Epileptogenic high-frequency oscillations skip the motor area in children with multilobar drug-resistant epilepsy.

OBJECTIVE: Subtotal hemispherectomy involves the resection of multiple lobes in children with drug-resistant epilepsy, skipping the motor area (MA). We determined epileptogenicity using the occurrence rate (OR) of high-frequency oscillations (HFOs) and the modulation index (MI), demonstrating strength of coupling between HFO and slow wave. We hypothesized that epileptogenicity increased over the multiple lobes but skipped the MA. METHODS: We analyzed 23 children (14 subtotal hemispherectomy; 9 multilobar resections). Scalp video-EEG and magnetoencephalography were performed before surgery. We analyzed the OR(HFO) and MI(5 phases=0.5-8 Hz) on electrodes of total area, resection areas, and MA. We compared the data between good [International League Against Epilepsy (ILAE) class I-II] and poor (III-VI) seizure outcome groups. RESULTS: ILAE class Ia outcome was achieved in 18 children. Among the MI(5 phases) in the resection areas, MI(3-4 Hz) was the highest. The OR(HFO) and MI(3-4 Hz) in both total area and resection areas were significantly higher in the good seizure outcome group than in the poor outcome group. The OR(HFO) and MI(3-4 Hz) in resection areas were significantly higher than in the MA. CONCLUSIONS: Our patients with multilobar drug-resistant epilepsy showed evidence of multifocal epileptogenicity that specifically skipped the MA. SIGNIFICANCE: This is the first study demonstrating that the electrophysiological phenotype of multifocal epilepsy specifically skips the MA using OR(HFO) and MI(3-4 Hz).

A novel methylthio metabolite of s-triazolo[3,4-a]phthalazine, a lead compound for the development of antianxiety drugs, in rats.

When s-triazolo[3,4-a]phthalazine (Tri-P) was orally administered in rats, a more lipophilic metabolite M-1 than the parent compound was isolated from the urine. The metabolite M-1 was identified as 7-methylthio Tri-P by means of high resolution MS and two-dimensional NMR spectrometry. Furthermore, the 7-methylthio conjugate was generated from the parent compound Tri-P in isolated rat hepatocytes. Although the contribution of the intestinal microflora to the formation of methylthio metabolite has been pointed out so far, the limited data in this study lead us to conclude that the liver plays a role in all metabolic reactions of Tri-P to its 7-methylthio conjugate in rats.

Side-chain metabolism of propranolol: involvement of monoamine oxidase and mitochondrial aldehyde dehydrogenase in the metabolism of N-desisopropylpropranolol to naphthoxylactic acid in rat liver.

We examined the metabolism of N-desisopropylpropranolol (NDP), which is generated from propranolol (PL) by side-chain N-desisopropylation, to naphthoxylactic acid (NLA) in rat liver. S(-)-NDP (S-NDP) and R(+)-NDP (R-NDP) were enantioselectively metabolized to NLA in isolated rat hepatocytes and in an enzyme reaction system of rat liver mitochondria with cofactor NAD+. Furthermore, the clearance profiles of NDP enantiomers were examined in an enzyme reaction system of rat liver mitochondria without NAD+. The amounts of S-NDP remaining in the incubation medium were similar to those of R-NDP, suggesting that monoamine oxidase (MAO) catalyzes the deamination of NDP to the aldehyde intermediate, but fails to deaminate enantioselectively S-NDP or R-NDP. Cyanamide, a potent inhibitor of aldehyde dehydrogenase (ALDH), markedly decreased the formation of NLA from racemic NDP in the enzyme reaction system of rat liver mitochondria with NAD+. When rat liver cytosol and microsomes were added to this enzyme reaction system, no significant alterations were observed in the amount of NLA generated from racemic NDP. We concluded that MAO deaminates NDP to an aldehyde intermediate, and that mitochondrial ALDH subsequently catalyzes the enantioselective metabolism of the aldehyde intermediate to NLA in rat liver.