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)

Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.
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PMID:Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic muscarinic system involvement. 1596 74

Treatment of status epilepticus (SE) has changed little over the last two decades, but the burden of this condition remains important. There is thus a need for alternative pharmacological therapies. Levetiracetam (LEV) has a wide spectrum of action and a favorable pharmacokinetic profile; however, little data exist regarding its use in SE. We identified patients with SE who received LEV, in a database comprising 127 SE episodes. Demographic, clinical and pharmacological data were analyzed, and compared to a control group consisting of 2 subjects from the database for each LEV patient, matched for age and sex. We identified 13 SE episodes occurring in 12 patients (10% of the database). Demographic, etiologic and clinical characteristics and outcome did not differ between the groups. Daily LEV dose ranged between 1,000-6,000 mg. Three patients were probable responders (23%), 1 responded to the treatment but subsequently died (8%), 4 were non-responders (31%, 1 died), and 5 had an undetermined response (38%). LEV may represent a useful alternative in the treatment of SE, particularly if a parenteral form of administration becomes available; to better define its role in this setting, prospective studies are needed.
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PMID:Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes. 1610 76

We report on a 3-year-old boy with myoclonic-astatic epilepsy who developed myoclonic status epilepticus with continuous twitching of the face and unresponsiveness under monotherapy with levetiracetam. Recently, a nonconvulsive status epilepticus in an adult epilepsy patient has also been described. Our observation points to the possibility of a causal relationship between the induction of myoclonic status by levetiracetam in certain patients with Doose's syndrome. However, a spontaneous evolution cannot be excluded. Levetiracetam is a well-known drug for the control of myoclonic seizures. A controlled study would provide a better understanding of any possible aggravating role in certain forms of myoclonic-astatic epilepsy.
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PMID:Levetiracetam-induced myoclonic status epilepticus in myoclonic-astatic epilepsy: a case report. 1698 44

Levetiracetam (LEV) is a structurally novel antiepileptic drug (AED) which has demonstrated a broad spectrum of anticonvulsant activities both in experimental and clinical studies. Previous experiments in the kindling model suggested that LEV, in addition to its seizure-suppressing activity, may possess antiepileptogenic or disease-modifying activity. In the present study, we evaluated this possibility by using a rat model in which epilepsy with spontaneous recurrent seizures (SRS), behavioral alterations, and hippocampal damages develop after a status epilepticus (SE) induced by sustained electrical stimulation of the basal amygdala. Two experimental protocols were used. In the first protocol, LEV treatment was started 24h after onset of electrical amygdala stimulation without prior termination of the SE. In the second protocol, the SE was interrupted after 4h by diazepam, immediately followed by onset of treatment with LEV. Treatment with LEV was continued for 8 weeks (experiment #1) or 5 weeks (experiment #2) after SE, using continuous drug administration via osmotic minipumps. The occurrence of SRS was recorded during and after treatment. In addition, the rats were tested in a battery of behavioral tests, including the elevated-plus maze and the Morris water maze. Finally, the brains of the animals were analyzed for histological lesions in the hippocampal formation. With the experimental protocols chosen for these experiments, LEV did not exert antiepileptogenic or neuroprotective activity. Furthermore, the behavioral alterations, e.g., behavioral hyperexcitability and learning deficits, in epileptic rats were not affected by treatment with LEV after SE. These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats.
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PMID:Prophylactic treatment with levetiracetam after status epilepticus: lack of effect on epileptogenesis, neuronal damage, and behavioral alterations in rats. 1826 88

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that is effective against a variety of seizure types. It is a pyrridoline derivative with a very favourable pharmacokinetic profile: excellent bioavailability, linear kinetics, minimal plasma protein binding and quick achievement of steady state concentrations. It is not metabolized through the P450 hepatic cytochrome system, does not induce its own metabolism and has no clinically relevant drug-drug interactions. It is available as film-coated tablets, liquid formulation for oral ingestion and intravenous concentrated solution. Controlled and open-label studies have shown its efficacy and safety as initial monotherapy and add-on treatment for partial-onset seizures in children and adults, and also as add-on therapy in refractory partial and primary generalized seizures. Its rapid onset of action, lack of drug-drug interactions and availability as an intravenous solution make it an optimal drug to treat epilepsy associated with other medical conditions. Preliminary reports also suggest potential efficacy in refractory status epilepticus, although this is not a registered indication. Levetiracetam is generally well tolerated, and no serious idiosyncratic side effects have been reported so far. Behavioral side effects (hostility up to aggressive behaviour) are not uncommon. Small, uncontrolled studies have suggested potential therapeutic potential in difficult-to-treat dyskinesias in Parkinson's disease, tremors of different etiologies, migraine prophylaxis and mood disorders. This needs to be confirmed in larger, controlled studies.
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PMID:Levetiracetam. 1817 64

Levetiracetam is an antiepileptic drug that was shown to be effective in various seizure types. Experience with this agent for treating status epilepticus is just emerging. To the best of our knowledge, there is no report in the literature regarding its use in children with nonconvulsive status epilepticus. We here report a liver-transplanted child with nonconvulsive status epilepticus who responded well to oral levetiracetam treatment.
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PMID:The use of levetiracetam in a child with nonconvulsive status epilepticus. 1819 52

Levetiracetam (LEV) is a broad-spectrum antiepileptic drug with no known interactions and a favorable profile of adverse events. These properties make it a good candidate for use in critically ill patients. An intravenous formulation of LEV was recently approved. The present study retrospectively assesses the safety and efficacy of LEV in the first 50 critically ill patients treated with intravenous LEV. Indications for use were seizure prophylaxis, acute symptomatic seizures, and all forms of status epilepticus. There were no major adverse effects, although less prominent changes may have been masked by the already severely compromised condition of these patients. Two patients (4%) had transiently lowered platelet counts (55,000 and 82,000, respectively). Efficacy, defined as cessation of seizure activity or prevention of its recurrence, was observed in 41 of 50 patients (82%). Antiepileptic treatment of critically ill patients with LEV seems to be effective and safe according to the data for this small cohort, but this observation warrants further prospective investigation in a larger number of patients.
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PMID:Intravenous levetiracetam: treatment experience with the first 50 critically ill patients. 1829 24

Levetiracetam (LEV) has been considered to undergo no significant change in bioavailability during pregnancy; however, it was recently demonstrated to display modifications leading to a drop in its serum level. We describe a patient who displayed impending status epilepticus following a fall in her LEV level during the first trimester. The oral LEV dosage was increased, and phenytoin and benzodiazepines were transiently prescribed. She experienced severe anxiety and an unbearable fear over the deleterious consequences for her baby despite repeated, reassuring explanations. Her anxiety was so strong that she aborted electively shortly after leaving the hospital. This observation emphasizes the need for LEV level monitoring during pregnancy to prevent unexpected seizure relapses. The rapid increase in levetiracetam dosage in parallel with the loss of seizure control is suspected of facilitating the induction of significant psychiatric changes.
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PMID:Impending status epilepticus and anxiety in a pregnant woman treated with levetiracetam. 1858 1

We investigated the clinical characteristics of children with continuous spike waves during slow-wave sleep syndrome and their treatment response to levetiracetam. Five boys and one girl, diagnosed with epilepsy with continuous spike waves during slow-wave sleep syndrome, were enrolled. Their clinical characteristics, including neuroimaging findings, were reviewed. The signs related to continuous spike waves during slow-wave sleep included increased seizure frequency (6/6), impaired responsiveness (3/6), and psychomotor regression (2/6). Magnetic resonance imaging disclosed lissencephaly in one patient, and porencephaly of the left hemisphere in another. The number of antiepileptic drugs before the use of levetiracetam was 0-4 (mean +/- SD, 2.3 +/- 1.5). Five of 6 children demonstrated a good response to levetiracetam, whereas 2 (40%) underwent a relapse of electrical status epilepticus during sleep pattern on electroencephalograms 4 and 5 months after clinical improvement. Both were 5 years old. The most common presenting sign in children with continuous spike waves during slow-wave sleep syndrome is increasing seizure frequency. Levetiracetam is effective in treating children with continuous spike waves during slow-wave sleep syndrome. However, the relapse rate of continuous spike waves during slow-wave sleep syndrome remains high in young children.
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PMID:Levetiracetam in continuous spike waves during slow-wave sleep syndrome. 1863 50

Levetiracetam (Keppra) is a new generation antiepileptic drug characterized by a unique profile of activity in experimental models of epilepsy. It also has a distinct binding site in the brain, i.e. the synaptic vesicle protein type 2 (SV2A). Levetiracetam has been reported to have antiepileptogenic and disease-modifying properties. In the present study the effects of chronic treatment with levetiracetam were assessed in rats that sustained pilocarpine-induced status epilepticus (SE). Hippocampal field potentials were recorded in vivo in anesthetized animals after 3-day washout period that followed 21-day treatment with different doses of levetiracetam (50, 150 or 300 mg/kg/day) administered via ALZET osmotic mini-pumps. Vehicle treated rats together with naive animals (not subjected to SE) were used as control groups. Chronic treatment with levetiracetam yielded clinically relevant plasma concentrations throughout the experiment with complete washout of the drug 3 days after treatment cessation. At this point in time post-SE rats chronically treated with vehicle developed clear signs of hippocampal hyperexcitability, i.e. increased amplitude of population spike (PS) recorded in the dentate gyrus and reduced paired-pulse inhibition in the CA1 area. Levetiracetam treatment dose-dependently counteracted these long-term effects of pilocarpine-induced SE. Furthermore, at the dose of 300 mg/kg/day levetiracetam restored these parameters back to control level. The present results indicate that chronic treatment with levetiracetam completely inhibits the development of hippocampal hyperexcitability following pilocarpine-induced SE.
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PMID:Effects of chronic treatment with levetiracetam on hippocampal field responses after pilocarpine-induced status epilepticus in rats. 1872 15


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