Concurrent EEG recordings from an epileptogenic cortical focus and subcortical, thalamic, and brainstem centers in the animal model have enabled investigators to construct a sequence of electrical and clinical events that characterize an evolving focal seizure. Firing of the involved neurons in the cortical focus is reflected in the EEG as a series of periodic spike discharges, which increase progressively in amplitude and frequency. Once the intensity of the seizure discharge exceeds a certain point, it overcomes the inhibitory influence of surrounding neurons and spreads to neighboring cortical regions via short corticocortical synaptic connections.
A provocative finding, based on sophisticated mathematical analysis of EEG tracings, indicates that subtle electrographic changes arise several minutes before the ictal discharge (see LeVan Quyen et al). This suggests that seizures could be triggered either by a change in central thalamic rhythm generators or a subtle alteration in the electrical activity in the region of a focal lesion. Of interest are the findings by Litt and colleagues that in a small number of patients there are prolonged bursts of seizure-like activity detected by sophisticated techniques even days before the onset of temporal lobe seizures. Their proposal is that these events cause a cascade of electrophysiologic changes that very gradually culminate in a seizure.
If unchecked, cortical excitation spreads to the adjacent cortex and to the contralateral cortex via interhemispheric pathways, and also to anatomically and functionally related pathways in subcortical nuclei (basal ganglionic, thalamic, and brainstem reticular nuclei). It is at this time that the clinical manifestations of the seizure begin. The excitatory activity from the subcortical nuclei is conceived to feed back to the original focus and to other parts of the cerebrum, a mechanism that serves to amplify their excitatory activity and to give rise to the characteristic high-voltage polyspike discharge in the EEG. The spread of excitation to the subcortical, thalamic, and brainstem centers corresponds to the tonic phase of the seizure and to loss of consciousness as well as to the signs of autonomic nervous system overactivity (mydriasis, tachycardia, hypertension) and to arrest or respiration. The development of unconsciousness and the generalized tonic contraction of muscles are reflected in the EEG by a diffuse high-voltage discharge pattern appearing simultaneously over the entire cortex. There is little evidence to support the conjecture made by Penfield that seizure activity originates in the thalamus; thus his term centrencephalic seizure is no longer used.
Soon after the spread of excitation, a diencephalic inhibition begins and intermittently interrupts the seizure discharge, changing it from the persistent tonic phase to the intermittent bursts of the clonic phase. In the surface EEG, a transition occurs from a continuous polyspike to a spike-and-wave pattern. The intermittent clonic bursts become decreasingly frequent and finally cease altogether, leaving in their wake an “exhaustion” (paralysis) of the neurons of the epileptogenic focus and a regional increase in permeability of the blood–brain barrier and regional edema in magnetic resonance images. An excess of these inhibitory mechanisms and metabolic exhaustion are thought to be the basis of Todd’s postepileptic paralysis and of postictal stupor, sensory loss, aphasia, hemianopia, headache, and diffuse slow waves in the EEG. Plum and associates observed a twoto threefold increase in cerebral glucose utilization during seizure discharges and suggested that the paralysis that follows might be a result of neuronal depletion of glucose and an increase in lactic acid. The exact roles played by each of these factors in postictal paralysis of function are not settled.