Epileptic activity

The widespread and diverging nature of ascending monoamine pathways to the cortex suggest that NA and 5-HT are more likely to have a secondary modifying rather than a primary effect on the initiation of epileptic activity. In reality this is the case and their secondary role is even a minor one. Generally a reduction in monoamine function facilitates experimentally induced seizures (see Meldrum 1989) while increasing it reduces seizure susceptibility. The variability of the procedures used and results obtained do not justify more detailed analysis here. 

Riban V, Bouilleret V, Pham-L BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112 101-111 Rudolph U, Crestani F, Benke D, Brunig I, Benson J, Fritschy JM, Martin JR, Bluethmann H, Mohler H (1999) Benzodiazepine actions mediated by specific y-aminobutyric acid A receptor subtypes. Nature 401 796-800... 

Engel J Jr, Ackermann RF, Caldecott-Hazard S, et al Epileptic activation of antagonistic systems may explain paradoxical features of experimental and human epilepsy, a review and hypothesis, in Kindling 2. Edited by Wada JA. New York, Raven, 1981, pp 193-217... 

Megho M, lanelli A, Anile C, et al Interaction of epileptic activities of bilateral deep temporal origin an experimental study. Epilepsia 17 437-448, 1976 Meguro H, Mori H, Araki K, et al Functional characterization of a heteromeric NMDA receptor channel from cloned cDNAs. Nature 357 70-74, 1992 Meichenbaum D, Turk DC Facilitating treatment adherence. New York, Plenum, 1987... 

A 62-year-old man treated with continuous mediastinal irrigation with a 1 10 solution of povidone-iodine developed seizures on the fifth day of drainage (14). After the seizure, his serum iodine concentration was raised (120 pg/ml). Renal insufficiency developed at the same time. The electroencephalogram showed no evidence of epileptic activity or other abnormalities. The povidone-iodine irrigation was replaced by continuous irrigation with a solution of neomycin and polymyxin B. Renal function improved and the creatinine concentration returned to normal 3 days after the seizure. 

Mode of action. The precise mode of action of carbamazepine has not been fully established. It has been shown to stabilize both pre- and postsynaptic neurons by blocking the use and frequency-dependent sodium channels. While this is probably its main action, the blockade of the glutamate NMDA ionotropic receptors also leads to a reduction in the influx of sodium and calcium ions into the neuron. The net effect of these changes is a reduction in the sustained high-frequency repetitive firing of the action potentials which characterize epileptic activity. There is also evidence that carbamazepine blocks purine, noradrenaline, serotonin and muscarinic acetylcholine receptors which probably accounts for the use of carbamazepine as a mood stabilizing agent. 

Blockade of the 5-HT7 receptor has been shown to reduce epileptic activity in animal models. Audiogenic seizures induced in DBA/2J mice could be prevented by drugs in a rank order of potency corresponding to their affinity for the 5-HT7 receptor (95). The selective 5-HT7 receptor antagonist SB-258719 has been shown to reduce epileptic activity in an animal model for absence epilepsy, the WAG/Rij rat (65). It is believed to do so by modulating the pacemaker current Ih within the thalamus (96,97). The 5-HT7 receptor has been demonstrated to mediate depolarization within the anterodorsal thalamus by increasing lh through a cAMP-dependent, PKA-independent mechanism (96,97). 

Graf M, Jakus R, Kantor S, Levay G, Bagdy G. Selective 5-HT(lA) and 5-HT(7) antagonists decrease epileptic activity in the WAG/Rij rat model of absence epilepsy. Neurosci Lett 2004 359 45-48. 

Lopes da Silva, F., Blanes, W., Kalitzin, S.N., Parra, J., Suffczynski, P., and Velis, D.N. Epilepsies as dynamical diseases of brain systems basic models of the transition between normal and epileptic activity. Epilepsia 2003,44[Suppl 12] 72 83. 

Mahyar et al. (2006) report the effect of the fruit essential oil of cumin on the epileptiform activity induced by pentylenetetrazol (PTZ), using the intracellular technique. The results demonstrate that extracellular application of the essential oil of cumin (1 and 3%) dramatically decreases the frequency of spontaneous activity induced by PTZ in a time- and concentration-dependent manner. In addition, it showed protection against PTZ-induced epileptic activity by increasing the duration and decreasing the amplitude of after-hyperpolarization potential (AHP) following the action potential, the peak of action potential and inhibition of the firing rate. 

The electroencephalogram is abnormal in approximately 75% of patients with cerebral venous thrombosis, but changes are non-specific, with generalized slowing, often asymmetric, with superimposed epileptic activity. 

Ben-Ari, Y., Ottersen, O.P., Meldrum, B.S. (1980). The role of epileptic activity in hippocampal and remote cerebral lesions induced by kainic acid. Brain Res. 191 19-91. 

Kubova, H., Herink, J., Mares, P. (1990). Effects of clonazepam on epileptic activity induced by local application of atropine into the septum. Activ. Nerv. Sup. (Prague) 32 211. 

MT MRI has been showm to be sensitive to other minor structural abnormalities caused by neurological disease. MTR maps were analyzed with a statistical package demonstrated that areas of epileptic activity which were not detected visually had statistically reduced MTR in the epileptic focus (Rugg-Gunn et al., 2003). When MT MRI was combined with DWI, reductions in both MTR and ADC were found in the epileptic focus of patients (Ferini-Strambi et al., 2000). 

Some exciting work was reported by Hitachi at a recent meeting in Japan [50]. The research, conducted at the Tokyo Metropolitan Police Hospital, used NIR to detect blood flow changes in the brain to determine sites of epileptic activity. The location of blood flow increases corresponded well with conventional methods such as intercranial electroencephalogram (EEG) or single photon emission computed topography (SPECT). The technique was able to determine the side of the brain where the episode was taking place in all the patients on which it was tried. This technique could replace the intrusive electrodes currently in use. Hitachi plans to expand this technique to other brain diseases. 

The action of glutamate in epilepsy is assumed to be the consequence of NMDA-receptor binding and of AMPA-receptor activation as well. In vivo kindling studies provoke epileptic activity. In vitro application of glutamate on hippocampal cell cultures burst firing. These phenomena can be reduced by NMDA antagonists. 

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