Faculty Bibliography

The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e. g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e. g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e. g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms

The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms

This study compared the potencies of epidurally delivered muscimol, lidocaine, midazolam, pentobarbital and gamma-aminobutyric acid (GABA) to prevent focal neocortical seizures induced by locally applied acetylcholine (Ach), in rats (n=5). An epidural cup was chronically implanted over the right somatosensory cortex in each animal, with epidural EEG electrodes placed posterior to the edge of the cup. After recovery, either artificial cerebrospinal fluid (ACSF; control solution) or one of the five drugs was delivered into epidural cup, followed by Ach administration into the cup to induce seizures. EEG seizure duration ratio was calculated for each drug delivery/seizure induction session to determine the potency of ACSF and the drugs to prevent the focal Ach-seizures. The concentration of all examined drug solutions was 1.0mM. ACSF, lidocaine, midazolam, pentobarbital and GABA all failed to prevent the Ach-induced neocortical EEG seizures, yielding EEG seizure duration ratios ranging from 0.41 to 0.80. In contrast, muscimol pretreatment fully prevented the development of ictal EEG in all animals. These results suggest that when used at low concentration muscimol was the best of the five drugs for transmeningeal pharmacotherapy trials for focal neocortical epilepsy

Intracranial pharmacotherapy is a novel strategy to treat drug refractory, localization-related epilepsies not amenable to resective surgery. The common feature of the method is the use of some type of antiepileptic drug (AED) delivery device placed inside the cranium to prevent or stop focal seizures. This distinguishes it from other nonconventional methods, such as intrathecal pharmacotherapy, electrical neurostimulation, gene therapy, cell transplantation, and local cooling. AED-delivery systems comprise drug releasing polymers and neuroprosthetic devices that can deliver AEDs into the brain via intraparenchymal, ventricular, or transmeningeal routes. One such device is the subdural Hybrid Neuroprosthesis (HNP), designed to deliver AEDs, such as muscimol, into the subdural/subarachnoid space overlaying neocortical epileptogenic zones, with electrophysiological feedback from the treated tissue. The idea of intracranial pharmacotherapy and HNP treatment for epilepsy originated from multiple sources, including the advent of implanted medical devices, safety data for intracranial electrodes and catheters, evidence for the seizure-controlling efficacy of intracerebral AEDs, and further understanding of the pathophysiology of focal epilepsy. Successful introduction of intracranial pharmacotherapy into clinical practice depends on how the intertwined scientific, engineering, clinical, neurosurgical and regulatory challenges will be met to produce an effective and commercially viable device.