Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00783 (Botox)
 415 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum toxin is a presynaptic neuromuscular blocking agent inducing selective and reversible muscle weakness up to several months when injected intramuscularly in minute quantities. Different medical disciplines have discovered the toxin to treat mainly muscular hypercontraction. In urology, indications for botulinum-A toxin have been neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, motor and sensory urge and, more recently, chronic prostatic pain. The available literature was reviewed using Medline Services. The keywords "botulinum-A toxin", "detrusor-sphincter dyssynergia", "neurogenic bladder", "spinal cord injury", "denervation", "chronic prostatic pain", "chronic urinary retention" were used to obtain references. A toxin injection is effective to treat detrusor-sphincter dyssynergia when injected either transurethrally or transperineally. After treatment, external urethral sphincter pressure, voiding pressure and post-void residual volume decreased. The effect lasts between 2 to 9 months depending on the number of injections. Best indications seem to be multiple sclerosis and incomplete spinal cord injury patients suffering from neurogenic detrusor overactivity and detrusor-sphincter dyssynergia. According to the previous results, the use of botulinum-A toxin injections into the external urethral sphincter has been extended to a variety of bladder obstructions and to decrease outlet resistance in patients with acontractile detrusor. In cases of successful treatment, spontaneous voiding re-occurs and catheterization can be resumed. Injections of the toxin into the external urethral sphincter also seem to have a beneficial effect on chronic prostatic pain, presumably by reducing hypertonicity and hyperactivity of the external urethral sphincter. Injections of botulinum-A toxin into the detrusor muscle has first been tested to treat neurogenic detrusor activity in spinal cord injured patients and in myelomeningocele children. Long lasting (mean 9 months) detrusor relaxation occurs after injection of usually 300 units of Botox). Continence is restored in about 95% of the patients and anticholinergic drugs can be markedly reduced or even stopped. Excellent results of botulinum-A toxin injections into the detrusor in neurogenic detrusor overactivity have lead to an expansion of this treatment to incontinence due to idiopathic detrusor overactivity. Although preliminary results are promising, adequate dosage of the toxin required for this indication is not yet known. In conclusion, it appears that botulinum toxin injection into either the external urethral sphincter or the detrusor offers new promising treatment options for many different urological dysfunctions. However, large controlled trials are absolutely required to establish the role of botulinum-A toxin injections in the fields of urology and neurourology on evidence based medicine.
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PMID:Botulinum toxin as a new therapy option for voiding disorders: current state of the art. 1287 34

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

Injections of botulinum toxin have revolutionised the treatment of focal spasticity. Before their advent, the medical treatment for focal spasticity involved oral anti-spasticity drugs, which had decidedly non-focal adverse effects, and phenol injections. Phenol injections could be difficult to perform, could cause sensory complications and had effects that were of uncertain duration and magnitude. Furthermore, few neurologists knew how to perform them as they were mostly the province of rehabilitation specialists. Botulinum toxin can produce focal, controllable muscle weakness of predictable duration, without sensory adverse effects. Randomised clinical trials (RCTs) involving patients with spasticity resulting from a variety of diseases (mainly stroke and multiple sclerosis) have clearly shown that botulinum toxin type A (Dysport and Botox) can temporarily (for approximately 3 months) reduce spastic hypertonia in the elbow, wrist and finger flexors of the upper limbs, and the hip adductors and ankle plantar flexors in the lower limbs. The clinical benefits from this reduction of neurological impairment are best shown in the upper limb, with less disability of passive function and reduced caregiver burden. In the lower limbs, there is improved perineal hygiene from hip adductor injections. The benefits of reducing ankle plantar flexor tone are less well established. Pain is also reduced, possibly by mechanisms other than muscle weakness. Improved active function has not yet been clearly demonstrated in RCTs, only in open-label trials. The safety of botulinum toxin-A is impressive, with minimal (mainly local) adverse effects. There are little data on the use of botulinum toxin type B (Myobloc or Neurobloc) in spasticity and the only RCT that has examined this did not show tone reduction; dry mouth appeared to be a very common adverse effect. There are also very little data to allow a benefit-risk comparison of phenol and botulinum toxin injections; each have their clinical and technical advantages and disadvantages, and phenol is much less costly than botulinum toxin.
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PMID:Botulinum toxin treatment of adult spasticity : a benefit-risk assessment. 1645 33

Spasticity is a complex disorder characterized by a velocity-dependent increase in muscle tone associated with exaggerated deep tendon reflexes. It can be caused by numerous diffuse or focal cerebral and spinal pathologic conditions. Spasticity indicates upper motor neuron dysfunction and if severe, can lead to considerable motion restriction and eventually to more serious disability. The therapeutic interventions available to treat spasticity are often of limited benefit. In the last decade, many open-label and several double-blind, placebo-controlled, studies have demonstrated the effectiveness of intramuscular botulinum toxin (BTX) injections for the management of spasticity caused by multiple sclerosis, brain / spinal cord injury, cerebral palsy, and stroke. BTX can also be beneficial in the treatment of spasticity, or a mixture of spasticity and rigidity, in many neurodegenerative conditions; including Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17, and in various sporadic and familial spinocerebellar ataxia syndromes. Currently, two BTX serotypes, which are serologically different but share a common subunit structure, are commercially available: type A (Botox(R), manufactured by Allergan, Inc, Irvine, California, USA; and Dysport(R), distributed by Beaufour-Ipsen Pharmaceuticals, Paris, France); and type B (manufactured by Elan Corporation, Dublin, Ireland, and available in the United States as MyoBloc(R) and in Europe as NeuroBloc(R)). BTX primarily affects the neuromuscular junction by inhibiting acetylcholine release. Dosages vary considerably depending on the particular preparation used, the muscle injected, the severity of the condition, and the duration of treatment.
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PMID:Treatment of spasticity with botulinum toxin. 1761 18

Patients with spinal cord injury or multiple sclerosis are often troubled by urinary incontinence due to detrusor (bladder muscle) overactivity. For patients who use intermittent self-catheterisation, empirical treatments for urinary incontinence include: optimisation of catheterisation; anticholinergic drugs; and, in some cases, surgery. The indications of botulinum toxin type A (Botox, Allergan) in France have been extended to cover this situation when anticholinergic drugs are ineffective. Clinical evaluation is based on 2 double-blind randomised placebo-controlled trials in a total of 691 patients who had an average of about 32 episodes of urinary incontinence per week.These trials tested the efficacy of a total dose of 300 or 200 units of botulinum toxin type A. Six weeks after toxin injection into the bladder wall, about 40% of patients had no further episodes of incontinence, compared to 10% of patients who received placebo injections. The median duration of the effect was 42 to 48 weeks after a dose of 200 units (13 to 18 weeks with placebo). It remains to be shown whether botulinum toxin has any long-term benefits in terms of complications (hospitalisation, urinary tract infections, etc.). The main adverse effects of botulinum toxin injections in these patients were urinary tract infections (51% versus 36% with placebo) and urinary retention (18% versus 3%). Both differences were statistically significant, and these events were most frequent in patients who had not yet started to self-catheterise (mainly patients with multiple sclerosis). Cases of autonomic hyperreflexia with favourable outcome were also reported. Botulinum toxin type A has been marketed since the 1990s in other indications. It has been linked to life-threatening adverse effects on tissues at a distance from the injection site, following its diffusion throughout the body. Muscle weakness, asthenia and constipation have been reported. A negative effect on the course of multiple sclerosis cannot be ruled out. Botulinum toxin type A injection into the bladder wall necessitates cystoscopy, an invasive and very inconvenient procedure that requires antibiotic prophylaxis and sometimes anaesthesia. Cystoscopy also carries a risk of punctures and tears, etc. In practice, existing treatment options are unsatisfactory for patients in whom anticholinergic drugs fail to control urinary incontinence due to neurogenic detrusor overactivity. Botulinum toxin type A temporarily prevents incontinence for a few months in about one-third of patients, but it is difficult to administer. In experienced hands, it may be beneficial for patients with very troublesome incontinence who self-catheterise.
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PMID:Botulinum toxin type A and neurogenic urinary incontinence: sometimes beneficial, if used safely. 2336 77