Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency

Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate, glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine, homocarnosine, and arginine) as compared to age-matched littermates both before, and following, the period of generalized convulsive seizures and status epilepticus. Our results reveal imbalanced amino acid levels potentially involved in the transition from absence seizures to generalized convulsive seizures resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a unique epileptic model with the potential to reveal novel aspects of excitatory/inhibitory interactions in the genesis of seizures.     

Taking charge of epilepsy: the development of a structured psychoeducational group intervention for adolescents with epilepsy and their parents

Children and adolescents with epilepsy frequently experience poor psychosocial outcomes due to numerous factors such as perceived stigma, behavior problems, academic difficulties, and depression. Health psychology research has documented the effectiveness of psychoeducational interventions aimed at improving psychosocial outcomes for individuals with a variety of health conditions. With increasing numbers of adolescents living with epilepsy, interest in improving the quality of life for this particular population has grown. There remains, however, a paucity of research concerning psychosocial interventions for adolescents with epilepsy. The present study outlines the development and initial implementation of a 6-week structured psychoeducational group intervention for adolescents with epilepsy and their parents. Preintervention, the QOLIE-AD-48, Childhood Depression Inventory, and Revised Children's Manifest Anxiety Scale were administered. Educational topics included medical aspects of epilepsy, healthy lifestyle behaviors, family and peer relationships, understanding self-image and self-esteem, and stress management techniques. Participants were introduced to a variety of cognitive-behavioral strategies, and were encouraged to share their own experiences with epilepsy. Feedback from adolescent and parent participants indicated that the intervention was relevant to their needs, helped them better understand their epilepsy, and allowed an opportunity for positive peer support. Also, postintervention outcome measurement indicated an overall positive trend for quality of life improvement in the adolescents.     

Spatiotemporal patterns of oscillatory brain activity during auditory word recognition in children: a synthetic aperture magnetometry study.

OBJECTIVE: We studied the task-induced spatiotemporal evolution and characteristics of cortical neural oscillations in children during an auditory word recognition task. METHODS: We presented abstract nouns binaurally and recorded the MEG response in eight healthy right-handed children (6-12 years). We calculated the event-related changes in cortical oscillations using a beamformer spatial filter analysis technique (SAM), then transformed each subject's statistical maps into standard space and used these to make group statistical inferences. RESULTS: Across subjects, the cortical response to words could be divided into at least two phases: an initial event-related synchronization in both the right temporal (100-300 ms, 15-25 Hz; 200-400 ms, 5-15 Hz) and left frontal regions (200-400 ms; 15-25 Hz); followed by a strong left-lateralized event-related desynchronization in the left temporal region (500-700 ms; 5-15 Hz). CONCLUSIONS: We found bilateral event-related synchronization followed by later left lateralized event-related desynchronization in language-related cortical areas. These data demonstrate the spatiotemporal time course of neural activation during an auditory word recognition task in a group of children. As well, this demonstrates the utility of SAM analyses to detect subtle sequential task-related neural activations.     

Plasma leptin concentrations in lean and obese human subjects and Prader-Willi syndrome: comparison of RIA and ELISA methods.

Immunoassays for circulating leptin are important research tools for examining the role and regulation of leptin expression in human obesity. However, uncertainty exists regarding the comparability between studies of reported plasma or serum leptin concentrations. The purpose of the present study was to directly compare plasma leptin concentrations by using two of the most widely reported immunoassay methods-namely, a commercially available radioimmunoassay (RIA) and a proprietary enzyme-linked immunosorbent assay (ELISA). Plasma leptin concentrations were measured in healthy lean and obese volunteers and in patients with Prader-Willi syndrome (PWS). Over a wide range of plasma concentrations (2 to 70 ng/mL), leptin measurements obtained with the RIA and ELISA methods were highly correlated (r = 0.957, P<.0001) and were essentially indistinguishable. Leptin levels measured by RIA and ELISA were highly correlated with body mass index (BMI) overall (r = 0.784, P<.0001 and r = 0.732, P<.0001, respectively) and in the lean and obese subgroups. When compared with the results in the lean individuals (mean +/- SEM, 11.6+/-3.2 ng/mL), plasma leptin was significantly higher in both the obese (35.5+/-4.0 ng/mL, P<.0001) and the PWS subjects (30.7+/-6.9 ng/mL, P<.05). However, after we controlled for differences in BMI, the leptin levels were similar in all three groups. In conclusion, we found that the RIA and ELISA used in the present study yield plasma leptin concentrations that are essentially indistinguishable. Our findings should facilitate comparisons of leptin levels measured by these two widely used immunoassays in previous and future studies that examine the role of leptin in body weight regulation.     

Prediction of lactate threshold (LT) and fixed blood lactate concentrations (FBLC) from 3200-m running performance in women

The present study evaluated the accuracy of predicting velocity and oxygen consumption (VO2) at the LT lactate threshold and FBLC fixed blood lactate concentrations from a 3200-m time trial in women. Forty-four women (mean age = 31.1 yrs, mean ht = 164.9 cm, mean wt = 65.0 kg) completed a treadmill protocol for the determination of LT and FBLC and a 3200-m time trial. Velocity and VO2 values at LT, FBLC of 2.0 2.5, and 4.0 mM, and peak were determined. Mean VO2 and velocity ranged from 27.8 +/- 10.8 ml/kg.min-1 at LT to 42.5 ml/kg.min-1 at peak and from 129.8 +/- 44.0 m.min-1 at LT to 187.0 +/- 52.4 m.min-1 at peak, respectively. Results indicated that a 3200-m time trial (mean time = 20.6 +/- 6.6 min) was a good predictor of VO2 and velocity at LT, FBLC, and peak. Correlation coefficients (using a quadratic model) for velocity ranged from R = 0.96 to R = 0.98 with SEE ranging from 9.0 to 13.1 m.min-1. Correlation coefficients for VO2 ranged from R = 0.94 to R = 0.96 with SEE ranging from 2.8 to 3.6 ml/kg.min. The validity of these regression equations was examined in 13 women who completed a 12-month running program (VO2 LT, VO2 at FBLC of 2.0, 2.5 and 4.0 mM, and VO2 peak increased by 34.7, 19.9, 16.9, 11.9, and 5.4%, respectively, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatosensory-evoked fields on magnetoencephalography for epilepsy infants younger than 4 years with total intravenous anesthesia.

OBJECTIVE: Patients must remain immobile for magnetoencephalography (MEG) and MRI recordings to allow precise localization of brain function for pre-surgical functional mapping. In young children with epilepsy, this is accomplished with recordings during sleep or with anesthesia. This paper demonstrates that MEG can detect, characterize and localize somatosensory-evoked fields (SEF) in infants younger than 4 years of age with or without total intravenous anesthesia (TIVA). METHODS: We investigated the latency, amplitude, residual error (RE) and location of the N20m of the SEF in 26 infants (mean age=2.6 years). Seventeen patients underwent TIVA and 9 patients were tested while asleep, without TIVA. RESULTS: MEG detected 44 reliable SEFs (77%) in 52 median nerve stimulations. We found 27 reliable SEFs (79%) with TIVA and 13 reliable SEFs (72%) without TIVA. TIVA effects included longer latencies (p<0.001) and lower RE (p<0.05) compared to those without TIVA. Older patients and larger head circumferences also showed significantly shorter latencies (p<0.01). CONCLUSIONS: TIVA resulted in reliable SEFs with lower RE and longer latencies. SIGNIFICANCE: MEG can detect reliable SEFs in infants younger than 4 years old. When infants require TIVA for MEG and MRI acquisition, SEFs can still be reliably observed.     

Zinc inhibition of gamma-aminobutyric acid(A) receptor function is decreased in the cerebral cortex during pilocarpine-induced status epilepticus.

Functional modulation of gamma-aminobutyric acid(A) (GABA(A)) receptors by Zn(2+), pentobarbital, neuroactive steroid alphaxalone, and flunitrazepam was studied in the cerebral cortex and cerebellum of rats undergoing status epilepticus induced by pilocarpine. Under control conditions, Zn(2+) dose-dependently inhibited muscimol-stimulated uptake of (36)Cl(-) in cortical and cerebellar membranes. However, Zn(2+) inhibition of stimulated (36)Cl(-) uptake was selectively decreased in the cortex (but not in the cerebellum) 1 to 2 h after the onset of status epilepticus. This loss of Zn(2+) response in the cortex appeared to be selective to Zn(2+) only, because pentobarbital-, alphaxalone-, or flunitrazepam enhancement of muscimol-stimulated (36)Cl(-) uptake did not change in this brain region either at 1 or 2 h after seizures. Because this loss of Zn(2+) response in the cortex was apparent only about 1 h after the onset of status epilepticus but not earlier, we tested whether status epilepticus was critical for the development of the loss of Zn(2+) response. We found that, in rats where status epilepticus was terminated by diazepam within 30 min after seizure onset, Zn(2+) response was preserved in the cortex. These findings suggest that continuous seizures of pilocarpine-induced status epilepticus caused a rapid and selective decrease in Zn(2+) inhibition of GABA(A) receptor function in the cortex. The possible relevance of such rapid seizure-induced GABA(A) receptor plasticity in the cerebral cortex is discussed.