Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is considerable evidence that injection of botulinum toxin (BTX) into muscles with spastic overactivity reduces resistance to passive movement in joints supplied by the injected muscles. The demonstration of improvement in active performance of the paretic limbs has been only anecdotal to date, and represents the most difficult challenge in research on BTX therapy in spastic paralysis. Data are reviewed that indicate several neurophysiological actions of BTX, other than the blocking of acetylcholine release at the neuromuscular ending: effects on the central nervous system, including retrograde axonal transport, reduced motoneuronal excitability, action on central synapses such as decreased Renshaw inhibition and increased presynaptic inhibition; action on gamma motoneuronal endings; action on most active terminals; spread of BTX to neighboring muscles; spread of BTX effects to remote muscles. Several of these neurophysiological actions are likely to contribute to improvement in active movements, as they may antagonize the primary mechanisms of functional impairment in patients with spastic paralysis: weakness, spastic cocontraction, spastic dystonia, and muscle shortening. We review the evidence for reduction of spastic cocontraction in both the injected muscle and its antagonist, and for improvement of antagonist weakness after BTX injection. The capacity of intramuscular BTX to reduce spastic dystonia and lengthen shortened muscles is also discussed based on prior literature. When injected into the more overactive of a pair of spastic antagonists around a joint, BTX should affect all the main mechanisms impairing active function around the joint.
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PMID:Physiological effects of botulinum toxin in spasticity. 1502 64

Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction, including cervical dystonia, blepharospasm and hemifacial spasm. It inhibits neurouscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient with normal neuronal signaling returning within approximately 3-6 months post injection. Recently, clinical findings suggest that BoNT/A may inhibit pain associated with migraine and other headache types. The mechanism by which this toxin inhibits pain is under investigation, recent findings suggest that it inhibits the release of neurotransmitters from nociceptive nerve terminals and in this way may exert an analgesic effect. A number of retrospective open-label chart reviews and three placebo-controlled double-blind trials have demonstrated that localized injections of BTX-A significantly reduce migraine frequency, severity, and migraine-associated disability. The majority of patients in these studies experienced no BoNT/A mediated side effects; however, a small percentage of patients did report transient minor side effects including blepharoptosis, dipolpia, and injection-site weakness. Currently there are several large-scale randomized, placebo-controlled clinical trials in progress evaluating the efficacy, optimal dosing and side effect profile of this toxin as a novel treatment for migraine and other headache types. These studies may provide further evidence that BoNT/A is an effective option for the preventive treatment of migraine.
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PMID:Botulinum neurotoxin for the treatment of migraine and other primary headache disorders. 1515 49

Idiopathic cervical dystonia (ICD) is the most common adult-onset focal dystonia. It is characterised by relatively sustained, involuntary contractions of neck muscles. Injections of botulinum toxin (BTX)-A are safe and effective for the treatment of ICD, and have substantially improved its treatment. BTX-A is manufactured by Allergan Pharmaceuticals in the US and Ireland, and is distributed as Botox. In Europe, BTX-A is manufactured and distributed by Ipsen Pharmaceuticals as Dysport. Success rates for BTX-A injections for ICD ranges 64-90%, with 76-93% of injected patients experiencing pain reduction. Side effects are generally mild and include dysphagia and neck weakness.
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PMID:Botulinum toxin A for the treatment of cervical dystonia. 1533 Jul 38

Spasticity results in a resistance to passive movement and decrease of passive mobility of the involved joints and is defined as a state of hypertonicity with exaggeration of tendon reflexes mediated by a loss of inhibitory control of upper motor neurons. In patients with severe stages of multiple sclerosis (MS) spasticity of the lower limbs often leeds to a spastic pattern with hip adduction resulting in decreased range-of-motion (ROM), increased pain, spasms, and functional disability (disturbed gait and sitting position) as well as difficulties with perineal hygiene. Local botulinum toxin type A (Btx-A) injections in spastic muscles offer a new treatment approach for managing spasticity and associated problems. Up to now Btx-A is approved for the treatment of blepharospasm and cervical dystonia and the treatment of equinous gait in children with cerebral palsy in Austria and Germany. Up to now only in Switzerland Botox is licensed for the treatment of focal spasticity. Btx-A is a neurotoxin derived from Clostridium botulinum. In most european countries Btx-A is available as Dysport (vial = 500 units) and Botox (vial = 100 units). In prospective studies a ratio of 1 unit Botox to 3-4 units Dysport was found. Following intramuscular injection Btx-A blocks the release of acetylcholine at the neuromuscular junctions, thereby inhibiting muscle contraction, and decreases spastic muscle tone and muscle spindles afferent information to the spinal cord. The spectrum of side effects includes local weakening of the injected and adjacent muscles as well as pain and haematoma at the injection site. At therapeutic doses side effects are local and transient. According to a double blind, placebo controlled, dose ranging study published by Hyman et al. (2000, Dysport in a dose of 500, 1000 and 1500 units reduced the degree of hip adductor spasticity associated with MS, and this benefit was evident despite concomitant use of oral antispasticity medication. According to the results of the study there was a clear trend towards greater efficacy and duration of effects with higher doses of Dysport. Taking efficacy and adverse events into account (incidence of muscle weakness was higher for the 1500 units group than for placebo) the optimal dose for hip adductor spasticity seems to be 1000 units Dysport divided between the adductor magnus, longus and brevis muscles and between both legs. To increase Btx-A effects following injection of hip adductors additional physiotherapy and casting or orthosis to increase passive hip-abduction is recommended. According to the literature anatomical localisation of the adductor muscles for injection and aspiration following insertion of the needle, to avoid injection of the toxin into a vessel, should be performed. A maximum dose of 1500 units Dysport (400 units Botox) per treatment session and 250 units Dysport (50 units Botox) per injection site is recommended. See table for dose-range of Dysport, and Botox in the treatment of adult patients with hip-adductor spasticity. For evaluation of treatment effects in hip adductor spasticity clinical examination with specific scales and measurements (see Appendix) at baseline, 4 and 12 weeks following BtxA injection is recommended:--Global rating of severity (0-4; patient's self assessment and physician's rating) --Global rating of response (-4 - +4; patient's self assessment and physician's rating)--Visual Analogue Scale (patient's self assessment of pain)--Active and passive ROM (manual goniometer)--Distance between the medial femur condyles in thigh extension (distance in cm)--Modified Ashworth scale (0-4)--Ten meter walking time (seconds)--Functional Ambulation Categories (0-5)--Score of perineal hygiene (0-5).
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PMID:[Botulinum toxin treatment of hip adductor spasticity in multiple sclerosis]. 1550 48

Allelic mutations of Scn8a in the mouse have revealed the range of neurological disorders that can result from alternations of one neuronal sodium channel. Null mutations produce the most severe phenotype, with motor neuron failure leading to paralysis and juvenile lethality. Two less severe mutations cause ataxia, tremor, muscle weakness, and dystonia. The electrophysiological effects have been studied at the cellular level by recording from neurons from the mutant mice. The data demonstrate that Scn8a is required for the complex spiking of cerebellar Purkinje cells and for persistent sodium current in several classes of neurons, including some with pacemaker roles. The mouse mutations of Scn8a have also provided insight into the mode of inheritance of channelopathies, and led to the identification of a modifier gene that affects transcript splicing. These mutations demonstrate the value of mouse models to elucidate the pathophysiology of human disease.
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PMID:Allelic mutations of the sodium channel SCN8A reveal multiple cellular and physiological functions. 1561 59

Botulinum toxin type A (Dysport) has been shown in European studies to be a safe and effective treatment for cervical dystonia. This multicenter, double-blind, randomized, controlled trial assessed the safety and efficacy of Dysport in cervical dystonia patients in the United States. Eighty patients were randomly assigned to receive one treatment with Dysport (500 units) or placebo. Participants were followed up for 4 to 20 weeks, until they needed further treatment. They were assessed at baseline and weeks 2, 4, 8, 12, 16, and 20 after treatment. Dysport was significantly more efficacious than placebo at weeks 4, 8, and 12 as assessed by the Toronto Western Spasmodic Torticollis Rating Scale (10-point vs. 3.8-point reduction in total score, respectively, at week 4; P < or = 0.013). Of participants in the Dysport group, 38% showed positive treatment response, compared to 16% in the placebo group (95% confidence interval, 0.02-0.41). The median duration of response to Dysport was 18.5 weeks. Side effects were generally similar in the two treatment groups; only blurred vision and weakness occurred significantly more often with Dysport. No participants in the Dysport group converted from negative to positive antibodies after treatment. These results confirm previous reports that Dysport (500 units) is safe, effective, and well-tolerated in patients with cervical dystonia.
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PMID:Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: results of the first US randomized, double-blind, placebo-controlled study. 1573 59

Efficacy of botulinum toxin type B (BoNT B) for the treatment of type A-resistant (AR) and non-A-resistant (NAR) cervical dystonia (CD) has been demonstrated in several single injection studies. There is little data available on long-term therapy with repeated injection sessions and it is unknown if AR and NAR patients respond in a similar manner over time. To evaluate the long-term efficacy and safety of BoNT B in AR and NAR CD patients, we carried out a prospective, open-label study examining 10 repeated dosing sessions of BoNT B in 34 patients with CD (15 AR and 19 NAR). Dosing was started at 10,000 units and could be increased to 25,000. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and a patient global assessment at each baseline (injection) and Week 4 (peak effect) visit. Change in TWSTRS total was the primary efficacy end point. Data was analyzed using repeated-measures analysis of variance. BoNT B therapy resulted in an overall significant improvement of CD (P<0.001) and improvement was seen in all 10 individual sessions (2.5 years). The magnitude of response decayed over time (P<0.001). There was no difference between AR and NAR patients with regard to dose, treatment effect, or decay in response. The AR group perceived (patient global) treatment as being less effective (P=0.047). Dry mouth frequency decreased with each session despite increasing doses whereas flu-like syndrome and weakness increased. BoNT B therapy provides long-term benefit for CD patients but the magnitude of response diminishes over time. The cause of this decay is probably multifactorial. AR and NAR CD patients respond in a similar fashion.
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PMID:Efficacy and safety of repeated doses of botulinum toxin type B in type A resistant and responsive cervical dystonia. 1595 34

Botulinum toxin (BoNT) treatment has been used extensively for the treatment of cervical dystonia. In most studies, there is significant improvement following treatment for head posture and pain. The common side effects following treatment include dysphagia, dry mouth, and neck weakness. There are five brands and two serotypes of BoNT available. The dosing of each serotype and brand differs. Perhaps more importantly, each brand and serotype may differ in immunogenic potential and occurrence of secondary unresponsiveness, an issue that is currently under active investigation. Although many aspects of the technique of injection have not been adequately studied, general guidelines are available.
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PMID:Treatment of cervical dystonia with botulinum toxins. 1641 93

Cerebral palsy is the main cause of immobility in children. This motor dysfunction is caused by several motor components such as weakness, lack of motor control and muscle hypertonia. Drug treatment, delineated in this review, mainly addresses the latter. Recently, new definitions for clinical features of hypertonia in children were published, assisting the distinction between the two common motor symptoms in cerebral palsy, spasticity and dystonia. The main functional symptoms disrupt functional daily life, dictating the overall approach and the specific drug treatment. There are an increasing number of treatments for this distressing disorder. For general spasticity, treatments provided include Baclofen. If symptoms are local, either dystonia, or spasticity, Botulinum toxin is the revolutionary drug used with significant success and relatively few side effects. For generalized dystonia, a trial of both Dopamine and Trihexyphenidyl should be considered. Cerebral palsy, like other complex disorders, requires individualized decision-making and a team approach. Drug therapy is only one aspect of treatment, yet sometimes it may serve as a window of opportunity to facilitate better motor control.
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PMID:[Drug treatment for children with cerebral palsy]. 1690 Jul 42

Torticollis is a clinical symptom and sign characterized by a lateral head tilt and chin rotation toward the side opposite to the tilt. Many conditions cause torticollis. The differential diagnosis is different for infants than for children and adolescents. Congenital muscular torticollis associated with a contracture of the sternocleidomastoid muscle is the most common etiology of torticollis in infants. The condition of most infants with congenital muscular torticollis improves with a regimen of manual cervical stretching. Congenital anomalies of the occipital condyles and upper cervical spine must be ruled out before performing a release of the sternocleidomastoid muscle in a child who fails to improve with physical therapy. Unusual nonmuscular causes of torticollis in the infant also must be considered and include ocular torticollis caused by eye muscle weakness, Sandifer's syndrome resulting from gastroesophageal reflux, neural axis abnormalities, and benign paroxysmal torticollis. Torticollis in the older child is most frequently a manifestation of atlantoaxial rotatory displacement resulting from trauma or oropharyngeal inflammation (Grisel's syndrome). Retropharyngeal abscesses and pyogenic cervical spondylitis are unusual infectious causes of torticollis. Intermittent torticollis associated with headaches, vomiting, or neurologic symptoms may be caused by tumors of the posterior fossa. Benign and malignant neoplasms of the upper cervical spine are rare causes of torticollis in children. Torticollis resulting from cervical dystonia is also rare in children but may be seen in older adolescents.
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PMID:Torticollis in infants and children: common and unusual causes. 1695 98


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