Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenobarbital, diazepam, lorazepam, and phenytoin are all currently used for the treatment of acute seizures, including status epilepticus. None of these drugs is considered ideal. Fosphenytoin is a new phenytoin prodrug that fulfills many of the properties of an ideal anticonvulsant drug. The safety, tolerance, and pharmacokinetics of intramuscularly administered fosphenytoin have been evaluated in three clinical trials involving patients requiring loading or maintenance doses of phenytoin. These investigations demonstrated that fosphenytoin is rapidly and completely absorbed after injection into muscle and is quickly converted to produce therapeutic phenytoin plasma concentrations within 30 min of administration. Plasma concentrations of phenytoin achieved with i.m. fosphenytoin exceeded those associated with an equimolar dose of oral phenytoin. i.m. fosphenytoin was well tolerated both locally and systemically. Only mild and transient reactions occurred at the injection site. The most common systemic adverse events reported--somnolence, nystagmus, dizziness, and ataxia--are side effects commonly seen with phenytoin and tended to be mild. Preexisting seizure disorders remained stable. Combination treatment with i.v. diazepam or lorazepam to attain rapid seizure control and i.m. fosphenytoin to maintain the anticonvulsant effect theoretically offers many advantages for control of acute seizures and should be studied.
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PMID:Intramuscular use of fosphenytoin: an overview. 864 11

A 49-year-old man presented with dizziness and altered behavior associated with a nonconvulsive seizure. He had a long history of well-controlled tonic-clonic seizures and daily episodes of 10-second staring spells. Despite normal neurological and laboratory examinations, an emergent electroencephalogram showed changes consistent with nonconvulsive generalized status epilepticus.
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PMID:Nonconvulsive status epilepticus. 937 47

Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of gamma-aminobutyric acid (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain. The absorption and elimination of tiagabine follow linear pharmacokinetics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzyme-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral contraceptives. In the perforant pathway stimulation model of status epilepticus, tiagabine reduced the seizure number and severity, and also prevented the loss of pyramidal cells in the hippocampus as well as alleviated impairment of the spatial memory impairment associated with hippocampal damage. Tiagabine has both antiepileptogenic and anticonvulsant effects in the kindling model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has been also possible in substantial amount of patients with partial seizures in three trials. Tiagabine is generally well-tolerated. The most common adverse events in controlled studies involve the central nervous system; for example, dizziness, asthenia, nervousness, tremor, depressed mood and emotional lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagabine represents an important new therapeutic option for patients with treatment-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially emphasized since tiagabine has a low side-effect profile in the cognitive area.
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PMID:Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy. 1003 Apr 35

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.
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PMID:Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study. 1107 88

Tiagabine (TGB) is a novel antiepileptic drug efficacious for the treatment of partial epilepsies. The aim of that work is short presentation of current data concerning long-term safety of TGB. Tolerance to TGB does not develop with long-term therapy. Idiosyncratic reaction and changes in haematology and chemistry values have not been associated with TGB therapy. The most common adverse effects are dizziness, asthenia, nervousness, tremor, diarrhoea and depression. The current data do not show any evidence of relationship between visual field constriction and TGB treatment. No adverse effects on cognitive abilities have been found. There are contradictory data concerning tiagabine-induced nonconvulsive status epilepticus. Because of high safety and efficacy TBG is an important new antiepileptic drug for the treatment of intractable partial epilepsies.
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PMID:[Long-term safety of using tiagabine in epilepsy]. 1125 88

Tiagabine (TGB) is now registered in >20 countries, and the total number of treated patients approaches 90,000. Short-term safety data were derived mainly from five placebo-controlled, add-on studies in adults with therapy-resistant partial epilepsy, and two conversion to TGB monotherapy studies. Central nervous system (CNS)-related adverse effects, most frequently dizziness, were common with TGB treatment during the titration period; the risk became similar to placebo rates during fixed-dose periods. Other adverse events that were more frequent in TGB- than in placebo-treated patients were asthenia, nervousness, tremor, concentration difficulties, depressive mood, and language problems. TGB doses should be titrated slowly and taken with food to avoid rapid increases in plasma concentrations, thus minimizing the risks of adverse events. Overall, >2,500 patients have been exposed to TGB during clinical trials, with 1,274 patients treated >12 months, the majority of whom received TGB 24-60 mg/day. No idiosyncratic reactions have been linked to the use of TGB, and no abnormalities in hematology or common chemistry values were reported. In all the epilepsy studies combined, 21% of patients discontinued treatment because of adverse events, usually during the first 6 months of treatment. No adverse effects on cognitive abilities were detected when the neuropsychological effects of TGB add-on therapy and monotherapy were evaluated. TGB does not appear to cause an excess risk of psychosis or increase the incidence of status epilepticus or spike/wave discharges. No evidence of a relationship between visual field constriction and TGB treatment was found in a study of 15 patients converted to TGB monotherapy (mean dose, 22 mg/day; mean duration, 2.5 years) who had a full ophthalmologic evaluation. In conclusion, the characteristics of TGB in the management of partial epilepsy are enhanced by its favorable side-effect profile in the cognitive area.
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PMID:Long-term safety of tiagabine. 1152 Mar 23

To define the incidence and type of neurological complications and associated factors, we reviewed 41 consecutive patients who had 45 procedures for liver transplantation. Encephalopathy occurred after 28 procedures (62%) with immediate onset and no significant recovery before death or re-transplantation in 11 (24%), slow recovery in eight (18%) and delayed onset (1-50 days, average 11) in six (13%). Intermittent confusion and agitation with full recovery followed three (6.6%), and focal and generalized seizures followed five (11%) procedures with multifocal myoclonus in two and status epilepticus in one; isolated focal seizures followed two and myoclonus or unclassified seizures, one each. All patients with seizures had encephalopathy. Three patients had neuropathy (2 generalised and 1 focal). Other complications included headache (2), tremors (2), fatigue (2), restlessness, nervousness, transient enuresis, intermittent dizziness, critical illness myopathy and detached retina. Brain imaging showed atrophy in three (6.6%) instances, intracerebral haemorrhage in two, multiple infarctions in one, and intracerebral and subarachnoid haemorrhage with infarction in one. Cerebrospinal fluid analysis showed increased protein in three, hemorrhage in one, and no abnormality in one patient. Of 12 patients (29%) who died before discharge, five in the first and three in the second week post-transplantation, 11 (92%) had encephalopathy post-operatively. Neurological complications after transplantation were associated with increased mortality. Post-operative hypomagnesaemia was associated with the development of nervous system complications. We did not identify any clear pre-operative predictors of development of post-operative neurological complications.
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PMID:Neurological complications in liver transplantation. 1201 80

Carisbamate is a novel drug with neuromodulator activity that is currently under development for the treatment of epilepsy, diabetic neuropathy and neuralgia. The compound possessed a promising pharmacological profile in tests in vivo, and demonstrated broad anticonvulsant activity in preclinical studies, both elevating seizure threshold and preventing seizure spread. Carisbamate was also effective in protecting against spontaneous recurrent seizures in kainate-treated animals and in genetic models of epilepsy, and displayed antiepileptic and neuroprotective activity in the lithium-pilocarpine model of status epilepticus. In a phase I clinical trial, orally administered carisbamate demonstrated efficacy at high doses of 500 to 1000 mg. A phase II clinical trial confirmed that oral carisbamate was efficacious at a 300- to 1600-mg dose range. The preliminary evaluations of carisbamate in humans indicated complete absorption, extensive metabolism, and carbamate ester hydrolysis. The most frequently reported side effects associated with carisbamate are dizziness, headache, somnolence and nausea. In clinical trials, carisbamate did not display any significant interactions with commonly used antiepileptic drugs such as carbamazepine, valproate and lamotrigine. At the time of publication, a phase III clinical trial for carisbamate in the treatment of epilepsy was ongoing, as well as phase II trials in neuropathy and neuralgia. Data from preclinical brain injury studies with carisbamate and the analog RWJ-333369-A have also been reported. This drug profile will focus on the development of carisbamate in epilepsy.
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PMID:Carisbamate, a new carbamate for the treatment of epilepsy. 1789 91

A 50-year-old woman presented with confusion, fever and drowsiness following an episode of headache and dizziness. On admission, neurological examination found positive pyramidal tract signs, meningeal irritation, and bilateral myoclonus in her arms. Laboratory tests revealed liver dysfunction, positive inflammatory reaction, elevated serum IgM antibody against cytomegalovirus, and increased cerebrospinal fluid protein of 67 mg/dl. MRI of brain by diffusion weighted imaging showed a wide spread hyperintense lesion in white matter and limbic areas. We administered aciclovir, ganciclovir and steroid pulse therapy that showed a limited effect in the initial stage. In spite of all these therapies, she suffered from status epilepticus, followed by persistent disturbance of consciousness for about 2 months. However, her level of consciousness and motor deficit were gradually improved by continuous administration of ganciclovir. The present case indicates that prolonged disturbance of consciousness due to cytomegalovirus encephalitis could be restored with continuous ganciclovir administration.
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PMID:[A case of probable cytomegalovirus encephalitis who restored from persistant disturbance of consciousness]. 1871 81

It has been reported that high intensity on diffusion-weighted image (DWI) in magnetic reasonance imaging (MRI) accompanying a reduction of the apparent diffusion coefficient (ADC) can be detected at the ictal or postictal stage of epileptic seizure. However, it remains unclear whether such a change results from persisting systemic convulsive seizure or from certain physiological changes such as recurrent epileptic discharge prior to the occurrence of obvious convulsion. We report here a case of symptomatic epilepsy displaying a high intensity area on DWI in MRI before convulsive seizure was initiated. A 64-year-old man was admitted to our hospital due to complaints of dizziness and motor weakness. CT and conventional MRI scans failed to reveal any new lesions except for the scar of a ventricular tube in the right parietal lobe, which had been removed due to shunt infection. The DWI, however, demonstrated an apparent high intensity in the right parietal cortex, and the ADC was significantly reduced as compared to that on the contralateral side. Five days after admission, the patient showed convulsive seizures beginning from the right face and upper extremity which subsequently developed to status epilepticus. Following recovery from the convulsions with administration of anticonvulsants, the high intensity of the right parietal lobe on DWI appeared to be diminished. The present case indicates that the manifestation of a high intensity on DWI concomitant with ADC reduction at the epileptic focus can be readily induced by the occurrence of epileptic discharges before convulsive seizure is evident.
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PMID:[Case of symptomatic epilepsy presenting with focal high intensity on diffusion-weighted image prior to initial convulsive seizure]. 1880 Jun 32


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