Classification of Seizures

The two main categories of seizures are partial (focal) seizures and generalized seizures (Table 20-1). A partial seizure originates in one cerebral hemisphere, and the patient does not lose consciousness during the seizure. A generalized seizure arises in both cerebral hemispheres and involves loss of consciousness. Seizures are accompanied by characteristic changes in the electroencephalogram (EEG), as shown in Figure 20-1. Most seizures are self-limited and last from about 10 seconds to 5 minutes. Some seizures are preceded by an aura, which is a sensation or mood that may help identify the anatomic location of the seizure focus.

About 60% of epileptic seizures are partial seizures. Electroencephalographic abnormalities are seen in one or more lobes of a cerebral hemisphere, and the patient may exhibit motor, sensory, and autonomic symptoms. In simple partial seizures, consciousness is not altered. In complex partial seizures, however, patients have an altered consciousness and exhibit repetitive behaviors (automatisms). Complex partial seizures often originate in the temporal lobe, in which case the disorder is called either temporal lobe epilepsy or psychomotor epilepsy. Some partial seizures progress along anatomic lines as the electrical discharges spread across the cortex. For example, a seizure may first involve the fingers, then the hand, and finally the entire arm. This is characteristic of jacksonian epilepsy, or “jacksonian march.” Partial seizures can also evolve into generalized seizures.

The two main types of generalized seizures are tonic-clonic seizures and absence seizures. Generalized tonic-clonic seizures, which were formerly called grand mal seizures, begin with a brief tonic phase that is followed by a clonic phase with muscle spasms lasting 3 to 5 minutes, and they conclude with a postictal period of drowsiness, confusion, and a glazed look in the eyes. Status epilepticus is a condition in which patients experience recurrent episodes of tonic-clonic seizures without regaining consciousness or normal muscle movement between episodes. Generalized absence seizures, or petit mal seizures, are characterized by abrupt loss of consciousness and decreased muscle tone, and they can include a mild clonic component, automatisms, and autonomic effects. On the EEG, generalized absence seizures exhibit a synchronous 3-Hz (three cycles per second) spike-and-dome pattern that usually lasts 10 to 15 seconds.

Less-common types of generalized seizures include myoclonic seizures and atonic seizures (see Table 20-1).

Neurobiology of Seizures

Epileptic seizures are caused by synchronous neuronal discharges within a particular group of neurons, or seizure focus, which is often located in the cerebral cortex but can be found in other areas of the brain. Once initiated, the abnormal discharges spread to other parts of the brain and produce abnormal movements, sensations, or thoughts. The neuronal mechanisms that initiate a seizure are not fully understood, but growing evidence indicates the involvement of excessive excitatory neurotransmission mediated by glutamate (Fig. 20-2). Investigators believe that excessive activation by glutamate of N-methyl-D-aspartate (NMDA) receptors displaces Mg²⁺ ions from the NMDA receptor–calcium ion channel and thereby facilitates calcium entry into neurons. Calcium contributes to the long-term potentiation of excitatory glutamate neurotransmission by activating the synthesis of nitric oxide.

Nitric oxide is a gas that can diffuse backward to the presynaptic neuron, where it facilitates glutamate release via stimulation of a G protein that activates the synthesis of cyclic guanosine monophosphate. These actions further increase NMDA receptor activation and calcium influx, which are believed to contribute to the depolarization shift that is observed in seizure foci. The depolarization shift consists of abnormally prolonged action potentials (depolarizations) that have spikelets. The shift recruits and synchronizes depolarizations by surrounding neurons and thereby initiates a seizure.

Several other mechanisms can be involved in seizures. One is the suppression of inhibitory neurotransmission of γ-aminobutyric acid (GABA), and another is an increase in calcium influx via T-type calcium channels in thalamic neurons.

Mechanisms of Antiepileptic Drugs

Antiepileptic drugs are believed to suppress the formation or spread of abnormal electrical discharges in the brain. As shown in Table 20-2, the currently available drugs accomplish these actions via three mechanisms: (1) inhibition of the sodium or calcium influx responsible for neuronal depolarization, (2) augmentation of inhibitory GABA neurotransmission, and (3) inhibition of excitatory glutamate neurotransmission.