Epilepsia
-
Randomized Controlled Trial
Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus.
Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). ⋯ Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.
-
Posttraumatic seizures develop in up to 20% of children following severe traumatic brain injury (TBI). Children ages 6-17 years with one or more risk factors for the development of posttraumatic epilepsy, including presence of intracranial hemorrhage, depressed skull fracture, penetrating injury, or occurrence of posttraumatic seizure were recruited into this phase II study. Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days, starting within 8 h postinjury. ⋯ This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at-risk traumatic brain injury population. Levetiracetam was safe and well tolerated in this population. This study sets the stage for implementation of a prospective study to prevent posttraumatic epilepsy in an at-risk population.
-
Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are electrographic seizures (ESz) that are not associated with overt clinical seizure activity. NCS are distinct ESz, whereas NCSE has ongoing, continuous electrographic seizure activity. Both are common in critically ill patients admitted to hospital intensive care units (ICUs), and studies have shown that about 20% of ICU patients undergoing continuous electroencephalography (cEEG) monitoring will have NCS/NCSE. ⋯ The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) Study will compare the efficacy and tolerability of fPHT and lacosamide in patients having NCS as noted by cEEG monitoring. The study is currently open to recruitment and has 13 sites in the United States. A total of 200 subjects will be randomized, 100 to each treatment arm.
-
A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. ⋯ The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
-
Review
Epilepsy therapy development: technical and methodologic issues in studies with animal models.
The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. ⋯ We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.