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)

Intrathecal baclofen (ITB) therapy is a widely recognized management technique for severe, disabling spasticity in individuals with cerebral palsy and spinal and brain injuries. Its utility in the stroke population has only been recognized recently. Unlike the aforementioned patient populations, many stroke survivors are ambulatory and are able to maintain a certain degree of functional independence through compensatory use of the uninvolved limbs. Clinicians often fail to recognize the potential enhancement in the function of these individuals if they gain better control of their spastic limbs. Other spasticity treatments, such as oral medications and neurolytic procedures, offer the advantage of being nonsurgical; however, not every stroke patient will respond well to them. Some patients may not tolerate the systemic side effects of oral medications, such as drowsiness and sedation. In patients with severe multilimb spasticity, phenol and even high doses of botulinum toxin may not adequately control spasticity. ITB therapy offers the advantage of effectively decreasing severe, diffuse spasticity without causing untoward effects on arousal and cognition. This article will review the efficacy of ITB therapy in treating spasticity and enhancing function in stroke survivors.
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PMID:Intrathecal baclofen therapy for stroke-related spasticity. 1452 50

To determine if oral/systemic delivery of baclofen can effectively decrease spastic hypertonia due to acquired brain injury (traumatic brain injury, stroke, anoxia, or encephalopathy). Tertiary care outpatient rehabilitation center directly attached to a university hospital. Patients were a convenience sample recruited consecutively who had been referred for treatment of their spastic hypertonia to our spasticity clinic over a 5-year period. The spastic hypertonia was due to an acquired brain injury by either traumatic brain injury (TBI), stroke, or anoxic brain injury. All patients were more than 6 months postinjury or illness. Retrospective review of patients before and after initiation of treatment with oral baclofen, per standardized clinical data sheets. Thirty-five patients (22 TBI patients) were started on oral baclofen and were reevaluated between 1 to 3 months after initiation of treatment. Data for motor tone (Ashworth scores), spasm scores (Penn spasm frequency score), and deep tendon reflex scores were collected on the affected upper extremity (UE) and lower extremity (LE) side(s). Normal extremities were not assessed. Differences over time were assessed via descriptive statistics and Wilcoxon signed-rank. After 1 to 3 months of treatment when subjects had reached their maximal tolerated dosage, the average LE Ashworth score in the affected lower extremities (LEs) decreased from 3.5 to 3.2 (P =.0003), the reflex score decreased from 2.5 to 2.2 (P =.0274), and there was no statistical difference in the spasm score (P >.05). When the 22 TBI patients are analyzed separately, the average LE Ashworth score decreased from 3.5 to 3.2 (P =.0044) and the reflex score decreased from 2.7 to 2.0 (P =.0003). There was no statistically significant change in UE tone, spasm frequency, or reflexes after 1 to 3 months of treatment (P >.05). The average dosage at follow-up was 57 mg/day of baclofen (range 15-120 mg/day). There was a 17% incidence of somnolence that limited the maximum daily dosage of the medication. The oral delivery of baclofen is capable of reducing LE spastic hypertonia resulting from acquired brain injury. The lack of effect upon the upper extremities may be due to receptor specificity issues. GABA-B receptors may be less involved in the modulation of UE spastic hypertonia.
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PMID:Orally delivered baclofen to control spastic hypertonia in acquired brain injury. 1524 21

Baclofen is used for treatment of the spasticity of spinal origin that is a common sequela of spinal cord injury and multiple sclerosis; spasticity occurs in about 50% of patients affected by these disorders. In open-label studies of oral baclofen, the drug improved spasticity in 70-87% of patients; additionally, improvement in spasms was reported in 75-96% of patients. In double-blind, crossover, placebo-controlled trials, baclofen was reported to be effective, producing statistically significant improvements in spasticity. Tizanidine is the antispasticity drug that has been most widely compared with oral baclofen; studies have generally found the two drugs to have equivalent efficacy. However, tizanidine has better tolerability, in particular weakness was reported to be occur less frequently with tizanidine than with baclofen. The main adverse effects of oral baclofen include: sedation or somnolence, excessive weakness, vertigo and psychological disturbances. The incidence of adverse effects is reported to range from 10% to 75%. The majority of adverse effects are not severe; most are dose related, transient and/or reversible. The main risks of oral baclofen administration are related to withdrawal: seizures, psychic symptoms and hyperthermia can occur. These symptoms improve after the reintroduction of baclofen, usually without sequelae. When not related to withdrawal; these symptoms mainly present in patients with brain damage and in the elderly. The limited data on baclofen toxicity in patients with renal disease suggest that administration of the drug in these persons may carry an unnecessarily high risk. Intrathecal baclofen is indicated for use in patients with spasticity of spinal origin unresponsive to treatment with maximum doses of oral baclofen, tizanidine and/or dantrolene. The benefits of continuous intrathecal baclofen infusion have been demonstrated: >80% and >65% of patients have improvement in tone and spasms, respectively. The main risks of intrathecal baclofen infusion are symptoms related to overdose or withdrawal; the latter is more important because of the associated severe effects on clinical status and the possibility of death, but it is responsive to rapid treatment. Overdose primarily arises from drug test doses or human error during refill and programming of the pump, and withdrawal most commonly occurs as a result of a problem with the delivery system. Since the adverse consequences do not exceed the benefits of oral and intrathecal baclofen for patients with spinal spasticity, the benefit/risk assessment is favourable.
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PMID:A benefit-risk assessment of baclofen in severe spinal spasticity. 1535 Jan 52

Tizanidine is a centrally acting alpha-2 adrenoreceptor agonist widely used in the treatment of spasticity in patients with cerebral or spinal injury, and it is causing drawsiness in some of them. Based on these drug actions, we administered tizanidine to 21 spastic quadriplegic children with severe sleep disturbance not improved by conventional therapies. All these patients were showing abnormalities of both the induction and maintenance of sleep. The dosage of tizanidine was 0.1 to 0.2 mg/kg/day, divided into two or three doses. If daytime drowsiness was severe, tizanidine admistration was restricted to just prior to bedtime. In 13 patients (61.9%), we found improvement in sleep induction and/or maintenance. Moreover, patients' families were satisfied with the treatment. There were no detectable side effects except facial pallor in two patients (9.5%) whose treatment was discontinued. Severe muscle hypertonia causes severe pain, which generates strong sympathetic nerve activity and subsequent sleep disturbance. We consider that tizanidine has direct effects on the induction of sleep, and promotes muscular relaxation bringing about good sleep. We conclude that tizanidine is useful for the treatment of refractory sleep disturbance in spastic quadriplegic patients.
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PMID:[Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia]. 1556 Mar 87

Muscle spasm and hypertonia limit mobility in children with spastic cerebral palsy. This double-blind, placebo-controlled, randomized controlled clinical trial studies the clinical efficacy of a low dose of diazepam in enhancing movement in children with spastic cerebral palsy. One hundred and eighty children fulfilled the criteria and were randomly allocated to receive one of two doses of diazepam or placebo at bedtime; 173 completed the study. There was a significant reduction of hypertonia, improvement in the range of passive movement, and an increase in spontaneous movement in the children who received diazepam. There was no report of daytime drowsiness. In developing countries, where cost factors often determine choice of drug, diazepam is a cheap and effective way of relieving spasm and stiffness, optimizing physical therapy and facilitating movement in children with spasticity.
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PMID:The efficacy of diazepam in enhancing motor function in children with spastic cerebral palsy. 1584 Jul 61

The evidence for the therapeutic efficacy of cannabinoids in the treatment of multiple sclerosis (MS) is increasing but is not as yet convincing. Although several trials have reported no significant effect, the majority of the evidence which supports a beneficial effect on spasticity and pain is based on subjective measurements in trials where unblinding was likely to be a problem. The available clinical trial data suggest that the adverse side effects associated with using cannabis-based medicinal extracts (CBMEs) are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication, and in no case did toxicity develop. However, most of these trials were run over a period of months and it is possible that other adverse side effects, not seen in these short-term studies, could develop with long-term use. Despite the evidence that cannabinoids can disrupt cognitive function and promote depression, on the basis of current data, such adverse effects seem unlikely to be associated with the use of CBMEs. Likewise, there is no evidence to suggest that their effects on balance and motor control, or immune function, may be clinically significant. There is, however, reason to be concerned about the use of therapeutic cannabinoids by people predisposed to psychosis and by pregnant women, given the increasing evidence of their adverse effects on the fetus. In conclusion, given the modest therapeutic effects of cannabinoids demonstrated so far, and the risk of long-term adverse side effects, there is reason to be cautious about their use in the treatment of MS.
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PMID:The safety of cannabinoids for the treatment of multiple sclerosis. 1593 52

Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.
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PMID:Sativex for the management of multiple sclerosis symptoms. 1631 25

About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from disabling spasticity-related pain not sufficiently correctable by conventional treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit in the treatment of pain in patients with multiple sclerosis (MS). The question arose whether synthetic cannabinoids with lower potential for psychotropic side effects could be effective as well. To evaluate the safety and efficacy of low dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on spasticity-related pain a placebo-controlled double-blind crossover trial was performed.11 out of 13 included patients completed the study. The 11-Point-Box-Test showed a significant decrease of pain under Nabilone (p < 0.05), while spasticity, motor function and activities of daily living did not change. 5 patients reported side effects: one moderate transient weakness of the lower limbs (Nabilone phase, drop out), three mild drowsiness (two Nabilone, one placebo) and one mild dysphagia (placebo). One patient was excluded from the study due to an acute relapse of multiple sclerosis (Nabilone phase, drop out). Nabilone 1 mg per day proved to be a safe and easily applicable option in the care of patients with chronic UMNS and spasticity-related pain otherwise not controllable.
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PMID:Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. 1698 92

Cannabinoids such as Cannabis-based medicinal extracts (CBMEs) are increasingly being used in the treatment of spasticity associated with multiple sclerosis (MS). They have been shown to have a beneficial effect on spasticity; however, this evidence is largely based on subjective rating scales. Objective measurements using the Ashworth scale have tended to show no significant effect; however, the validity of this scale has been questioned. The available clinical trial data suggest that the adverse side effects associated with using CBMEs are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication. However, most of these trials were run over a period of months and it is possible that other adverse side effects could develop with long-term use. There may be reason to be concerned about the use of therapeutic cannabinoids by adolescents, people predisposed to psychosis and pregnant women.
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PMID:New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids. 2023 85

The study included 54 patients with multiple sclerosis, aged from 23 to 53 years (mean age 37.7 +/- 8.5 years). To reduce muscle tension, 34 patients of the main group received tizanidine with the modified release of active substance (sirdalud MR) in dosage one capsule (6 mg) per day. Twenty-two patients of the comparison group received a standard form of tizanidine--sirdalud in tablets (2 mg) 3 times daily. Patients were examined at baseline, 1, 2 and 4 weeks of the treatment and 2 weeks after the end of the trial. The use of different forms of sirdalud had no effect on disability (the EDSS) scores in patients. Spasticity scores (the Ashworth scale) were decreased during the treatment with different forms of sirdalud but sirdalud MR had more stable effect which remained for 2 weeks after the end of treatment (p < 0.05). Significant differences were observed between tolerability of two forms: side-effects (sleepiness, asthenia) were more frequents in patients treated with the standard form of sirdalud (p < 0.05), the rate of their reduction was significantly higher in the sirdalud MR group (p < 0.05).
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PMID:[The use of sirdalud MR in patients with multiple sclerosis]. 2132 81


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