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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Common Ictal and Interictal Perfusion Patterns: A Window into the Epileptogenic Network and SUDEP Mechanism in Drug-Resistant Focal Epilepsy

Author(s): Lilia M. Morales Chacón*, Lidice Galan García, Karla Batista García-Ramón, Margarita Minou Báez Martin, Jorge Bosch-Bayard, Maydelis Alfonso Alfonso, Sheyla Berrillo Batista, Tania de la Paz Bermudez, Judith González González, Abel Sánchez Coroneaux, Ángel Águila Ruiz, Marlene Perera Roque and Leysi Murada Matamoro

Volume 28, Issue 14, 2022

Published on: 09 June, 2022

Page: [1198 - 1209] Pages: 12

DOI: 10.2174/1381612828666220603125328

Price: $65

Abstract

Background: Focal epilepsies have been described as a network disease. Noninvasive investigative techniques have been used to characterize epileptogenic networks.

Objective: This study aimed to describe ictal and interictal cortical and subcortical perfusion patterns using single- photon emission computed tomography (SPECT) in patients with drug-resistant epilepsy (DRE).

Methods: Thirty-five interictal-ictal SPECT scans were obtained from 15 patients with DRE. A methodology was developed to get a relative perfusion index (PI) of 74 cortical and sub-cortical brain structures. K-means algorithm, together with modified v-fold cross-validation, was used to identify the two regions of interest (ROIs) that represent hypoperfused and hyperperfused areas.

Results: In common with the individual analysis, the statistical analysis evidenced that the hyperperfusion ROIs resulting from group analysis during interictal and ictal involved mainly the cingulate gyrus, cuneus, lingual gyrus, and gyrus rectus as well as the putamen. ROIs hypoperfused included the red nucleus, the substantia nigra, and the medulla. The medians of the group analysis of the hypoperfusion and hyperperfusion ROIs were 0.601-0.565 and 1.133-1.119 for the ictal and interictal states, correspondingly. A group of mostly cortical structures involved in the hyperperfused ROIs in both interictal and ictal states showed no change or negative change in the transition from interictal to ictal state (mean change of -0.002). On the other hand, the brain stem, basal ganglia, red nucleus, and thalamus revealed a mean global change of 0.19, indicating a mild increase in the PI. However, some of these structures (red nucleus, substantia nigra, and medulla oblongata) remained hypoperfused during the interictal to ictal transition.

Conclusion: The methodology employed made it possible to identify common cortical and subcortical perfusion patterns not directly linked to epileptogenicity, for a better epileptogenic network and sudden unexpected death (SUDEP) mechanism in DRE.

Keywords: Single photon emission computed tomography, ictal SPECT, interictal SPECT, drug-resistant focal epilepsy, SUDEP, hypoperfused.

[1]
Bartolomei F, Lagarde S, Wendling F, et al. Defining epileptogenic networks: Contribution of SEEG and signal analysis. Epilepsia 2017; 58(7): 1131-47.
[http://dx.doi.org/10.1111/epi.13791] [PMID: 28543030]
[2]
Englot DJ, Konrad PE, Morgan VL. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings. Epilepsia 2016; 57(10): 1546-57.
[http://dx.doi.org/10.1111/epi.13510] [PMID: 27554793]
[3]
Englot DJ, Morgan VL. Impaired vigilance networks in temporal lobe epilepsy Mechanisms and clinical implications 2020; 61(2): 189-202.
[http://dx.doi.org/10.1111/epi.16423]
[4]
González Otárula KA, Schuele S. Networks in temporal lobe epilepsy. Neurosurg Clin N Am 2020; 31(3): 309-17.
[http://dx.doi.org/10.1016/j.nec.2020.02.001] [PMID: 32475481]
[5]
Larivière S, Rodríguez-Cruces R, Royer J, et al. Network-based atrophy modeling in the common epilepsies A worldwide ENIGMA study 2020; 6(47): 698-700.
[http://dx.doi.org/10.1126/sciadv.abc6457]
[6]
Whelan CD, Altmann A, Botía JA, et al. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain 2018; 141(2): 391-408.
[http://dx.doi.org/10.1093/brain/awx341] [PMID: 29365066]
[7]
Chang C, Pastor J, Sola RG, Vega-Zelaya L, Garnes Ó, Ortega GJ. Functional connectivity and complex networks in focal epilepsy. Pathophysiology and therapeutic implications. Epilepsia 2014; 58(9): 411-9.
[8]
Morales-Chacon LM, Alfredo Sanchez Catasus C, Minou Baez Martin M, Rodriguez Rojas R, Lorigados Pedre L, Estupiñan Diaz B. Multimodal imaging in nonlesional medically intractable focal epilepsy. Front Biosci (Elite Ed) 2015; 7(1): 42-57.
[PMID: 25553362]
[9]
Smit DJA, Andreassen OA, Boomsma DI. Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity 2021.: e02188.
[http://dx.doi.org/10.1002/brb3.2188]
[10]
Liu J, Peedicail JS, Gaxiola-Valdez I, et al. Postictal brainstem hypoperfusion and risk factors for sudden unexpected death in epilepsy. Neurology 2020; 95(12): e1694-705.
[http://dx.doi.org/10.1212/WNL.0000000000010360]
[11]
Scorza FA, Cavalheiro EA, Costa JC. Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith. Arq Neuropsiquiatr 2016; 74(7): 570-3.
[http://dx.doi.org/10.1590/0004-282X20160086] [PMID: 27487377]
[12]
de Palma L, De Benedictis A, Specchio N, Marras CE. Epileptogenic network formation. Neurosurg Clin N Am 2020; 31(3): 335-44.
[http://dx.doi.org/10.1016/j.nec.2020.03.012] [PMID: 32475484]
[13]
Allen LA, Harper RM, Kumar R, et al. Dysfunctional brain networking among autonomic regulatory structures in temporal lobe epilepsy patients at high risk of sudden unexpected death in epilepsy. Front Neurol 2017; 8: 544.
[http://dx.doi.org/10.3389/fneur.2017.00544] [PMID: 29085330]
[14]
Aupy J, Wendling F, Taylor K, Bulacio J, Gonzalez-Martinez J, Chauvel P. Cortico-striatal synchronization in human focal seizures. Brain 2019; 142(5): 1282-95.
[http://dx.doi.org/10.1093/brain/awz062] [PMID: 30938430]
[15]
He X, Doucet GE, Sperling M, Sharan A, Tracy JI. Reduced thalamocortical functional connectivity in temporal lobe epilepsy. Epilepsia 2015; 56(10): 1571-9.
[http://dx.doi.org/10.1111/epi.13085] [PMID: 26193910]
[16]
McNally KA, Paige AL, Varghese G, et al. Localizing value of ictal-interictal SPECT analyzed by SPM (ISAS). Epilepsia 2005; 46(9): 1450-64.
[http://dx.doi.org/10.1111/j.1528-1167.2005.06705.x] [PMID: 16146441]
[17]
Varghese GI, Purcaro MJ, Motelow JE, et al. Clinical use of ictal SPECT in secondarily generalized tonic-clonic seizures. Brain 2009; 132(Pt 8): 2102-13.
[http://dx.doi.org/10.1093/brain/awp027] [PMID: 19339251]
[18]
Batista García-Ramó K, Sanchez Catasus CA, Morales Chacón L, et al. A novel noninvasive approach based on SPECT and EEG for the location of the epileptogenic zone in pharmacoresistant non-lesional epilepsy. Medicina (Kaunas) 2019; 55(8): 478.
[http://dx.doi.org/10.3390/medicina55080478] [PMID: 31416172]
[19]
Morales Chacón L, Estupiñán B, Lorigados Pedre L, et al. Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: An electrocorticography study. Seizure 2009; 18(8): 593-600.
[http://dx.doi.org/10.1016/j.seizure.2009.06.008] [PMID: 19679496]
[20]
Morales Chacón LM, Garcia Maeso I, Baez Martin MM, et al. Long-term electroclinical and employment follow up in temporal lobe epilepsy surgery. A Cuban Comprehensive Epilepsy Surgery Program. Behav Sci (Basel) 2018; 8(2): 19.
[http://dx.doi.org/10.3390/bs8020019] [PMID: 29389846]
[21]
Walczak TS, Leppik IE, D’Amelio M, et al. Incidence and risk factors in sudden unexpected death in epilepsy: A prospective cohort study. Neurology 2001; 56(4): 519-25.
[http://dx.doi.org/10.1212/WNL.56.4.519] [PMID: 11222798]
[22]
Smith SM. Fast robust automated brain extraction. Hum Brain Mapp 2002; 17(3): 143-55.
[http://dx.doi.org/10.1002/hbm.10062] [PMID: 12391568]
[23]
Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002; 17(2): 825-41.
[http://dx.doi.org/10.1006/nimg.2002.1132] [PMID: 12377157]
[24]
Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 2001; 20(1): 45-57.
[http://dx.doi.org/10.1109/42.906424] [PMID: 11293691]
[25]
Thomas BA, Erlandsson K, Modat M, et al. The importance of appropriate partial volume correction for PET quantification in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2011; 38(6): 1104-19.
[http://dx.doi.org/10.1007/s00259-011-1745-9]
[26]
Oishi K, Faria A, Jiang H, et al. Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: Application to normal elderly and Alzheimer’s disease participants. Neuroimage 2009; 46(2): 486-99.
[http://dx.doi.org/10.1016/j.neuroimage.2009.01.002] [PMID: 19385016]
[27]
Xia M, Wang J, He Y. BrainNet Viewer: A network visualization tool for human brain connectomics. PLoS One 2013; 8(7): e68910.
[http://dx.doi.org/10.1371/journal.pone.0068910]
[28]
DLaDC W. Clustering Academic Press Library in Signal Processing (Signal Processing Theory and Machine Learning) 2004; 1: 1115-49.
[29]
Tousseyn S, Dupont P, Goffin K, Sunaert S, Van Paesschen W. Correspondence between large-scale ictal and interictal epileptic networks revealed by single photon emission computed tomography (SPECT) and electroencephalography (EEG)-functional magnetic resonance imaging (fMRI). Epilepsia 2015; 56(3): 382-92.
[http://dx.doi.org/10.1111/epi.12910] [PMID: 25631544]
[30]
Blumenfeld H, Varghese GI, Purcaro MJ, et al. Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures. Brain 2009; 132(Pt 4): 999-1012.
[http://dx.doi.org/10.1093/brain/awp028] [PMID: 19339252]
[31]
Ogren JA, Tripathi R, Macey PM, et al. Regional cortical thickness changes accompanying generalized tonic-clonic seizures. Neuroimage Clin 2018; 20: 205-15.
[http://dx.doi.org/10.1016/j.nicl.2018.07.015] [PMID: 30094170]
[32]
Harden C, Tomson T, Gloss D, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the guideline development, dissemination, and implementation subcommittee of the american academy of neurology and the american epilepsy society. Neurology 2017; 88(17): 1674-80.
[http://dx.doi.org/10.1212/WNL.0000000000003685] [PMID: 28438841]
[33]
Hong SJ, Bernhardt BC, Schrader DS, Bernasconi N, Bernasconi A. Whole-brain MRI phenotyping in dysplasia-related frontal lobe epilepsy. Neurology 2016; 86(7): 643-50.
[http://dx.doi.org/10.1212/WNL.0000000000002374] [PMID: 26764030]
[34]
Kamson DO, Pilli VK, Asano E, et al. Cortical thickness asymmetries and surgical outcome in neocortical epilepsy. J Neurol Sci 2016; 368: 97-103.
[http://dx.doi.org/10.1016/j.jns.2016.06.065] [PMID: 27538609]
[35]
Lin JJ, Salamon N, Lee AD, et al. Reduced neocortical thickness and complexity mapped in mesial temporal lobe epilepsy with hippocampal sclerosis. Cereb Cortex 2007; 17(9): 2007-18.
[http://dx.doi.org/10.1093/cercor/bhl109] [PMID: 17088374]
[36]
Kumar A, Alhourani H, Abdelkader A, Shah AK, Juhász C, Basha MM. Frontal lobe hypometabolism associated with Sudden Unexpected Death in Epilepsy (SUDEP) risk: An objective PET study. Epilepsy Behav 2021; 122: 108185.
[37]
Allen LA, Harper RM, Lhatoo S, Lemieux L, Diehl B. Neuroimaging of Sudden Unexpected Death in Epilepsy (SUDEP): Insights From Structural and Resting-State Functional MRI Studies. Front Neurol 2019; 10: 185.
[http://dx.doi.org/10.3389/fneur.2019.00185] [PMID: 30891003]
[38]
Thorn M. Neuropathologic findings in postmortem studies of sudden death in epilepsy. Epilepsia 1997; 38(11)(Suppl.): S32-4.
[http://dx.doi.org/10.1111/j.1528-1157.1997.tb06123.x] [PMID: 19909322]
[39]
Tang Y, Chen Q, Yu X, et al. A resting-state functional connectivity study in patients at high risk for sudden unexpected death in epilepsy. Epilepsy Behav 2014; 41: 33-8.
[http://dx.doi.org/10.1016/j.yebeh.2014.08.140]
[40]
Klugah-Brown B, Luo C, Peng R, et al. Altered structural and causal connectivity in frontal lobe epilepsy. BMC Neurol 2019; 19(1): 70.
[http://dx.doi.org/10.1186/s12883-019-1300-z] [PMID: 31023252]
[41]
Wang H, David O, Zhou W, et al. Distinctive epileptogenic networks for parietal operculum seizures. Epilepsy Behav 2019; 91: 59-67.
[http://dx.doi.org/10.1016/j.yebeh.2018.08.031] [PMID: 30269938]
[42]
Hogan RE, Kaiboriboon K, Osman M. Composite SISCOM images in mesial temporal lobe epilepsy: Technique and illustration of regions of hyperperfusion. Nucl Med Commun 2004; 25(6): 539-45.
[http://dx.doi.org/10.1097/01.mnm.0000126631.55284.de] [PMID: 15167511]
[43]
Bernedo Paredes VE, Buchholz HG, Gartenschläger M, Breimhorst M, Schreckenberger M, Werhahn KJ. Reduced D2/D3 receptor binding of extrastriatal and striatal regions in temporal lobe epilepsy J Neural Transmn (Vienna, Austria: 1996) 2015; 10(11): e0141098.
[44]
Huaijantug S, Theeraphun W, Suwanna N, Thongpraparn T, Chanachai R, Aumarm W. Localization of cerebral hypoperfusion in dogs with refractory and non-refractory epilepsy using [99mTc] ethyl cysteinate dimer and single photon emission computed tomography. J Vet Med Sci 2020; 82(5): 553-8.
[http://dx.doi.org/10.1292/jvms.19-0372] [PMID: 32188799]
[45]
Bouilleret V, Semah F, Chassoux F, et al. Basal ganglia involvement in temporal lobe epilepsy: A functional and morphologic study. Neurology 2008; 70(3): 177-84.
[http://dx.doi.org/10.1212/01.wnl.0000297514.47695.48] [PMID: 18195263]
[46]
Slaght SJ, Paz T, Mahon S, Maurice N, Charpier S, Deniau JM. Functional organization of the circuits connecting the cerebral cortex and the basal ganglia: Implications for the role of the basal ganglia in epilepsy. Epileptic Disord 2002; 4(Suppl. 3): S9-S22.
[PMID: 12495871]
[47]
Bonhaus DW, Rigsbee LC, McNamara JO. Intranigral dynorphin-1-13 suppresses kindled seizures by a naloxone-insensitive mechanism. Brain Res 1987; 405(2): 358-63.
[http://dx.doi.org/10.1016/0006-8993(87)90306-4] [PMID: 2882815]
[48]
Schmidt-Kastner R, Heim C, Sontag KH. Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: Immunohistochemical study of neurons, astrocytes and serum-protein extravasation. Exp Brain Res 1991; 86(1): 125-40.
[http://dx.doi.org/10.1007/BF00231047] [PMID: 1756784]
[49]
Töllner K, Wolf S, Löscher W, Gernert M. The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: A new mechanism of pharmacoresistance. J Neurosci 2011; 31(45): 16423-34.
[http://dx.doi.org/10.1523/JNEUROSCI.2506-11.2011] [PMID: 22072692]
[50]
Keihaninejad S, Heckemann RA, Gousias IS, et al. Classification and lateralization of temporal lobe epilepsies with and without hippocampal atrophy based on whole-brain automatic MRI segmentation. PLoS One 2012; 7(4): e33096.
[http://dx.doi.org/10.1371/journal.pone.0033096] [PMID: 22523539]
[51]
Zhang GQ, Cui L, Lhatoo S, Schuele SU, Sahoo SS. MEDCIS: Multi-Modality Epilepsy Data Capture and Integration System In: AMIA Annual Symposium proceedings AMIA Symposium. 2014; 2014: pp. 1248-57.
[52]
Morimoto K, Goddard GV. The substantia nigra is an important site for the containment of seizure generalization in the kindling model of epilepsy. Epilepsia 1987; 28(1): 1-10.
[http://dx.doi.org/10.1111/j.1528-1157.1987.tb03613.x] [PMID: 3792287]
[53]
De Sarro G, De Sarro A, Meldrum BS. Anticonvulsant action of 2-chloroadenosine injected focally into the inferior colliculus and substantia nigra. Eur J Pharmacol 1991; 194(2-3): 145-52.
[http://dx.doi.org/10.1016/0014-2999(91)90098-B] [PMID: 2060598]
[54]
Patodia S, Tachrount M, Somani A, et al. MRI and pathology correlations in the medulla in sudden unexpected death in epilepsy (SUDEP): A postmortem study 2021; 47(1): 157-70.
[55]
Jansen NA, Schenke M, Voskuyl RA, Thijs RD, van den Maagdenberg AMJM, Tolner EA. Apnea associated with brainstem seizures in Cacna1aS218L mice is caused by medullary spreading depolarization. J Neurosci 2019; 39(48): 9633-44.
[http://dx.doi.org/10.1523/JNEUROSCI.1713-19.2019] [PMID: 31628185]
[56]
Katayama PL. Cardiorespiratory dysfunction induced by brainstem spreading depolarization: A potential mechanism for SUDEP. J Neurosci 2020; 40(12): 2387-9.
[http://dx.doi.org/10.1523/JNEUROSCI.3053-19.2020] [PMID: 32188743]
[57]
Brennan M, Scott S, Bergin P. Sudden unexpected death in epilepsy (SUDEP) in New Zealand; a retrospective review. N Z Med J 2020; 133(1508): 65-71.
[PMID: 31945043]
[58]
Forsgren L, Sundelin H, Sveinsson O. Epilepsy: Incidens, prevalens and causes Lakartidningen 2018; 115: E6FD.
[59]
Surges R, von Wrede R, Porschen T, Elger CE. Knowledge of sudden unexpected death in epilepsy (SUDEP) among 372 patients attending a German tertiary epilepsy center Epilepsy & behavior : E&B 2018; 80: 360-4.

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