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

An autosomal dominant striatonigral degeneration is present in a family of Portuguese ancestry numbering in excess of 329 persons in eight generations. The illness begins in the second, third, or fourth decade, and progresses for about 15 years with parkinsonian rigidity, spasticity, spastic dysarthria, and abnormalities of eye movement. Neuropathologic findings are severe neuronal loss and astrocytic gliosis in the corpus striatum and substantia nigra, with a moderate neuronal loss in the dentate nucleus of the cerebellum and nucleus ruber of the midbrain. This is a new genetic entity, distinct from other autosomal dominant neurologic disorders such as nigrospinodentatal degeneration, olivopontocerebellar degeneration, dystonia musculorum deformans, Machado's disease, and Huntington's disease.
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PMID:Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. 94 67

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported. PNP-deficient patients suffer from recurrent infections, usually beginning in the first year of life. Two thirds of patients have evidence of neurologic disorders. Findings range from spasticity to developmental delay, to mental retardation. One third of patients develop autoimmune disease. The most common manifestation of this is autoimmune hemolytic anemia. Idiopathic thrombocytopenic purpura and systemic lupus erythematosis have also been reported. Patients usually present with infections but approximately one fourth have come to medical care initially for neurological problems. In PNP deficiency, T- and B-cell immunity are affected. T-cell function may be profoundly deficient, may be normal at birth and then decrease with time, or may fluctuate repeatedly between low and normal. B-cell function can be normal but is deficient in approximately one third of patients. PNP protein is a trimer of approximately 90,000 daltons. It is found in most tissues of the body but is at highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. Many mechanisms have been proposed to explain the metabolic toxicity in PNP deficiency. The elevated dGTP found in PNP deficiency is thought to inhibit ribonucleotide reductase and, thus, impede cell division. Depressed GTP levels may correlate with neurologic dysfunction. The gene for PNP has been cloned; it is located on the long arm of chromosome 14. Studies of a mutant PNP gene isolated from one patient showed that a point mutation resulting in an amino acid substitution was responsible for PNP deficiency. PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. Many different therapies have been utilized for PNP deficiency including bone marrow transplantation, red cell transfusions, and supplementation of the diet with purines and pyrimidines. None of these therapies has been consistently successful. In light of the poor prognosis for PNP deficiency, bone marrow transplantation should be considered for all patients. In the future, improved forms of therapy such as gene therapy may become available.
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PMID:Purine nucleoside phosphorylase deficiency. 193 Oct 7

The Cas-Br-E and ts-Mo BA-1 murine leukemia viruses (MuLV) induce a spongiform neurodegenerative disease with different clinical manifestations, namely, either hind limb paralysis (Cas-Br-E) or tremors, spasticity, and hind limb weakness (ts-Mo Ba-1). We constructed the chimeric NEBA-1 MuLV by replacing the long terminal repeat of Cas-Br-E MuLV with that of ts-Mo BA-1 MuLV. In SWR/J or CFW/D mice, NEBA-1 MuLV induced an ataxic neurological disease characterized by clinical signs different from those induced by both parents. Although NEBA-1 MuLV did not induce lesions in novel brain areas, the spongiform lesions were more severe in deep cerebellar nuclei and in the spinal cord than those found in paralyzed mice inoculated with Cas-Br-E MuLV. By in situ hybridization, we found that the distribution of the spongiform lesions closely correlated with the distribution of the infected central nervous system cells. In the spinal cord, a close correlation was found between the number of infected cells and the severity of the spongiform degeneration. Sequencing of the substituted ts-BA-1 MuLV fragment and comparison with homologous sequences of Cas-Br-E and Moloney MuLV showed differences mainly in the U3 tandem direct repeats. Our results show that a few modifications within the U3 long terminal repeat allow the virus to cause more severe lesions in some central nervous system regions and that the severity of the spongiform degeneration correlates with the level of viral replication.
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PMID:Substitution of the U3 long terminal repeat region of the neurotropic Cas-Br-E retrovirus affects its disease-inducing potential. 216 94

A survey of the literature of neurological manifestations associated with the acquired immune deficiency syndrome (AIDS) shows a broad disease spectrum affecting approximately one third of the patients in large hospital series. The complications include focal cerebral lesions caused by abscesses, lymphomas, leucoencephalopathy or infarcts as well as encephalitis, meningitis and myelitis. Most opportunistic infections of the central nervous system presumably are caused by toxoplasma gondii, cytomegalovirus and cryptococcus neoformans. One tenth of all patients have neurological disease as their initial symptom of AIDS. The diagnosis should always be considered in patients at risk and in males with an unusual neurological history or with a peculiar CT scan of the brain. Besides the opportunistic complications of AIDS, LAV/HTLV-III itself probably attacks the nervous system and gives rise to concomitant lesions of the long tracts of the spinal cord with ataxia, paresis and spasticity and to subacute encephalopathy and peripheral nerve abnormalities as well.
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PMID:Neurological complications and concomitants of AIDS. 303 38

The authors report a series of 47 patients suffering from disseminated sclerosis who required neuro-urological management because of micturition disturbances. They were in general young (mean age 43 years) and had been suffering from disseminated sclerosis for 10 years (on average). The neurological disease was in general severe since it was progressive in 32 cases and pure remittent in 13 only. Two-thirds of the patients were autonomous from a locomotor standpoint. Micturition disturbances developed in the first five years of the disease in 2/ 3rds of the patients and became really troublesome only after disseminated sclerosis had been progressive for five years. Dysuria, frequency and incontinence with urgency were the commonest symptoms. Persistent or transient retention of urine remained relatively common. Nocturnal urine loss was rarer. Sphincter incompetence was marked in half of the patients but this did not necessarily go hand in hand with locomotor incapacity. Symptoms and signs were grouped as irritative, obstructive and mixed syndromes. From a urodynamic standpoint, the detrusor was sometimes normal but more often behaved pathologically, being either hyperactive or hypoactive. Hypoactivity of the detrusor was accompanied in 9 cases out of 10 by spasticity of the striate sphincter. Spasticity of the striate sphincter was the commonest type of behaviour, although normal striate sphincter electromyography was possible and; rarely, results were of peripheral neurogenic type. There was no evidence of any correlation between the type of micturition syndrome, detrusor function and striate sphincter function. Similarly, no correlation could be established between the type of detrusor dysfunction and the period for which disseminated sclerosis had been present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Urinary disorders in multiple sclerosis. Apropos of 47 cases]. 672 76

Five children, three sisters and two brothers aged between three months and 12 years, are described. They all developed a facial desquamating rash of butterfly distribution at the age of about two months, and motor retardation which later was characterized by spasticity, predominantly affecting the lower limbs. The three children who were old enough for speech to be tested had dysarthria. There was no family history of neurological disease, nor was there consanguinity among the parents or grandparents. EEGs were diffusely abnormal in four of the five children, but did not show any specific or diagnostic features. Plasma immunoglobulin tests were normal, and tests for collagen disease were negative. The authors are not aware of previous reports of this condition, but believe that it is a variant of familial spastic paraplegia, with atypical features.
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PMID:Heredofamilial syndrome of spastic paraplegia, dysarthria and cutaneous lesions in ive siblings. 711 11

Treating severe spasticity with the continuous infusion of intrathecal baclofen through an implantable delivery system is a new and successful alternative to oral medications and ablative surgical procedures. Nurses have a vital role in patient care throughout all phases of therapy. Advances in this technology hold promise for our future in treating other neurologic disorders.
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PMID:Intrathecal baclofen for spinal spasticity: implications for nursing practice. 822 99

Plasma amino acid levels were measured following oral glycine loading in 43 patients with motor neurone disease (MND), eight normal subjects and 18 neurological disease controls with wasting or spasticity from a variety of other causes. Levels at baseline and 1.5 h after loading did not differ, but at 4 h, plasma glycine levels in MND patients remained significantly higher than in normal and neurological controls (P < 0.013). Cerebrospinal fluid glycine levels, which were maximal at 2.5 h, were also significantly higher in MND patients than neurological controls (P < 0.04). These observations suggest a defect of glycine 'housekeeping' in the central nervous system in MND which may be relevant to the pathogenesis of the disease.
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PMID:Abnormal glycine metabolism in motor neurone disease: studies on plasma and cerebrospinal fluid. 841 Aug 84

Spasticity is associated with damage to the corticospinal tract and is a common complication of neurological disease. Patients with spasticity complain of stiffness, involuntary spasm and pain. The majority of patients are managed conservatively with physiotherapy and/or oral medication. However, 25-35% of patients will develop unacceptable side-effects or fail to respond to oral doses of antispasmodics. Surgical procedures such as myelotomy, rhizotomy and neurotomy have not been universally successful. More recently, intrathecal baclofen has become established as an important adjunct in the management of spasticity. This article describes the mechanism of action of baclofen, the delivery systems available and the criteria for patient selection. The screening phase, surgical procedure and specific postoperative observations are also described.
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PMID:A review of intrathecal baclofen in the management of spasticity. 915 75


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