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

Levetiracetam (LEV) is approved as second line treatment for partial onset seizures in adults and children older than four years of age. Recently, an intravenous formulation was developed as an alternative to standard oral medication. We report the successful treatment of two children suffering from myoclonic status epilepticus with intravenous LEV. Intravenous application of LEV was safe and not associated with significant side effects. In conclusion, intravenous application of LEV appears to be a further option in treatment of children with myoclonic status epilepticus.
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PMID:Levetiractam in the treatment of two children with myoclonic status epilepticus. 1901 72

Status epilepticus (SE) is a major neurological emergency with an incidence of about 20/100,000 and a mortality between 3 and 40% depending on etiology, age, status type, and status duration. Generalized tonic-clonic SE, in particular, requires immediate, aggressive, and effective treatment to stop seizure activity, and to prevent neuronal damage and systemic complications and death. Benzodiazepines and phenytoin/fosphenytoin are traditionally used as first-line drugs and are effective in about 60% of all episodes. However, a notable portion of patients remain in SE. For those, narcotics and induction of general anesthesia are used as second-line treatment. Therefore, there is a need for more effective first-line treatment options. Recently, valproic acid was approved for the treatment of status epilepticus in some European countries, and two of the newer antiepileptic drugs have become available for intravenous use: Levetiracetam (LEV) and lacosamide (LCM) should be evaluated in prospective controlled trials as possible treatment options. Standardized protocols for the management of SE are useful to improve immediate care.
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PMID:Status epilepticus: a critical review. 2545 47

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.) application. It could be an alternative when standard drugs fail or should be avoided. We retrospectively identified patients from two German teaching hospitals who were treated with LEV i.v. for SE. Their charts were reviewed regarding sociodemographic data, type, etiology, onset and duration of SE, dose of LEV, concurrent antiepileptic drugs (AED) treatment, tolerability, and outcome. Thirty-two patients (15 female) were found who were treated with i.v. LEV for SE (median age 71 years). Two patients were exclusively treated with LEV. Eight received a low and further 20 patients a high dose of benzodiazepines before LEV. Two patients were treated with LEV to enable discontinuation of narcosis. SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients. Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology. Therapy was initiated within a median time of 3 h and LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3,500 mg. Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min. LEV could not terminate SE in seven patients. We documented nausea and emesis in one and elevation of liver enzymes in another patient that were likely to be attributed to LEV. LEV i.v. seems to be safe with relevant efficiency for the treatment of SE in elderly and multimorbid patients when comorbidity and respiratory insufficiency precludes high doses of benzodiazepines or phenytoin.
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PMID:Intravenous levetiracetam as treatment for status epilepticus. 1945 86

Levetiracetam was approved by the US FDA in 1999 after failing the traditional screening tests for antiepileptic drugs. In the 10 years since its introduction, it has become one of the first-line antiepileptic agents and has been evaluated in small uncontrolled studies and case series as an off-label treatment for status epilepticus, for nonepileptic neurological conditions, such as movement disorders, neuropathic pain and headaches, and for some psychiatric conditions. It has not been approved for any indication other than chronic epilepsy. A significant factor in using levetiracetam for seizures and other disorders has been its ease of dosing and tolerability. In this article, we outline how levetiracetam was discovered, the animal and human data showing its antiepileptic activity, its potential use in other neurological conditions and the significant adverse events. We also discuss the direction antiepileptic drug development will take in the future.
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PMID:Levetiracetam: a comprehensive review. 2013 75

In this review study, second-generation antiepileptic drugs (AEDs) (levetiracetam, gabapentin, topiramate, lamotrigine, zonisamide, oxcarbazepine, vigabatrin, pregabalin, rufinamide, tiagabine, lacosamide, and felbamate) and injectable AEDs (levetiracetam, lacosamide, fosphenytoin, lorazepam, and valproic acid) available in North America were compared with those available in Japan. Three second-generation AEDs (gabapentin, topiramate, and lamotrigine) were recently approved in Japan. Levetiracetam is currently under review for approval by the Japanese regulatory agency. An ideal AED would have a broad-spectrum activity to control multiple types of seizures, favorable safety profile, limited potential for drug-drug interaction, many bioequivalent formulations, long half life to allow infrequent administration, and antiepileptogenic effects that may provide a fundamental cure of epileptic patients by suppressing the development of epileptogenic network and neutralizing previously established epileptogenic foci in the brain. The second-generation AEDs have been developed to possess some of these ideal properties. All the second-generation AEDs are efficacious for the treatment of patients with partial seizures. In addition, levetiracetam, topiramate, lamotrigine, and zonisamide are effective for the treatment of patients with generalized tonic-clonic seizures, absences, myoclonic seizures, Lennox-Gastaut syndrome, and West syndrome; however, lamotrigine is not effective for the treatment of patients with myoclonic seizures. Rufinamide and felbamate are useful for the treatment of patients with Lennox-Gastaut syndrome; however owing to its serious adverse effects, including aplastic anemia and hepatic failure, felbamate is used as the last resort for the treatment of patients with intractable seizures. Vigabatrin is particularly effective for the treatment of patients with West syndrome; however, the patients need to be regularly monitored for the development of peripheral visual field defect. Gabapentin, oxcarbazepine, vigabatrin, and tiagabine are ineffective for the treatment of patients with absences and/or myoclonic seizures and may aggravate these conditions. Treatment with levetiracetam or topiramate (off-label use) is the new option for patients with refractory status epilepticus, which is characterized by downregulation of the inhibitory gamma-aminobutyric acid system, because these drugs act via different mechanisms and are rapidly titratable, especially intravenous levetiracetam. The pharmacokinetic profiles of levetiracetam, gabapentin, and pregabalin are favorable: these drugs exhibit minimal protein binding, do not undergo hepatic metabolism, are not involved in any clinically relevant drug interactions, and rarely lead to the development of serious adverse effects. In general, levetiracetam is probably the closest to being the ideal AED because of its broad-spectrum favorable pharmacokinetic profile and safety profile as well as because of the availability of its parenteral formulation. Among the injectable AEDs, fosphenytoin is a water-soluble prodrug and is used to treat patients with status epilepticus. Systemic and local side effects of this drug are fewer than those of phenytoin. Lorazepam, a benzodiazepine is used as the first-line AED for the treatment of patients with status epilepticus. The effects of this drug are more prolonged than those of diazepam. Intravenous administration of valproic acid is regarded as a new treatment option for patients with status epilepticus, because sedative and negative effects on the cardiorespiratory system of this drug are lesser than those of the traditional injectable AEDs. These novel medications will aid the improvement of the quality of life of epileptic patients through improved seizure control and reduced adverse effects.
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PMID:[Antiepileptic drugs in North America]. 2045 99

Electroencephalographic (EEG) seizures and behavioral convulsions begin to appear spontaneously a few weeks after chemoconvulsant-induced status epilepticus (SE) and thereafter become more intense. This indicates the progressive development of a long-lasting epileptic focus. In addition, chemoconvulsant-induced SE increases neuronal proliferation in the dentate subgranular zone (SGZ) and ectopic migration of newborn neurons into the dentate hilus of adult animals. These seizure-induced newborn neurons, especially ectopic granule cells in the dentate hilus, are believed to facilitate the development of epileptic foci in animal models of temporal lobe epilepsy. In the present study, we examined the effects of a novel antiepileptic drug, levetiracetam, on the appearance of spontaneous EEG seizures and on the generation of newborn neurons, especially of ectopic granule cells in the dentate hilus, following kainate-induced SE. Levetiracetam treatment for 25 days, initiated 24 hours after induction of kainate-induced SE, significantly decreased the mean duration of spontaneous EEG seizures 58 days later. Levetiracetam treatment also prevented an SE-induced increase in the number of ectopic granule cells observed 58 days after kainate administration by suppressing neuronal proliferation in the dentate SGZ and abnormal migration of newborn neurons from the dentate SGZ to the hilus. These results are in accord with a previous report that an antimitotic agent that reduced the number of newborn neurons significantly decreased the frequency of spontaneous convulsions 1 month after pilocarpine-induced SE. This evidence from the kainate model of temporal lobe epilepsy suggests that levetiracetam may exert antiepileptogenic effects through the suppression of seizure-induced neurogenesis.
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PMID:Levetiracetam suppresses development of spontaneous EEG seizures and aberrant neurogenesis following kainate-induced status epilepticus. 2059 5

Levetiracetam may be effective in children with acute seizures or status epilepticus. We performed a retrospective chart review of children who received intravenous levetiracetam within 30 minutes of a seizure. Seventy-three patients during a 2-year study period met our inclusion criteria. The mean (+/- S.D.) age and weight of the patients were 5.59 +/- 5.6 years (range, 1 day to 17.8 years) and 23.1 +/- 21 kg (range, 1.97-97 kg), respectively. Patients received a mean (+/- S.D.) levetiracetam dose of 29.4 +/- 13.5 mg/kg. Most children (n = 49, or 67%) received additional antiepileptic drugs to abort their seizure. Overall, the mean (+/- S.D.) total (abortive plus chronic) number of concomitant antiepileptic drugs used by the population was 2.53 +/- 1.7 (1.07 +/- 0.98 as additional abortive therapy, and 1.42 +/- 1.29 as chronic therapy). Most patients received levetiracetam for serial seizures (79%), whereas 12% and 8% manifested a single seizure or status epilepticus, respectively. Clinical effectiveness at 1, 12, 24, 48, and 72 hours after the initial levetiracetam dose constituted the primary study outcome. Eighty-nine percent of patients remained seizure-free at 1 hour. This rate decreased at each evaluation time point. Most patients (71%) were placed on maintenance levetiracetam within 24 hours of their loading dose. The predictive ability of patient and drug regimen variables in outcomes was poor. Only the number of concomitant antiepileptic drugs consistently predicted outcomes. Levetiracetam was well tolerated at the doses studied, and appears most effective in single seizure events.
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PMID:Intravenous levetiracetam in the management of acute seizures in children. 2061 Jan 22

Systemic injection of high doses of 11-deoxycortisol succinate had been reported to induce status epilepticus in rats and cats that was associated with paroxysmal epileptiform activity refractory to first generation antiepileptic drugs (AEDs). Using patch clamp recordings we have investigated the mechanisms of 11-deoxycortisol-induced excitability and we have discovered that this molecule accelerates the decay time of the inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors, both in neuronal cultures and in hippocampal slices. In addition, it reduces the amplitude and frequency of IPSCs. Thus, 11-deoxycortisol action on GABAergic neurotransmission may be one of the underlying causes of convulsive seizures that had been observed in rats. In the present study, we have reproduced the ability of 11-deoxycortisol to induce convulsive seizures after intravenous infusion in mice. The threshold dose of 11-deoxycortisol necessary for seizure induction was also determined (0.95 mmol/kg). Furthermore, we have established that these seizures are completely refractory to several AEDs such as phenytoin (up to 100 mg/kg), carbamazepine (up to 56 mg/kg), and valproate (up to 300 mg/kg). Levetiracetam and diazepam afforded only limited protection at high doses, 540 and 3-10 mg/kg, respectively. Interestingly, long-lasting seizures induced by 11-deoxycortisol in mice were not associated with typical neuropathological changes observed in other models of status epilepticus. We propose that 11-deoxycortisol-induced seizures may be an advantageous experimental model of drug-resistant epilepsy. Finally, better understanding of the pro-epileptic properties of 11-deoxycortisol is very important, because this endogenous steroid precursor may play a role in the pathophysiology of epilepsy. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
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PMID:11-Deoxycortisol impedes GABAergic neurotransmission and induces drug-resistant status epilepticus in mice. 2088 6

The effectiveness of Levetiracetam (LEV) in the treatment of focal and generalised epilepsies is well established. LEV has a wide spectrum of action, good tolerability and a favourable pharmacokinetic profile. An injectable formulation has been released as an intravenous (IV) infusion in 2006 for patients with epilepsy when oral administration is temporarily not feasible. Bioequivalence to the oral preparation has been demonstrated with good tolerability and safety enabling a smooth transition from oral to parenteral formulation and vice versa. Although IV LEV is not licensed for treatment of status epilepticus (SE), open-label experience in retrospective case series is accumulating. Until now (August 2008) 156 patients who were treated with IV LEV for various forms of SE have been reported with an overall success rate of 65.4%. The most often used initial dose was 2000-3000 mg over 15 minutes. Adverse events were reported in 7.1%, and were mild and transient. Although IV LEV is an interesting alternative for the treatment of SE due to the lack of centrally depressive effects and low potential of drug interactions, one has to be aware of the nonrandomised retrospective study design, the heterogenous patient population and treatment protocols, and the publication bias inherent in these type of studies. Only a large randomised controlled trial with an adequate comparator will reveal the efficacy and effectiveness of this promising new IV formulation.
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PMID:New treatment options in status epilepticus: a critical review on intravenous levetiracetam. 2118 Jun 43

Acute seizure and status epilepticus constitute one of the major medical emergencies in children. Among children, the incidence ranges from 4-38/100,000 children per year respectively. The incidence in developing countries is somewhat higher because of infections. Although, the definition of status epilepticus is based on duration of seizures, the operational definition is to treat any child who is brought seizing to the emergency room, as status epilepticus. An urgent time bound approach is of paramount importance when managing a child in status epilepticus. Benzodiazepines remain the first line antiepileptic drugs in the emergency room; a long acting drug (Lorazepam) is preferred when available. This is followed by Phenytoin (20 mg/kg) loading. In patients refractory to above drugs, valproate (30 mg/kg) loading is commonly used and if effective, followed by an infusion (5 mg/kg/h) for seizure free period of 6 h. In non-responders, a trial of Levetiracetam (40 mg/kg infused at 5 mg/kg/min) can be used before starting benzodiazepine or thiopental coma (3-4 mg/kg loading dose, followed by 2 mg/kg/min infusion). When pharmacological coma is initiated, the child needs to be shifted to pediatric intensive care unit for proper monitoring and titration of medications.
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PMID:Management of acute seizure and status epilepticus in pediatric emergency. 2212 Jun 13


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