Predicting the antiepileptic drug response by brain connectivity in newly diagnosed focal epilepsy

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Growing evidence has suggested that epilepsy is a disease with alterations in brain connectivity. The aim of this study was to investigate whether the changes in brain connectivity can predict the response to an antiepileptic drug (AED) in patients with a newly diagnosed focal epilepsy of unknown etiology.


This observational study was independently performed at two tertiary hospitals (Group A and B). Thirty-eight patients with newly diagnosed focal epilepsy of unknown etiology were enrolled in Group A and 46 patients in Group B. We divided these patients into two groups according to their seizure control after AED treatment: AED good and poor responders. We defined the AED good responders as those in whom had seizure free for at least the last 6 months while AED poor responders who were not. All of the subjects underwent diffusion tensor imaging, and graph theoretical analysis was applied to reveal the brain connectivity. We investigated the difference in the clinical characteristics and network measurements between the two groups.


Of the network measures, the assortativity coefficient in the AED good responders was significantly higher than that in the AED poor responders in both Groups A and B (− 0.0239 vs. − 0.0473, p = 0.0110 in Group A; 0.0173 vs. − 0.0180, p = 0.0024 in Group B). The Kaplan–Meier survival analysis revealed that the time to failure to retain the first AED was significantly longer in the patients with assortative networks (assortativity coefficient > 0) than in those with disassortative networks (assortativity coefficient < 0) in Group B.


We demonstrated that the assortativity coefficient differed between patients with newly diagnosed focal epilepsy of unknown etiology according to their AED responses, which suggests that the changes in brain connectivity could be a biomarker for predicting the responses to AED.

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  1. 1.

    Goldenberg MM (2010) Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. P T 35:392–415

  2. 2.

    Chen Z, Brodie MJ, Liew D, Kwan P (2018) Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol 75:279–286

  3. 3.

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

  4. 4.

    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 51:1069–1077

  5. 5.

    Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B, Cavalcanti D, Baulac M (1998) Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 51:1256–1262

  6. 6.

    Liimatainen SP, Raitanen JA, Ylinen AM, Peltola MA, Peltola JT (2008) The benefit of active drug trials is dependent on aetiology in refractory focal epilepsy. J Neurol Neurosurg Psychiatry 79:808–812

  7. 7.

    Camfield C, Camfield P, Gordon K, Dooley J (1996) Does the number of seizures before treatment influence ease of control or remission of childhood epilepsy? Not if the number is 10 or less. Neurology 46:41–44

  8. 8.

    MacDonald BK, Johnson AL, Goodridge DM, Cockerell OC, Sander JW, Shorvon SD (2000) Factors predicting prognosis of epilepsy after presentation with seizures. Ann Neurol 48:833–841

  9. 9.

    Park KM, Shin KJ, Ha SY, Park J, Kim SE, Kim SE (2014) Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI. Clin Neurol Neurosurg 123:64–68

  10. 10.

    Park KM, Hur Y, Kim HY, Ji KH, Hwang TG, Shin KJ, Ha SY, Park J, Kim SE (2014) Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy. J Clin Neurosci 21:923–926

  11. 11.

    Kim SE, Park KM, Kim SH, Kwon OY, No SK (2010) Presence of epileptiform discharges on initial EEGs are associated with failure of retention on first antiepileptic drug in newly diagnosed cryptogenic partial epilepsy: a 2-year observational study. Seizure 19:536–539

  12. 12.

    Englot DJ, Hinkley LB, Kort NS, Imber BS, Mizuiri D, Honma SM, Findlay AM, Garrett C, Cheung PL, Mantle M, Tarapore PE, Knowlton RC, Chang EF, Kirsch HE, Nagarajan SS (2015) Global and regional functional connectivity maps of neural oscillations in focal epilepsy. Brain 138:2249–2262

  13. 13.

    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde BW, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on classification and terminology, 2005–2009. Epilepsia 51:676–685

  14. 14.

    Miro J, Gurtubay-Antolin A, Ripolles P, Sierpowska J, Juncadella M, Fuentemilla L, Sánchez V, Falip M, Rodríguez-Fornells A (2015) Interhemispheric microstructural connectivity in bitemporal lobe epilepsy with hippocampal sclerosis. Cortex 67:106–121

  15. 15.

    Hu Y, Mi X, Xu X et al (2015) The brain activity in brodmann area 17: a potential bio-marker to predict patient responses to antiepileptic drugs. PLoS ONE 10:e0139819

  16. 16.

    Miao A, Wang Y, Xiang J, Zeng K, Yang M, Li C, Wang S, Li M, Wang X (2019) Ictal source locations and cortico-thalamic connectivity in childhood absence epilepsy: associations with treatment response. Brain Topogr 32:178–191

  17. 17.

    Tenney JR, Kadis DS, Agler W, Rozhkov L, Altaye M, Xiang J, Vannest J, Glauser TA (2018) Ictal connectivity in childhood absence epilepsy: associations with outcome. Epilepsia 59:971–981

  18. 18.

    Hallquist MN, Hillary FG (2019) Graph theory approaches to functional network organization in brain disorders: a critique for a brave new small-world. Netw Neurosci 3:1–26

  19. 19.

    Newman ME (2003) Mixing patterns in networks. Phys Rev E Stat Nonlin Soft Matter Phys 67:026126

  20. 20.

    Newman ME (2002) Assortative mixing in networks. Phys Rev Lett 89:208701

  21. 21.

    Bharath RD, Sinha S, Panda R, Raghavendra K, George L, Chaitanya G, Gupta A, Satishchandra P (2015) Seizure frequency can alter brain connectivity: evidence from resting-state fMRI. AJNR Am J Neuroradiol 36:1890–1898

  22. 22.

    Wandschneider B, Stretton J, Sidhu M, Centeno M, Kozák LR, Symms M, Thompson PJ, Duncan JS, Koepp MJ (2014) Levetiracetam reduces abnormal network activations in temporal lobe epilepsy. Neurology 83:1508–1512

  23. 23.

    Newman ME, Park J (2003) Why social networks are different from other types of networks. Phys Rev E Stat Nonlin Soft Matter Phys 68:036122

  24. 24.

    Eguiluz VM, Chialvo DR, Cecchi GA, Baliki M, Apkarian AV (2005) Scale-free brain functional networks. Phys Rev Lett 94(1):018102

  25. 25.

    Albert R, Jeong H, Barabasi AL (2000) Error and attack tolerance of complex networks. Nature 406:378–382

  26. 26.

    Bialonski S, Lehnertz K (2013) Assortative mixing in functional brain networks during epileptic seizures. Chaos 23:033139

  27. 27.

    Motter AE, Zhou C, Kurths J (2005) Network synchronization, diffusion, and the paradox of heterogeneity. Phys Rev E Stat Nonlin Soft Matter Phys 71:016116

  28. 28.

    Sone D, Matsuda H, Ota M, Maikusa N, Kimura Y, Sumida K, Yokoyama K, Imabayashi E, Watanabe M, Watanabe Y, Okazaki M, Sato N (2016) Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal sclerosis: a graph theoretical approach. Epilepsy Behav 62:239–245

  29. 29.

    Geier C, Lehnertz K, Bialonski S (2015) Time-dependent degree-degree correlations in epileptic brain networks: from assortative to dissortative mixing. Front Hum Neurosci 9:462

  30. 30.

    Keller SS, Richardson MP, Schoene-Bake JC, O'Muircheartaigh J, Elkommos S, Kreilkamp B, Goh YY, Marson AG, Elger C, Weber B (2015) Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy. Ann Neurol 77:760–774

  31. 31.

    Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kälviäinen R, Mattson R, French JA, Perucca E, Tomson T (2013) Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 54:551–563

  32. 32.

    Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P (2012) Patterns of treatment response in newly diagnosed epilepsy. Neurology 78:1548–1554

  33. 33.

    Choi H, Heiman GA, Munger Clary H, Etienne M, Resor SR, Hauser WA (2011) Seizure remission in adults with long-standing intractable epilepsy: an extended follow-up. Epilepsy Res 93:115–119

  34. 34.

    Dlugos DJ, Sammel MD, Strom BL, Farrar JT (2001) Response to first drug trial predicts outcome in childhood temporal lobe epilepsy. Neurology 57:2259–2264

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Correspondence to Sung Eun Kim.

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Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The study was carried out in accordance with the Declaration of Helsinki and approved by the Institutional Review Board at our hospital.

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Park, K.M., Cho, K.H., Lee, H. et al. Predicting the antiepileptic drug response by brain connectivity in newly diagnosed focal epilepsy. J Neurol (2020) doi:10.1007/s00415-020-09697-4

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  • Epilepsy
  • Connectivity
  • Anticonvulsants