Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dantrolene sodium or dantrolene1 is 1([5-(nitrophenyl)furfurylidend] amino) hydantoin sodium hydrate. It is indicated for use in chronic disorders characterised by skeletal muscle spasticity, such as spinal cord injury, stroke, cerebral palsy and multiple sclerosis. Dantrolene is believed to act directly on the contractile mechanism of skeletal muscle to decrease the force of contraction in the absence of any demonstrated effects on neural pathways, on the neuromuscular junction, or on the excitable properties of the muscle fibre membranes. Controlled trials have demonstrated that dantrolene is superior to placebo in adults or children with spasticity from various causes, as evidenced by clinical assessments of disability and daily activities, and by muscle and reflex responses to mechanical and electrical stimulation. It is somewhat less effective in patients with multiple sclerosis than in those with spasticity from other causes. There has been a general clinical impression in controlled trials that dantrolene caused less sedation than would have been expected from therapeutically comparable doses of diazepam. In 2 controlled trials, there was no significant difference between dantrolene and diazepam in terms of reductions in spasticity, clonus, and hyperreflexia, but side-effects such as drowsiness and inco-ordination occurred significantly more frequently on diazepam. Long-term studies have indicated continuing benefit for patients taking dantrolene, though the incidence of side-effects has often been high and there has been a suggestion of exacerbation of seizures in children with cerebral palsy. Dantrolene may be of value in the medical treatment of spasm of the external urethral sphincter due to neurological and non-neurological disease, and animal studies suggest a potential use in the management of malignant hyperpyrexia. Chemical evidence of liver dysfunction may occur in 0.7 to 1% of patients on long-term treatment with dantrolene, with symptomatic hepatitis in 0.35 to 0.5% and fatal hepatitis in 0.1 to 0.2%. The drug commonly causes transient drowsiness, dizziness, weakness, general malaise, fatigue and diarrhoea at the start of therapy. Muscle weakness may be the principal limiting side-effect in ambulant patients, particularly in those with multiple sclerosis, and therapy could be hazardous in patients with pre-existing bulbar or respiratory weakness. The dosage of dantrolene has been fixed in most controlled trials, though long-term studies have indicated the need for individualisation of dosage. The initial dose is usually 25mg once daily, increasing to 25mg two, three or four times daily, and then by increments of 25mg up to as high as 100mg two, three or four times daily. The lowest dose compatible with optimal response is recommended.
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PMID:Dantrolene sodium: a review of its pharmacological properties and therapeutic efficacy in spasticity. 31 89

Ten children with cerebral palsy are presented on whom stereotaxic operations on the central nervous system were performed with the aim of ameliorating athetosis and spasticity. Tere were seven alert and co-operative children with spastic hemiplegia or diplegia, of whom six received benefit from thalamotomy or dentatotomy. The seventh, a child with diplegia, had improvement of his left lower limb, but the right became worse. One child with spastic diplegia, in whom a thoracic meningocoele had been closed at birth, was not improved by bilateral dentatotomy. Two severely quadriplegic children each had bilateral dentatotomy; one was a child with dystonic and spastic quadriplegia. In both cases the resulting reduction in tone and extensor spasm rendered the nursing of these patients much easier. The place of stereotaxic surgery in the central nervous system in the management of children with cerebral palsy is discussed. We suggest that in selected cases the stereotaxic operation should be performed early in order to gain the greatest benefit. Stereotaxic surgery should be regarded as an integral part of the management which involves close co-operation of paediatrician, physiotherapist, neurosurgeon and orthopaedic surgeon.
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PMID:Stereotaxic neurosurgery in the management of cerebral palsy. 110 96

Spasticity is a hyper-excitable state of the reflex arcs in the spinal cord below the level of injury. Not only is the skeletal motor system affected, but bladder, bowel, blood pressure, and erection reflex mechanisms are also involved. Spasticity gradually emerges from the initial phase of spinal shock one to two months after the injury, and usually reaches a plateau of a mild to moderate degree in 3 to 4 months. Neurophysiological mechanisms indicate an increase in the alpha and gamma reflex systems and that central excitability through the interneurons is also involved in these systems. Excessive spasticity should be recognized as a substitute for pain in the spinal cord injured patient, as infections, calculi, pressure ulcers, and other normally painful conditions set off the hyper-sensitive reflexes causing more spasticity. Education and health maintenance is the best prevention of severe spasticity. Definitive treatment of incapacitating spasticity is to find and treat the underlying disease condition, as well as to introduce medication which will also suppress the spasm (Valium and/or Dantrolene). Muscle motor points and/or nerve blocks with neurolytic agents is perhaps the best technique for quietening excessive spasticity. Intrathecal neurolytic agents, anterior or posterior rhizotomies and cordectomies are not advocated even in severe incapacitating spasticity as they are too destructive. Selective longitudinal myelotomy is by far the best surgical technique for disrupting excessive spasticity, if any such procedure is to be done. Tendonotomies may be necessary in chronic contractures of joints after the muscle spasticity has been reduced. Excessive spasticity is not regarded as a normal state in the spinal cord injured patient. The cause should be sought and treated. Nerve destruction techniques should not be used unless medical and nursing techniques have failed. Prevention is so important and can be achieved by education, health maintenance, and especially motivation.
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PMID:Spasticity following spinal cord injury. 119 52

Intramuscular injections of botulinum toxin (Botox) are followed by a dose-dependent focal paresis which can be used to treat several focal movement disorders. Botox injections are recommended as effective for the treatment of blepharospasm, hemifacial spasm, and cervical dystonia (torticollis). Focal dystonias elsewhere (for example, writer's cramp) can often be treated with similar success. Others, such as oromandibular dystonia, are more difficult to treat. In the case of more generalized dystonias, some focal muscle spasms can be treated with success by local intramuscular injections. New indications are still being investigated, for example in focal tremors and spasticity. Side effects are in general slight and disappear at the end of toxin effect. In general, it is necessary to repeat the injections after a couple of months, due to a cessation of effect after regrowth of nerve terminals. New injections have similar effects even over years of treatment.
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PMID:[Treatment of movement disorders using botulinum toxin]. 141 87

In 19 patients, who suffered from severe spinal spasticity of different etiologies and did not respond sufficiently to oral antispastic therapy, intrathecal Baclofen test boli were administered. In 11 patients a DAD (Drug Administration Device) [SynchroMedR Model 8611 H, Medtronic Inc. Minneapolis, USA] was implanted. Catheter dislocation or torsion was the most common complication to be observed in these 11 patients. Long term intrathecal Baclofen application was effective in all patients, as reducing spasticity, flexor spasms and spasm induced pain. In some cases the motor performance ameliorated.
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PMID:Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity. 144 17

Continuous intrathecal infusion of the well known antispastic medication baclofen was evaluated in ten consecutive patients. One year after pump implantation the average Ashworth scale for muscle tone decreased, compared with before treatment, 2.32 points (P < 0.0001), reflexes decreased 2.22 points (P < 0.0001) and the spasm score decreased 1.65 points (P < 0.0001). The average dose increased from 92.22 to 290.95 micrograms (P < 0.0001) between the 1st month of treatment and 1 yr of treatment. The dosage for all patients more than doubled (P < 0.0022) between 3 months and 1 yr postimplantation. There was no significant difference for muscle tone, reflexes or spasms at 3 months v 1 yr. Complications were not unusual and included temporary atelectasis, orthostatic hypotension with escalation of baclofen dose, loss of penile erections, postsurgical pseudo-meningoceles, catheter disruptions and exhausted pump reservoirs. One patient suffered a seizure apparently related to a rapid withdrawal from intrathecal baclofen as a result of catheter sequestration. All patients required a period of intensive inpatient rehabilitation to benefit functionally from the decreased motor tone and/or increased voluntary motor control. The procedure is expensive and close follow-up is necessary for assessing efficacy and refilling the pump. Intrathecal baclofen infusion by subcutaneous pump is useful in treating the effects of spinal spasticity resistant to oral medications. However, there appears to be accommodation to intrathecal baclofen necessitating escalating doses to maintain clinical effects.
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PMID:Continuous intrathecal baclofen in spinal cord spasticity. A prospective study. 146 69

A total of 66 consecutive patients with severe spasticity of spinal cord origin were screened with intrathecal baclofen, and all but two responded with a two-point decrease in their Ashworth spasticity scale and/or spasm scale score. Of these, 62 elected to receive chronic intrathecal baclofen administration by means of an implanted delivery system. These patients have been followed for an average of 30 months (the first three for 81 months). Intrathecal baclofen has been well tolerated and all serious side effects were transient and have been managed by dose adjustments. The pump presently available has worked safely; the only problem has been stalling in 7% of these devices. The catheter system has had to be repaired in just over one-half of the patients and is the main cause of interruption of drug delivery. Of the 62 patients implanted, 52 (84%) continue to be treated adequately for spasticity; there are three poor long-term responders, four deaths due to underlying disease, and three whose participation has been voluntarily withdrawn. It is suggested that long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients.
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PMID:Intrathecal baclofen for spasticity of spinal origin: seven years of experience. 162 11

Vigabatrin was specifically designed to enhance gamma-aminobutyric acid (GABA) function in the CNS. By increasing brain concentrations of this inhibitory neurotransmitter the drug appears to decrease propagation of abnormal hypersynchronous discharges, thereby reducing seizure activity. At this stage in its development, clinical experience with vigabatrin is limited primarily to patients with refractory seizure disorders. In this difficult-to-treat population, 'add-on' therapy with vigabatrin greater than or equal to 2 g/day has shown impressive efficacy, reducing seizure frequency by greater than or equal to 50% in approximately half of patients. Clinical efficacy does seem to vary with seizure type with the best response reported in adults with complex partial seizures with or without generalisation and in children with cryptogenic partial epilepsy or symptomatic infantile spasm. Vigabatrin appears to have a negative effect on absences and myoclonic seizures. Some disorders of motor control may also be amenable to enhanced GABAergic function. In the small number of patients with tardive dyskinesia treated to date, vigabatrin produced mild to moderate improvement in hyperkinetic symptom scores but Parkinsonism or schizophrenic symptoms occasionally worsened. The best response was reported in a study of patients who had been withdrawn from neuroleptic therapy. In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis. Most adverse reactions to vigabatrin are mild and transient with central nervous system (CNS) changes being reported most frequently. Of particular note, serial evoked potential studies and the few available histology reports have not found evidence of intramyelinic oedema during therapeutic use, as was reported in rats and dogs on chronic high-dose treatment. Thus, vigabatrin is a promising new anticonvulsant drug. Current evidence supports a trial of this agent as adjunctive therapy in patients with refractory seizure disorders, and future investigation of vigabatrin monotherapy and its efficacy relative to established agents is awaited with interest. Wider experience should help to clarify which patients - by seizure type and concurrent CNS pathology - are likely to benefit from vigabatrin and ongoing monitoring should further clarify the potential detrimental effects, if any, of long term use. In the meantime, it is a welcome addition in the difficult setting of resistant epilepsy.
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PMID:Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. 171 66

To investigate coronary vasospastic activity after percutaneous transluminal coronary angioplasty (PTCA), we performed intracoronary injection of acetylcholine in 55 patients, mean 3.3 months after successful PTCA. Coronary spasm was defined as transient total or subtotal occlusion of the PTCA sites. Sixty-nine lesions of the 55 patients were examined to determine whether spasm was provoked by incremental doses of acetylcholine. Restenosis was defined as coronary luminal narrowing of > or = 50% after nitroglycerin or isosorbide dinitrate. Twenty of the 55 patients (36%) and 23 of the 69 lesions (33%) had coronary spasm. There was no correlation between the incidence of coronary spasm and the interval from PTCA to the acetylcholine test. The spasm was provoked in 17 lesions of the 50 non-restenotic lesions (34%) and was also provoked in 6 of the 19 restenotic lesions (32%). On the other hand, restenoses occurred in 6 of the 23 spastic lesions (26%) and in 13 of the 43 non-spastic lesions (28%). There was no correlation between the incidence of coronary spasm and the occurrence of restenoses. Twenty-four patients had undergone acetylcholine provocative test before PTCA. Among these 24 patients, 11 had coronary spasm before PTCA, and 7 had coronary spasticity after PTCA. Four patients who had positive evidence of coronary spasm before PTCA did not show negative spasm after PTCA. On the other hand, 3 patients who did not show evidence of coronary spasm showed positive evidence of coronary spasm after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Coronary vasospastic activity at sites of percutaneous transluminal coronary angioplasty: evaluation using intracoronary acetylcholine administration]. 184 42

Even in patients with complete loss of sensation and paraplegia after cervical spinal trauma, abdominal operations usually require general or spinal anesthesia due to spasms and increased muscle tone. Both anesthetic types have serious drawbacks under these circumstances, e.g. hyperkalemia induced by relaxation or the impossibility of adequate monitoring of the level of spinal blockade. After an onset time of 1-2 h the intrathecal injection of approx. 100 micrograms baclofen, a spinally acting GABAB-agonist, led to complete and long-lasting suppression of surgically induced spasticity. This could be demonstrated by neurological examination (spasticity scores: Ashworth score, spasm score, clonus score) during 5 neurosurgical operations in 3 patients with paraplegia. Except for slight sedation, the patients had no discomfort during operation. Intrathecal baclofen was also effective against autonomic hyperreflexia, i.e. vegetative dysregulation such as bradycardia or hypertension, provoked by catheterization or bladder surgery.
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PMID:[Intraoperative suppression of spasticity using intrathecal baclofen]. 230 48


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