Effects of Focal Paroxysmal Discharges on Sustained Attention in Children with Frontal Lobe Epilepsy

Abstract

Purpose: It has become well accepted that clinically nonobvious generalized or focal spike‐and‐wave discharges result in cognitive impairment detectable with psychological testing. However, the precise temporal relation between spikes and cortical dysfunction remains unknown because the psychological tests were given over a broader time scale than the individual spikes. Furthermore, the neurophysiological mechanism has yet to be fully investigated, because it is not well known whether the cognitive impairment reflects a disturbance of sensory or perceptual mechanisms, or an impairment of memory. This study was designed to elucidate the correlation between the timing of spikes with fluctuations in an anatomically corresponding function by using a computerized system of spike detection, stimulus presentation, and the recording of somatosensory event‐related potentials (SERPs). Methods: The subjects were five patients with epilepsy (with a mean age of 10 years) without any neurologic deficits. The diagnosis was frontal lobe epilepsy (RE) in three, and benign childhood epilepsy with centrotemporal spikes (BECT) in two. All subjects had received carhamazepine (CBZ). Their EEG findings during the awake state showed left frontal spikes in all subjects with FLE, and left central spikes in the two subjects with BECT. All discharges could occur without apparent simultaneous clinical manifestations. Eight health age‐matched subjects served as controls. SERPs, were recorded from Fz, Cz, and F3 in patients with FLE or C3 in patients with BECT. The median nerve was stimulated at the right wrist contralateral to the side of the spike foci. All subjects were required to direct their attention to the electrical stimuli with all their force. Spikes in a predetermined EEG channel were detected with an amplitude‐threshold device, which triggered the computer to present a stimulus and analyze the response immediately. The SERP triggered by the spike was superposed on the spike. Therefore, the triggered SERP was obtained by subtracting the averaged spike discharges from the SERP obtained by stimulation at an intensity of 3 times the sensory threshold. Control stimuli were presented at random intervals between the spikes (control SERPs). The subjects performed a sustained attentive paradigm along with a series of 32 stimuli, and the responses were divided into four blocks. The averaged SERPs based on eight stimuli for each block were scored for P250 latency and amplitude. The coefficient of variation (CV) values for latency and amplitude for the four blocks of P250 responses were measured. Results: The patients with FLE showed more variability of their serial responses in the triggered SERPs than those for the control SERPs. The CV values of serial P250 amplitude and latency for triggered SERPs were significantly increased compared with those in control subjects (amplitude, 82 ± 5% in FLE vs. 50 ± 12% in controls; and latency, 10 ± 2% in FLE vs. 6 ± 3% in controls) because of response jitter in both latency and amplitude for the triggered SERPs, whereas the CV values for those of the control SERPs were normal (amplitude, 30 ± 5%; and latency, 5 ± 2%). In the two patients with BECT, on the other hand, CV values were normal in both the triggered and control SERPs. Conclusions: These results indicate that the neuropsychological deficits in patients with FLE may not be due to static effects, such as medication, education, and frequency of seizures, but to the intermittent attentive impairment produced by focal paroxysmal discharges in the frontal regions. The results support the concept that these deficits are associated with the inability to expect the next stimuli and to maintain awareness, a conclusion explicable in terms of a reduced capacity of working memory.