Epileptic focus

Figure 2.14 Relation between the EEG recorded from an epileptic focus on the surface of the cerebral cortex (EEG) and the activity of a single cortical neuron recorded extracellularly (e.c.) and intracellularly (i.c.) during an experimental epilepsy induced by topical application of penicillin. Note that the large EEG excursions correspond to the large (synchronised) depolarisations of the neuron, not to action potential discharges. (Adapted from Brain Res. 52 Ayala, GF et al. Genesis of Epileptic Interictal Spikes. New Knowledge of Cortical Feedback systems suggests a Neurophysiological Explanation of Brief Paroxysms, 1-17 (1973) with permission from Elsevier Science)...

A seizure is accompanied by a burst of spikes in the EEG. Between these so-called iclal phases are solitary EEG interictal spikes. Each of them represents the field potential associated with a burst of action potentials in a group of neurons within the epileptic focus (Fig. 16.2). 

There are many studies on the induction and spread of spiking in animals both in vivo and in isolated brain slices, generally initiated by the use of GABA antagonists or removal of Mg + ions in vitro). Unfortunately since neither of these events is likely to occur in or around a human epileptic focus the results do not tell us much about how focal activity arises and spreads in humans. This needs to be achieved by the use of human epileptic tissue even though the procedures found to control experimentally induced spiking may well be applicable to humans. 

Nadi N. S., Wyler A. R., and Porter R. J. (1987). Amino acids and catecholamines in the epileptic focus from the human brain. Neurology 37 106. 

In cell culture preparations, diphenylhydantoin, carbamazepine and valproate have been shown to reduce membrane excitability at therapeutically relevant concentrations. This membrane-stabilizing effect is probably due to a block in the sodium channels. High concentrations of diazepam also have similar effects, and the membrane-stabilizing action correlates with the action of these anticonvulsants in inhibiting maximal electroshock seizures. Intracellular studies have shown that, in synaptosomes, most anticonvulsants inhibit calcium-dependent calmodulin protein kinase, an effect which would contribute to a reduction in neurotransmitter release. This action of anticonvulsants would appear to correlate with the potency of the drugs in inhibiting electroshock seizures. The result of all these disparate actions of anticonvulsants would be to diminish synaptic efficacy and thereby reduce seizure spread from an epileptic focus. 

Actions Carbamazepine [kar ba MAZ a peen] reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potentials in the epileptic focus. 

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). 

Gabapentin-induced myoclonus may be more common than initially thought. In a retrospective survey, 13 of 104 consecutive patients developed myoclonus at gabapentin dosages of 800-3200 mg/day (11). Six of the patients had severe chronic static encephalopathy. Three had focal myoclonus, contralateral to the epileptic focus, and two had exacerbation of pre-existent myoclonus. In aU cases the myoclonus was mild and did not interfere with daily activities. The fact that in three patients the electroencephalogram did not show epileptiform discharges suggests that, at least in some cases, the myoclonus is non-epileptic in nature. 

The mode of action of phenytoin has been attributed to its membrane-stabihzing effects because it (1) limits the development of maximal seizure activity, and (2) reduces the spread of the seizure process from an epileptic focus. The precise mechanisms responsible for stabihzation of the neuronal membrane are uncertain, though several concepts have been advanced (Figure 76). 

Jerger, K. S.S. Schiff. 1995. Periodic pacing an in vitro epileptic focus. J. 

Several trials of deep brain stimulation are currently underway. In addition, direct electrical stimulation of the epileptic focus in the cortex or hippocampus, in some cases coupled to contingent and others to closed-loop stimulation algorithms are being examined by a number of investigators. 

To evaluate the antiepileptic effects of SAHCS on temporal lobe epileptogenesis, the number and type of clinical seizures/day and the number of interictal negative EEG spikes at the epileptic focus/10 sec was... 

Once the precise epileptic focus was defined, the transitory electrodes were replaced by four contact depth brain stimulation electrodes (3789 DBS and IPG by Medtronic, Inc., Minneapohs, MN) (Figure 36.4) and connected to an independent IPG system that were placed in a subcutaneous subclavicular pocket on each side. The target of the electrode contacts was the site of maximal interictal and ictal activities. AH antiepileptic drugs were withdrawn to avoid any possible interference with the neuromodulation procedure [Velasco et al., 2000e] and were replaced with phenytoin. 

Velasco, E, Velasco, A.L., Velasco, M., Rocha, L., and M6nes, D. Electrical stimulation of the epileptic focus in cases of temporal lobe seizures. In Liiders, H.O. (Ed.), Electrical Stimulation jbrEpilepsy. London Taylor and Frances Health Sciences, 2003, pp. 287-300. 

Kunz, W.S., Kudin, A.P., Vielhaber, S., Blumcke, 1., Zuschratter, W., Schramm, J., Beck, H., and Eiger, C.E. 2000. Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann Neurol 48(5) 766—773 Kwan, R, and Brodie, M.J. 2000. Early identification of refractory epilepsy. N Engl J Med... 

Dodd D R. and Bradford H F (1976) Release of ammo acids from the maturing cobalt-induced epileptic focus Brain Res 111, 377-388... 

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