Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases.
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Nocturnal frontal lobe epilepsy (NFLE) has been delineated as a distinct syndrome in the heterogeneous group of paroxysmal sleep-related disturbances. The variable duration and intensity of the seizures distinguish three non-rapid eye movement-related subtypes: paroxysmal arousals, characterized by brief and sudden recurrent motor paroxysmal behaviour; nocturnal paroxysmal dystonia, motor attacks with complex dystonic-dyskinetic features; and episodic nocturnal wanderings, stereotyped, agitated somnambulism. We review the clinical and polysomnographic data related to 100 consecutive cases of NFLE in order to define the clinical and neurophysiological characteristics of the different seizure types that constitute NFLE. NFLE seizures predominate in males (7:3). Age at onset of the nocturnal seizures varies, but centres during infancy and adolescence. A familial recurrence of the epileptic attacks is found in 25% of the cases, while 39% of the patients present a family history of nocturnal paroxysmal episodes that fit the diagnostic criteria for parasomnias. A minority of cases (13%) have personal antecedents (such as birth anoxia, febrile convulsions) or brain CT or MRI abnormalities (14%). In many patients, ictal (44%) and interictal (51%) EEGs are uninformative. Marked autonomic activation is a common finding during the seizures. NFLE does not show a tendency to spontaneous remission. Carbamazepine completely abolishes the seizures in approximately 20% of the cases and gives remarkable relief (reduction of the seizures by at least 50%) in another 48%. VideoEEG recordings confirm that NFLE comprises a spectrum of distinct phenomena, different in intensity but representing a continuum of the same epileptic condition. We believe that the detailed clinical and videoEEG characterization of patients with NFLE represents the first step towards a better understanding of the pathogenic mechanisms and different clinical outcomes of the various seizure types that constitute the syndrome. (+info)
Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug.
(10/1232)
Studies with knockout mice lacking mdr1a P-glycoprotein (P-gp) have previously shown that blood-brain barrier P-gp is important in preventing the accumulation of several drugs in the brain. Asimadoline (EMD 61753) is a peripherally selective kappa-opioid receptor agonist which is under development as a therapeutic analgaesic. From the structural characteristics of this drug and its peripheral selectivity, we hypothesized that it is transported by P-gp. Using a pig-kidney polarized epithelial cell line transfected with mdr cDNAs, we demonstrate that asimadoline is transported by the mouse mdr1a P-gp and the human MDR1 P-gp. Furthermore, we show that in mdr1a/1b double knockout mice, the absence of P-gp leads to a 9 fold increased accumulation of asimadoline in the brain. In line with this accumulation difference, mdr1a/1b (-/-) mice are at least 8 fold more sensitive to the sedative effect of asimadoline than wild-type mice. Interestingly, the oral uptake of asimadoline was not substantially altered in mdr1a/1b (-/-) mice. Our results demonstrate that for some drugs, P-gp in the blood-brain barrier can have a therapeutically beneficial effect by limiting brain penetration, whereas at the same time intestinal P-gp is not a significant impediment to oral uptake of the drug. (+info)
Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig.
(11/1232)
Development of drug treatments for obstructive sleep-disordered breathing has been impeded by the lack of animal models. The obese pig may be a suitable animal model, as it has been reported to experience sleep-disordered breathing resembling human obstructive sleep apnea. The purpose of this paper is to describe in detail techniques for chronic instrumentation of the obese Vietnamese pot-bellied pig and to study respiratory function during sleep. Under general anesthesia, four obese pigs were instrumented for long-term recording of intrapleural and tracheal pressures, genioglossal EMG, and bioelectric signals related to sleep. A custom-fitted face mask was used to record respiratory variables including airflow, snoring, and expired CO(2). Most chronic instrumentation provided robust signals for up to 6 wk after installation. All pigs displayed sleep-disordered breathing characterized by increased resistance to airflow, snoring, inspiratory flow limitation, and possible sleep disruption. Apneas and hypopneas were not a feature of breathing during sleep in these animals. Nonetheless, this animal preparation may be useful for exploring possible drug treatments for obstructive sleep-disordered breathing. (+info)
Toxicity of major histocompatibility complex class II specific monoclonal antibodies: audietur et altera pars.
(12/1232)
AIM: To investigate whether in vivo toxicity of class II major histocompatibility complex (MHC) specific monoclonal antibodies (mAb) is contributed by mAb's constant region binding to Fc receptor (FcR). METHODS: Laboratory mice were injected intravenously (i.v.) with class II MHC-specific mAb of various isotypes and respective antigen-binding fragments, and their clinical status was observed subsequently. RESULTS: All anti-class II mAb of the IgG2a isotype exhibit acute toxicity, manifested in severe lethargy and a frequent death. No adverse effects were observed after the FcR-binding capability of the toxic mAb was eliminated via deletion or mutation of its Fc segment. CONCLUSION: In vivo toxicity of anti-class II mAb appears to be the consequence of the crosslinking of class II+ cells with cells expressing FcR. (+info)
Effects of prior fluoxetine treatment on EEG sleep in women with recurrent depression.
(13/1232)
We examined whether fluoxetine treatment has persistent effects on electroencephalographic sleep after drug discontinuation in patients with recurrent major depression. Age-matched groups of 23 women were treated with interpersonal psychotherapy alone (IPT) or fluoxetine plus interpersonal psychotherapy (IPT + FLU). Sleep studies were conducted when patients were depressed, and again at remission, at least four weeks after fluoxetine discontinuation. The groups did not differ in depression ratings pre- to post-treatment. Significant group*time interaction effects were noted for REM sleep (p = .04) and slow wave sleep (p = .02). REM percentage and phasic REM activity increased in the IPT + FLU group but decreased in the IPT group. The effects of fluoxetine treatment on electroencephalographic sleep can be observed for at least four weeks after drug discontinuation and appear to represent both drug discontinuation and neuroadaptation effects. (+info)
Ventilatory instability during sleep onset in individuals with high peripheral chemosensitivity.
(14/1232)
Previous work has shown that the magnitude of state-related ventilatory fluctuations is amplified over the sleep-onset period and that this amplification is partly due to peripheral chemoreceptor activity, because it is reduced by hyperoxia (J. Dunai, M. Wilkinson, and J. Trinder. J. Appl. Physiol. 81: 2235-2243, 1996). These data also indicated considerable intersubject variability in the magnitude of amplification. A possible source of this variability is individual differences in peripheral chemoreceptor drive (PCD). We tested this hypothesis by measuring state-related ventilatory fluctuations throughout sleep onset under normoxic and hyperoxic conditions in subjects with high and low PCD. Results demonstrated that high-PCD subjects experienced significantly greater amplification of state-related ventilatory fluctuations than did low-PCD subjects. In addition, hyperoxia significantly reduced the amplification effect in high-PCD subjects but had little effect in low-PCD subjects. These results indicate that individuals with high PCD are likely to experience greater sleep-related ventilatory instability and suggest that peripheral chemoreceptor activity can contribute to sleep-disordered breathing. (+info)
Serotonin-2 receptors and human sleep: effect of a selective antagonist on EEG power spectra.
(15/1232)
To investigate the effect on the sleep EEG, a 1-mg oral dose of SR 46349B, a novel 5-HT2 antagonist, was administered three hours before bedtime. The drug enhanced slow wave sleep (SWS) and reduced stage 2 without affecting subjective sleep quality. In nonREM sleep (NREMS) EEG slow-wave activity (SWA; power within 0.75-4.5 Hz) was increased and spindle frequency activity (SFA; power within 12.25-15 Hz) was decreased. The relative NREMS power spectrum showed a bimodal pattern with the main peak at 1.5 Hz and a secondary peak at 6 Hz. A regional analysis based on bipolar derivations along the antero-posterior axis revealed significant 'treatment' x 'derivation' interactions within the 9-16 Hz range. In enhancing SWA and attenuating SFA, the 5-HT2 receptor antagonist mimicked the effect of sleep deprivation, whereas the pattern of the NREMS spectrum differed. (+info)
Comparison study of combined DTPw-HB vaccines and separate administration of DTPw and HB vaccines in Thai children.
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The safety, immunogenicity and tolerability of two different DTPw-HBV combination vaccines, containing 5 and 10 microg of HBsAg; were investigated in comparison with separate administration of DTPw and HBV (10 microg of HBsAg). A three dose primary vaccination course at 2, 4 and 6 months of age was followed by a booster dose at 18 months. All vaccines were safe and well tolerated. The DTPw-HBV combination vaccine containing 10 microg of HBsAg elicited significantly higher anti-HBs titres than the other two vaccines after the primary and booster vaccination course. All vaccines elicited a high response against the other components. Based on these results, DTPw-HBV (10 microg HBsAg) was the most effective vaccine at this schedule. (+info)