Seizure focus affects regional language networks assessed by fMRI.

OBJECTIVE: To investigate the degree of language dominance in patients with left and right hemisphere seizure foci compared to normal volunteers using a fMRI reading comprehension task. METHODS: Fifty patients with complex partial epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI (1.5 T) and neuropsychological testing. Participants silently named an object described by a sentence compared to a visual control. Data were analyzed with region of interest (ROI) analysis based on t maps for inferior frontal gyrus (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices (AIs) were calculated [(L - R)/(L + R)]; AI > 0.20 was deemed left dominant and AI < 0.20 as atypical language. RESULTS: Left hemisphere focus patients had a higher likelihood of atypical language than right hemisphere focus patients (21% vs 0%, chi2 < 0.002). Left hemisphere focus patients, excluding those with atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right hemisphere focus patients were all left language dominant and had a lower AI than controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between left hemisphere focus/left language patients and right hemisphere focus patients. Patients activated more voxels than healthy volunteers. Lower AIs were attributable to greater activation in right homologous regions. Less activation in the right-side WA correlated with better verbal memory performance in right focus/left hemisphere-dominant patients, whereas less strongly lateralized activation in IFG correlated better with Verbal IQ in left focus/left hemisphere-dominant patients. CONCLUSIONS: Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus.

Pharmacokinetic study of levetiracetam in children.

PURPOSE: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open-label, single-dose study. METHODS: Twenty-four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24-h pharmacokinetic evaluation. RESULTS: In children, the half-lives of levetiracetam and its metabolite ucb L057 were 6.0 +/- 1.1 and 8.1 +/-2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1-mg/kg dose were lower in children (Cmax, norm=1.33 plus minus 0.35 microg/ml; AUCnorm=12.4 +/- 3.5 microg/h/ml) than in adults (Cmax, norm=1.38 +/- 0.05 microg/ml; AUCnorm=11.48 +/- 0.63 microg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 +/- 0.36 ml/min/kg) was approximately 30-40% higher in children than in adults. Levetiracetam was generally well tolerated. CONCLUSIONS: On the basis of these data, a daily maintenance dose equivalent to 130-140% of the usual daily adult maintenance dosage (1,000-3,000 mg/day) in two divided doses, on a weight-normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.

Nonepileptic events in childhood.

The medical records of 27 children admitted to the MINCEP Epilepsy Program for evaluation of intractable epilepsy but later shown to have nonepileptic events by EEG with simultaneous video monitoring were reviewed. Four groups were identified: pure psychogenic events (5 patients), psychogenic events plus epileptic seizures (3 patients), pure nonepileptic physiologic events (5 patients), and nonepileptic physiologic events plus seizures (14 patients). Historical data, physical examinations, and neurodiagnostic evaluations (including previous EEGs, neuroradiologic evaluations, and neuropsychologic testing) were reviewed. Children in all groups, except for those with pure psychogenic seizures, had a history of multiple seizure types identified by parents or caretakers. A history of status epilepticus was obtained in 64% (of 22 patients), including 11 of 14 patients with physiologic events plus seizures. Abnormal findings on neurologic examination were common, especially in children with nonepileptic physiologic events. All but two patients had a history of interictal epileptiform abnormalities on previous routine EEGs. Based on identification of nonepileptic events, antiepileptic drugs (AEDs) were discontinued completely in eight patients (30%) and the total number of AEDs was reduced in nine others (33%). A diagnosis of nonepileptic events should be considered in all children with refractory seizures or multiple seizure types. Abnormal findings on routine (interictal) EEG may actually confound the diagnosis. Intensive neurodiagnostic EEG-video recording is the preferred method for distinguishing nonepileptic from epileptic seizures.

Adjunctive therapy for intractable epilepsy with ethotoin.

In a retrospective study, records of 46 patients (24 women and 22 men aged 17-51 years; mean 29.2 years), who had been treated with ethotoin (EHN) as adjunctive therapy for control of intractable seizures were reviewed. Overall, approximately 51% of this highly selected patient population had a reduction greater than 50% in overall seizure frequency 1 month after initiation of treatment. This was reduced to approximately 25% for the last 3 months of follow-up (mean follow-up period 10.6 months). Tonic seizure frequency was reduced most dramatically, by greater than 50%, in 60% of patients at 1 month and in 35% of patients for the last 3 months of follow-up. This study suggests that prospective controlled trials of EHN, especially for tonic seizures, are needed.

Studies on sex pheromone of American cockroach, with emphasis on structure elucidation of periplanone-A.

Two independently biologically active compounds, periplanone A and periplanone B can be isolated from fecal material of the American cockroach,Periplaneta americana. In fecal material these occur in a ratio of 1 ∶ 10 while, in intestinal tracts only periplanone B has been found. The latter has been identified as (1Z,5E)-1,10(14)-diepoxy-4(15),5-germacradien-9-one; the identification was confirmed by synthesis. Only the CD (-) enantiomer (1R,2R,5E,7S,10R) exhibited activity. The lower threshold of activity of both natural and synthetic CD (-) pheromone, is 10(-6)-10(-7) µg. Periplanone A has been identified (apart from its stereochemical configuration) as 7-methylene-4-isopropyl-12-oxa-tricyclo[4.4.2.0(1,5)]-9-dodecen-2-one). The structure of this rather unstable compound could be deduced by comparing its NMR, UV, IR, and mass spectra with the NMR and mass spectra of its rearrangement product. Both structures still require confirmation by synthesis, but their spectral data are in complete agreement with the proposed structures. The presence of only periplanone B in the gut and the presence of both periplanone A and periplanone B in the feces suggests that periplanone B is a genuine sex pheromone, whereas peri-planone A might be a biologically active transformation product, which in turn can isomerize into a more stable, but inactive compound.

Reproductive isolation of two tortricid moth species by different ratios of a two-component sex attractant.

Two tortricid mitoth species, Adoxophyes orana and Clepsis spectrana, utilize the samne two isomers, cis-9- and cis-l1-tetradecenyl acetate, as their sex attractant. Commnlunication between the sexes of each species is separated effectively by a different blendinig of both compounds by the females and a different response to these blends by the males.

Sex Pheromones of Summer Fruit Tortrix Moth Adoxophyes orana: Two Synergistic Isomers.

Both cis-9-and cis-11-tetradecenyl acetate were isolated from 2500 virgin females of the summer fruit tortrix moth Adoxophyes orana (F.v.R.) by gel permeation, column chromatography on silica gel, and gas chromatography. Their chemical, physical, and biological properties were identical to those of the synthetic compounds. In contrast to the single compounds, mixtures of these pheromones were highly active in laboratory and field tests. Catches, in traps, with the pheromone mixture were comparable to those obtained when live females were used as bait. This is the first example of a member of the lepidoptera in which the presence of two isomers is an absolute requirement for activity in laboratory and in field experiments.