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Interictal high-frequency oscillations, spikes, and connectivity profiles: A fingerprint of epileptogenic brain pathologies

. 2023 Nov ; 64 (11) : 3049-3060. [epub] 20230905

Language English Country United States Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

Grant support
PJT-175056 CIHR - Canada

OBJECTIVE: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for preresective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. METHODS: Interictal awake stereoelectroencephalographic recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. RESULTS: Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures, with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. SIGNIFICANCE: The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

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Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD. Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014.

von Oertzen J, von Oertzen J. Standard magnetic resonance imaging is inadequate for patients with refractory focal epilepsy. J Neurol Neurosurg Psychiatry. 2002;73:643-647. https://doi.org/10.1136/jnnp.73.6.643

Wang ZI, Alexopoulos AV, Jones SE, Jaisani Z, Najm IM, Prayson RA. The pathology of magnetic-resonance-imaging-negative epilepsy. Mod Pathol. 2013;26(8):1051-1058.

Blumcke I, Spreafico R, Haaker G, Coras R, Kobow K, Bien CG, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med. 2017;377(17):1648-1656.

Staley KJ, Dudek FE. Interictal spikes and epileptogenesis. Epilepsy Curr. 2006;6(6):199-202.

Jacobs J, Zijlmans M. HFO to measure seizure propensity and improve prognostication in patients with epilepsy. Epilepsy Curr. 2020;20(6):338-347.

Staba RJ, Bragin A. High-frequency oscillations and other electrophysiological biomarkers of epilepsy: underlying mechanisms. Biomark Med. 2011;5:545-556. https://doi.org/10.2217/bmm.11.72

Jacobs J, LeVan P, Châtillon C-É, Olivier A, Dubeau F, Gotman J. High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type. Brain. 2009;132:1022-1037. https://doi.org/10.1093/brain/awn351

Kerber K, LeVan P, Dümpelmann M, Fauser S, Korinthenberg R, Schulze-Bonhage A, et al. High frequency oscillations mirror disease activity in patients with focal cortical dysplasia. Epilepsia. 2013;54:1428-1436. https://doi.org/10.1111/epi.12262

Ferrari-Marinho T, Perucca P, Mok K, Olivier A, Hall J, Dubeau F, et al. Pathologic substrates of focal epilepsy influence the generation of high-frequency oscillations. Epilepsia. 2015;56:592-598. https://doi.org/10.1111/epi.12940

Fingelkurts AA, Fingelkurts AA, Kähkönen S. Functional connectivity in the brain-is it an elusive concept? Neurosci Biobehav Rev. 2005;28(8):827-836.

Luo C, Qiu C, Guo Z, Fang J, Qifu Li X, Lei YX, et al. Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study. PLoS One. 2011;7(1):e28196.

Voets NL, Beckmann CF, Cole DM, Hong S, Bernasconi A, Bernasconi N. Structural substrates for resting network disruption in temporal lobe epilepsy. Brain. 2012;135(Pt 8):2350-2357.

Liao W, Zhang Z, Pan Z, Mantini D, Ding J, Duan X, et al. Altered functional connectivity and small-world in mesial temporal lobe epilepsy. PLoS One. 2010;5(1):e8525.

Luo C, An D, Yao D, Gotman J. Patient-specific connectivity pattern of epileptic network in frontal lobe epilepsy. NeuroImage Clin. 2014;4(April):668-675.

Hyder F, Rothman DL. Quantitative fMRI and oxidative Neuroenergetics. Neuroimage. 2012;62(2):985-994.

Yuan J, Chen Y, Hirsch E. Intracranial electrodes in the presurgical evaluation of epilepsy. Neurol Sci. 2012;33(4):723-729.

Bartolomei F, Bettus G, Stam CJ, Guye M. Interictal network properties in mesial temporal lobe epilepsy: a graph theoretical study from intracerebral recordings. Clin Neurophysiol. 2013;124(12):2345-2353.

Bettus G, Wendling F, Guye M, Valton L, Régis J, Chauvel P, et al. Enhanced EEG functional connectivity in mesial temporal lobe epilepsy. Epilepsy Res. 2008;81(1):58-68.

Zaveri HP, Pincus SM, Goncharova II, Duckrow RB, Spencer DD, Spencer SS. Localization-related epilepsy exhibits significant connectivity away from the seizure-onset area. Neuroreport. 2009;20(9):891-895.

Klimes P, Duque JJ, Brinkmann B, Van Gompel J, Stead M, St EK, et al. The functional organization of Human epileptic hippocampus. J Neurophysiol. 2016;115(6):3140-3145.

Warren CP, Sanqing H, Stead M, Brinkmann BH, Bower MR, Worrell GA. Synchrony in Normal and focal epileptic brain: the seizure onset zone is functionally disconnected. J Neurophysiol. 2010;104:3530-3539. https://doi.org/10.1152/jn.00368.2010

Rampp S, Rössler K, Hamer H, Illek M, Buchfelder M, Doerfler A, et al. Dysmorphic neurons as cellular source for phase-amplitude coupling in focal cortical dysplasia type II. Clin Neurophysiol. 2021;132(3):782-792.

Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a task force report from the ILAE commission on diagnostic methods. Epilepsia. 2013;54(7):1315-1329.

Blümcke I, Thom M, Aronica E, Armstrong DD, Vinters HV, Palmini A, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia. 2011;52(1):158-174.

Engel J. (Ed). Surgical treatment of the epilepsies, 2nd edition. New York: Raven Press;1993. p. 786.

Barkmeier DT, Shah AK, Flanagan D, Atkinson MD, Agarwal R, Fuerst DR, et al. High inter-reviewer variability of spike detection on intracranial EEG addressed by an automated multi-channel algorithm. Clin Neurophysiol. 2012;123(6):1088-1095.

Cimbalnik J, Hewitt A, Worrell G, Stead M. The CS algorithm: a novel method for high frequency oscillation detection in EEG. J Neurosci Methods. 2018;293:6-16.

Cimbalnik J, Klimes P, Sladky V, Nejedly P, Jurak P, Pail M, et al. Multi-feature localization of epileptic foci from Interictal, intracranial EEG. Clin Neurophysiol. 2019;130:1945-1953. https://doi.org/10.1016/j.clinph.2019.07.024

Baulac M. MTLE with hippocampal sclerosis in adult as a syndrome. Rev Neurol. 2015;171(3):259-266.

Mohamed A, Wyllie E, Ruggieri P, Kotagal P, Babb T, Hilbig A, et al. Temporal lobe epilepsy due to hippocampal sclerosis in pediatric candidates for epilepsy surgery. Neurology. 2001;56(12):1643-1649.

Riban V, Bouilleret V, Pham-Lê BT, Fritschy J-M, Marescaux C, Depaulis A. Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience. 2002;112(1):101-111.

Menezes Cordeiro I, von Ellenrieder N, Zazubovits N, Dubeau F, Gotman J, Frauscher B. Sleep influences the intracerebral EEG pattern of focal cortical dysplasia. Epilepsy Res. 2015;113:132-139.

Tassi L, Garbelli R, Colombo N, Bramerio M, Russo GL, Mai R, et al. Electroclinical, MRI and surgical outcomes in 100 epileptic patients with type II FCD. Epileptic Disord. 2012;14(3):257-266. https://doi.org/10.1684/epd.2012.0525

Jacobs J, LeVan P, Chander R, Hall J, Dubeau F, Gotman J. Interictal high-frequency oscillations (80-500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain. Epilepsia. 2008;49(11):1893-1907.

Zijlmans M, Jacobs J, Zelmann R, Dubeau F, Gotman J. High-frequency oscillations Mirror disease activity in patients with epilepsy. Neurology. 2009;72(11):979-986.

Besseling RMH, Jansen JFA, de Louw AJA, Mariëlle CG, Vlooswijk MC, Hoeberigs AP, et al. Abnormal profiles of local functional connectivity proximal to focal cortical dysplasias. PLoS One. 2016;11(11):e0166022.

Liu W, Lin M, Yue Q, Gong Q, Zhou D, Xintong W. Brain functional connectivity patterns in focal cortical dysplasia related epilepsy. Seizure. 2021;87(April):1-6.

Hong S-J, Bernhardt BC, Gill RS, Bernasconi N, Bernasconi A. The Spectrum of structural and functional network alterations in malformations of cortical development. Brain. 2017;140(8):2133-2143.

Morgan RJ, Soltesz I. Nonrandom connectivity of the epileptic dentate gyrus predicts a major role for neuronal hubs in seizures. Proc Natl Acad Sci US A. 2008;105(16):6179-6184.

Wilke C, Worrell G, He B. Graph analysis of epileptogenic networks in human partial epilepsy. Epilepsia. 2011;52(1):84-93.

Kim DW, Lee SK, Chu K, Park KI, Lee SY, Lee CH, et al. Predictors of surgical outcome and pathologic considerations in focal cortical dysplasia. Neurology. 2009;72(3):211-216.

Krsek P, Maton B, Jayakar P, Dean P, Korman B, Rey G, et al. Incomplete resection of focal cortical dysplasia is the Main predictor of poor postsurgical outcome. Neurology. 2009;72:217-223. https://doi.org/10.1212/01.wnl.0000334365.22854.d3

McIntosh AM. Temporal lobectomy: long-term seizure outcome, late recurrence and risks for seizure recurrence. Brain. 2004;127:2018-2030. https://doi.org/10.1093/brain/awh221

Perucca P, Dubeau F, Gotman J. Intracranial electroencephalographic seizure-onset patterns: effect of underlying pathology. Brain. 2014;137(Pt 1):183-196.

Deshpande T, Li T, Herde MK, Becker A, Vatter H, Schwarz MK, et al. Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy. Glia. 2017;65(11):1809-1820.

do Canto AM, Donatti A, Geraldis JC, Godoi AB, da Rosa DC, Lopes-Cendes I. Neuroproteomics in Epilepsy: what do we know so far? Front Mol Neurosci. 2020;13:604158.

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