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PubMed2004

Anticonvulsant effects of levetiracetam and levetiracetam-diazepam combinations in experimental status epilepticus.

Status epilepticus (SE) is a neurological emergency, with high mortality and high morbidity among survivors, and novel therapeutic agents are needed to improve this picture. We examined the effects of the antiepileptic drug levetiracetam (LEV) in an experimental model of self-sustaining status epilepticus (SSSE), induced in rats by electrical stimulation of the perforant path. LEV's unique spectrum of anticonvulsant activity, very high therapeutic index, and neuroprotective properties, make it a potentially interesting agent in the treatment of SE. Pretreatment with LEV intravenously reduced (30 mg/kg) or prevented (50-1000 mg/kg) the development of self-sustaining seizures. Treatment during the maintenance phase of SSSE diminished (at 200 mg/kg) or aborted seizures (in doses of 500 or 1000 mg/kg). Addition of LEV significantly enhanced the anticonvulsant effects of diazepam (DZP), even when both drugs where given in doses far below their therapeutic level. We conclude that LEV deserves further evaluation in the treatment of status epilepticus.

Action Potentials↗

PubMed2001

The etiology and diagnosis of status epilepticus.

Status epilepticus (SE) is a common, serious, potentially life-threatening, neurologic emergency characterized by prolonged seizure activity. Generalized convulsive status epilepticus (GCSE) is the most widely recognized form of SE. Direct consequences of convulsive movements from SE can result in injury to the body and brain. Nonconvulsive status epilepticus (NCSE) is underrecognized, with controversy surrounding the consequences and treatment. High mortality rates with GCSE have been noted in the past. New treatments for SE are emerging with new parenteral drug formulations as well as new agents for refractory SE, offering an opportunity to improve outcome. Special drug delivery systems, drug combinations, and neuroprotective agents that prevent the subsequent development of epilepsy may soon emerge as future options for treating SE.

Journal Article↗

PubMed1996

Emergency treatment of status epilepticus.

Status epilepticus occurs in more than 50,000 people in the United States each year and should be considered a neurologic emergency. A variety of drugs are used to treat status epilepticus, including i.v. benzodiazepines, phenytoin, and barbiturates. They are all short of being ideal, primarily because of difficulties with administration or associated toxicity. Fosphenytoin, a prodrug and phosphate ester of phenytoin, was developed to overcome the drawbacks associated with i.v. phenytoin. With its efficacy, safety, and ease of administration, fosphenytoin is a valuable option for the treatment of status epilepticus.

Anticonvulsants↗

PubMed1987

Non-convulsive status epilepticus.

Status epilepticus can complicate any type of seizure activity. A group of 13 children with non-convulsive status has been studied. Five presented with chronic fluctuating neurological features, while eight had intermittent episodes of their atypical status, although each of these lasted for several days. The clinical features, treatment, and outcome for these groups of children are described. Most of the children in both groups are mentally retarded after regressing at the time of their status epilepticus. The recognition and aggressive treatment of atypical status is important in reducing the risk of subsequent mental handicap.

Anticonvulsants↗

PubMed2001

[Treatment of status epilepticus].

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.

Animals↗

PubMedDate not supplied

[Status epilepticus].

Status Epilepticus can assume as many forms as there are types of epileptic seizures, and its clinical outcome largely depends on the etiology. Convulsive Status Epilepticus is a common emergency associated with high morbidity and mortality, but prompt and appropriate pharmacological therapy can reduce both. The authors present a rational treatment protocol for this syndrome.

Anticonvulsants↗

PubMed2005

Treatment of seizure emergencies: convulsive and non-convulsive status epilepticus.

Status epilepticus (SE), defined as recurrent epileptic seizures without complete recovery between seizures, is one of the most serious manifestations of epilepsy. Generalized convulsive status epilepticus (GCSE) is the most common and most life-threatening form of SE, and aging increases the mortality risk. In a recent study of treatment of GCSE, 226 of 518 evaluable patients (43.6%) were of age 65 or older. In the 157 elderly patients with overt GCSE, phenobarbital was successful as first-line treatment in 71.4%, lorazepam in 63%, diazepam and phenytoin in 53.3%, and phenytoin alone in 41.5%. Phenobarbital and lorazepam were more successful than phenytoin alone. In the 69 elderly patients with subtle GCSE, success as the first treatment was 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 7.7% for diazepam and phenytoin. Overall, the results were similar to those reported for the entire study. Lorazepam, because of ease of use, is probably the best drug for the initial treatment of overt GCSE in the elderly; phenobarbital may be the best drug for subtle GCSE in this group, but more data are needed. The term "nonconvulsive SE" has been used to include complex partial SE and absence SE - both of which present as an "epileptic twilight state" - and SE in comatose patients. The diagnosis can be challenging, particularly in the elderly, as overlapping clinical features and electroencephalogram patterns can be seen in SE and in a variety of encephalopathic conditions. There is a suggestion that aggressive treatment of elderly patients with nonconvulsive SE may worsen prognosis. Clearly, there is a need for more data to better understand management of elderly patients with both convulsive and nonconvulsive SE.

Aged↗

PubMed1993

Status epilepticus.

Status epilepticus is defined as having two tonic-clonic convulsive seizures in a row without regaining consciousness or continuous absence, complex partial, or partial seizure activity for 30 minutes or longer. This article discusses classification and prognosis of status epilepticus, principles of management, and drug treatment in adults and adolescents.

Humans↗

PubMed1993

Treatment of status epilepticus.

Status epilepticus, particularly the convulsive form, is a medical emergency, warranting prompt and aggressive treatment. To do this, one must have a thorough understanding of the pharmacology of the anticonvulsant agents. Therapy should be directed toward rapid termination of the status epilepticus, prevention of seizure recurrence, and treatment of any underlying cause. Most importantly, one should establish and adhere to a standard treatment protocol for best results.

Anticonvulsants↗

PubMed1997

[Concept, classification and pathophysiology of status epilepticus].

Status epilepticus (prolonged or repetitive seizures without a period of recovery between them) is a life-threatening medical emergency for which appropriate diagnosis and treatment are imperative. It is usually classified with a practical aim as convulsive and non-convulsive, generalized and partial. In convulsive status there is a critical period of 30 min before irreversible metabolic alterations appear. The factors that influence the beginning and endpoint of a status epilepticus are unknown but a role has been proposed for both glutamate mediates excitation and lack of GABA mediated inhibition.

Brain↗

PubMed2003

Treatment options for status epilepticus.

Status epilepticus is a neurological emergency requiring prompt pharmacological intervention. Recent advances in the treatment of this condition include the introduction of treatment algorithms that are tailored more specifically to clinical situations, a trend towards more aggressive therapies if initial treatment with front-line agents fail, and a better understanding of the role of treatment for patients in status epilepticus in the out-of-hospital setting.

Ambulatory Care↗

PubMed1999

Midazolam and pentobarbital for refractory status epilepticus.

Status epilepticus, a serious, life-threatening emergency characterized by prolonged seizure activity, occurs most commonly in pediatric patients. Although initial therapies with agents such as diazepam, phenytoin, or phenobarbital generally terminate seizure activity within 30-60 minutes, patients with refractory status epilepticus (RSE) lasting longer require additional intervention. High-dose pentobarbital has been the most commonly prescribed agent for the management of RSE in children; however, midazolam has emerged as a new treatment option. This review compares the use of midazolam with pentobarbital in published reports of pediatric RSE. Both drugs effectively terminated refractory seizure activity, although pentobarbital use was complicated by hypotension, delayed recovery, pneumonia, and other adverse effects. Midazolam use was effective and well tolerated, affirming its value in pediatric RSE management.

Adolescent↗

PubMed1989

Rectal diazepam in pediatric status epilepticus.

Status epilepticus is a neurologic emergency with an 8% to 12% mortality. Rapid ablation of seizure activity is imperative. Although intravenous administration of diazepam is the preferred immediate treatment, vascular access is often difficult to achieve. Rectal administration of diazepam is easily accomplished during status epilepticus. Five cases in which diazepam administered in the rectal lumen stopped seizure activity are reported. Rectal diazepam appears to be safe and efficacious. It should be considered as an alternate to intravenous therapy when immediate vascular access is delayed. Rectal diazepam may have great benefit in the prehospital setting.

Administration, Rectal↗

PubMed1993

Status epilepticus and pseudostatus epilepticus.

Status epilepticus is a life-threatening disorder whose early recognition is essential. Non-epileptic seizures (pseudoseizures, hysterical seizures) may be confused with true epileptic seizures presenting a diagnostic dilemma which can result in inappropriate, expensive and potentially harmful treatment. We describe a male patient with no prior history of epilepsy who presented with status epilepticus and developed multiple types of non-epileptic seizures during his hospital stay.

Adult↗

PubMed2005

Treatment options for status epilepticus.

Adult↗

PubMed1996

Status epilepticus.

Status epilepticus is a condition in which multiple epileptic seizures occur without complete recovery from the physiological effects of one seizure before another seizure occurs. There are as many types of SE as there are kinds of epileptic seizures. Generalized convulsive status epilepticus initially presents with repeated generalized convulsions without full recovery of consciousness between seizures. If untreated or undertreated, the convulsive activity becomes progressively subtle and is accompanied by a predictable series of progressive EEG changes. Non-convulsive SE refers to complex partial SE or absence SE, both of which exhibit an epileptic twilight state of altered contact with the environment. In simple partial SE there is no impairment of consciousness, and the behavioural changes reflect focal ictal discharges confined to one area of the cortex. There are between 65,000 and 150,000 cases of the SE in the US each year. Both acute and remote cerebral insults can cause SE, as can severe systemic disease that causes SE secondary to a toxic-metabolic encephalopathy. Mortality is high, but is largely a reflection of underlying aetiology when SE is treated appropriately and aggressively. Treatment is focused on terminating ongoing seizure activity as quickly as possible, both because the longer SE persists the more likely permanent neuronal damage will ensure and also because of strong evidence that the longer SE persists the more refractory to treatment it will be. Currently the most commonly accepted treatment protocol involves rapid initiation of therapy with intravenous lorazepam (0.1 mg/kg), followed, if necessary, by 20 mg/kg of phenytoin, followed, if necessary, by 20 mg/kg of phenobarbital. However, some neurologists still use intravenous diazepam (because of its more rapid antistatus effect) followed by phenytoin. New experimental data in the rat suggest that phenytoin followed by diazepam may be more effective, but this order of administration still has to tested in properly designed clinical trials.

Clinical Protocols↗

PubMed2004

The treatment of status epilepticus.

Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure, and identification of etiology. Symptomatic SE is more common in younger children. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Here we emphasize definitions, clinical and electroencephalography stages, early treatment, special circumstances that may require immediate seizure control, and treatment of RSE. Because much clinical research in SE has been done in adults, we indicate the patient population studied.

Electroencephalography↗

PubMed1998

A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group.

BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

Aged↗