Roger J. Porter

The secondarily generalized tonic‐clonic seizure A videotape analysis

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 nonsignificant 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.

Complex partial seizures Clinical characteristics and differential diagnosis

Videotape analysis of 163 complex partial seizures in 40 patients showed that the mean duration of the attack was 128 seconds. Automatisms occurred in 159 seizures (97%) and involved more than the face and arms in 132 (80%). Most automatisms were simple, stereotypic, or aimless movements. Postural tone increased in 24 seizures and decreased in 62. Clonic movements of the eyelids occurred in 19 attacks, and clonic movements of the extremities in 4. Only nine patients reported auras. Distinct ictal and postictal phases could be distinguished in 132 seizures (80%); in these, the mean ictal duration was 54 seconds and the mean postictal duration 89 seconds. Videotape analysis provides objective criteria by which complex partial seizures may be differentiated from other seizure types.

Responsiveness before, during, and after spike‐wave paroxysms

In 26 patients 5 to 20 years of age with absence seizures, 413 auditory reaction times were determined by a paroxysm detection device during 310 spike-wave paroxysms. All reaction times during the 1 second before a paroxysm were within normal limits, but only 43 percent of reaction times at the onset of a paroxysm were normal and after a delay of 0.500 second into a paroxysm, only 20 percent were normal. After 4 seconds of spike-wave discharge, 52 percent of reaction times were normal. Responsiveness was recovered quickly after a paroxysm. The degree of impairment of response to auditory stimuli markedly decreased when spike-wave discharge was fully generalized. The degree of maximal impairment of auditory responsiveness was the same in paroxysms of both long and short duration. Thus, any spike-wave paroxysm, regardless of duration, can impair consciousness, and therapy for absence seizures should aim at controlling all spikewave paroxysms, not just the longer bursts.

Responsiveness at the onset of spike-wave bursts.

Abstract A clear understanding of responsiveness during generalized spike-wave discharge has been the goal of many investigators. No previous studies have enabled a precise evaluation of a particular time point in the spike-wave bursts. A paroxysm-triggered method for measuring reaction time at specific time points during spike-wave discharge has been developed. The apparatus used was a modified reaction-time device consisting of an auditory stimulus, a response unit, and a digital clock. A threshold detector constantly monitored the EEG voltage; when a large amplitude spike-wave discharge occurred, a pulse was sent to a triggering device that turned on the stimulus unit and the clock, permitting testing of responsiveness at the exact onset of the paroxysm. Fourteen patients were tested in the Clinical Neurophysiology Laboratory of the University of Virginia Medical Center. A total of 286 stimuli during 235 spike-wave discharges were delivered. Of the 137 stimuli delivered simultaneously with paroxysm onset, 56% of the responses were abnormal (>2 S.D.) when compared to the normal reaction time for each patient at each session. In paroxysms of brief duration, more than 50% of the responses to stimuli delivered simultaneously with onset of the paroxysms were abnormal. Reaction times measured at varying intervals after the onset of the paroxysm were more frequently abnormal than at paroxysm onset; this could be considered evidence for a gradual decrease in responsiveness. Degree of spike-wave generalization, however, appeared to be inversely related to responsiveness. Further investigations will employ a variable delay after paroxysm onset; this method should further define the decrement in responsiveness during spike-wave bursts.

Mechanism of valproate‐phenobarbital interaction in epileptic patients

Valproate effects on phenobarbital biodisposition were examined in a search for the mechanisms of the valproate‐induced elevation of plasma phenobarbital during antiepileptic therapy. The study involved patients who were treated with phenobarbital alone and phenobarbital plus valproate. Several kinetic parameters were determined after a pulse dose of stable isotope‐labeled phenobarbital, with plasma phenobarbital levels at a steady state. Plasma elimination of labeled phenobarbital was studied by selected ion monitoring. The addition of valproate to the phenobarbital regimen resulted in elevation of plasma phenobarbital and increase in urinary output of unchanged phenobarbital. There was no effect on urinary pH. The rise in plasma phenobarbital was paralleled by lengthening of phenobarbital elimination half‐life while the decrease of plasma phenobarbital clearance paralleled the decrease in phenobarbital elimination rate constant. These findings suggest that inhibition of phenobarbital metabolism by valproate is the mechanism for this clinically important drug‐drug interaction.

Levels of Catechols in Epileptogenic and Nonepileptogenic Regions of the Human Brain

Abstract: Recent reports about tyrosine hydroxylase and α1‐adrenoceptors in epileptic foci have suggested increased regional catecholaminergic activity, which may serve a compensatory, inhibitory role. We measured levels of catechols, including the precursor 3,4‐dihydroxyphenylalanine (Dopa) and the catecholamines dopamine (DA) and nor‐epinephrine (NE), in surgically removed foci identified by electrocorticography and in nonepileptogenic sites from 23 patients with intractable temporal lobe epilepsy. The following values (mean ± 1 SD) were obtained: DOPA = 142 ± 60 ng/g of protein in the focus vs. 115 ± 39 ng/g in the nonfocus (p < 0.01); DA = 168 ± 85 vs. 106 ± 54 ng/g (p < 0.001); and NE = 267 ± 117 vs. 181 ± 80 ng/g (p < 0.001). The results are consistent with increased catecholaminergic activity in epileptic foci.

Diagnostic and therapeutic reevaluation of patients with intractable epilepsy

Intensive monitoring techniques were used to improve seizure diagnosis and control in 23 patients with intractable epilepsy: (1) Video recording of clinical seizures and the ictal EEG, (2) long-term telemetered EEG recordings, and (3) frequent determination of plasma antiepileptic drug concentrations. Patients were monitored in the hospital for an average of 8 weeks and after discharge were followed for an average of 8 months. At follow-up, 70 percent of the patients continued to have improved seizure control as compared with baseline studies, 83 percent had decreased toxicity, and about half had made gains in social adjustment. Use of the techniques described can make a significant contribution to patients previously considered intractable to therapy.

Complex Partial Seizures: Cerebral Structure and Cerebral Function

Summary: We studied the relationships between cerebral structure and function in 10 patients with complex partial seizures who had major cerebral lesions, including porencephalic cysts, tuberose sclerosis, agenesis of the corpus callosum, and cerebral hemiatrophy. Evaluation included computed tomography (CT) and magnetic resonance imaging (MRI) scanning, EEG, and positron emission tomography (PET) using [18F]‐2‐deoxyglucose. Surface EEG usually showed widespread, bilateral epileptiform discharges even if pathology was clearly restricted to one hemisphere. In several cases, interictal PET hypometabolism was more widespread than structural changes seen on CT and MRI, extending to involve the ipsilateral temporal lobe in patients with extratemporal lesions. This study shows that patterns of metabolic and electrophysiologic dysfunction may not be predicted by structural lesions in patients with partial seizure disorders.

Visual evoked potentials and eye dominance

The amplitudes of pattern-reversal VEPs in 25 healthy volunteers were significantly higher from the dominant eye than the non-dominant eye in right eye dominant subjects. The difference was present over both hemispheres and over the midline. Handedness did not appear to influence the amplitude asymmetry. A similar trend was noted in left eye dominant subjects, but the difference was significantly only at O2. The mean latency of the P100 peak was significantly shorter with stimulation of the dominant eye. These amplitude and latency disparities between dominant and non-dominant eyes provide electrophysiological evidence of lateralization in the nervous system.

Mechanisms of Action of New Antiepileptic Drugs

Summary: Our understanding of how new antiepileptic drugs work mirrors what we know about how currently marketed antiepileptic compounds exert their action–that information is scarce and elusive. The mechanism of action of antiepileptic drugs is nevertheless inextricably linked to epileptogenesis itself, and investigations of several promising new compounds are underway to establish the levels at which these drugs act. Compounds act on synapses and membranes as well as affecting receptors, neurotransmitters, and peptides. The most extensive data are available on drugs that inhibit the action of GABA or its receptors, including new benzodiazepine‐like agents and barbituric‐acid derivatives. The few drugs that act by inhibiting the effects of excitatory amino acids are reviewed. Finally, the maximal electroshock test is an empirical method to determine the antiepileptic properties of a drug; several agents under development have been effective in this screening technique.