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

In 19 patients with multiple sclerosis and 1 with subacute sclerosing panencephalitis the mean increase in muscle tonus was found to be 3.1 (range 1--4 according to Burke-Ashwort). In 10 controls with multiple sclerosis the mean spasticity was 2.4. Dantrium was given in doses up to 800 mg for 14--16 days and it caused a greater reduction of spasticity than placebo (p less than 0.05). In 12 patients (60%) varying degrees of muscle tonus reduction was observed. In 11 patients the efect of Dantrium was compared with that of other drugs (Clonazepam, Tetradiazepam, Carisoprodol and Lyoresal). In 6 cases Dantrium was a more effective drug than other muscle relaxants and in 5 cases no difference was observed or other drugs were superior to Dantrium.
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PMID:[Dantrium in the treatment of increased muscle tonus in patients with multiple sclerosis]. 32 Apr 94

A double-blind, five-week, multicenter trial was conducted to compare the effect of baclofen, a unique amino acid derivative, with that of placebo in the treatment of 106 patients with spasticity secondary to multiple sclerosis. A spasticity assessment method that included a neurological examination, physicians' clinical impressions of changes during treatment, and a patient's self-evaluation was used to determine efficacy. This method showed baclofen (70 to 80 mg daily maximum, titrated) is effective relative to placebo in relieving symptoms of spasticity, such as flexor spasms, pain and stiffness, resistance to passive joint movements, and tendon stretch reflexes. Patient self-evaluation results also showed a significant reduction in clonus. Side effects were generally mild and transient.
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PMID:Baclofen, a new antispastic drug. A controlled, multicenter trial in patients with multiple sclerosis. 32 87

25 patients with multiple sclerosis (MS) and other spastic disorders, 33 MS patients and 10 control patients with MS were given clonazepam, baclofen or placebo over a period of 5 days to 20 weeks. Both clonazepam and baclofen were significantly more effective than placebo in the treatment of spasticity (p less than 0.005 or p less than 0.01). A clinical trial of clonazepam versus baclofen was carried out and this showed no significant difference between the two drugs. However, there was indication that clonazepam influenced with better improvement in patients with slight muscle hypertonia mainly of cerebral origin. Patients with more severe forms, mainly of spinal spasticity, benefited rather from baclofen treatment (Fisher's test, p = 0.003). There was suggestion that combination of the two drugs may be more effective in some patients than than clonazepam or baclofen alone.
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PMID:Clonazepam, baclofen and placebo in the treatment of spasticity. 35 38

Baclofen is a safe and effective means for treating spasticity associated with multiple sclerosis. We found no toxic effects on hepatologic, hematopoietic, or renal function, acutely or for over 3 years of follow-up. A statistically significant reduction was noted in frequency of spasms, and clonus, and there was improved range of joint movement, which enabled patients to maintain functional status for prolonged periods. For the more disabled patients, treatment with baclofen gave symptomatic relief of painful spasms and made immobility more tolerable. Optimum effect was achieved when baclofen was administered in the early stages of disease, before major disabilities became permanent.
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PMID:Baclofen for spasticity in multiple sclerosis. Double-blind crossover and three-year study. 36 34

Baclofen was used in a double-blind crossover placebo-controlled trial to treat spasticity in patients with multiple sclerosis (MS). While on Baclofen, patients obtained a significant (p less than 0.001) reduction in spasticity compared to controls. The drug was particularly effective in alleviating flexor and extensors spasms, as well as their associated pain. Side effects were common in this study, but were usually well tolerated by the patients. The commonest side effects were sedation, nausea and vomiting. There were no changes in hepatic, renal, or hematological function in any patients. Increase weakness due to loss of spasticity for support was also a fairly common complaint. The drug seems best indicated in patients in whom spasticity is not required for support or other activities of daily living. Careful monitoring of the patient is essential for effective use of this drug.
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PMID:The use of baclofen in treatment of spasticity in multiple sclerosis. 38 32

Patients with spinal cord injury or multiple sclerosis were surveyed for the presence of extreme foot deformities and spasticity. Pes cavus and claw toes were found in eight of 80 spastic spinal cord injury and two of 20 multiple sclerosis patients. Pes cavus and claw toes were not found in 29 flaccid spinal cord injury patients. Pes cavus and claw toes were associated with flexor reflexes which could be elicited by pin prick proximal to the knee, suggesting extreme spasticity--and by low excitatory thresholds for the anterior tibialis as indicated electromyographically. Complications of severe spasticity associated with spinal cord injury and multiple sclerosis include pes cavus and claw toes, mediated in part by spasms of the anterior tibialis.
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PMID:Pes cavus and claw toes deformity in patients with spinal cord injury and multiple sclerosis. 43 69

Theiler's encephalomyelitis virus (TMEV) in mice represents one of the few existing animal models of virus-induced demyelination and may provide further information about the human disease, Multiple Sclerosis. An inbred strain of mice (SJL/j) employed in the present ultrastructural study, develops a life-long neurologic illness characterized by profound spasticity after intracerebral inoculation of TMEV. Anesthetized animals were sacrificed sequentially by total body perfusion with gluteraldehyde from 7 days to 9 months after infection. An intense mononuclear inflammatory infiltrate appeared in the leptomeninges and white matter of spinal cord by 15 days and persisted for as long as one year. These infiltrates contained numerous plasma cells, and perivascular demyelination could be found in almost every 1 micron section. Vesiculation and stripping of myelin by mononuclear cell processes were seen as mechanisms of myelin break-down. However, virions were not found in cells in grey or white matter and the integrity of oligodendrocytes was maintained. At one year, active demyelination was still seen in areas containing naked and remyelinated axons. The relevance of these ultrastructural findings to postulated mechanisms of virus-induced demyelination will be discussed.
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PMID:A new model of persistent viral infection with primary demyelination. 61 47

There are inherent difficulites in the rehabilitation of patients with multiple sclerosis (MS). The clinical manifestations of the disease vary tremendously, as does its natural course. The many theories on the etiology, pathogenesis and treatment of MS are presented. However, at the current time, the patient with MS may be treated with the realistic goal of minimizing the effects of the disease. This is accomplished best in a rehabilitation setting. Diagnosis, prognosis, and factors associated with precipitaiton or exaggeration of symptoms, are discussed. Specific techniques of rehabilitation of decreased motor power, spasticity, ataxia and intention tremor, speech and optic defects, and impaired sensation are presented. Decubiti and ulcerations, bladder and bowel problems, and sexual dysfunction are recognized as common problems and attention must be directed to these. The importance and wide array of emotional difficulties in patients with MS is emphasized, and those patients who may benefit from psychotherapy are discussed.
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PMID:Rehabilitation of patients with multiple sclerosis. 68 58

The effects of dantrolene sodium and diazepam were compared in a double crossover study of 42 patients with spasticity due to stable multiple sclerosis. Both drugs reduced the findings of spasticity, clonus, and hyperreflexia, and the complaints of muscle stiffness and cramping. Each drug had different side effects which suggest indications and contraindications for its use in spastic patients.
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PMID:Comparison of dantrolene sodium and diazepam in the treatment of spasticity. 77 44


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