Roger J. Porter

The modern era of antiepileptic drug therapy began with the use of phenobarbital in 1912. In the years thereafter, many new drugs were introduced, including other barbiturates, hydantoins, succinimides, and oxazolidinediones. Then, for various reasons, the marketing of new antiepileptic drugs was dramatically curtailed. To help reverse this trend, the Epilepsy Branch of the National Institute of Neurological and Communicative Disorders and Stroke sponsored clinical trials of drugs which had already been marketed abroad, resulting in the distribution of clonazepam, carbamazepine, and valproic acid in the U.S. These trials were followed by the establishment of the Antiepileptic Drug Development Program, which encompasses both the preclinical and clinical elements of drug development, including the Anticonvulsant Screening Project, the Toxicology Project, and support for controlled clinical trials.

Forty-eight patients, 4 to 24 years of age, with recurring absence seizures were studied prospectively for twenty-seven months. Each patient and his EEG were recorded simultaneously by a multicamera videotape technique and each recording was repeatedly viewed and described in writing by two observers who subsequently resolved any differences by joint viewing. From the 48 patients, 374 clinical absence seizures were recorded and classified according to the International Classification of Epileptic Seizures. Automatisms accompanied at least one attack in 88 per cent of the patients. Mild clonic components occurred in 71 per cent, and decreased postural tone in 41 per cent. Only one patient experienced an attack comprising only "blank staring" accompanied by unawareness and amnesia, but 40 per cent of patients exhibited this type of attack in addition to more complex absence attacks. Seizures of ten seconds or less in duration occurred among 85 per cent of patients. Each of the 374 seizures were readily classified according to the International Classification, but simple absence constituted only 9-4 per cent of the seizures. The others most often contained, in order of prevalence, either automatisms, mild clonic components, or decreased postural tone, or a combination of two or more of these features. The relationship between increased duration of the seizures and the occurrence of automatisms was significant. The findings are discussed in relation to differential diagnosis and mechanisms of automatisms. Absence seizures differ from complex partial (temporal lobe, psychomotor) seizures because an aura does not precede the abruptly beginning absence attack, the seizure usually lasts less than ten seconds, and mental clarity returns instantly at the end of the seizure.

We studied 120 generalized tonic-clonic seizures (GTCSs) in 47 patients with video-EEG telemetry. GTCSs were preceded by antecedent seizures, including 13 simple partial, 70 complex partial, 17 simple partial leading to complex partial, seven tonic, seven clonic, and one typical absence. We divided GTCSs into the following phases: onset of generalization, pretonic clonic, tonic, tremulousness, and clonic. The mean GTCS duration was 62 seconds. There was a non-significant trend toward longer duration on reduced antiepileptic drug doses. Marked heterogeneity in GTCS phenomenology was present; only 27% of seizures included all five phases. Individual phase duration and clinical expression, including tonic and clonic phases, was highly variable. The clinical phenomena suggest that multiple cortical and subcortical routes of spread may exist. When GTCSs last longer than 2 minutes, intravenous antiepileptic drug treatment should be initiated.

Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.