Magnetic source imaging guidance of gamma knife radiosurgery for the treatment of epilepsy.

OBJECT: The purpose of this study was to determine if magnetic source (MS) imaging could provide useful information in the planning and performance of gamma knife radiosurgery (GKS) for epilepsy. METHODS: Magnetic source imaging of interictal epileptiform dipoles was studied in 53 epilepsy surgery candidates. All patients underwent volumetric magnetic resonance (MR) imaging. Subsequently, magnetoencephalography (MEG) was performed using single or dual 37-channel units. The MR images and MEG recordings were then coregistered to produce the MS imaging data. Magnetic source imaging epileptiform data were reviewed in a blinded fashion and spatial distributions were classified as focal, regional, multiple, scattered, or none. Postresection operative photographs were compared with MS image results to determine whether extensive or partial/no resection of the MS image focus had been accomplished. Magnetoencephalography dipoles were identified in 47 patients (89%), in 46 of whom the lesions were resected. This included 20 (80%) of 25 anterior temporal lobe (ATL) cases, and 26 (93%) of 28 extratemporal lobe (ETL) cases. Of the six patients who underwent extensive ATL resections, three (50%) were seizure free. Of 14 patients who underwent partial/no resection of the ATL, seven (50%) were seizure free. There was no clear relation between MS image spatial distribution and surgery-related outcome. Of the seven ATL cases with hippocampal atrophy, five patients (71%) were seizure free. Of 12 ETL cases (three lesional), 10 patients (83%) were seizure free. Of 14 patients who underwent partial/no ETL resections (three lesional), two (14%) were seizure free. Of five nonlesional ETL cases with focal MS image dipoles, four patients (80%) were seizure free. Of five nonlesional ETL cases with regional dipoles, three patients (60%) were seizure free. Of eight ETL cases with multiple MS image dipoles, two patients (25%) were seizure free. Spatial agreement of MS imaging and electrographic data had no apparent effect on outcome of either ATL or ETL cases. CONCLUSIONS: Nonlesional ETL cases with focal (and in some cases multiple or regional) epileptiform MS image dipole distributions benefit significantly from inclusion of the MS image epileptiform focus in the resections. Nonlesional ETL cases suitable for GKS may similarly benefit from including the MS image focus in the irradiated area.

A 13-year experience with epilepsy surgery.

Between 1985 and 1997, 563 therapeutic craniotomies were performed: 311 anterior temporal (ATL) and 158 extramesial temporal (XMT) resections, 67 callosotomies, 20 hemispherectomies and 7 multiple subpial transections. Sixty-seven percent of nonlesional ATL cases were seizure free (SF), and 76% of nonlesional ATL cases < or =18 years old were SF. Seventy-eight percent of lesional ATL cases with complete resection were SF. Seventy-three percent of lesional cases < or =18 were SF. Thirty-seven percent of nonlesional XMT cases were SF. Seventy percent of XMT lesional cases with complete resection were SF, and 82% of lesional XMT cases < or =18 were SF. Of the anterior callosotomy cases, there was a > or =90% decrease in generalized tonic-clonic seizures in 50% of patients, and in tonic seizures, drop attacks, absence and myoclonic seizures in approximately 60-70% of patients. Of 20 hemispherectomies, 65% were SF. Of 7 multiple subpial transections, 29% were SF.

Peptidomimetic aminomethylene ketone inhibitors of interleukin-1 beta-converting enzyme (ICE).

Pyridone-based peptidomimetic inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with an aminomethylene ketone activating group in the P1' position are described. Several analogues with sub-nanomolar Ki's versus ICE and improved aqueous solubility are reported.

Cerebrospinal fluid from morphine-dependent rats precipitates opiate abstinence syndrome.

Cerebrospinal fluid (CSF) was withdrawn from opiate-dependent rats following six hours of abstinence. It was infused into the third ventricle of opiate-dependent rats, precipitating immediate abstinence signs. The effect was similar to that of infusing the opiate antagonist naloxone, suggesting that opiate-dependent organisms may secrete an endogenous opiate antagonist substance. CSF withdrawn from non-dependent rats failed to precipitate an abstinence syndrome in morphine-dependent recipients. Conversely, CSF withdrawn from opiate-dependent rats following six hours of abstinence failed to precipitate an abstinence syndrome in non-dependent recipients. The active factor in the CSF is probably a peptide since it is filterable through a 10,000 MW filter and its activity is destroyed by three different proteolytic enzymes.