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At least 19 recordsLinked to original sources
PubMed1978

Drug therapy reviews: drug therapy of status epilepticus.

Drug treatment of status epilepticus is reviewed. Tonic-clonic, focal motor, complex partial and absence status epilepticus are discussed. In managing tonic-clonic status epilepticus one should: (1) maintain vital functions at all times, (2) identify and treat precipitating factors and (3) administer an intravenous loading dose of phenytoin sodium or phenobarbital sodium. Careful use of i.v. diazepam sometimes helps to achieve these objectives. Intravenous phenytoin sodium and phenobarbital sodium provide definitive, long-term control of tonic-clonic seizures but must be administered slowly and require time to reach peak brain concentrations. Intravenous diazepam appears to enter and exit from the brain rapidly and may control seizures while therapeutic brain concentrations of long-acting drugs are being achieved. Phenytoin, phenobarbital and diazepam should not be administered intramuscularly in treating status epilepticus. Treatment of focal motor and complex partial status epilepticus is similar to that of tonic-clonic status epilepticus, but i.v. diazepam is required less frequently and loading doses of phenytoin and phenobarbital sometimes can be given more slowly. Status epilepticus of the absence type is managed with i.v. acetazolamide sodium or diazepam. Paraldehyde, muscle relaxants, general anesthesia and lidocaine may be tried when conventional therapies fail.

Anesthesia, General↗
PubMed2024

Drug repurposing in status epilepticus.

The treatment of status epilepticus (SE) has changed little in the last 20 years, largely because of the high risks and costs of new drug development for SE. Moreover, SE poses specific challenges to drug development, such as patient diversity, logistical hurdles, and the need for acute treatment strategies that differ from chronic seizure prevention. This has reduced the appetite of industry to develop new drugs in this area. Drug repurposing is an attractive approach to address this unmet need. It offers significant advantages, including reduced development time, lower costs, and higher success rates, compared to novel drug development. Here I demonstrate how novel methods integrating biological knowledge and computational methods can be applied to drug repurposing in status epilepticus. Biological approaches focus on addressing mechanisms underlying drug resistance in SE (using for example ketamine, tacrolimus and safinamide) and longer-term consequences (using for example omaveloxolone, celecoxib and losartan). Additionally, artificial intelligence platforms, such as ChatGPT, can rapidly generate promising drug lists, while in silico methods can analyze gene expression changes to predict molecular targets. Combining AI and in silico approaches has identified several candidate drugs, including metformin, sirolimus and riluzole, for SE treatment. Despite the promise of repurposing, challenges remain, such as intellectual property issues and regulatory barriers. Nonetheless, drug repurposing presents a viable solution to the high costs and slow progress of traditional drug development for SE. This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, in April 2024.

Animals↗
PubMed1978

Rectal administration of sodium valproate in status epilepticus.

Six patients suffering from status epilepticus were refractory to parenteral treatment with either diazepam, amobarbital or both, and were given sodium valproate 200 to 800 mg every 6 hours. The drug was administered rectally as 200 mg lipid-based suppositories, thereby avoiding impaired absorption, which occurs in the presence of paralytic ileus. Plasma levels of sodium valproate in all patients reached the therapeutic range within 36 hours of starting therapy. Seizures were totally controlled in five patients and a 75 percent reduction was noted in the sixth. In two patients, the route of administration was changed from rectal to an equivalent oral dose with continuing control of seizures and minimal change in plasma levels, suggesting that bioavailability is similar for the two forms of the drug. The rectal route of administration was effective in achieving systemic absorption of sodium valproate in the treatment of status epilepticus.

Adolescent↗
PubMed1978

Enzyme histochemistry of the rat hippocampus during experimental status epilepticus.

EEG registered hippocampal status epilepticus (HSE) was provoked in 41 adult albino rats by intraseptal injection of ouabain, and the hippocampus was studied from 1 1/2 to 24 hr with the enzyme histochemical tests for succinic dehydrogenase (SDH), lactic dehydrogenase (LDH), thiaminopyrophosphatase (TPPase), acid phosphatase (AcPase), Mg2+ adenosine triphosphatase (Mg2++ ATPase), and with general and neurohistological stains. In a first group of animals (1 1/2 to 10 hr of HSE), a stage of general increase in enzymatic activity was detected in the pyramidal neurons (SDH, LDH, AcPase, and TPPase). Mg2+ ATPase showed a marked increase in astrocytes. In a second group (more than 10 hr of HSE), SDH was found decreased in the dendritic fields. LDH activity persisted in neuronal bodies, and AcPase and TPPase showed diffuse activity in the cytoplasm of some pyramidal neurons. In a third group (more than 18 hr of HSE), SDH activity was low. No AcPase granules were observed in some pyramidal neurons and TPPase was negative in some areas of pyramidal layer. Mg2+ ATPase reaction showed scare and retracted astroglial processes. These changes were coincident with "cellular ghosts" observed with hematoxylin-eosin techniques of the same samples in the pyramidal field and were interpreted as cellular death, attributed to relative anoxia following neuronal discharge.

Acid Phosphatase↗
PubMed1978

Complex partial status epilepticus: case report and proposal for diagnostic criteria.

A child had complex partial status epilepticus after resection of a craniopharyngioma. The status epilepticus was manifested by confusion and documented electroencephalographically by continuous focal seizure patterns in the right temporal region. Complex partial status epilepticus is an electroclinical syndrome of prolonged or repetitive complex partial seizures (with continuous interictal confusion) accompanied by electroencephalographic seizure patterns, which are either focal (usually temporal lobe) or secondarily generalized from a focal pacemaker.

Child, Preschool↗
PubMed1978

Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia.

The influence of hypercapnia, hypoxia and status epilepticus on cerebral cortex concentrations of adenosine, adenine nucleotides and cyclic AMP was studied on lightly anaesthetized (70% N2O) and artificially ventilated rats. Neither hypercapnia (arterial PCO2 about 80 and about 300 mmHg) nor hypoxia (minimal values of 19 mmHg) altered tissue concentrations of AMP, cyclic AMP or adenosine. Bicuculline-induced status epilepticus was accompanied by increased concentrations of cyclic AMP but adenosine concentration did not change. Experiments with ischemia, and those in which tissue hypoxia was exaggerated by unilateral carotid artery ligation, showed that tissue adenosine concentrations were elevated only when AMP concentration rose. It is concluded that the marked increase in cerebral blood flow which occurs in hypoxia and status epilepticus is unrelated to changes in tissue adenosine concentration and that the increase in cyclic AMP during neuronal hyperactivity is triggered by other mechanisms than adenosine accumulation.

Adenine Nucleotides↗
PubMed1979

Lorazepam in status epilepticus.

Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.

Adolescent↗
PubMed1979

Status epilepticus controlled by althesin infusion.

Althesin will control status epilepticus when other agents fail. Its major advantage over other agents is its lack of accumulation because it is readily metabolized. Three patients are reported and relevant literature is discussed.

Adolescent↗
PubMed1977

Hypervascular pattern associated with idiopathic focal status epilepticus.

Cerebral angiography in 5 patients in idiopathic focal status epilepticus demonstrated a hypervascular pattern consisting of arteriolar or capillary "blush" with early filling veins and corresponding to the seizure focus; however, there was no evidence of vascular occlusion, neovascularity, or mass effect except for minimal local brain swelling. All showed clearing of neurological deficits; repeat angiograms in 2 patients after arrest of seizure activity returned to normal with complete disappearance of the hypervascular pattern. This reversible but potentially misleading angiographic pattern should be recognized as a benign process.

Adult↗
PubMed1977

[Electroclinical correlations during anticonvulsive therapy of status epilepticus and chronic focal epilepsies using clonazepam].

Clonazepam was used in 22 instances of status epilepticus by intravenous route with particularly good results. Severe etiologies in status were common. Therapy of partial and secondarily generalized convulsion is favoured. 18 patients with epilepsies of similar classification were treated by long term oral administration with inconstant results. Spatio-temporal and dose related profiles of convulsive and electroencephalographic desactivation are demonstrated. Signs of secondary generalisation were abolished first whereas focal signs turned out more resistent proved by repeated EEG recordings. Hypnotic effect as constituent or not in parenteral status therapy is discussed.

Adolescent↗
PubMed1977

Electrographic and clinical effects of intracarotid sodium amobarbital on bilateral myoclonic status epilepticus.

The effects of rapid intracarotid injection of 20 to 100 mg of sodium amobarbital were studied in three patients with bilateral myoclonic status epilepticus due to Jakob-Creutzfeldt disease, sequelae to anoxic encephalopathy, and hepatic coma, respectively. In each instance, the drug produced prompt abatement of clonic jerks contralaterally and attenuation of electroencephalographic epileptiform discharges ipsilaterally. These results suggest that the cerebral cortex actively participates in the elaboration of certain types of bilateral myoclonus in human beings.

Aged↗
PubMed1978

[Benign focal epilepsy and "electrical status epilepticus" during sleep (author's transl)].

The authors describe the electro-clinical state of four children having a type of epilepsy clinically characterized by rare partial motor seizures and frequent absences. From E.E.G. point of view they had focal (mainly frontal) and diffuse abnormalities. Such diffuse abnormalities became continuous during slow sleep, thus realizing an electrical status epilepticus. During such status partial subclinical seizures were recorded. At the onset such cases have electroclinical features resembling those observed in the form of epilepsy so-called "benign partial epilepsy of children with rolandic or mid-temporal foci". All cases, however, have behavioural problems (instability, desorientation) and decreased school performances. The epilepsy evolution, however, is favourable and such form should consequently be distinguished from the Lennox-Gastaut Syndrome.

Child↗
PubMed1979

[Unusual course of a status epilepticus. (Case contribution to the problem of "interparoxysmal petit-mal-status")].

This is a record of a strange course of the petit mal status which persisted for almost four days following a series of grands maux. During the status, it was possible to observe in electroencephalogram a 2-2.5/sec and, finally, 2.5-3.5/sec spike and wave pattern which could be interrupted after the administration of 100 mg of diazepam. In contrast with the normally observed twilight state, this particular course of the petit mal status ("interparoxysmal petit mal status") is characterized by a marked disturbance of consciousness. There was no response to an intravenous administration of 750 mg of diphenylhydantoin.

Electroencephalography↗
PubMedDate not supplied

Preliminary study of parenteral lorazepam in status epilepticus.

The authors report their experience with parenteral lorazepam in the acute treatment of 11 patients with EEG-confirmed status epilepticus. Ten adults and one 6-year-old child were injected respectively with 5 mg and 2.5 mg lorazepam. All of these patients exhibited prompt cessation of seizures both electrical and clinical. Some data indicate a longer lasting relief than that provided by an equal dose of diazepam.

Adolescent↗