Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.69 (botulinum neurotoxin)
1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.
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PMID:Safety and efficacy of botulinum toxin type A following long-term use. 1711 48

Hereditary spastic paraplegia (HSP) is characterized by lower extremity spasticity. Symptomatic therapy generally includes physical therapy and oral antispastic agents, in selected cases intrathecal baclofen. Because of the positive results in other treatments of spasticity, the use of botulinum neurotoxin type A (BoNT-A) might also be considered for patients with HSP. We report the effect of BoNT-A injections in 19 unselected patients with HSP treated by the members of the German Spasticity Education Group. In 17 patients, the modified Ashworth scale had improved by one point. In one patient, it improved by three points. Most of the patients reported reduction of spasticity. BoNT-A injections were continued in 11 of 19 patients (57.9%). All of the patients with continued injections had a good or very good global subjective improvement. Patients with less pronounced spasticity and patients with accompanying physical therapy tended to exhibit a better effect. Only four patients reported adverse effects which were increased weakness in three patients and pain in one patient. BoNT-A injections appear to reduce spasticity effectively and safely, especially in patients with mild to moderate spasticity. The preliminary results of our case series should encourage larger studies of BoNT-A injections in HSP.
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PMID:Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia--report of 19 cases. 1799 30

Spasticity is characterized by increased muscle resistance. It is usually associated with muscle weakness or poor motor control. This condition not only reduces activities of daily living (ADLs), but also interferes personal hygiere and causes caregiuer's difficulty. The use of botulinum neurotoxin (BoNT) intramuscular injections is a simple and effective therapy for spasticity. The use of BoNT to treat adult patients with spasticity was first reported in 1989, since then, using the neurotoxin to treat spasticity became popular in some European countries. Now in Japan, BoNT can be used to treat only torticollis, blepharospasm and hemifacial spasm because of the legal limitation on its use. However, clinical research on the use of BoNT in spasticity caused by stroke is presently underway, and an adaptation of the toxin may be available in the near future. This article reviews the characteristics of BoNT and the techniques for injecting this neurotoxin.
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PMID:[Use of botulinum neurotoxin for spasticity]. 1911 Jul 53

Botulinum toxin type A (BoNT-A) therapy has gained wide acceptance in the management of spasticity in cerebral palsy (CP). Clinical experience from numerous case reports and series, retrospective and prospective open label cohort studies, and randomized controlled trials (RCT) has grown over the past 10 years. Several independent systematic reviews on the role of BoNT-A for upper and lower limb spasticity have been written by various authors. The objective of this paper is to summarize past systematic reviews and recent RCT not yet included in the systematic reviews that assess the effectiveness of BoNT-A in upper and lower limb spasticity in children with CP. We reviewed four Class II RCT discussed in five independent systematic reviews and two new Class II trials on the use of BoNT-A alone or with occupational therapy compared to placebo or occupational therapy alone in children with upper limb spasticity. There were 229 children recruited in these six trials and of those, 115 children received BoNT-A in the upper limbs. Five of six RCT showed a time limited decrease in muscle tone most especially at the wrist. Four of six trials showed improvement of hand function on a few specific functional tests. Four systematic reviews concluded that there is insufficient and inconsistent evidence to support or refute the effectiveness of BoNT-A in upper limb spasticity but one recent review recommended that BoNT-A should be considered as a treatment option in upper limb spasticity. For lower limb spasticity, we reviewed 13 RCT discussed in six systematic reviews and two new trials comparing BoNT-A with placebo or other rehabilitation modalities such as physiotherapy, occupational therapy, casting or electrical stimulation. In these studies, 617 children were recruited and of those, 360 children received BoNT-A in the lower limbs. There were six Class I and nine Class II trials. Three Class I trials documented significant improvement in gait pattern in children with gastrocnemius spasticity and one Class I study showed significant reduction in tone in the hip adductors. The most recent review establishes BoNT-A as an effective treatment for equinovarus deformity. Adverse events in these trials were mild and self-limited. The most common complaints were pain in the injection sites and transient weakness. BoNT-A is considered safe for use in children. In conclusion, there is now growing convincing evidence for the time limited beneficial effect of BoNT-A in decreasing muscle tone in children with upper and lower limbs spasticity associated with CP. Decrease muscle tone in the lower limbs translates to improved gait in CP children with spastic equinovarus however more systematic studies are necessary to show sufficient evidence for improved hand function from BoNT-A injection in the upper limbs.
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PMID:Effectiveness of botulinum toxin A for upper and lower limb spasticity in children with cerebral palsy: a summary of evidence. 1914 73

The upper motor neuron (UMN) syndrome is a collection of interactive positive signs (associated with spastic hypertonia) and negative signs, such as muscle weakness and loss of voluntary control. In clinical practice, the distinction between active and passive functions allows identifying appropriate treatment objectives. During the last decades, many studies have evaluated the possibility to treat UMN syndromes with botulinum neurotoxin (BoNT). They have shown that BoNT is effective in controlling upper limb spasticity in adults. The clinical improvement is more consistent in the distal joints and the reduction of muscle hypertonia is dose-dependent. The functional efficacy of BoNT for lower limb spasticity has not been documented as well, as some series report efficacy in reducing muscle tone in the lower limb, but not in improving walking. The functional benefit arising from the reduction of spasticity is often difficult to judge in the context of the complex phenomenology of the UMN syndrome. Certain data indicate that some disabilities related to passive and active function in the upper limb can improve with treatment. However, to date, the functional improvement after BoNT treatment in patients with UMN symptoms remains a point of ambiguity in the literature. BoNT is overall well tolerated and must be regarded as a safe treatment intervention. Safety data are abundant in the literature for type-A toxin and scant for type-B toxin. There is no clear evidence to suggest the best time to introduce BoNT injections in the management of UMN syndromes. A common sense approach would be to introduce BoNT treatment as early as possible, in order to prevent further complications including contractures.
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PMID:Botulinum toxin for the management of adult patients with upper motor neuron syndrome. 1947 Mar 35

Lower limb disorders of movement and muscle tone in adults significantly impact quality of life. The management of the patient with hypertonia is complex and requires a multidisciplinary team working with the patient and family/carers. Botulinum neurotoxin type A (BoNT-A) has been used as a component of this management to reduce lower limb hypertonia, increase passive range of motion and reduce associated pain and requirements for bracing. Adjunctive treatments to augment the effect of BoNT-A include electrical muscle stimulation of the injected muscles and stretching. When determining suitability for injection, the patient's main goals for intervention need to be established. Muscle overactivity must be distinguished from contracture, and the effect of underlying muscle weakness taken into account. Explanation of the injection process, potential adverse effects and post-injection interventions is essential. Assessment at baseline and post-treatment of impairments such as hypertonia, range of motion and muscle spasm are appropriate; however, the Goal Attainment Scale and other validated patient-centred scales can also be useful to assess therapy outcomes. In the future, initiatives should be directed towards examining the effectiveness of BoNT treatment to assist with achievement of functional and participation goals in adults with hypertonia and dystonia affecting the lower limb.
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PMID:Botulinum toxin assessment, intervention and aftercare for lower limb disorders of movement and muscle tone in adults: international consensus statement. 2063 79

The use of intramuscular injections of Botulinum neurotoxin A (BoNT-A) is common in the treatment of hypertonicity and movement disorders. Although most side effects are mild, systemic effects, manifested by generalized weakness distant from the site of injection, have been reported. Previously reported occurrences are discussed, and 3 new cases of patients, who developed systemic weakness after administration of BoNT-A (Botox), despite having tolerated similar injections on several previous occasions, are presented. A review of the literature and reported cases indicate that risk of developing systemic effects does not seem to be related to dose based on body weight. It may be more likely that risk for systemic effects is related to total injection dose and injection frequency. The results of our 3 patients would indicate that injections of greater than 600 units of Botox with follow-up injections occurring every 3 months may lead to an increased risk. We would recommend careful consideration of reinjection frequency if injections of greater than 600 units of Botox are given. Reduction in systemic side effects may occur if reinjection frequency occurs in intervals of 4 months or greater in these individuals.
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PMID:Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature. 2085 12

An 8-month old girl, weighing 9 kg, was brought by her parents at 8.15 am to the Emergency Department (ED) for a progressive worsening of weakness and acute respiratory failure. On admission, the baby presented with poor oral intake, a weak cry and extremely weak muscular body control. Poor gag and suck, unreactive mydriasis, hypotonia, lethargy and absence of peristalsis were noted. Laboratory data showed severe respiratory acidosis. Chest X-ray, electroencephalography, encephalic CT scan and MRI were all normal, as were cerebrospinal fluid analysis and viral tests. Orotracheal intubation and continuous mechanical ventilation were applied. The patient received fluids, corticosteroids, aerosol therapy, large-spectrum antibiotics and enteral-nutrition. Further investigation revealed ingestion of an improperly prepared home-canned homogenized turkey meal. Type A botulinum neurotoxin was identified. Trivalent botulinum antitoxin, prostigmine and oral activated charcoal were administered. Generalized flaccid paralysis, areflexic bilateral mydriasis, gastric stasis and deep coma persisted for the duration of the hospital stay, and the patient died of severe respiratory failure and cardiac arrest 12 days after ED admission. Botulism poisoning should be suspected in any infant presenting with feeding difficulties, constipation, descendent paralysis or acute respiratory failure. Supportive treatment and antidotal therapy should be performed as soon as a clinical diagnosis is made. We describe a case of foodborne botulism in an 8-month old infant caused by ingestion of an improperly prepared home-canned homogenized turkey meal, representing the youngest fatal case reported in medical literature.
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PMID:Fatal course of foodborne botulism in an eight-month old infant. 2235 16

In September 2010, an outbreak of type A botulism involved 4 horses in northern California that were fed grass clippings obtained from a nearby park. All 4 animals developed a progressive flaccid paralysis syndrome clinically consistent with exposure to preformed Clostridium botulinum neurotoxin (BoNT). Within 48 hr of consuming the grass clippings, all 4 horses showed marked cervical weakness (inability to raise their heads to a normal position) and died or were euthanized within 96 hr. One horse was submitted for diagnostic examination and subsequent necropsy. At necropsy, extensive edema was observed in areas of the nuchal ligament and inguinal fascia. A sample of the grass clippings tested positive for preformed BoNT type A by the mouse bioassay test. Emphasis should be placed on early case recognition, rapid initiation of treatment with the trivalent antitoxin product, and preventing exposure to BoNT in spoiled forages.
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PMID:An outbreak of equine botulism type A associated with feeding grass clippings. 2252 34

This prospective, open study was carried out in order to assess changes in the swallowing and dietary status after injection of Botulinum toxin A (BoNT-A) into the upper esophageal sphincter (UES) in a series of patients with cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness during at least 1 year follow-up after treatment. Patients who had a cricopharyngeus (CP) muscle dysfunction associated with pharyngo-laryngeal weakness and who were at risk for aspiration were included in the study. The upper border of the cricoid cartilage was identified and the CP muscle localized using a standard electromyogram (EMG). The dose of BoNT-A was determined depending on the results of EMG performed just before the injection. Outcomes were assessed by the penetration-aspiration scale (PAS), the level of residue in the pyriform sinus and the National Institute of Health-Swallow Safety Scale (NIH-SSS) on a video fluoroscopic swallowing (VFSS) assessment, the patient's subjective impressions of their ability to swallow by the Deglutition Handicap Index (DHI), and changes in dietary status by the Functional Oral Intake Scale. Eleven patients underwent the complete assessment of swallowing function at 1, 3, 6, and 12 months. After the first set of treatment, seven patients had a good response and four did not respond. A significant decrease in the PAS score (p = 0.03), the amount of residue (p = 0.04) and the NIH-SSS score (p = 0.03) was observed 3 months after the injection in comparison with the first VFSS before the treatment. A relapse of dysphagia occurred in 3 out of the 11 treated patients; at 3 and 4 months for 2 patients with a Wallenberg syndrome, and at 11 months for a patient with cranial nerve paralysis after a surgery for a glomus tumor. Two of them underwent a second injection. One patient had a good response and remained stable for at least 1 year. The second did not respond either to the second injection or to a myotomy of the cricopharyngeal muscle. The third one is waiting for further surgery (myotomy). Therefore, at the end of the study and after a follow-up of at least 12 months, 5 patients out of the 11 enrolled had a good result. Percutaneous injection of BoNT-A into the UES can be a useful solution to improve cricopharyngeal dysfunction, despite the underlying pharyngo-laryngeal weakness.
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PMID:The effects of botulinum toxin injections into the cricopharyngeus muscle of patients with cricopharyngeus dysfunction associated with pharyngo-laryngeal weakness. 2286 4


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