Markers Of Epileptogenicity Research Articles

Chronic intracranial recordings after resection for epilepsy reveal a "running down" of epileptiform activity.

We describe an electrical "running down" phenomenon and also a consistent spectral change (in the aperiodic component of the power spectrum) derived from chronic interictal electrocorticography (ECoG) after surgery in a patient with drug-resistant epilepsy. These data were recorded using a closed-loop neurostimulation system that was implanted after resection. The patient has been seizure-free for 2.5 years since resection without requiring the neurostimulator to be turned on to stimulate. Concurrently, there was an exponential decrease in the number of epileptiform electrographic detections recorded by the device, particularly over the first 26 weeks, indicative of an electrical running down phenomenon as the brain adapted to an extended period of seizure freedom. We also find that the aperiodic exponent of the power spectrum gradually decreases over time. The aperiodic component of intracranial ECoG may represent a novel marker of epileptogenicity, independent of seizures.

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach. We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median=5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike-high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations. Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus. These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. 18 F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology

<i>Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, &amp; Neuroimaging</i> Advancing the Field of Neurology

Interictal Functional Connectivity in Focal Refractory Epilepsies Investigated by Intracranial EEG.

Introduction: Focal epilepsies are diseases of neuronal excitability affecting macroscopic networks of cortical and subcortical neural structures. These networks ("epileptogenic networks") can generate pathological electrophysiological activities during seizures, and also between seizures (interictal period). Many works attempt to describe these networks by using quantification methods, particularly based on the estimation of statistical relationships between signals produced by brain regions, namely functional connectivity (FC). Results: FC has been shown to be greatly altered during seizures and in the immediate peri-ictal period. An increasing number of studies have shown that FC is also altered during the interictal period depending on the degree of epileptogenicity of the structures. Furthermore, connectivity values could be correlated with other clinical variables including surgical outcome. Significance: This leads to a conceptual change and to consider epileptic areas as both hyperexcitable and abnormally connected. These data open the door to the use of interictal FC as a marker of epileptogenicity and as a complementary tool for predicting the effect of surgery. Aim: In this article, we review the available data concerning interictal FC estimated from intracranial electroencephalograhy (EEG) in focal epilepsies and discuss it in the light of data obtained from other modalities (EEG imaging) and modeling studies.

Hippocampal spindles and barques are normal intracranial electroencephalographic entities

ObjectiveTo assess whether hippocampal spindles and barques are markers of epileptogenicity. MethodsFocal epilepsy patients that underwent stereo-electroencephalography implantation with at least one electrode in their hippocampus were selected (n = 75). The occurrence of spindles and barques in the hippocampus was evaluated in each patient. We created pairs of pathologic and pathology-free groups according to two sets of criteria: 1. Non-invasive diagnostic criteria (patients grouped according to focal epilepsy classification). 2. Intracranial neurophysiological criteria (patient’s hippocampi grouped according to their seizure onset involvement). ResultsHippocampal spindles and barques appear equally often in both pathologic and pathology-free groups, both for non-invasive (Pspindles = 0.73; Pbarques = 0.46) and intracranial criteria (Pspindles = 0.08; Pbarques = 0.26). In Engel Class I patients, spindles occurred with similar incidence both within the non-invasive (P = 0.67) and the intracranial criteria group (P = 0.20). Barques were significantly more frequent in extra-temporal lobe epilepsy defined by either non-invasive (P = 0.01) or intracranial (P = 0.01) criteria. ConclusionsBoth spindles and barques are normal entities of the hippocampal intracranial electroencephalogram. The presence of barques may also signify lack of epileptogenic properties in the hippocampus. SignificanceUnderstanding that hippocampal spindles and barques do not reflect epileptogenicity is critical for correct interpretation of epilepsy surgery evaluations and appropriate surgical treatment selection.

High-Frequency Oscillations in Pediatric Epilepsy: Methodology and Clinical Application

Increasing evidence indicates that the brain generates signals in a wide-frequency range, including high-frequency brain signals. High-frequency brain signals are also called high-frequency oscillations (HFOs), ripples, or fast ripples. There are no established terms for describing HFOs in a variety of frequency ranges. HFOs are clinically important because early detection of epileptic (or pathologic) high-frequency brain signals may significantly change the clinical management of epilepsy, including pediatric epilepsy. In this article, we review the cerebral mechanisms of HFOs and the maturational changes of HFOs in the developing brain. Newly developed methods for the detection and localization of HFOs are discussed. We describe many recent findings in the literature from invasive electrocorticography recordings, scalp electroencephalography, and magnetoencephalography. We also discuss the clinical importance of HFOs as markers of epileptogenicity and their application in different types of epilepsies. As successful surgical treatment in medically refractory epilepsies largely depends on the identification of epileptogenic zones, the use of HFOs may significantly improve surgical outcomes. Indeed, the removal of brain tissue generating pathological high-frequency signals has been related to better postsurgical outcomes than removal of the seizure onset zones. This indicates that HFOs may mark cortex that needs to be removed to achieve seizure control. The link between the epileptogenic zone and HFOs suggests that their study can elucidate the pathophysiology of epileptogenesis and ictogenesis. In addition, HFOs may reflect the predisposition of the tissue to generate seizures. Finally, we discuss how HFOs can be used to study childhood absence epilepsy, which can only be studied noninvasively.

High‐frequency electroencephalographic oscillations correlate with outcome of epilepsy surgery

High-frequency oscillations (HFOs) in the intracerebral electroencephalogram (EEG) have been linked to the seizure onset zone (SOZ). We investigated whether HFOs can delineate epileptogenic areas even outside the SOZ by correlating the resection of HFO-generating areas with surgical outcome. Twenty patients who underwent a surgical resection for medically intractable epilepsy were studied. All had presurgical intracerebral EEG (500Hz filter and 2,000Hz sampling rate), at least 12-month postsurgical follow-up, and a postsurgical magnetic resonance imaging (MRI). HFOs (ripples, 80-250Hz; fast ripples, >250Hz) were identified visually during 5 to 10 minutes of slow-wave sleep. Rates and extent of HFOs and interictal spikes in resected versus nonresected areas, assessed on postsurgical MRIs, were compared with surgical outcome (Engel's classification). We also evaluated the predictive value of removing the SOZ in terms of surgical outcome. The mean duration of follow-up was 22.7 months. Eight patients had good (Engel classes 1 and 2) and 12 poor (classes 3 and 4) surgical outcomes. Patients with a good outcome had a significantly larger proportion of HFO-generating areas removed than patients with a poor outcome. No such difference was seen for spike-generating regions or the SOZ. The correlation between removal of HFO-generating areas and good surgical outcome indicates that HFOs could be used as a marker of epileptogenicity and may be more accurate than spike-generating areas or the SOZ. In patients in whom the majority of HFO-generating tissue remained, a poor surgical outcome occurred.