Periodic Lateralized Epileptiform Discharges and Afterdischarges: Common Dynamic Mechanisms

Abstract

Purpose: No neurophysiological hypothesis currently exists addressing how and why periodic lateralized epileptiform discharges (PLEDs) arise in certain types of brain disease. Based on spectral analysis of clinical scalp EEG traces, the authors formulated a general mechanism for the emergence of PLEDs.

Methods: The authors retrospectively analyzed spectra of PLED time series and control EEG segments from the opposite hemisphere in 25 hospitalized neurological patients. The observations led to the development of a phenomenological model for PLED emergence.

Results: Similar to that observed in our previous work with afterdischarges, an analytic relationship is found between the spectrum of the baseline EEG and the PLED EEG, characterized by "condensation" of the main baseline spectral cluster, with variable inclusion of higher harmonics of the condensate.

Conclusions: Periodic lateralized epileptiform discharges may arise by synchronization of preexisting local field potentials, through a variable combination of enhancement of excitatory neurotransmission and inactivation of inhibitory neurotransmission provoked by the PLED-associated disease process. Higher harmonics in the PLED spectrum may arise by recurrent feedback, possibly from entrained single units. A mechanism is suggested for PLED emergence in certain diseased brain states and the association of PLEDs with EEG seizures. The framework is a spatially extended version of that, which the authors proposed, underlies afterdischarge and analogous to the cooperative behavior seen in a variety of natural multi-oscillator systems.

Figure 1

a) Regular PLED pattern in Patient #14 with serial seizures from leukemic involvement of the CNS. 10-second EEG epoch, x-axis: time (seconds; secs); y-axis: voltage (microvolts; μV).The PLED waveforms occur uniformly in time, yielding a spectrum c) that possesses a well-defined peak at just below 1 Hz, the fundamental period of the pattern. x-axis: frequency (Hz); y-axis: normalized units (NU) of power spectral density. b) An irregular PLED pattern in Patient #3 with seizures related to ventriculitis and CNS lymphoma. Frequent sharp discharges are present but variable in time, with polymorphic and variably long stretches of background between complexes. The spectrum d) has less structure, despite the appearance of local maxima at ~1 Hz, ~2 Hz and ~3 Hz.

Figure 2

Figure 2A. A regular PLED in a patient with an acute left posterior quadrant lobar hemorrhage (Patient #1) illustrating condensation and low-pass filtering. a) A10-s EEG epoch from the normal right hemispheric mid-temporal derivation, showing a mix of polymorphic fast and slow rhythms and irregular larger amplitude transients b) A typical epoch of the homologous left mid-temporal chain showing PLEDs at frequency ~1 Hz. c) Power spectrum of the entire T4–T6 EEG epoch. The spectrum is wide-band with broad maxima in the δ and α Berger bands, the latter indicating a preserved posterior dominant rhythm. d) Power spectrum of the entire T3–T5 EEG epoch. Comparison of the spectra illustrates spectral condensation, with the broad δ band of the normal side appearing to coalesce into sharply defined peaks in the PLED spectrum. Indeed, the small local maximum on the normal side (at ~2 Hz) ‘grows’ in the same location into the dominant frequency component of the PLED. The two spectra also illustrate low-pass filtering, with the α-band frequencies on the normal side flattening out on the PLED side, in keeping with the visually-obvious absence of the α rhythm in the raw PLED time series. Figure 2B. Example of the condensation-plus-harmonics transformation in Patient #7 with serial seizures and a previously resected brain tumor. a) Continuous slowing on the normal (but encephalopathic) left side. b) Right-sided ~1 Hz PLED pattern. c) Left sided power spectrum shows a relatively narrow base with significant power only below ~4 Hz in keeping with the slowing seen in the time series. A prominent peak at ~2 Hz is however present. d) The PLED spectrum shows more discrete and condensed appearance, with three main peaks: a fundamental (at ~1 Hz), a second harmonic (at ~2 Hz) that corresponds to the maximum peak of the normal side, and a third harmonic (at ~3 Hz). A further smaller peak at ~3.5 Hz appears, of uncertain origin.

Figure 2

Figure 2A. A regular PLED in a patient with an acute left posterior quadrant lobar hemorrhage (Patient #1) illustrating condensation and low-pass filtering. a) A10-s EEG epoch from the normal right hemispheric mid-temporal derivation, showing a mix of polymorphic fast and slow rhythms and irregular larger amplitude transients b) A typical epoch of the homologous left mid-temporal chain showing PLEDs at frequency ~1 Hz. c) Power spectrum of the entire T4–T6 EEG epoch. The spectrum is wide-band with broad maxima in the δ and α Berger bands, the latter indicating a preserved posterior dominant rhythm. d) Power spectrum of the entire T3–T5 EEG epoch. Comparison of the spectra illustrates spectral condensation, with the broad δ band of the normal side appearing to coalesce into sharply defined peaks in the PLED spectrum. Indeed, the small local maximum on the normal side (at ~2 Hz) ‘grows’ in the same location into the dominant frequency component of the PLED. The two spectra also illustrate low-pass filtering, with the α-band frequencies on the normal side flattening out on the PLED side, in keeping with the visually-obvious absence of the α rhythm in the raw PLED time series. Figure 2B. Example of the condensation-plus-harmonics transformation in Patient #7 with serial seizures and a previously resected brain tumor. a) Continuous slowing on the normal (but encephalopathic) left side. b) Right-sided ~1 Hz PLED pattern. c) Left sided power spectrum shows a relatively narrow base with significant power only below ~4 Hz in keeping with the slowing seen in the time series. A prominent peak at ~2 Hz is however present. d) The PLED spectrum shows more discrete and condensed appearance, with three main peaks: a fundamental (at ~1 Hz), a second harmonic (at ~2 Hz) that corresponds to the maximum peak of the normal side, and a third harmonic (at ~3 Hz). A further smaller peak at ~3.5 Hz appears, of uncertain origin.

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 3

Figure 3A-H. Eight different examples (from Patients #4, #8, #9, #12, #13, #20, #21 and #23 respectively), illustrating the diversity of the condensation, harmonic generation and low-pass filtering dynamics observed. See Table 1 for clinical details. All three dynamic effects are appreciated in 3G; condensation and harmonic generation are particularly prominent in 3C, 3E and 3H; condensation and low-pass filtering are prominent in 3D and 3F (the former also has a fine superimposed toothcomb harmonic structure); low-pass filtering alone is prominent in 3A and 3B (in the latter, an incipient PLED waveform is seen on the ‘normal’ side as well).

Figure 4

Resolution of the PLED waveform over time in a patient who received continuous monitoring (Patient #19, with an old left hemispheric structural lesion and status epilepticus). Traces a), b) and c) are all of the same T5-O1 channel (channel label marked only once for clarity); figures d), e) and f) are the corresponding power spectra. a) A robust regular PLED waveform, whose spectrum d) shows a clear 2-peaked structure of a fundamental (at ~0.9 Hz) and its second harmonic (at ~1.8 Hz) along with a small third harmonic (~2.7 Hz). b) The waveform later in the illness becomes somewhat irregular with some reduction of sharp components. The spectrum at this stage e) has broadened out and lost the third harmonic, though a clear two-peak structure remains. c) In the immediate post-recovery phase the EEG has returned to near baseline with continuous polymorphic slowing only; its spectrum f) is wide-band, but exists largely in the same domain (~0–4 Hz) that gave rise to the PLED peaks earlier. There is peak at ~3.1 Hz not present in the PLED waveforms that represents faster frequencies that were filtered out in the formation of the PLED; the remainder of the spectrum (< 3 Hz) does possess a small local maximum at ~0.9 Hz that condenses and accrues harmonics to yield the PLED.

Figure 5

Emergence of the PLED waveform from the normal background rhythms in Patient #11. a) A 10-s epoch in light sleep from the right occipital region shows well-formed polymorphic rhythms, composed of c) two broad spectral peaks centered at ~1 Hz and ~5.5 Hz. Following a cluster of seizures, the patient exhibited b) a PLED pattern. Its spectrum d) has a clear multi-peak, low-pass filtered structure. The fundamental (left-most peak; arrow) arises at ~1 Hz, which is approximately concordant with a local maximum of the baseline spectrum (arrow).

Figure 6

Spectral condensation in electrocorticographic afterdischarge (AD). Figure adapted from Figure 2 of Kalamangalam et. al. (2014). a) An 8-second epoch from a single channel of a lateral temporal subdural electrode contact in a patient undergoing cortical stimulation mapping, though prior to any stimulation. x-axis: time (seconds); y-axis: waveform amplitudes referenced to a common average (μvolts). b) The power spectrum of the baseline epoch is an irregular mix of components that is biased towards the lower frequencies. x-axis: frequency (Hz); y-axis: power spectral density (μV²/Hz). c) An 8-second afterdischarge elicited by a 6 mA stimulus at the same electrode. d) The AD’s power spectrum is a ‘condensed’ version of the baseline spectrum: less spread out, more sharply peaked, and of much greater amplitude at the maximum.