Differential expression of alpha1, alpha2, alpha3, and alpha5 GABAA receptor subunits in seizure-prone and seizure-resistant rat models of temporal lobe epilepsy.
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Temporal lobe epilepsy remains one of the most widespread seizure disorders in man, the etiology of which is controversial. Using new rat models of temporal lobe epilepsy that are either prone or resistant to develop complex partial seizures, we provide evidence that this seizure susceptibility may arise from arrested development of the GABAA receptor system. In seizure-prone (Fast kindling) and seizure-resistant (Slow kindling) rat models, both the mRNA and protein levels of the major alpha subunit expressed in adult brain (alpha1), as well as those highly expressed during development (alpha2, alpha3, and alpha5), were differentially expressed in both models compared with normal controls. We found that alpha1 subunit mRNA expression in the Fast kindling strain was approximately half the abundance of control rats, whereas in the Slow kindling strain, it was approximately 70% greater than that of controls. However, Fast rats overexpressed the alpha2, alpha3, and alpha5 ("embryonic") subunits, having a density 50-70% greater than controls depending on brain area, whereas the converse was true of Slow rats. Using subunit-specific antibodies to alpha1 and alpha5 subunits, quantitative immunoblots and immunocytochemistry revealed a concordance with the mRNA levels. alpha1 protein expression was approximately 50% less than controls in the Fast strain, whereas it was 200% greater in the Slow strain. In contrast, alpha5 subunit protein expression was greater in the Fast strain than either the control or Slow strain. These data suggest that a major predispositional factor in the development of temporal lobe epilepsy could be a failure to complete the normal switch from the GABAA receptor alpha subunits highly expressed during development (alpha2, alpha3, and alpha5) to those highly expressed in adulthood (alpha1). (+info)
Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of fluoroquinolones in rats.
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The in vivo convulsant activities in rats of five representative fluoroquinolones (FQs), norfloxacin, enoxacin, sparfloxacin, fleroxacin, and pefloxacin, were compared. The experimental approach allowed distinction between the drugs' ability to reach the pharmacological receptors at the level of the central nervous system (pharmacokinetic contribution) and their ability to interact with these receptors (pharmacodynamic contribution). The presence of a methyl group on the piperazine moiety decreased the pharmacodynamic contribution to the convulsant activity by severalfold, and the ratios of concentrations of the FQs in cerebrospinal fluid (CSF) to concentrations of unbound FQs in plasma varied from about 5 to 75% as a function of lipophilicity. Interestingly, FQs with the highest intrinsic convulsant activities had the lowest levels of diffusion in CSF and vice versa. This in vivo approach provides information complementary to that of in vitro experiments and should be recommended for early preclinical assessment of a new FQ's epileptogenic risk. (+info)
Hyponatraemic convulsion secondary to desmopressin treatment for primary enuresis.
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The case of a 6 year old child who presented with convulsions and coma after unsupervised self administration of intranasal desmopressin (DDAVP) for nocturnal enuresis is presented. Children with enuresis can be embarassed by their condition and may believe that multiple doses of their nasal spray may bring about a rapid resolution. Water intoxication is an uncommon but serious adverse effect of treatment with intranasal DDAVP. These patients may present with seizure, mental state changes, or both. Basic management consists of stopping the drug, fluid restriction, and suppressive treatment for seizures. Recovery is usually rapid and complete. Administration of the nasal spray in children should be supervised by parents to prevent highly motivated children from accidental overdose. The risks of high fluid intake need to be carefully explained to both parents and children. (+info)
Forebrain ischaemia with CA1 cell loss impairs epileptogenesis in the tetanus toxin limbic seizure model.
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There is a long-standing controversy as to whether Ammon's horn sclerosis is the result or the cause of severe limbic epilepsy. In the tetanus toxin model of limbic epilepsy, rats have intermittent spontaneous fits over a period of 3-6 weeks after injection of tetanus toxin into the hippocampus. The fits then usually remit and the EEG returns to normal. In a few rats, however, the fits recur some weeks to months later, and it was previously found that in these rats there was gross cell loss in area CA1 of the dorsal hippocampus (distant from the injection site in ventral hippocampus). Such cell loss might either promote recurrence of fits or be the result of the recurrence. In the present experiment, the effect of previous induction of CA1 cell loss by transient 4-vessel occlusion cerebral ischaemia on the subsequent development of the tetanus toxin-induced epilepsy was studied, using continuous time-lapse video monitoring to assess the number of fits. The hypothesis that the previous forebrain ischaemia would predispose rats to reoccurring fits was not supported: no rats in the ischaemia group had reoccurring fits and additionally fits were delayed and fewer occurred than in the control groups. (+info)
Follow-up of psychogenic, non-epileptic seizures: a pilot study - experience in a Dutch special centre for epilepsy.
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A follow-up study was performed in 33 patients with proven (ictal EEG-CCTV) psychogenic, non-epileptic seizures (PNES). These patients received a questionnaire to evaluate seizures, treatment and rehabilitation. The response group consisted of 21 females (80% response) and seven males (100% response). Follow-up after diagnosis varied from 23-67 months. Seven patients (25%) reported that seizures had ceased and of the patients not seizure-free seven did report a seizure-free period after diagnosis of an average 6.7 months. Eight patients were on antiepileptic drugs again. Of 13 patients referred for psychotherapy, who also did receive treatment, six became free of seizures and seven did not. Of seven patients also referred, but who did not receive psychotherapy, all continued to have seizures. On a self-rating scale to compare "overall function" at the time of diagnosis and follow-up, 75% considered themselves to have "improved", but no improvement could be detected in psychosocial functioning. (+info)
Postictal symptoms help distinguish patients with epileptic seizures from those with non-epileptic seizures.
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The aim of the study was to assess whether post-ictal symptoms can help distinguish patients who have epileptic seizures from those with non-epileptic seizures (NES). We reviewed the spontaneous responses to the question 'What symptoms do you have after a seizure?' in 16 patients with epileptic seizures (predominantly focal with secondary generalization or generalized tonic-clonic) and 23 NES patients. Six of the 16 patients (38%) vs. only one of 23 NES patients (4.3%) noted post-ictal headache (P = 0.008). Nine epilepsy patients (56%) vs. three NES patients (13%) reported post-ictal fatigue (P = 0.004). Confusion or other symptoms did not distinguish epilepsy patients from those with NES. All epilepsy patients had at least one post-ictal symptom while 12 NES patients (52%) had none (P = 0.001). Therefore, patients evaluated for epileptic vs. non-epileptic seizures who have post-ictal fatigue or headache, are more likely to have epileptic seizures. Patients with a diagnosis of NES who note post-ictal fatigue or headache should be investigated further. (+info)
The value of provocation methods in patients suspected of having non-epileptic seizures.
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Non-epileptic seizures (NES) are reported in 18-23% of patients referred to comprehensive epilepsy centres. Non-epileptic seizures may also be present in 5-20% of the patients who are diagnosed as having refractory seizures. Because of their prevalence, financial and psychosocial outcomes cannot be ignored and accurate diagnosis is of the utmost importance. Various methods of seizure induction have been developed with the aim of differentiating epileptic from non-epileptic seizures. However, recording the attacks by video-EEG monitoring is the gold standard. In our outpatient EEG laboratory we try to induce seizures with verbal suggestion or IV saline infusion in patients who are referred by a clinician with the diagnosis of probable non-epileptic seizures. In this study we investigated the results of 72 patients who were referred between January 1992-June 1996. Non-epileptic seizures were observed in 52 (72.2%) patients. Thirteen of these patients still had risk factors for epilepsy. We could not decide whether all of their previous attacks were non-epileptic because 10-30% of the patients with NES also have epileptic seizures. For a more accurate diagnosis it was decided that these 13 patients, together with the 20 patients who did not have seizures with induction, needed video-EEG monitoring. Thirty-nine patients who had NES and no risk factors for epilepsy were thought to have pure non-epileptic seizures. We claim that not all patients suspected of having NES need long-term video-EEG monitoring and almost half (54.2%) of the cases can be eliminated by seizure induction with some provocative techniques. (+info)
Neurotoxic effects of 2,5-hexanedione on normal and neurofilament-deficient quail.
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The neurotoxic effects of 2,5-hexanedione (2,5-HD) were investigated using neurofilament (NF)-deficient (Quv) Japanese quail in comparison with normal Japanese quail. Both Quv and normal Japanese quail were inoculated intraperitoneally with 350 mg/kg/day 2,5-HD for 6 consecutive wk. The results of 2,5-HD exposure differed substantially between the 2 strains of Japanese quail. The 2,5-HD-exposed normal quail showed leg paralysis about 4 wk after initiation of dosing. Some treated normal quail fell into dysstasia and died of nutritional disturbances. Histologically, 2,5-HD-treated normal quail had NF-rich axonal swellings and degeneration in the distal parts of the peripheral nerves, spinal cord, and cerebellar peduncles. In contrast, 2,5-HD-injected Quv quail showed tonic convulsion, ataxia gait, severe quivering, and excitation about 2-3 days after administration. Some treated Quv birds died immediately after systemic tonic convulsion, probably because of asphyxia. Although all treated Quv quail showed neurologic signs, there were no recognizable 2,5-HD-induced lesions in the nervous system. After about 4-6 wk of dosing, 2,5-HD induced distal axonopathy in normal quail and acute neurotoxicity in Quv quail. (+info)