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)

The adamantane derivative memantine (1-amino-3,5-dimethylaminoadamantane, D-145, Akatinol) is clinically used as well in the therapy of neurogenic motor diseases (e.g. spasticity) as in the treatment of cerebral disorders like coma, cerebrovascular and geronto-psychiatric disturbances. The aim of the paper is to summarize experimental evidences that may help to explain the clinical observations. Biochemical, pharmacological, and electrophysiological studies show that memantine interferes with the metabolism of the transmitters dopamine, noradrenaline (norepinephrine), and serotonin and modulates synaptic transMission. In order to explain the antispastic activity of memantine, a spinal action must be assumed in addition to the supraspinal effect on transmitter systems. Since memantine reduces the membrane resistance as well as the membrane conductance of sodium, potassium, and chloride ions, it is very likely that memantine Is directly involved in the generation of action potentials.
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PMID:[Pharmacodynamics and pharmacokinetics of memantine]. 635 2

Heterotopic ossification (HO) occurs in up to 75% of patients who survive severe head injury and is a major factor in prolonging their rehabilitation. Prevention of HO has not been emphasized in acute care management of patients with head injury. But with spinal cord injuries and total hip arthroplasty, HO has been prevented by use of disodium etidronate (EHDP). This study compares the incidence and severity of HO in 10 patients with severe head injury who were treated with EHDP and 10 matched controls without drug treatment. Patients selected for EHDP treatment were consecutive admissions who had Glasgow Coma Scores (GCS) less than nine. Treatment was begun within two to seven days of injury with 20mg/kg/day via nasogastric tube and was discontinued if the patient awakened within two weeks (low risk of HO). After three months EHDP was given orally at 10mg/kg/day for an additional three months. Ten patients completed the treatment regime and were compared to 10 patients with similar injuries. Of the 10 patients treated with EHDP, two developed HO, while clinically significant HO was found in seven of the 10 nontreated patients (chi square = p less than 0.025). This finding could not be explained on the basis of differences in the two groups; the groups were alike in age, sex, length of coma, extracranial fracture, spasticity, type of head injury, and injury severity (GCS). These data suggest that HO may be prevented by early use of EHDP, and the results warrant further clinical trials.
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PMID:Disodium etidronate: its role in preventing heterotopic ossification in severe head injury. 641 24

Neuromuscular biopsies were obtained in 10 patients with traumatic spinal cord lesions at various levels and in one patient with cerebral lesions due to a long lasting coma. In all cases, there was a rapid onset of both fibers types atrophy, with numerous transitional type III and intermediate fibers. Only the two patients with cervical lesions had an increased terminal innervation ratio suggesting denervation. Our observations do not support the hypothesis of a transneuronal degeneration. These changes cannot be related to disuse only as the atrophy does not preferentially involve type II fibers. The underlying neural mechanism of spasticity in muscle of patients with cortico-spinal lesions could explain the change of the histochemical pattern of the muscle fibers.
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PMID:[Changes in the motor units in patients with traumatic paraplegia]. 667 76

A patient with head trauma who had been comatose for 6 years and residing in a nursing home, began to respond to her environment and subsequently underwent rehabilitation that resulted in significant recovery. Speech and psychologic functions that had been severely affected improved considerably after 9 months training. Surgical release of immobilization contractures that had prevented significant use of any extremity, resulted in healing of several decubitus ulcers and allowed the patient to regain some ADL skills in a wheelchair. Further urethral erosion was prevented by adequate hygiene and release of adductor spasticity. After 14 months of intensive rehabilitation and family teaching, the patient was able to live at home with her family.
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PMID:Physical and surgical examination of patient after 6-year coma. 705 18

Many therapeutic effects of benzodiazepines are mediated by neuronal high-affinity binding sites, i.e. benzodiazepine receptors (BR), located on GABAA receptors. Recently, endogenous BR ligands have partially been identified which, as agonists, either increase or, as inverse agonists, decrease GABAergic inhibition in the brain. BR antagonists, previously described as intrinsically inactive, induce effects in animals and humans under particular circumstances emphasizing a functional relevance of endogenous BR ligands. Several brain disorders, e.g. anxiety, insomnia, epilepsy, spasticity, alcoholism, coma, dementia, may be associated with a disequilibrium of opposing endogenous BR ligands changing the excitability of neurons implicated in aforementioned diseases. It is proposed that, depending on the relative role endogenous BR ligands play in the pathophysiology of these disorders, BR antagonists might demonstrate a variable efficacy in improving their symptomatology. In fact, such therapy would restore the homeostatic balance among various endogenous BR ligands being disturbed during an illness.
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PMID:Involvement of endogenous benzodiazepine receptor ligands in brain disorders: therapeutic potential for benzodiazepine antagonists? 747 87

A 74-year-old woman with corticobasal degeneration (CBD) had a 9-year history of progressive loss of strength and rigidity of her right hand and then arm, followed by speech difficulties, dyskinesia, rigidity, spasticity and weakness of the ipsilateral lower limb, ultimately also involving the opposite side. She later developed supranuclear gaze palsy. Her memory remained intact during most of the duration of her disease. Laboratory tests and anti-Parkinsonian medications were not helpful. At autopsy, frontal lobe atrophy, discoloration of putamen (Pt) and pallor of substantia nigra (Sn) were observed. Neuronal loss and gliosis were extensive in motor cortex and milder in frontal cortex, abruptly ending at the central sulcus and junction of cingulate gyrus. "Achromatic" neurons were present. Neuronal loss and gliosis were seen in Pt and Sn and corticobasal inclusions in Sn. Numerous Gallyas/tau-positive, Bielschowsky/ubiquitin-negative coil, sickle, or coma-shaped tangles and thread-like processes were found in affected cortex, Pt and Sn. Some of the tangles were in neurons, but most occurred in astroglia, and their processes. The presence of Gallyas/tau-positive glia in CBD may have the same diagnostic significance as in progressive supranuclear palsy, analogous to the argyrophilic ubiquinated inclusions in oligodendroglia in multisystem atrophy. We suggest that in CBD: (1) cytoskeletal protein metabolism in neurons and glia can simultaneously be perturbed in certain neurodegenerative diseases, and (2) the astrocytosis in CBD may not be simply a reactive process but an integral part of the disease.
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PMID:Unusual case of corticobasal degeneration with tau/Gallyas-positive neuronal and glial tangles. 787 9

We report a 47-year-old woman with SLE, who developed meningeal signs and consciousness disturbance. She noted an onset of fever, and swelling and pain in her face, hands and feet in 1990. She was seen in another hospital and the diagnosis of SLE was made. She was treated with prednisolone with marked improvement in her symptoms. She was well with 5 mg of oral prednisolone daily until January of 1991, when she developed fever, myalgia and weakness in her legs. She was admitted to the medical service of our hospital on August 5. She was receiving 15 mg of prednisolone daily. Gram positive rods were cultured from her blood on August 5. She became incoherent 2 days later, and had a convulsive episode on August 8. After the convulsion, she lost consciousness from which she did not recover. Her CSF contained 304/3 microliters cells, 29 of which were neutrophils, 6 lymphocytes, 90 others, and 179 destructed cells. The CSF protein content was 345 mg/dl, and glucose 23 mg/dl. A neurological consultation was asked on August 9. Physical examination at that time revealed a semicomatous woman. Respiration was 30/min and regular. BP 132/82 mmHg, heart rate 122/min and regular, and BT 39.6 degrees C. General physical examination was unremarkable. Pertinent neurologic findings were positive Kernig sign and spasticity in all four limbs. Brain stem reflexes were retained. Upon painful stimulation, withdrawal response was elicited both lower extremities. She was treated with pipiracillin, latamoxef and phenobarbital, however, she had frequent seizures. She was deeply comatose on December 10. She became flaccid and no more meningeal signs were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A 47-year-old woman with meningeal signs and consciousness disturbance]. 821 15

Deficiency of liver arginase (AI) is characterized clinically by hyperargininemia, progressive mental impairment, growth retardation, spasticity, and periodic episodes of hyperammonemia. The rarest of the inborn errors of urea cycle enzymes, it has been considered the least life-threatening, by virtue of the typical absence of catastrophic neonatal hyperammonemia and its compatibility with a longer life span. This has been attributed to the persistence of some ureagenesis in these patients through the activity of a second isozyme of arginase (AII) located predominantly in the kidney. We have treated a number of arginase-deficient patients into young adulthood. While they are severely retarded and wheelchair-bound, their general medical care has been quite tractable. Recently, however, two of the oldest (M.U., age 20, and M.O., age 22) underwent rapid deterioration, ending in hyperammonemic coma and death, precipitated by relatively minor viral respiratory illnesses inducing a catabolic state with increased endogenous nitrogen load. In both cases, postmortem examination revealed severe global cerebral edema and aspiration pneumonia. Enzyme assays confirmed the absence of AI activity in the livers of both patients. In contrast, AII activity (identified by its different cation cofactor requirements and lack of precipitation with anti-AI antibody) was markedly elevated in kidney tissues, 20-fold in M.O. and 34-fold in M.U. Terminal plasma arginine (1500 mumols/l) and ammonia (1693 mmol/l) levels of M.U. were substantially higher than those of M.O. (348 mumols/l and 259 mumols/l, respectively). By Northern blot analysis, AI mRNA was detected in M.O.'s liver but not in M.U.'s; similarly, anti-AI crossreacting material was observed by Western blot in M.O. only. These findings indicate that, despite their more long-lived course, patients with arginase deficiency remain vulnerable to the same catastrophic events of hyperammonemia that patients with other urea cycle disorders typically suffer in infancy. Further, unlike those other disorders, an attempt is made to compensate for the primary enzyme deficiency by induction of another isozyme in a different tissue. Such substrate-stimulated induction of an enzyme may be unique in a medical genetics setting and raises novel options for eventual gene therapy of this disorder.
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PMID:Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme. 845 80

We report a case of inadvertent overdose of baclofen given intrathecally resulting in coma. This was unresponsive to flumazenil and required supportive intensive therapy. With the increasing use of baclofen intrathecally for spasticity and its wide interpatient dose variability, there is a need to find a safe antagonist to baclofen for routine medical use.
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PMID:Flumazenil: an unreliable antagonist in baclofen overdose. 869 64

Major neurologic complications secondary to cyclosporine are well documented and are known to include confusion, cortical blindness, seizure, spasticity, paresis, ataxia and coma. Most previous reports attribute these to white matter central nervous system (CNS) lesions or white/grey matter border lesions. Many predisposing factors have been identified, including: elevated levels of cyclosporine, hypomagnesemia, hypocholesterolemia, aluminium toxicity, high dose steroids, hypertension and infection. However CNS events attributed to cyclosporine have been reported without any of these risk factors. We report a case of a child developing multiple white and grey matter thalamic and cortical lesions along with acute neurologic deterioration, and then review cyclosporine mediated CNS injury, including the roles of P-glycoprotein and cyclophilin.
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PMID:Cyclosporine-induced white and grey matter central nervous system lesions in a pediatric renal transplant patient. 1008 60


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