Ictal activity

Figure 16.3 Changes in neuronal function required for the development of epileptic seizures. The factors that may control or induce the changes in neuronal function that turn a normal neuron into a focal one (A) recruit other neurons (focal epileptogenesis) to produce an interictal EEG spike (B) and ensure the spread of activity (general epileptogenesis) to full ictal activity (C) are discussed in the text. They include alterations to various ion channels, especially those for Na, a reduction in local inhibitory activity or an increase in local excitatory drive. The electrophysiological counterparts of some of the events involved are shown in Fig. 16.2...

The patient and family should be asked to characterize the seizure for frequency, duration, precipitating factors, time of occurrence, presence of an aura, ictal activity, and postictal state. 

From these experiments it appears that the inward current that drives the neuronal bursts that underlie the ictal activity is a persistent Na current. We were not able to get large numbers of experiments in which whole cell activity could be correlated with single channel events from the same neuron. Therefore it is not clear whether the endogenous bursting in t he neurons with ictal activity is due to an increase in overall persistent Na current, a specific increase in burst openings, or a decrease in countervailing K currents. 

In summary, it appears that the persistent Na current has a major role in driving the ictal activity that underlies seizures. Although mutations of Na channels are likely to underlie only a small fraction of cases of epilepsy, it is likely that the persistent Na current represents a final common pathway in many cases of epilepsy. A good strategy for developing new anticonvulsants with fewer side effects may be to search for drugs that more selectively block the persistent Na current at depolarized voltages. 

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 AH antiepileptic drugs were withdrawn to avoid any possible interference with the neuromodulation procedure [Velasco et al., 2000e] and were replaced with phenytoin. 

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