Simultaneous Electroencephalographic and Electocorticographic Recordings of Lateralized Periodic Discharges in Temporal Lobe Epilepsy

Introduction

The term “periodic lateralized epileptiform discharges” (PLEDs), which was initially described more than 6 decades ago, is used to describe an EEG pattern consisting of lateralized sharp waves, spikes, or other complex wave forms occurring in a periodic fashion.^1,2 PLEDs were recently renamed “lateralized periodic discharges” (LPDs) by the American Clinical Neurophysiology Society to de-emphasize epileptiform properties, which were considered to be clinically nonessential. ³ Most often, LPDs are observed in critically ill patients with acute pathological conditions commonly caused by acute or subacute structural lesions of the cerebral cortex that can be either diffuse or focal.^2-4 Whether LPDs represent ictal or interictal phenomena remains highly controversial, ⁵ while the widespread use of continuous EEG monitoring in critically ill patients took on new importance with the increased prevalence of LPDs and the growing speculation regarding their pathological significance. ⁴ Chong and Hirsch ⁶ proposed a conceptual framework spanning from clearly interictal patterns to definitively ictal patterns, known as “the ictal-interictal continuum,” and stressed the need to consider the likelihood of occurrence of neuronal injury underlying LPD in a given clinical setting.

These EEG abnormalities are less frequently found in chronic conditions like focal epilepsies, including temporal lobe epilepsy (TLE). ⁷ However, the pathophysiological significance of these EEG abnormalities in patients with TLE, including the question of whether they represent ictal or interictal phenomena, remains uncertain.^5,7 Our previous study used arterial spin labeling perfusion magnetic resonance imaging in patients with epilepsy to demonstrate the occurrence of ictal hyperperfusion associated with nonconvulsive status epilepticus in the area where LPDs were recorded. ⁸

To clarify the interrelations of cortical sources with scalp EEG, several studies simultaneously performed extra- and intracranial recordings; the amplitude ratio of cortical potentials to their scalp EEG correlates, the extent of the cortical area involved in the synchronized discharge, and the localization of the cortical source and its geometry have been independently linked to recordings with scalp electrodes.^9,10 The proposal by Cooper et al ¹¹ was the first to gain widespread acceptance; they proposed that the minimum area of synchronized cortical activity necessary to record scalp EEG is 6 cm². However, their study design involved the use of fresh cadaver skulls and estimation of the source area in the absence of EEG background activity, thus rendering any conclusions uncertain. Tao et al ¹² simultaneously performed EEG and ECoG using chronic subdural electrodes; they found that at least 10 cm² of interictal ECoG activity in the lateral convexity is necessary to record scalp EEG. Our previous study ¹³ demonstrated that the relationship between ictal EEG and ECoG is not straightforward; however, the degree of synchronization of ictal ECoG activities, the amplitude of the ictal discharges, and the width of the cortical area involved, all play important roles in the appearance of ictal EEG discharges.

In the present study, we assessed the pathophysiological significance of LPDs in 3 patients with chronic TLE by simultaneously recording scalp EEG and ECoG using chronic subdural electrode sampling from the medial and lateral temporal lobes.

Materials and Methods

Patients

Between January 2008 and December 2019, 98 patients with drug-resistant epilepsy underwent simultaneous EEG-ECoG monitoring with chronic subdural electrodes for presurgical evaluation. From these, we retrospectively selected 3 patients with TLE who demonstrated LPDs on EEG (Table 1). In the present study, LPDs were defined as periodic discharges (PDs) or repeated polyspikes, spikes, or sharp waves followed by slow waves (spike-and-wave or sharp-and-wave; SW) occurring at nearly regular intervals and having at least 6 phases.

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Table 1.

The Relationship Between Lateralized Periodic Discharges (LPDs) on Scalp Electroencephalography (EEG) and Electrocorticography (ECoG) Findings.

Patient no.	Age, y/gender	Diagnosis a	EEG-ECoG monitoring time	Number (series) and waveform of LPD	ECoG findings when LPDs were recorded on EEG
					Ictal or interictal	Amplitude	No. of electrodes involved
1	26/male	Rt nonlesional TLE  Rt medial onset: 5  Rt lateral onset: 1	7 days	85 SW	Interictal	800-1500 μV	10-17
2	43/male	Bil nonlesional lateral TLE  Lt lateral onset: 4  Rt lateral onset: 4	8 days	63 PD	Interictal	600-1200 μV	6-7
3	18/male	Rt lesional TLE  Rt medial onset: 4  Rt lateral onset: 11	2 days 6 hours	1 SW	Ictal at medial cortex	800-900 μV	10-18

Abbreviations: Rt, right; Lt, left; Bil, bilateral; TLE, temporal lobe epilepsy; SW, spike-and-wave complex; PD, periodic discharge.

a

With numbers and temporal locations of ictal events.

Because this was a retrospective study, ethical review board approval was not necessary.

ECoG and EEG Monitoring

Simultaneous recordings of ECoG and EEG were performed as previously described.^13-15 Through a fronto-parieto-temporal craniotomy, grid electrodes were unilaterally placed over the lateral surfaces of the temporal and fronto-parietal lobes in patients 1 and 3 (Figure 1) and bilaterally in patient 2. The electrode contacts were 5 mm in diameter, and the center-to-center distance between neighboring contacts was 10 mm. In addition, a trapezoid strip electrode with 8 electrode contacts was placed adjoining the medial and basal aspects of the temporal lobe, so that 4 contacts were placed at the medial aspect of the parahippocampal gyrus in an antero-posterior orientation and another 4 were at the basal surface with a medio-lateral orientation.

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Figure 1.

The positions and numbers of the subdural electrode contacts (indicated in yellow) are plotted on a 3-dimensional reconstruction based on T2-weighted magnetic resonance images of patient 3, who had right lesional temporal lobe epilepsy. The tumor (indicated in green) is located in the white matter of the right inferior temporal gyrus. (a) 5 × 4 and 2 × 5 grid electrodes (nos. 1-30) are placed on the lateral aspect of the temporal lobe; 5 × 2 grid electrodes (nos. 1-10) are also placed on the lateral aspect of the fronto-parietal lobes. (b) In addition, a trapezoid strip electrode with 8 electrode contacts is placed adjoining the medial and basal aspects of the temporal lobe so that 4 contacts (nos. 1-4) are located at the medial aspect of the parahippocampal gyrus in an antero-posterior orientation, and another 4 (nos. 5-8) are located at the basal surface with a medio-lateral orientation.

For simultaneous EEG monitoring, disc electrodes were placed over the scalp according to the international 10-20 EEG system. When electrodes were required to be placed near the operative wound, they were placed as close as possible without interfering with the wound. Simultaneous EEG and ECoG recordings were collected using a digital EEG recorder (Neurofax; Nihon Kohden). For both ECoG and EEG sampling, the time constant and lowpass filter cutoffs were 10 seconds and 2 kHz, respectively. A notch filter was not used.

Results

Patient 1

Patient 1 with right nonlesional TLE underwent EEG-ECoG monitoring for 7 days, which captured 5 epileptic attacks of right medial temporal onset and 1 of right lateral temporal onset.

During interictal periods, 85 series of LPDs consisting of repeated SWs were recorded on the right temporal region of the scalp (Figure 2, lower traces). The simultaneous ECoG recordings revealed that the corresponding SWs were predominantly on the right lateral temporal lobe (Figure 2, upper traces). On ECoG, most SW spike components consisted of polyspikes, and their peaks did not completely coincide at all leads. Subsequent slow-wave components were not observed on all leads of the lateral temporal lobe, and they tended to appear following a spike component of high amplitude. When the spike components of SWs with amplitudes of 800 to 1500 µV appeared at the 10 to 17 ECoG electrode contacts (Table 1), which are equivalent to those produced by a source area of 10 to 17 cm² (Figure 2, red dotted lines), the corresponding SWs were recorded on the right temporal region of the scalp. While the polyspike components with various peaks on ECoG were not represented on EEG and were recorded as monophasic sharp waves (Figure 2, lower traces, red asterisk), the slow wave component was clearly recorded on EEG (Figure 2, lower traces, blue asterisk). No SW was recorded on EEG when spike components of ECoG discharges with amplitudes of less than 800 µV appeared on source areas of less than 10 cm² (Figure 2, black dotted lines).

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Figure 2.

Simultaneous recordings by scalp electroencephalography (EEG) (lower traces) and electrocorticography (ECoG) (upper traces) with subdural electrodes on the medial and basal temporal lobes, lateral temporal lobe, and lateral fronto-parietal lobes, during interictal periods in patient 1. When a spike component of the spike-and-wave complex (SW) showing an amplitude of 800 to 1500 µV appears on the 10 to 17 ECoG electrode contacts (red dotted lines), the corresponding SWs are recorded on the right temporal region of the scalp. However, no repeated SWs are recorded when ECoG discharges with amplitudes of less than 800 µV appear on less than 10 contacts (black dotted lines). Red and blue asterisks indicate the spike and slow-wave components of SWs, respectively. Av, averaged reference.

The patient underwent right anterior temporal lobectomy with amygdalohippocampectomy and experienced a good postoperative seizure outcome (Engel class IA). ¹⁶ Histologically, no abnormalities such as hippocampal sclerosis or cortical dysplasia were observed.

Patient 2

In patient 2, EEG-ECoG monitoring of nonlesional TLE for 8 days demonstrated 4 paroxysms of right lateral temporal onset and four of left lateral temporal onset.

During interictal states, 63 series of LPDs consisting of PDs were observed on the right temporal region of the scalp (Figure 3, lower traces). The simultaneous ECoG recordings revealed the corresponding PDs on the right lateral temporal lobe (Figure 3, upper traces). While PDs consisted of monophasic spikes, their peaks did not completely coincide at all leads. When the PDs on ECoG with amplitudes of 600 to 1200 µV appeared on a 6 to 7 cm² area of the right lateral temporal lobe (Figure 3, red dotted lines; Table 1), they could be synchronously recorded on the right temporal region of the scalp (Figure 3, red asterisks). Spike components with various peaks on ECoG were recorded as monophasic sharp waves on EEG (Figure 3, lower traces, red asterisk). However, no PDs were recorded on EEG when ECoG discharges with amplitudes of less than 600 µV appeared on source areas of less than 6 to 7 cm² (Figure 3, lower traces, black dotted lines).

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Figure 3.

Simultaneous electrocorticography (ECoG) and electroencephalography (EEG) recordings during interictal periods in patient 2. When periodic discharges (PDs) on ECoG with amplitudes of 600 to 1200 µV appear on the 6 yo 7 ECoG electrode contacts on the lateral temporal lobe, PDs are synchronously recorded on the right temporal region of the scalp (red asterisks). However, no PDs are recorded on EEG when ECoG discharges with amplitudes of less than 600 µV appear on source areas of <6 to 7 cm² (black dotted lines).

With the diagnosis of bilateral lateral TLE, the patient underwent resection of the ictal onset zone on the nondominant right lateral temporal lobe and multiple subpial transections of the ictal onset zone on the dominant left lateral temporal lobe. With the combined use of vagal nerve stimulation, a favorable seizure outcome was obtained (Engel class IIB). ¹⁶ Histological diagnosis of the resected right lateral temporal lobe failed to reveal any abnormalities.

Patient 3

Patient 3 presented with right lesional TLE and underwent EEG-ECoG monitoring (Figure 1) for 2 days and 7 hours, which captured 11 epileptic attacks of right lateral temporal onset and 4 of right medial temporal onset.

During 1 of the 4 medial temporal-onset paroxysms, a series of LPDs consisting of repeated SWs were recorded on the right temporal region of the scalp (Figure 4, lower traces). The simultaneous ECoG recordings demonstrated that ictal discharges with a maximum amplitude of 3000 µV, localized in the medial temporal lobe (Figure 4, upper traces), were not reflected in the EEG (Figure 4, lower traces). On the lateral temporal lobe, however, the corresponding SWs were recorded predominantly on the right lateral temporal lobe (Figure 4, upper traces). The spike components of the SWs were monophasic, and their peaks coincided at all leads. Subsequent slow wave components were observed in most leads of the lateral temporal lobe. When the spike components of SWs with amplitudes of 800 to 900 µV appeared on a 10 to 18 cm² area of the lateral temporal lobe (Figure 4, red dotted lines; Table 1), the corresponding discharges were recorded on EEG (Figure 4, lower traces, red asterisks). However, when the spike components of SWs with amplitudes of less than 800 µV were noted in an area of the lateral temporal lobe of less than 10 cm², no LPDs were recorded on EEG (Figure 4, lower traces, black dotted lines).

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Figure 4.

Simultaneous electrocorticography-electroencephalography (ECoG-EEG) recordings of the medial temporal lobe during an ictal period in patient 3. The positions of numerous subdural electrode contacts are indicated in Figure 1. Although ictal ECoG discharges with maximum amplitudes of 3000 µV can be observed on the medial temporal lobe, no corresponding ictal activities are recorded on the EEG. On the lateral temporal lobe, repeated SWs are recorded. When spike components of SWs with amplitudes of 800 to 900 µV appear on the 10 to 18 ECoG contacts of the lateral temporal lobe (red dotted lines), the corresponding SWs are recorded on the right temporal region of the scalp (red and blue asterisks).

During ictal periods with seizure activity at the medial temporal lobe, the patient exhibited automatism in his right hand and motion arrest of his left hand with mildly impaired awareness. During the interictal periods, neither LPDs on EEG nor repeated SWs on ECoG were recorded.

The patient underwent amygdalohippocampectomy with anterior temporal lobectomy to include the tumor and obtained a good seizure outcome (Engel class IA). ¹⁶ Histological diagnosis of the tumor was polymorphous low-grade neuroepithelial tumor of the young,^17,18 while hippocampal sclerosis was not demonstrated.

Discussion

In patients 1 and 2 of the present study, the appearance of LPDs on the temporal region of the scalp depended on the amplitude and the cortical extent of the synchronized periodic ECoG discharge on the lateral temporal lobe during the interictal periods. LPDs were recorded when synchronized periodic ECoG discharges with an amplitude of more than 600 to 800 µV appeared on an area of the lateral temporal lobe of more than 10 cm², which is consistent with previous findings.^10,12,13,19 On ECoG, both the SW polyspikes in patient 1 and the PD spike components with various peaks in patient 2 were recorded as monophasic sharp waves on EEG, which reflects a “smearing effect.” ¹³ In contrast, a subsequent slow wave in patient 1 was clearly recorded on EEG. This was probably based on the fact that cortical potentials are not substantially attenuated on the scalp for components below 15 Hz, while the 15 to 30 Hz components show clear attenuation.^20,21 In patients 1 and 2, one of the ictal onset zones was located in the lateral temporal lobe, and it is conceivable that the LPDs of both patients represent a highly irritable state of the lateral temporal cortex during the interictal period.

In contrast, in patient 3, the LPD was recorded when ictal discharges persisted in the medial temporal lobe. Ictal ECoG discharges confined to the medial temporal lobe were not detected on scalp EEG, which is in agreement with the findings of previous studies by us^13,14 and other authors. ²² The major reasons for the limited sensitivity of EEG to ictal discharges in the medial temporal lobe are likely to be the rapid decay of the electrical field with depth and the formation of a closed field in the spiral geometry of the hippocampus.^13,15

Our previous studies demonstrated that, once the ictal discharges in the medial temporal lobe propagate to the lateral cortical convexity, synchronous ictal ECoG discharges with amplitudes of 200 to 2000 µV on an area of the lateral cortex greater than 8 to 15 cm² can be recorded on EEG.^13,14 In patient 3, however, the ictal discharges in the medial temporal lobe did not directly propagate to the lateral cortex, but instead provoked repeated SWs. When a spike component of the SWs with an amplitude of more than 800 µV appeared in more than 10 cm² of the lateral temporal lobe, the corresponding SWs were recorded on the right temporal region of the scalp. Thus, it is conceivable that the LPDs in patient 3 represent a highly irritable state of the lateral temporal cortex during an ictal state of the medial temporal lobe.

The present study has some limitations. First, because we included patients with epilepsy, our results do not directly demonstrate the pathophysiological mechanism of LPDs in critically ill patients. However, we basically follow the critical care EEG terminology proposed by the American Clinical Neurophysiology Society. ³ Second, patients with medial TLE showing typical hippocampal sclerosis were not included in the present study. Because these patients undergo epileptic surgery without invasive examination in our institute, we rarely have the chance to perform simultaneous EEG and ECoG recordings. Third, as in our previous reports,^13-15 the cortical source area was calculated based on 1 cm² per electrode contact, which can overestimate the source area. To minimize this problem, Tatum et al ¹⁹ used high-density ECoG electrodes to demonstrate that the minimum area required to capture PDs was 1.5 to 3 cm at a single gyrus during awake craniotomy. Fourth, during chronic subdural electrode recording, it is necessary to recognize that EEG recording conditions are not physiological. Both the subdural electrode itself and the postoperative edema of the scalp further reduce the conduction of potentials.^13,21 It is possible that the craniotomy site acts as an electrical leak, which would influence the amplitude and waveforms of the potentials recorded from the overlying scalp electrode to produce a breach rhythm. ²³ Although the use of simultaneous scalp EEG and depth electrodes with stereotactic EEG techniques may minimize the problem, ²⁴ this method could not measure the extent of the cortical area involved in the discharge. Finally, this was a retrospective study, with a small number of TLE patients with a variety of epileptogenic mechanisms.

Conclusions

LPDs in TLE patients might represent a highly irritable state of the lateral temporal cortex during both interictal and ictal periods, although further studies with a larger number of TLE patients are required to verify this.