Treatment Of Convulsive Seizures Research Articles

Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial.

To assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2 to 18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine 0.2 mg/kg/day, or fenfluramine 0.7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose, 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure (MCSF) frequency during baseline and during the combined titration-maintenance period in patients given fenfluramine 0.7 mg/kg/day vs. patients given placebo. 169 patients were screened and 143 were randomized to treatment. Mean age was 9.3±4.7 years (±SD), 51% were male, and median baseline MCSF in the 3 groups ranged from 12.7-18.0 per 28 days. Patients treated with fenfluramine 0.7 mg/kg/day demonstrated a 64.8% (95% CI, 51.8%-74.2%) greater reduction in MCSF compared with placebo (P<0.0001). Following fenfluramine 0.7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% of the placebo group (P<0.0001). The median longest seizure-free interval was 30 days in the fenfluramine 0.7 mg/kg/day group compared with 10 days in the placebo group (P<0.0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected. The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the anti-seizure response of fenfluramine in children with Dravet syndrome.

K+ Channels and Some Familiar Antiepileptic Drugs: Evaluation of Their the Structure-Activity Relationships with Molecular Docking Analysis

This study includes the structure-activity relationship of active molecules that are commonly used in the treatment of convulsive seizures in epileptic diseases. Well-known epileptic active molecules studied are: Vigabatrin, Lokosamidine, Zonisamide, Oxcarbazepine, Levetiresetam, Tiagabine, Topiramate, Lamotrigin, Gabapentin, Felbamat, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidon, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules, which were selected considering the physiopathological mechanisms of action of epileptic disease, were considered suitable for molecular docking studies since they were used as a potential antiepileptic agent. In addition, it was focused on the potassium channels, which were prominent in the mechanisms of epilepsy. During the action potential that triggers seizure formation, inward rectifying potassium channels (KIR3.2) make a important role providing the flow of K+ ions. &#x0D; Thus, PDB ID: 4KFM receptor was chosen for molecular docking study, since its act as an agonist according to its activity on the canal in the case of epileptic seizures formation. The result of molecular docking analysis demonstrated that Phenytoin gave the best binding affinity for 4KFM with a value of -6.2 kcal/mol. Other analysis in descending order (as kcal/mol); Oxcarbazepine (-6,0), Remasemide (-5.9), Topiramate and Primidon (-5.8), Tiagabine, Felbamat and Mesuximide (-5.7), Lamotrigin (-5.6) Zonisamide, Ethotoin and Mephenytoin, Lokosamidine (-5.5), Gabapentin (-4.8), Trimethadion (-4.7), Ethosuximide (-4.6), Levetiresetam (-4.5), Vigabatrin (-4.0), Valproic Acid (-3.9) determined as.

Investigation Of Structure-Activity Relationships With Molecular Docking For Some Antiepileptic Drugs And Voltage-Gated Calcium (CaV) Channels

In the study, the active drugs molecules used in the treatment of convulsive seizures occurring in epilepsy disease were used. These molecules; Vigabatrin, Lokosamidin, Zonisamide, Oxcarbazepine, Levetiracetam, Tiagabin, Topiramate, Lamotrigine, Gabapentin, Felbamate, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidone, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules have been selected considering the physiopathological mechanisms of action of epilepsy. Since the selected molecules are used as a potential antiepileptic agent, they were deemed suitable for molecular insertion studies. In addition, voltage-gated calcium channels, which play an important role in epilepsy, are emphasized. Voltage-gated calcium channels (CaV) act by providing the flow of Ca+ ions during the action potential that triggers seizure formation, and among the ten subtypes of voltage-gated calcium (CaV) channels, CaV3.1- CaV3.3, T-type or abnormal activities are associated with epilepsy, psychiatric form the associated low-voltage-activated subfamily. For this reason, the PDB ID: 6KZP receptor, which acts as an antagonist according to its activity on the channel in the formation of epileptic seizures, was chosen for the molecular insertion study. As a result of molecular placement studies; Oxcarbazepine and Phenytoin gave the best binding affinity for 6KZP with a value of -7.5 kcal/mol. Other results are in descending order (in kcal/mol); Tiagabine (-7.4), Mesuximide (-7.3), Primidone (-7.1), Remasemide (-7.0), Topiramate (-6.9) Mephenytoin (-6.7), Lomotrigine and Ethotoin (-6.4), Locosamide and Zonisamide (-6.1) , Felbamate (-6.0), Levetiracetam and Gabapentin (-5.4), Esuximide (-5.1), Valproic Acid (-4.9), Trimethadione (-4.7), Vigabatrin (-4.4) determined as.

Translating Nature to Nurture: Back to the Future for "New" Epilepsy Therapies.

An emerging strategy for finding new epilepsy therapies is focused on botanicals (as illustrated by recent attention to medical marijuana), given their centuries-old traditions of use in treatment of convulsive seizures, contemporary anecdotal reports of efficacy in persons with epilepsy, and identification of underlying mechanisms of action that are relevant to epilepsy. Hundreds of plant extracts have been found to block seizures in acute animal seizure models, with actions that include effects on GABA receptors and voltage-gated ion channels as well as anti-inflammatory and neuroprotective effects. While existing published clinical studies of botanicals and seizure control are generally of inadequate quality to determine safety and efficacy, recent developments at the FDA may encourage sponsors to develop and commercialize botanicals for epilepsy.

Les explorations neurophysiologiques chez l’enfant cérébrolésé : quand, comment ?

Neurophysiological tests complete clinical and radiological assessments in brain-injured children. Electroencephalogram (EEG) is clearly helpful to diagnose seizures and brain death while auditory evoked potentials (EP) to assess brainstem dysfunction and predict poor neurological outcome in post-anoxic coma. During the acute phase of severe traumatic brain injury (TBI) and bacterial meningitis, early recognition and treatment of convulsive seizures is essential. The incidence of non-convulsive seizures remains, however, high, varying between 7 and 48%. Although costly and time consuming, continuous EEG monitoring techniques may allow improving seizure detection. Therefore, amplitude integrated EEG techniques have been developed; however, they still require assessment in paediatrics. Some EEG patterns are indicative of a final bad outcome, including burst suppression, isoelectric pattern, and status epilepticus. EEG predictive value remains limited and less useful than somatosensory EP (SEP). SEP have excellent predictive value in post-anoxic coma in adults as well as in children (94 to 100%), especially in combination to pupillary reflexes and motor responses assessed after 48 h. In contrast, their predictive value of a good outcome is less reliable. In severe TBI and bacterial meningitis, this performance is also limited. Investigation of cognitive EP or mismatch negativity (MMN) could improve awakening prediction.

Clinical practice

An adequate early treatment of a long-lasting convulsive seizure is critical in reducing potential morbidity, and in particular, brain damage. In pre-hospital settings the use of benzodiazepines should become standard. Nowadays, rectal diazepam is used frequently, but midazoloam and lorazepam are becoming more popular, both being given either intranasally or orally. The buccal route is to be preferred because of its easy use and high efficacy. A generally accepted policy for early treatment of convulsive seizures is a crucial issue in the elaboration of an overall treatment plan for the child with epilepsy. Such a plan should include instruction and education of the parents and the caregivers surrounding the child.

Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report.

Five patients with clinical and EEG primary generalized or multifocal uncontrollable seizures underwent stereotaxic implantation of electrodes in both centromedian thalamic nuclei (CM). Each electrode consisted of a semiflexible array of three platinum-iridium wires, isolated except at their tips, which were separated by 4 mm. Bipolar, biphasic rectangular pulses were delivered in trains of 1 min every 5 min, alternating right and left side for sessions 2 h/day. Patients were followed for 3 months with charting of clinical seizures, daily 4-h EEG recordings from scalp and depth for 5 days and weekly thereafter. Baseline and 3-month evaluation of psychological performance through selected Beta R, Wechsler memory scale, visual discrimination, MMPI, and Zung's rated depression scale. Tests were evaluated for significant changes by the parametric student's t test and Mann Whitney nonparametric test. Clinical seizures were significantly reduced by electrical stimulation (ES), as were EEG interictal spikes and EEG slow waves. Psychological performance improved beyond that expected by reduction in seizure activity. ESCM induced a local afterdischarge (AD) that progressively developed in time and intensity, and the beneficial effects outlasted ES for periods of weeks to months, suggesting that a state of hyperexcitability of stimulated tissue, similar to "kindling," was created by chronic ES.

Treatment of Convulsive Seizures in Childhood With Special Reference to Epilepsy

Treatment of Convulsive Seizures in Childhood With Special Reference to Epilepsy