Neurobiology of Epilepsy (Continued)

Epilepsy is a paroxysmal disorder characterized by abnormal neuronal discharges. Although epilepsy has many causes, the fundamental disorder is secondary to abnormal synchronous discharges of a network of neurons. Epilepsy is secondary to an imbalance between excitatory and inhibitory input to cells.

The hallmark of epileptic neurons in experimental models of epilepsy is membrane depolarization, which results in an interictal spike recorded by EEG. During an interictal discharge, the cell membrane near the soma undergoes a relatively high-voltage (approximately 10 to 15 mV) and relatively long (100 to 200 µsec) depolarization. The long depolarization has the effect of generating a train of action potentials that are conducted away from the soma along the axon of the neuron. This large depolarization is called the paroxysmal depolarization shift (PDS). The PDS is caused by an imbalance of excitation over inhibition. This enhanced excitation, or reduced inhibition, can be secondary to a variety of abnormalities, including disturbances in the intrinsic properties of neuronal membranes, excess excitation through NMDA and AMPA receptors, reduced inhibition through GABA channels, and abnormalities of potassium and calcium channels. The net effect is an imbalance of excitation over inhibition. The interictal PDS is followed by a large hyperpolarization, which serves to limit the duration of interictal paroxysms. It is important to remember that an epileptic area is made up of numerous abnormal neurons that discharge in an abnormal synchronous manner. The PDS may occur because of intrinsic membrane abnormalities in a group of neurons or because of excessive excitatory input (or reduced inhibitory input) to a group of neurons.

With time, a progressive loss of hyperpolarization after the PDS may occur in the epileptic focus. During seizures, the epileptic neurons undergo prolonged depolarization with waves of action potentials during the tonic phase of the seizure and oscillations of membrane potentials with bursts of action potentials, separated by quiet periods during the clonic phase. An EEG recorded at the scalp at this time shows continuous spikes, which generally coincide with the tonic stage of a generalized tonic-clonic seizure. During the next stage, large inhibitory potentials occur (with slowing or flattening on surface EEG) and alternate with recurrent, rhythmic PDSs (with spikes on surface EEG). This pattern generally coincides with the clonic stage of the seizure.

Focal seizures may spread along the cortex and propagate to distant regions via white matter tracts. Many patients with focal seizures will have an aura at the onset. The type of aura is dependent upon the region of the brain in which the seizure originated. For example, patients with temporal lobe onset may experience déjà vu (the experience of feeling sure that one has already witnessed or experienced a current situation), whereas a patient with parietal lobe onset may experience a sensation of numbness or tingling. With propagation, more and more neurons are recruited into synchronous firing, which could culminate in a generalized tonic-clonic seizure.

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