PLATFORM SESSION 89

Pharmacokinetics

Clinical Effects and Blood Concentration of Ethyl Lofurazepate in Epilepsy. Takateru Ishitsu (National Saisyunsou Hospital, Kuma- moto, Japan).

We evaluated the effects of ethyl lofurazepate on epilepsy. We studied 57 patients with epilepsy who had not responded to valproate, carbamazepine, or clonazepam. Ethyl lofurazepate was effective in eight patients including six with primarily myoclonic seizures. Blood concentration of ethyl lofurazepate was determined a total of 40 times in 20 patients. Blood concentration was expressed as nanograms per milliliter and the dose as milligrams per kilogram. There was a relation between dose and blood con- centration in all patients: y = 1,560~ k 79; cor- relation coefficient, 0.58. In the responders, the

mean dose was 0.14 t 0.05 mg/kg, and the blood concentration was 396 k 207 ng/ml. In the same patients, blood concentration increased nearly linearly with dose. In four patients who underwent multiple measurements, the correlation coeffi- cient for the blood concentration was ~ 0 . 8 . In the responders, the blood concentration!dose ratio ranged from 1,086 to 4,183, showing marked individ- ual differences.

Ethyl lofurazepate had some effects in patients who did not respond to other antiepileptic drugs and may be worth trying in such patients.

Surgery

Pathoetiology and Seizure Outcome After Surgical Treatment of In- tractable Temporal Lobe Epilepsy. Takayasu Tottori, Tadahiro Mihara, Kazumi Matsuda, Toshiaki Ohtsubo, Yushi Inoue, Tateki Fujiwara, Kazuichi Yagi, and Masakazu Seino (National Epilepsy Center, Shizuoka Higashi Hospital, Shizuoka, Japan).

To clarify correlation between pathoetiology and seizure outcome after surgical treatment of intracta- ble temporal lobe epilepsy (TLE), we studied 132 patients who underwent either temporal lobe resec- tion or selective amygdalohippocampectomy for sei- zure control at the National Epilepsy Center, Shizu- oka, whose postsurgical course was followed-up for >2 years. To confirm the epileptogenic zone, 105 of these patients underwent long-term intracranial EEG monitoring and functional mapping by using intracranial and subdural electrodes before surgery.

Studied were 75 male and 57 female patients age 9-50 years (mean, 26 years). Age at epilepsy onset was from 0 to 45 years (mean, 12 years), and duration of epilepsy from 2 to 33 years (mean, 12 years). We obtained details of presumed causative disorders and precise onset age through interviews with the patients’ families. Seizure outcome after surgery was classified according to Engel’s criteria. In this study, we classified the subtype of TLE of each patient depending on the results of intracranial EEG

recordings and their correlation with clinical mani- festations.

Twenty-nine (22%) patients had a history of con- vulsive status epilepticus (convulsions lasting >30 min). Twenty-six of the 29 patients had initial con- vulsive status epilepticus. Age at the convulsive sta- tus ranged from 0 to 3 years in 27 patients, to 6 years in one patient, and 12 years in one. Fifteen (11%) patients had encephalitis or head trauma. Of 70 pa- tients having no presumed cause, 54 (41%) showed computed tomography (CT)/magnetic resonance im- aging (MRI) lesions.

After surgery, 104 (79%) patients were in class 1 (seizure free), 10 (8%) patients in class 11, eight (6%) patients in class 111, and 10 (8%) patients in class IV.

Twenty-six (90%) of 29 patients having convulsive status epilepticus and 43 (80%) of 54 patients having CT/MRI lesions were in class I, whereas eight (53%) of 15 patients having encephalitis or head trauma were in class I.

Mean age at onset was significantly lower for pa-

90 PLATFORM SESSION

tients having convulsive status epilepticus (8.9 2 4.7 years) as compared with patients having CT/ MRI lesions (13.9 ? 8.8 years).

We also studied pathoetiology and subtypes of TLE in a separate group of 105 patients who under- went long-term intracranial recording before resec- tion. Seventy-four patients were classified with me- sial temporal epilepsy (MTE). Of these 74,24 (32%) patients were classified with convulsive status epi- lepticus, and three (4%) had CT/MRI lesions. Thirty- one were classified with lateral temporal epilepsy (LTE). Of these 31, one (3%) with convulsive status

epilepticus and 22 (70%) with CT/MRI lesion had LTE .

Patients having convulsive status epilepticus in infancy or childhood were prone to develop MTE, and the majority had an initial epileptic seizure of TLE by age 15 years. Considering the excellent sei- zure outcome after surgery in this type of patient, if their epilepsy is confirmed to be intractable, earlier surgical intervention should be recommended. Most of the patients having CT/MRI lesions showed good seizure outcome after surgery; therefore surgery in an early stage should be recommended.

A New Surgical Method for the Treatment of Hemispheric Dysplastic Lesions. H. Shimizu, T. Maehara, and *N. Arai (Department of Neurosurgery , Tokyo Metropolitan Neurological Hospital, and "De- partment of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan).

Various types of modified hemispherectomy have been developed to prevent superficial cerebral hem- osiderosis by preserving the cerebral tissue as much as possible while pursuing the maximum disruption of the nerve connections. However, another prob- lem that cannot be ignored, intraoperative bleeding, remains to be completely resolved, especially in in- fantile patients who are often emaciated by intracta- ble seizures, or hemimegalencephalic children in whom anomalous blood circulation may cause tor- rential bleeding during resection. We developed a new method of hemispherectomy in which only neu- ronal fibers are disconnected, and all of the hemi- spheric mass is preserved. This innovative proce- dure can prevent both superficial cerebral hemosid- erosis and intraoperative massive bleeding.

The intracranial procedures can be divided roughly into five steps: (a) total corpus callosotomy, (b) disruption of the temporal stem and mesial limbic fibers, (c) unroofing of the lateral ventricle, (d) dis- connection of the frontal pole, and (e) disruption of the internal capsule by undercutting of the insula. First, through the frontal interhemispheric fissure, total corpus callosotomy is performed as one stage. Then the cortical incision is made in the superior temporal gyrus, and the white matter is tunneled to the inferior ventricle. The anterior portion of the mesial temporal structures is emptied by aspirating

the amygdala, hippocampal head, and uncus. By connecting the cortical surface and the ventricle, the inferior horn is unroofed posterior to the trigonum, and the tail of the hippocampus and the fornix are severed at this point. The procedure of the ventricu- lar unroofing is continued through the trigonum to the anterior tip of the lateral ventricle. To disrupt the horizontal fibers originating in the frontal pole, the brain is vertically transected at the level of the sphenoid ridge. Finally, the resection is started at the upper margin of the lateral wall and directed toward the center of the middle fossa. By this dissec- tion through the brain parenchyma, the internal cap- sule and fibers arising from the insula are completely disconnected.

In the last 2.5 years, five patients (two boys and three girls; ranging, age 1-8 years) have undergone this fiber-disruptive hemispherectomy . The etiology of their seizures was hemimegalencephaly in three and unilateral diffuse cortical dysplasia in two cases. We encountered no mortality or morbidity during or after surgery. Postoperative sequential magnetic resonance imaging (MRI) indicated the viability of the disconnected hemispheres in all the cases. Al- though the follow-up periods are too short (mean, 16 months), seizures ceased in four cases and have been rare in the other case. Compared with hitherto developed modified hemispherectomy procedures,

Epikppsiu, V d . 37, Suppl . 3 , 1996