoclonus were treated with intramuscular botulinum toxin type A. All patients were evaluated with neuroimaging, routine and limb-monitored electroencephalography, electromyography, evoked potentials and appropriate biochemical studies. Patients were aged 2 to 22 years, with duration of myoclonus from 1 month to 10 years. Multiple medication trials included antiepileptic drugs, benzodiazepines, tryptophan, L-dopa/carbidopa, baclofen, and dantrolene. Patients were injected with botulinum toxin in their affected area with electromyographic guidance to affected muscles with different doses (8 to 20 units/kg), except two patients who were injected with 32 and 45 units/kg, respectively, at 4- to 8-month intervals. One patient did not complete botulinum toxin treatment because of subjective weakness, although there were virtually no side effects reported in patients completing therapy. Patients reported a dramatic reduction in painful myoclonus. In addition, patients exhibited improved functional skills, as demonstrated by markedly improved use of affected extremities and improvements in ambulation. One patient, who was nonambulatory prior to treatment, was able to walk afterward. Long-term benefits could be related to higher dosage used or negative feedback effect.     

Botulinum toxin in writer''s cramp: objective response evaluation in 31 patients.

OBJECTIVES--To quantify the treatment effect of local botulinum toxin injections in writer's cramp a newly developed rating scale of writing performance and a computer assisted analysis of writing speed were used in 31 patients undergoing botulinum toxin therapy. METHODS--Baseline data of the writer's cramp rating scale (WCRS, see appendix) and computer based writing speed analysis were compared with those obtained at the time of subjective best response as recorded during follow up visits. RESULTS--The mean dose injected per session was 133.2 units Dysport divided between two forearm muscles. Of all 124 injection sessions during mean follow up of one year 76% produced a good improvement. The most common side effect was weakness (72% of the follow up visits). The WCRS scores as assessed by a blinded videotape review by four independent raters showed good reliability between raters and a significant improvement after treatment (P < 0.001). The speed of pen movements showed a significant (P < 0.05) increase after treatment at subjective best effect recordings and a significant correlation with WCRS subscores, documenting the validity of the scale. CONCLUSION--The present study is the first to show significant effects of botulinum toxin treatment in patients with writer's cramp on the basis of a quantifiable scale for writing performance which correlates significantly with writing speed measurements. The WCRS as employed in this study might therefore prove a useful rating instrument in other studies assessing severity and treatment response in patients with writer's cramp.     

Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment

The muscular patterns of cervical dystonia were identified by polymyographic recordings in 76 patients before botulinum toxin treatment. The leading muscles were considered to be those which started dystonic movement and which showed constant and maximal activity during all dystonic movements. The dystonic muscles were repeatedly treated by local Injections of botulinum toxin. Sixteen patients showed (after repeated injections) loss of the benefit of local applications of botulinum toxin after various periods of time. Repeated polymyographic recordings were performed in these patients during the loss of the benefit of injected botulinum toxin. In four patients repeated polymyographic recordings showed an Identical pattern of cervical dystonia, but the activity of previously injected muscles was apparently decreased. In 12 patients only minimum or no activity was recorded in muscles which had previously been treated with botulinum toxin, but the pattern of cervical dystonia was changed. Different patterns of cervical dystonia with different leading muscles, but with identical directions of head deviation, were observed in six patients. In another six patients, the head deviation direction was to the opposite side and was accompanied by a change of the leading muscle and a change of the muscular pattern of dystonia. These results suggest either that dystonic activity from the cerebral generator changes to new effectors during the peripheral blockade of primary dystonic muscles, or that a change of generators at different levels of the CNS occurs. It may be neccessary to carry out repeated polymyographic recordings throughout the period of loss of benefit of previously successful local botulinum toxin injections.     

Use of botulinum toxin in stroke patients with severe upper limb spasticity.

OBJECTIVES--Spasticity can contribute to poor recovery of upper limb function after stroke. This is a preliminary evaluation of the impact of botulinum toxin treatment on disability caused by upper limb spasticity after stroke. METHODS--Seventeen patients with severe spasticity and a non-functioning arm were treated with intramuscular botulinum A neurotoxin (median age at treatment 54.5 years; median time between onset of stroke and treatment 1.5 years). Baseline and assessments two weeks after treatment were compared to assess efficacy. The duration of improvement in disability was documented. Outcome measures used were; passive range of movement at the shoulder, elbow, wrist, and fingers; modified Ashworth scale to assess spasticity of biceps and forearm finger flexors; an eight point scale to assess the degree of difficulty experienced by the patient or carer for each functional problem defined before treatment; the presence of upper limb pain. The biceps, forearm finger flexors, and flexor carpiulnaris were treated with intramuscular botulinum toxin. Up to a total dose of 400-1000 mouse units (MU) of Dysport (Speywood) or 100-200 MU of BOTOX (Allergan) was used in each patient. RESULTS--Functional problems reported by the patients before treatment were difficulty with cleaning the palm, cutting fingernails, putting the arm through a sleeve, standing and walking balance, putting on gloves, and rolling over in bed. Hand hygiene improved in 14 of 17 patients; difficulty with sleeves improved in four of 16; standing and walking balance improved in one of four; shoulder pain improved in six of nine; wrist pain improved in five of six. Passive range of movement at shoulder, elbow, and wrist improved after treatment. Benefit was noted within two weeks and lasted one to 11 months. No adverse effects occurred. CONCLUSION--This preliminary study suggests that intramuscular botulinum toxin is a safe and effective treatment for reducing disability in patients with severe upper limb spasticity.     

Botulinum toxin a in management of cerebral palsy

The efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in children with cerebral palsy was studied in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. Fifteen children with cerebral palsy (mean age: 6 years, 8 months) were included in the study. All had limb deformities associated with nonfixed joint contractures that had not responded to physical therapy. Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while barefooted. The study provides evidence that the intramuscular injection of botulinum toxin A in selected skeletal muscles decreases muscle tone and contractures, and increases range of motion and motor function.     

A型肉毒毒素重复治疗偏头痛的临床疗效

目的 探讨A型肉毒毒素重复注射治疗偏头痛的疗效与安全性。方法 对30例偏头痛患者均进行2次A型内毒毒素注射治疗,两次均采用颅周固定位点注射,初次治疗间隔6个月以上后进行第2次治疗,2次治疗后分别于第1,2,3个月评定头痛发作天数、头痛发作次数、疼痛程度、偏头痛残疾程度及不良反应。结果 二次A型肉毒毒素注射治疗后偏头痛发作天数、发作次数、疼痛程度、残疾程度均较治疗前缓解（F分别为3．86,5．23,9．37,5．67;P〈0．05）,但两次治疗后各观察点评定指标比较差异无统计学意义（P〉0．05）。结论 A型肉毒毒素重复治疗偏头痛有效、安全,较初次治疗无差异．     

Secondary nonresponsiveness to new bulk botulinum toxin A (BCB2024).

We report on a patient with cranio-cervical dystonia injected with the new, lower protein formulation of botulinum toxin A who developed secondary resistance to this toxin. Subsequent injections with botulinum toxin B provided substantial reduction of blepharospasm. This is the first reported case of secondary resistance to the new preparation of botulinum toxin A.     

Botulinum toxin A injection in the treatment of hemifacial spasm

Introduction – There are conflicting reports concerning the variation in duration of symptoms relief for patients with hemifacial spasm who have undergone several injections of botulinum A toxin (BOTX-A). We present our experience of BOTX-A injections in Taiwanese patients to analyze this issues, and to inspect whether the efficacy of treatment depends on the pre-injection severity. Material and method — From July 1992 to December 1994, 137 patients received injections of BOTX-A. We used objective and subjective score system to evaluate the efficacy and side effects of BOTX-A injection. Results — The overall successful rate of substantial relief of spasm was 88%. The mean duration of response was 20 weeks. Patents with more severe spasm tended to have shorter duration of improvement. The effects of consecutive injections remained fairly constant over the first 4 injections. Conclusion — The BOTX-A injection is an effective and safe treatment for patients with hemifacial spasm and the effect could be sustained over the consecutive injections.     

Botulinum toxin and intractable trigeminal neuralgia

The effects of botulinum toxin have been demonstrated in pain syndromes such as migraine, tension headache, and postherpetic neuralgia. With this background data in hand, the authors planned a randomized, open-ended study to investigate the efficacy of botulinum injections in cases of refractory trigeminal neuralgia. In 8 patients with trigeminal neuralgia, 100 U botulinum toxin was injected into the region of the zygomatic arch. The results of their statistical analyses demonstrated that the medication can be effective in treating trigeminal neuralgia. The patients did not develop any significant adverse effects. Botulinum toxin can be used in the treatment of refractory trigeminal neuralgia.     

Botulinum toxin as a treatment for blepharospasm, spasmodic torticollis and hemifacial spasm.

Fifty-two patients affected by focal dystonia or hemifacial spasm were treated with repeated injections of botulinum toxin. A clinical improvement was observed in all patients with blepharospasm; clinical benefit had a mean duration of 10 weeks. Clinical results were less impressive, but also favorable in patients affected by spasmodic torticollis and by hemifacial spasm. In the latter, the incidence of drug-induced paresis was much higher than that observed in patients with blepharospasm, even though the doses of toxin injected were significantly lower.     

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.     

Treatment of sialorrhoea with ultrasound guided botulinum toxin type A injection in patients with neurological disorders

OBJECTIVES: To investigate the safety and efficacy of ultrasound guided botulinum toxin type A (BTX-A) injections into salivary glands for the treatment of sialorrhoea in patients with neurological disorders. METHODS: The parotid and submandibular glands of 10 patients were injected with BTX-A using ultrasound guidance. Before injection, the baseline rate of salivation was assessed using a visual analogue scale. Postinjection, assessments were repeated at regular intervals for up to 1 year. RESULTS: Of the 10 patients treated, nine (90%) reported a subjective reduction in salivation post-treatment and one patient (10%) found no improvement. Visual analogue scale scores showed a reduction of 55% in the mean rate of salivation for all patients and a reduction of 60.8% for the group of responders. No serious adverse events occurred and no procedure related complications were reported. CONCLUSIONS: This is the first study to report (1) the injection of BTX-A (BOTOX) into both parotid and submandibular glands, and (2) the use of ultrasound guidance during the administration of BTX-A into salivary glands. The results suggest that the technique is safe and that BTX-A injections are effective for the treatment of sialorrhoea in patients with neurological disorders.     

Effectiveness of botulinum toxin administered to abolish acquired nystagmus.

We injected botulinum toxin into the horizontal rectus muscles of the right eyes of 2 patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In 1 patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic-adaptive changes in response to paresis caused by the botulinum toxin. Such plastic-adaptive changes and direct side effects of the injections--such as diplopia and ptosis--may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment.