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R M Dasheiff

Publications and source records attributed to R M Dasheiff.

47 records · Page 3Linked to original sources

Benzodiazepine receptor increases after repeated seizures: evidence for localization to dentate granule cells.

Repeated seizures, whether induced by kindling or electroshock, result in increased numbers of benzodiazepine receptors in hippocampal formation membranes. We sought to determine the cellular constituents containing the receptor increases. Binding studies of microdissected samples localized the receptor increases to fascia dentata. [3H]Flunitrazepam autoradiographic studies showed increases of silver grain density over the granule cell and molecular layers of fascia dentata but not in other regions of hippocampal formation. Destruction of granule cells by colchicine or neonatal x-irradiation was associated with marked decrease of benzodiazepine receptor binding. Together, these results provide evidence for localization of the receptor increases to the somata and dendritic tree of the granule cells. We suggest that this cellular localization may provide a clue to the network of altered neural circuitry underlying amygdala kindling.

Animals↗

Evidence for an agonist independent down regulation of hippocampal muscarinic receptors in kindling.

Kindling induces a decline of hippocampal muscarinic cholinergic receptors. To test the hypthesis that the decline was mediated by the agonist, acetylcholine, adult male Sprague--Dawley rats were lesioned in the medial septum prior to kindling. Despite the marked destruction of presynaptic cholinergic terminals in the hippocampus, amygdala kindling proceeded normally and the hippocampal muscarinic receptor decline was not blocked. A small but significant decline in choline acetyltransferase activity was demonstrated in non-lesioned kindled rats. It is proposed that the kindling induced decline of hippocampal muscarinic receptors is mediated by repeated neuronal depolarization.

Acetylcholine↗

Efficacy of second line antiepileptic drugs in the treatment of patients with medically refractive complex partial seizures.

The efficacy of second-line antiepileptic drugs (AEDs) was evaluated in the treatment of 66 patients with complex partial seizures who had previously failed first-line AEDs. Methsuximide, valproate, or clorazepate had eliminated seizures in 11% of the patients at the end of the study. However, these good results deteriorated on longer follow-up and were not expected to be permanent. It is recommended that suitable patients with partial epilepsy be referred for surgical evaluation after failing the first-line AEDs, and that second-line AEDs be reserved for nonsurgical candidates.

Anticonvulsants↗

Effectiveness of multiple EEGs in supporting the diagnosis of epilepsy: an operational curve.

Interictal epileptiform activity (IIEA) on EEG may be useful in the diagnosis and characterization of epilepsy. A single scalp EEG may fail to detect this abnormality, which is then discovered on repeat recordings. Since many people with epilepsy have persistently normal EEGs, a practical question arises concerning the yield of multiple EEGs. To determine the probability of finding IIEA with serial EEGs (the operational curve), we reviewed data from 1,201 EEGs on 429 adult patients, most with definite epilepsy presenting in adulthood. The diagnosis was made either clinically or with the support of the EEG. In 50% of our patients with IIEA, the abnormality is present on the first record, in 84% by the third EEG, and in 92% by the fourth. There is relatively little yield to serial EEGs beyond this point.

Adult↗

Comparison of steady-state blood levels of two carbamazepine formulations.

The steady-state plasma level produced by brand-name carbamazepine (CBZ) (Tegretol, Ciba-Geigy) was compared with a generic formulation (Parke-Davis) in 10 subjects with partial epilepsy in a randomized, double-blind, cross-over clinical trial. In addition, seizure frequency and clinical and laboratory signs of toxicity were evaluated. Our results failed to show any difference in CBZ blood levels, seizure frequency, or clinical or laboratory signs of toxicity in patients receiving either the brand-name or generic formulation.

Adult↗

Role of the frontal lobes in the propagation of mesial temporal lobe seizures.

The depth ictal electroencephalographic (EEG) propagation sequence accompanying 78 complex partial seizures of mesial temporal origin was reviewed in 24 patients (15 from the University of Pittsburgh Epilepsy Center and 9 from UCLA). All patients were monitored with bilateral mesial frontal and mesial temporal depth electrodes and later received anterior temporal lobectomy. Ictal EEG records were categorized according to sequence of spread from the temporal focus to the other regions. Although propagation patterns varied both within and between patients, certain features were notable: (a) It was very common for seizure activity to spread initially to the ipsilateral frontal lobe (observed in 22 of 24 patients). (b) The most common mode of spread (15 of 24 patients) was initiating temporal lobe----ipsilateral frontal lobe----contralateral frontal lobe----contralateral temporal lobe. (c) Occasionally, seizure discharges invaded the frontal lobes but failed to invade the contralateral temporal lobe (2 of 24 patients). (d) Seizure activity occasionally invaded the contralateral temporal lobe prior to invading the frontal lobes (2 of 24 patients). Other notable features included (i) a clear tendency for mesial temporal seizure discharges initially to invade orbitofrontal (as opposed to anterior cingulate) cortex and (ii) the emergence of a period of clear asymmetry in the frontal lobes during which high-amplitude, rapid discharges were present on the side ipsilateral to the initiating temporal lobe. These results suggest that the prefrontal region, especially the orbitofrontal cortex, is strongly influenced by mesial temporal ictal activity. This region appears to be frequently involved in the propagation of seizures initiated in the mesial temporal lobe and may play a role in the interhemispheric propagation of mesial temporal seizures.

Brain Mapping↗