On the Origin of PLEDs: Are Cortical and Subcortical PLEDs Electrographically Different?

Abstract & Commentary

By Padmaja Kandula, MD, Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Medical College of Cornell University. Dr. Kandula reports no financial relationships relevant to this field of study.

Synopsis: This retrospective study correlates neuroimaging lesion distribution with periodic lateralized epileptiform discharges (PLEDS) and points out the different characteristics of PLEDS from cortical vs. subcortical origin.

Sources: Kalamangalam GP, et al; Neuroimaging and neurophysiology of periodic lateralized epileptiform discharges: observations and hypotheses. Epilepsia. 2007; 48(7):1396-1405.

The occurrence of pleds during a routine electroencephalographic study is not a new concept. In fact, the relevance of this elusive discharge has been the focus of interest over the last 2 decades, particularly since the advent of higher resolution imaging techniques. This recent retrospective study performed at the Cleveland Clinic aims to answer whether PLED morphology has any association with lesion location.

Over a 4-year period, 106 patients with PLEDs were retrospectively identified from an EEG database. These 106 patients were then classified into one of 5 groups based upon corresponding imaging (CT and/or MRI) characteristics: normal, acute cortical, acute subcortical, chronic cortical, and chronic subcortical. Classification of imaging abnormalities prioritized acute over chronic changes, and cortical over subcortical changes. This stratification of data based on neuroimaging constituted part I of the study.

In part II of the study, raw EEG data was scored quantitatively and/or qualitatively by a senior epileptologist, blinded to the neuroimaging findings in 95/106 patients where the original, complete EEG record was available. The selected 30 seconds of artifact free EEG was then scored, based on the following characteristics: inter-PLED interval (repetition rate), duration of complex, amplitude, prominent polarity, morphology (number of sharp phases and total number of phases), distribution, degree of intervening slow rhythms (subjective estimate) and reactivity. Of the 95 patients, 35 patient EEG records were excluded due to greater than one independent PLED population (eg. BIPLED), unsustained PLEDS (< 20 seconds during the recording), and physician disagreement with the original EEG classification. EEGs associated with normal neuroimaging were also excluded. Of the remaining 60 records, 49 of the records were associated with a cortical lesion (group A) and 11 records with a subcortical lesion (group B).

The results of part I of the study showed that acute cortical lesions were the most common abnormality (40.5%). However, subcortical lesions (both acute and chronic combined) were not infrequent (23.6%).

In part II of the study, the electrographic characteristics of group A (cortical) and group B(subcortical ) were compared. Overall, the duration of a typical cortical PLED (sharp or spike-and-slow wave discharge) was longer (mean 574 msec) than a subcortical one (mean 420 msec). Cortical PLEDSs were also more variable in morphology (mean of 2.367 in group A vs. mean of 1.727 in group B). However, repetition rate and degree of intervening background slowing between successive PLEDs was not statistically significant between the 2 groups.


Over the years, much debate has ensued regarding the neuroanatomic and pathophysiologic aspects of this periodic entity. Although retrospective in nature, this study is one of few that correlates electrographic activity with neuroimaging. Clinically, the appearance of PLEDs in instances of cortical lesions is not surprising, as epileptiform discharges in general are thought to arise from cortical gray matter. However, the fairly high frequency of both acute and chronic subcortical PLEDs in this study is surprising and interesting.

Inherent drawbacks to this study are classification of the imaging abnormalities, where cortical or subcortical reflected the location of the predominant imaging abnormality as regarded by the senior author. In reality, most lesions involve both subcortical and cortical structures, making definitive stratification difficult. Also, the proportion of lesion type may have been influenced by lack of MRI confirmation (only CT evidence) of lesions in one third of patients. The retrospective nature of the study also limited the number of full EEG recordings available for review.

The authors present a unifying theory of PLED genesis where discharges can arise from perturbation of a segment(s) of the interconnected cortical-subcortical circuit. The electroencephalographic "signature" or synchronous oscillations seen on scalp EEG may reflect the spatial origin of PLEDs. This theory seems plausible as established animal models for sleep neurophysiology have shown reproducible 12-14 Hz rhythms (sleep spindles) originating from reticular-thalamocortical connections. The authors further speculate that subcortical PLEDs are relatively shorter duration and stereotyped due to the restricted extent of the lesion and rapidly conducting white matter projections, in comparison to cortical PLEDs. Although the number of subcortical PLEDs (n = 11) analyzed in this study were small, the finding of shorter duration and stereotypical morphology of subcortical vs cortical PLEDs supports the above hypothesis.

This paper and other recent papers (Gurer et al, Clin EEG 2004;35:88-93 and Gross et al, EEG Clin Neurophysiol 1998;107:434-438) support the idea of subcortical PLEDs, challenging the classical notion that PLEDs are only a manifestation of acute cortical lesions. However, further, large-scale prospective studies, with concomitant EEG and adjunctive neurophysiologic monitoring, such as magnetoencephalographic analysis, may help shed further light on the origin of periodic patterns such as PLEDs.