Impact of epilepsy duration, seizure control and EEG abnormalities on cognitive impairment in drug-resistant epilepsy patients

  • Aleksandar GavrilovicEmail author
  • Gordana Toncev
  • Tatjana Boskovic Matic
  • Katarina Vesic
  • Jelena Ilic Zivojinovic
  • Jagoda Gavrilovic
Original article


Cognitive impairment frequently occurs in epilepsy patients. Patients with drug-resistant epilepsy (DRE) have poor drug responsivity and higher seizure frequency which consequently lead to brain damage and may have implications on cognitive status. In the present study, we assessed a frequency and degree of cognitive impairment in 52 patients with drug-sensitive epilepsy (DSE) and 103 DRE patients at three time points (baseline, after 12 and 18 months). Degree of cognitive decline was assessed with Montreal Cognitive Assessment (MoCA) scale. We examined the possible correlation between demographic and clinical characteristics and cognitive deterioration in epilepsy patients. Patients in the DRE group had significantly lower MoCA score than patients in the DSE group at baseline (28.83 ± 2.05 vs. 29.69 ± 0.61, p = 0.003), after 12 months (27.36 ± 2.40 vs. 29.58 ± 1.22, p = 0.000) and 18 months (26.86 ± 2.73 vs. 29.33 ± 1.47, p = 0.000). Patients with DRF epilepsy had significantly lower MoCA score than patients with DSF epilepsy at three time points (28.71 ± 2.48 vs. 29.86 ± 0.35, p = 0.015; 27.22 ± 2.72 vs. 29.52 ± 1.37, p = 0.000; 26.80 ± 2.99 vs. 29.31 ± 1.56, p = 0.000). After 12 and 18 months of follow-up, patients with DRG epilepsy had significantly lower MoCA score than patients with DSG epilepsy (27.52 ± 2.01 vs. 29.65 ± 1.02, p = 0.000; 26.94 ± 2.43 vs. 29.35 ± 1.40, p = 0.000). Illness duration negatively correlated with cognitive status (p = 0.005); seizure control and EEG findings positively correlated with MoCA score (p = 0.000). Illness duration, seizure control, drug responsivity, and EEG findings are significant predictors of MoCA score (p < 0.05). Clinicians have to pay attention to patients with drug-resistant epilepsy and concepts of aggressive treatment to minimize the adverse effects of epilepsy on cognition.


Epilepsy Drug resistance Drug sensitive Seizure control Cognitive impairment 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethic Committee of the Clinical Centre Kragujevac and conducted in compliance with the ethical principles of the Declaration of Helsinki.



Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Gao L, Li S (2016) Emerging drugs for partial-onset epilepsy: a review of brivaracetam. Ther Clin Risk Manag 12:719–734. Google Scholar
  2. 2.
    Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55(4):475–482. Google Scholar
  3. 3.
    Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J Jr (2005) Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 46(4):470–472. Google Scholar
  4. 4.
    Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM (2017) ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58(4):512–521. Google Scholar
  5. 5.
    Schmitz B, Montouris G, Schauble B, Caleo S (2010) Assessing the unmet treatment need in partial-onset epilepsy: looking beyond seizure control. Epilepsia 51:2231–2240. Google Scholar
  6. 6.
    Fisher RS, Cross JH, D’Souza C, French JA, Haut SR, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Schulze-Bonhage A, Somerville E, Sperling M, Yacubian EM, Zuberi SM (2017) Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 58(4):531–542. Google Scholar
  7. 7.
    Kwan P, Schachter SC, Brodie MJ (2011) Drug-resistant epilepsy. N Engl J Med 365(10):919–926. Google Scholar
  8. 8.
    Beleza P (2009) Refractory epilepsy: a clinically oriented review. Eur Neurol 62(2):65–71. Google Scholar
  9. 9.
    Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, Resnick T, Benbadis SR (2014) The consequences of refractory epilepsy and its treatment. Epilepsy Behav 37:59–70. Google Scholar
  10. 10.
    Elger CE1, Helmstaedter C, Kurthen M (2004) Chronic epilepsy and cognition. Lancet Neurol 3(11):663–672. Google Scholar
  11. 11.
    D’Agati E, Cerminara C, Casarelli L, Pitzianti M, Curatolo P (2012) Attention and executive functions profile in childhood absence epilepsy. Brain Dev 34:812–817. Google Scholar
  12. 12.
    Cerminara C, D’Agati E, Casarelli L, Kaunzinger I, Lange KW, Pitzianti M (2013) Attention impairment in childhood absence epilepsy: an impulsivity problem? Epilepsy Behav 27: 337–341.
  13. 13.
    Neri ML, Guimarães CA, Oliveira EP, Duran MH, Medeiros LL, Montenegro MA, Boscariol M, Guerreiro MM (2012) Neuropsychological assessment of children with rolandic epilepsy: executive functions. Epilepsy Behav 24:403–407. Google Scholar
  14. 14.
    Elger CE, Helmstaedter C, Kurthen M (2004) Chronic epilepsy and cognition. Lancet Neurol 3(11):663–672. Google Scholar
  15. 15.
    Helmstaedter CA (1999) Prediction of memory reserve capacity. Adv Neurol 81:271–279Google Scholar
  16. 16.
    Sutula TP1, Hagen J, Pitkänen A (2003) Do epileptic seizures damage the brain? Curr Opin Neurol 16(2): 189–195. Google Scholar
  17. 17.
    Lado FA, Laureta EC, Moshé SL (2002) Seizure-induced hippocampal damage in the mature and immature brain. Epileptic Disord 4(2):83–97Google Scholar
  18. 18.
    Helmstaedter C, Elger CE, Lendt M (1994) Postictal courses of cognitive deficits in focal epilepsies. Epilepsia 35:1073–1078. Google Scholar
  19. 19.
    Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshe SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang Y-H, Zuberi SM (2017) ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58(4):512–521. Google Scholar
  20. 20.
    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. Google Scholar
  21. 21.
    Nasreddine ZS1, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4): 695–699. Google Scholar
  22. 22.
    Berg AT, Zelko FA, Levy SR, Testa FM (2012) Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a prospective cohort study. Neurology 79:1384–1391. Google Scholar
  23. 23.
    Najm IM, Wang I, Shedid D, Luders HO, Ng TC, Comair YG (1998) MRS metabolic markers of seizures and seizure-induced neuronal damage. Epilepsia 39:244–250. Google Scholar
  24. 24.
    Lukoyanov NV, Sa MJ, Madeira MD, Paula-Barbosa MM (2004) Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizures. Exp Brain Res 154:192–200. Google Scholar
  25. 25.
    Holmes MD, Dodrill CB, Wilkus RJ, Ojemann LM, Ojemann GA (1998) Is partial epilepsy progressive? Ten-year follow-up of EEG and neuropsychological changes in adults with partial seizures. Epilepsia 39:1189–1193. Google Scholar
  26. 26.
    Helmstaedter C, Kurthen M, Lux S, Reuber M, Elgers CE (2003) Chronic epilpsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol 54:425–432. Google Scholar
  27. 27.
    National Institute of Neurological Disorders and Stroke (NINDS), U.S. National Institutes of Health (NIH) (2016) The epilepsies and seizures: hope through research, NINDS (1 February 2016). Visited online: 18.10.2018Google Scholar
  28. 28.
    Sweatt JD (2004) Hippocampal function in cognition. Psychopharmacology 174:99–110. Google Scholar
  29. 29.
    Sendrowski K, Sobaniec W (2013) Hippocampus, hippocampal sclerosis and epilepsy. Pharmacol Rep 65:555–565. Google Scholar
  30. 30.
    Schiffer D, Cordera S, Tereni A (1994) Neuropathological findings in surgical specimens of temporal lobe epilepsy. Crit Rev Neurosurg 4:339–350Google Scholar
  31. 31.
    Thom M (2009) Hippocampal sclerosis: progress since Sommer. Brain Pathol 19:565–572. Google Scholar
  32. 32.
    Kotloski R, Lynch M, Lauersdorf S, Sutula T (2002) Repeated brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog Brain Res 135:95–110. Google Scholar
  33. 33.
    Sass KJ, Sass M, Westerveld M, Lencz R, Novelly A, Kim JH, Spencer DD (1992) Specificity in the correlation of verbal memory and hippocampal neuron loss: dissociation of memory, language, and verbal intellectual ability. J Clin Exp Neuropsychol 14(5):662–672. Google Scholar
  34. 34.
    Patrikelis P, Angelakis E, Gatzonis S (2009) Neurocognitive and behavioral functioning in frontal lobe epilepsy: a review. Epilepsy Behav 14(1):19–26. (Elsevier Inc)Google Scholar
  35. 35.
    Helmstaedter C, Kemper B, Elger CE (1996) Neuropsychological aspects of frontal lobe epilepsy. Neuropsychologia 34(5):399–406. Google Scholar
  36. 36.
    McDonald CR, Delis DC, Norman MA, Wetter SR, Tecoma ES, Iragui VJ (2005) Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy. Epilepsy Behav 7(3):438–446. Google Scholar
  37. 37.
    Drane DL, Lee GP, Cech H, Huthwaite JS, Ojemann GA, Ojemann JG (2006) Structured cueing on a semantic fluency task differentiates patients with temporal versus frontal lobe seizure onset. Epilepsy Behav 9(2):339–344. Scholar
  38. 38.
    Cahn-Weiner D, Wittenberg D, McDonald C (2009) Everyday cognition in temporal lobe and frontal lobe epilepsy. Epileptic Disord 11(3):222–227. Google Scholar
  39. 39.
    Jokeit H, Ebner A (2002) Effects of chronic epilepsy on intellectual functions. Prog Brain Res 135:455–463. Google Scholar
  40. 40.
    Dodrill CB (2004) Neuropsychological effects of seizures. Epilepsy Behav 5(1):S21–S24Google Scholar
  41. 41.
    Seidenberg M, Pulsipher DT, Hermann B (2007) Cognitive progression in epilepsy. Neuropsychol Rev 17(4):445–454. Google Scholar
  42. 42.
    Piazinni A, Canevini MP, Turner K, Chifari R, Canger R (2006) Elderly people and epilepsy:cognitive function. Epilepsia 47:82–84. Google Scholar
  43. 43.
    Arinzechi EO, Ogunrin OA, Nwosu CM, Nwamu PO, Enwereji KO, Asomugha LA, Dimkpa U (2018) Seizure frequency and risk of cognitive impairment in people living with epilepsy in a sub-urban community in South Eastern Nigeria. J Clin Neurosci S0967–5868(18):30129–30132. Google Scholar
  44. 44.
    Centeno M, Thompson PJ, Koepp MJ, Helmstaedter C, Duncan JS (2010) Memory in frontal lobe epilepsy. Epilepsy Res 91(2–3):123–132. Google Scholar
  45. 45.
    Voltzenlogel V, Vignal JP, Hirsch E, Manning L (2014) The influence of seizure frequency on anterograde and remote memory in mesial temporal lobe epilepsy. Seizure 23(9):792–798. Google Scholar
  46. 46.
    Holmes GL (2013) EEG abnormalities as a biomarker for cognitive comorbidities in pharmacoresistant epilepsy. Epilepsia 54(2):60–62. Google Scholar
  47. 47.
    Huang C, Wahlund L, Dierks T, Julin P, Winblad B, Jelic V (2000) Discrimination of Alzheimer’s disease and mild cognitive impairment by equivalent EEG sources a cross-sectional and longitudinal study. Clin Neurophys 111(11):1961–1967Google Scholar
  48. 48.
    Kwak YT (2006) Quantitative EEG findings in different stages of Alzheimer’s disease. J Clin Neurophys 23(5):456–461. Google Scholar
  49. 49.
    Flicker C, Ferris SH, Reisberg B (1991) Mild cognitive impairment in the elderly: predictors of dementia. Neurology 41(7):1006–1009. Google Scholar

Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  • Aleksandar Gavrilovic
    • 1
    • 2
    Email author
  • Gordana Toncev
    • 1
    • 2
  • Tatjana Boskovic Matic
    • 1
    • 2
  • Katarina Vesic
    • 1
  • Jelena Ilic Zivojinovic
    • 3
  • Jagoda Gavrilovic
    • 4
    • 5
  1. 1.Faculty of Medical Sciences, Department of NeurologyUniversity of Kragujevac, SerbiaKragujevacSerbia
  2. 2.Clinic of NeurologyClinical Center KragujevacKragujevacSerbia
  3. 3.Institute of Hygiene and Medical Ecology, Faculty of MedicineUniversity of BelgradeBelgradeSerbia
  4. 4.Faculty of Medical Sciences, Department of Infectious DiseasesUniversity of Kragujevac, SerbiaKragujevacSerbia
  5. 5.Clinic of Infectious DiseaseClinical Center KragujevacKragujevacSerbia

Personalised recommendations