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Network differences based on arterial spin labeling related to anti-seizure medication response in focal epilepsy

  • Functional Neuroradiology
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Abstract

Purpose

The aim of this study was to determine whether anti-seizure medication (ASM) response is associated with structural connectivity in diffusion tensor imaging (DTI) or functional co-variance network in arterial spin labeling (ASL) magnetic resonance imaging (MRI) in patients with focal epilepsy.

Methods

In this retrospective study conducted at a tertiary hospital, we enrolled 105 patients with focal epilepsy, of which 64 patients were good ASM responders, and 41 patients were poor ASM responders. All patients showed normal MRI findings on visual inspection and underwent DTI and ASL MRI from August 2018 to July 2020, with regular follow-up for at least 12 months after epilepsy diagnosis while taking ASMs. We calculated the structural connectivity based on DTI and functional co-variance network based on ASL MRI by using graph theory and analyzed their differences in relation to the ASM response.

Results

No differences were observed in structural connectivity between the good and poor ASM responders. However, significant differences were observed in functional co-variance network between the good and poor ASM responders. In comparison with good ASM responders, poor ASM responders showed a significantly greater characteristic path length (2.557 vs. 1.753, p = 0.034) and a lower local efficiency (2.311 vs. 3.927, p = 0.048).

Conclusion

Significant differences were observed in functional co-variance network based on ASL MRI between the good and poor ASM responders. These findings suggest that functional co-variance network could serve as a new biomarker of ASM response in focal epilepsy.

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Availability of data and material

Data that support the findings of this study are available upon reasonable request.

Code availability

Not applicable

References

  1. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51(6):1069–1077

    Article  CAS  Google Scholar 

  2. Brodie M, Barry S, Bamagous G, Norrie J, Kwan P (2012) Patterns of treatment response in newly diagnosed epilepsy. Neurology 78(20):1548–1554

    Article  CAS  Google Scholar 

  3. Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342(5):314–319

    Article  CAS  Google Scholar 

  4. Kwan P, Brodie MJ (2001) Effectiveness of first antiepileptic drug. Epilepsia 42(10):1255–1260

    Article  CAS  Google Scholar 

  5. Sillanpää M, Anttinen A, Rinne JO, Joutsa J, Sonninen P, Erkinjuntti M, Hermann B, Karrasch M, Saarinen M, Tiitta P (2015) Childhood-onset epilepsy five decades later A prospective population-based cohort study. Epilepsia 56(11):1774–1783

    Article  Google Scholar 

  6. Chen G, Zhou B, Zhu H, Kuang W, Bi F, Ai H, Gu Z, Huang X, Lui S, Gong Q (2018) White matter volume loss in amyotrophic lateral sclerosis: a meta-analysis of voxel-based morphometry studies. Prog Neuropsychopharmacol Biol Psychiatry 83:110–117. https://doi.org/10.1016/j.pnpbp.2018.01.007

    Article  PubMed  Google Scholar 

  7. Roy PL, Ronquillo LH, Ladino LD, Tellez-Zenteno JF (2019) Risk factors associated with drug resistant focal epilepsy in adults: a case control study. Seizure 73:46–50

    Article  Google Scholar 

  8. Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V (2018) The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia 59(12):2179–2193

    Article  Google Scholar 

  9. Larivière S, Bernasconi A, Bernasconi N, Bernhardt BC (2021) Connectome biomarkers of drug-resistant epilepsy. Epilepsia 62(1):6–24

    Article  Google Scholar 

  10. Bernhardt BC, Chen Z, He Y, Evans AC, Bernasconi N (2011) Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cereb Cortex 21(9):2147–2157

    Article  Google Scholar 

  11. Liu M, Chen Z, Beaulieu C, Gross DW (2014) Disrupted anatomic white matter network in left mesial temporal lobe epilepsy. Epilepsia 55(5):674–682

    Article  Google Scholar 

  12. Liao W, Zhang Z, Pan Z, Mantini D, Ding J, Duan X, Luo C, Lu G, Chen H (2010) Altered functional connectivity and small-world in mesial temporal lobe epilepsy. PloS One 5(1):e8525

    Article  Google Scholar 

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

    Article  Google Scholar 

  14. Wang J, Qiu S, Xu Y, Liu Z, Wen X, Hu X, Zhang R, Li M, Wang W, Huang R (2014) Graph theoretical analysis reveals disrupted topological properties of whole brain functional networks in temporal lobe epilepsy. Clin Neurophysiol 125(9):1744–1756

    Article  Google Scholar 

  15. Pedersen M, Omidvarnia AH, Walz JM, Jackson GD (2015) Increased segregation of brain networks in focal epilepsy: an fMRI graph theory finding. Neuroimage Clin 8:536–542

    Article  Google Scholar 

  16. Tavakol S, Royer J, Lowe AJ, Bonilha L, Tracy JI, Jackson GD, Duncan JS, Bernasconi A, Bernasconi N, Bernhardt BC (2019) Neuroimaging and connectomics of drug-resistant epilepsy at multiple scales: from focal lesions to macroscale networks. Epilepsia 60(4):593–604

    Article  Google Scholar 

  17. Kreilkamp BAK, McKavanagh A, Alonazi B, Bryant L, Das K, Wieshmann UC, Marson AG, Taylor PN, Keller SS (2021) Altered structural connectome in non-lesional newly diagnosed focal epilepsy: relation to pharmacoresistance. Neuroimage Clin 29:102564. https://doi.org/10.1016/j.nicl.2021.102564

    Article  PubMed  PubMed Central  Google Scholar 

  18. Park KM, Cho KH, Lee HJ, Heo K, Lee BI, Kim SE (2020) Predicting the antiepileptic drug response by brain connectivity in newly diagnosed focal epilepsy. J Neurol 267(4):1179–1187. https://doi.org/10.1007/s00415-020-09697-4

    Article  CAS  PubMed  Google Scholar 

  19. Li Z, Vidorreta M, Katchmar N, Alsop DC, Wolf DH, Detre JA (2018) Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI. Neuroimage 173:165–175

    Article  Google Scholar 

  20. Detre JA, Wang J, Wang Z, Rao H (2009) Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Curr Opin Neurol 22(4):348–355

    Article  Google Scholar 

  21. Detre JA, Rao H, Wang DJ, Chen YF, Wang Z (2012) Applications of arterial spin labeled MRI in the brain. J Magn Reson Imaging 35(5):1026–1037

    Article  Google Scholar 

  22. Yakushev I, Drzezga A, Habeck C (2017) Metabolic connectivity: methods and applications. Curr Opin Neurol 30(6):677–685

    Article  Google Scholar 

  23. Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M (2015) Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med 73(1):102–116

    Article  Google Scholar 

  24. Haller S, Zaharchuk G, Thomas DL, Lovblad K-O, Barkhof F, Golay X (2016) Arterial spin labeling perfusion of the brain: emerging clinical applications. Radiology 281(2):337–356

    Article  Google Scholar 

  25. Liu F, Zhuo C, Yu C (2016) Altered cerebral blood flow covariance network in schizophrenia. Front Neurosci 10:308

    PubMed  PubMed Central  Google Scholar 

  26. Deckers C, Hekster Y, Keyser A, Meinardi H, Renier W (1997) Reappraisal of polytherapy in epilepsy: a critical review of drug load and adverse effects. Epilepsia 38(5):570–575

    Article  CAS  Google Scholar 

  27. Park BS, Kim SE, Lee H-J, Kim YW, Kim IH, Park JH, Park SH, Lee YJ, Seo SA, Park KM (2020) Alterations in structural and functional connectivities in patients with end-stage renal disease. J Clin Neurol 16(3):390

    Article  Google Scholar 

  28. Park BS, Lee YJ, Park JH, Kim IH, Park SH, Lee HJ, Park KM (2018) Alterations of brain network hubs in reflex syncope: evidence from a graph theoretical analysis based on DTI. Brain Behav 8(6):e01006

    Article  Google Scholar 

  29. Wang Z, Aguirre GK, Rao H, Wang J, Fernandez-Seara MA, Childress AR, Detre JA (2008) Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. Magn Reson Imaging 26(2):261–269. https://doi.org/10.1016/j.mri.2007.07.003

    Article  PubMed  Google Scholar 

  30. Wang Z (2012) Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations. Magn Reson Imaging 30(10):1409–1415. https://doi.org/10.1016/j.mri.2012.05.004

    Article  PubMed  PubMed Central  Google Scholar 

  31. Farahani FV, Karwowski W, Lighthall NR (2019) Application of graph theory for identifying connectivity patterns in human brain networks: a systematic review. Front Neurosci 13:585. https://doi.org/10.3389/fnins.2019.00585

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bernhardt BC, Bonilha L, Gross DW (2015) Network analysis for a network disorder: the emerging role of graph theory in the study of epilepsy. Epilepsy Behav 50:162–170

    Article  Google Scholar 

  33. Kim J, Lee WG, Park S, Park KM (2020) Can we predict drug response by functional connectivity in patients with juvenile myoclonic epilepsy? Clin Neurol Neurosurg 198:106119

    Article  Google Scholar 

  34. Maccotta L, He BJ, Snyder AZ, Eisenman LN, Benzinger TL, Ances BM, Corbetta M, Hogan RE (2013) Impaired and facilitated functional networks in temporal lobe epilepsy. Neuroimage Clin 2:862–872

    Article  Google Scholar 

  35. Douw L, DeSalvo MN, Tanaka N, Cole AJ, Liu H, Reinsberger C, Stufflebeam SM (2015) Dissociated multimodal hubs and seizures in temporal lobe epilepsy. Ann Clin Transl Neurol 2(4):338–352

    Article  Google Scholar 

  36. Maccotta L, Lopez MA, Adeyemo B, Ances BM, Day BK, Eisenman LN, Dowling JL, Leuthardt EC, Schlaggar BL, Hogan RE (2017) Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy. Epilepsia 58(11):1842–1851

    Article  Google Scholar 

  37. Lee DA, Kim BJ, Lee H-J, Kim SE, Park KM (2020) Network characteristics of genetic generalized epilepsy: are the syndromes distinct? Seizure 82:91–98

    Article  Google Scholar 

  38. Damoiseaux JS, Greicius MD (2009) Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity. Brain Struct Funct 213(6):525–533

    Article  Google Scholar 

  39. Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran J-P, Meuli R, Hagmann P (2009) Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci 106(6):2035–2040

    Article  CAS  Google Scholar 

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Acknowledgements

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Funding

This study has not been funded.

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Author notes

  1. Dong Ah Lee and Ho-Joon Lee contributed equally to the manuscript

Authors and Affiliations

  1. Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Haeundae-ro 875, Haeundae-gu, Busan, 48108, Korea

    Dong Ah Lee, Hyung Chan Kim & Kang Min Park

  2. Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea

    Ho-Joon Lee

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  1. Dong Ah Lee
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Correspondence to Kang Min Park.

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All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Lee, D.A., Lee, HJ., Kim, H.C. et al. Network differences based on arterial spin labeling related to anti-seizure medication response in focal epilepsy. Neuroradiology 64, 313–321 (2022). https://doi.org/10.1007/s00234-021-02741-8

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  • DOI: https://doi.org/10.1007/s00234-021-02741-8

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