Long-term follow-up of a large cohort with focal epilepsy of unknown cause: deciphering their clinical and prognostic characteristics
- 10 Downloads
Background and purpose
Focal epilepsy of unknown cause (FEUC) is an under-investigated topic despite its remarkable frequency. We aimed to report the long-term follow-up findings along with the drug-response, 5 year remission rates and diagnostic changes to give an insight about the heterogeneous characteristics of FEUC.
Demographic, clinical, neurophysiological and imaging data of 196 patients diagnosed as FEUC according to ILAE criteria, with a minimum 5-year follow-up were evaluated in a tertiary epilepsy center. The drug resistance, 5 years of remission and relapse rates were investigated and the subgroups were compared statistically.
The rate of drug resistance was 21.8% and status epilepticus (p < 0.001), abnormal neurological examination (p = 0.020), seizure onset before 10 years (p = 0.004) and a high initial seizure frequency (p = 0.006) were significant predictors of drug resistance. The rates of terminal 5-year remission, 5-year remission ever and relapse were 39.9%, 44.26% and 24.04%, respectively. There were 13 patients (6.6%) with a changed final diagnosis. Drug resistance (p = 0.004), pathological EEG (p = 0.034) and status epilepticus (p = 0.021) were negative variables for achieving remission. The lobar localization of seizures was not a predictor of remission or relapse. Onset after 10 years of age had a higher probability of achieving a 5-year remission according to Kaplan–Meier curves (p < 0.001).
Focal epilepsy of unknown cause has a benign electroclinical subgroup with favorable long-term course, lower drug resistance and higher 5 years of terminal remission and remission ever rates, when appropriately treated. Our findings might be valuable in terms of counseling and management of patients with FEUC at the first referral to epilepsy clinics.
KeywordsFocal epilepsy with unknown cause Prognosis Cryptogenic epilepsy Long-term follow-up MRI-negative epilepsy Focal epilepsy
This study was supported by the Istanbul University Research Fund (Project No: BAP-2018-31114).
Compliance with ethical standards
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
All procedures performed in 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.
Informed consent was obtained from all individual participants included in the study.
- 1.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 51:676–685PubMedCrossRefPubMedCentralGoogle Scholar
- 5.Gasparini S, Ferlazzo E, Beghi E, Tripepi G, Labate A, Mumoli L, Leonardi CG, Cianci V, Latella MA, Gambardella A, Aguglia U (2013) Family history and frontal lobe seizures predict long-term remission in newly diagnosed cryptogenic focal epilepsy. Epilepsy Res 107:101–108PubMedCrossRefPubMedCentralGoogle Scholar
- 10.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 58:512–521PubMedPubMedCentralCrossRefGoogle Scholar
- 11.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 58:531–542PubMedCrossRefPubMedCentralGoogle Scholar
- 12.Kane N, Acharya J, Benickzy S, Caboclo L, Finnigan S, Kaplan PW, Shibasaki H, Pressler R, van Putten MJAM (2017) A revised glossary of terms most commonly used by clinical electroencephalographers and updated proposal for the report format of the EEG findings. Revision 2017. Clin Neurophysiol Pract 2:170–185PubMedPubMedCentralCrossRefGoogle Scholar
- 14.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 51:1069–1077PubMedCrossRefPubMedCentralGoogle Scholar
- 16.Engel J Jr (1987) Outcome with respect to epileptic seizures. In: Engel J Jr (ed) Surgical treatment of the epilepsies. Raven Press, New York, pp 535–571Google Scholar
- 17.Vanli-Yavuz EN, Erdag E, Tuzun E, Ekizoglu E, Baysal-Kirac L, Ulusoy C, Peach S, Gundogdu G, Sencer S, Sencer A, Kucukali CI, Bebek N, Gurses C, Gokyigit A, Baykan B (2016) Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis. J Neurol Neurosurg Psychiatry 87:684–692PubMedCrossRefPubMedCentralGoogle Scholar
- 24.Silva-Alves MS, Secolin R, Carvalho BS, Yasuda CL, Bilevicius E, Alvim MK, Santos RO, Maurer-Morelli CV, Cendes F, Lopes-Cendes I (2017) A prediction algorithm for drug response in patients with mesial temporal lobe epilepsy based on clinical and genetic information. PLoS ONE 4:e0169214. https://doi.org/10.1371/journal.pone.0169214 CrossRefGoogle Scholar
- 26.Dasarı A, Bansal D, Gudala K (2017) Brivaracetam add-on therapy for epilepsy: evidence based meta-analysis and metaregression of randomized controlled trials. Neurol Sci Neurophysiol 34:1–15Google Scholar
- 28.Gilioli I, Vignoli A, Visani E, Casazza M, Canafoglia L, Chiesa V, Gardella E, La Briola F, Panzica F, Avanzini G, Canevini MP, Franceschetti S, Binelli S (2012) Focal epilepsies in adult patients attending two epilepsy centers: classification of drug-resistance, assessment of risk factors, and usefulness of "new" antiepileptic drugs. Epilepsia 53:733–740PubMedCrossRefPubMedCentralGoogle Scholar
- 33.Orozco-Hernández JP, Quintero-Moreno JF, Marín-Medina DS, Valencia-Vásquez A, Villada HC, Lizcano A, Martínez JW (2018) Multivariable prediction model of drug resistance in adult patients with generalized epilepsy from Colombia: a case-control study. Epilepsy Behav 88:176–180PubMedCrossRefGoogle Scholar
- 38.Alexandre V Jr, Capovilla G, Fattore C, Franco V, Gambardella A, Guerrini R, La Briola F, Ladogana M, Rosati E, Specchio LM, Striano S, Perucca E, SOPHIE Study Group (2010) Characteristics of a large population of patients with refractory epilepsy attending tertiary referral centers in Italy. Epilepsia 51:921–925PubMedCrossRefGoogle Scholar
- 42.Ochoa-Gómez L, López-Pisón J, Fuertes-Rodrigo C, Fernando-Martínez R, Samper-Villagrasa P, Monge-Galindo L, Peña-Segura JL (2016) Prognosis of non-symptomatic epilepsy in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years. Rev Neurol 62:145–151PubMedPubMedCentralGoogle Scholar
- 49.Sander JW, Sillanpaa M (2008) The natural history and prognosis of epilepsy. In: Engel J, Pcdley TA (eds) Epilepsy: a comprehensive textbook. Lippincott Williams & Wilkins, Philadelphia, pp 69–96Google Scholar
- 56.Beghi E, Beretta S, Carone D, Zanchi C, Bianchi E, Pirovano M, Trentini C, Padovano G, Colombo M, Cereda D, Scanziani S, Giussani G, Gasparini S, Bogliun G, Ferrarese C, PRO-LONG Study Group (2019) Prognostic patterns and predictors in epilepsy: a multicentre study (PRO-LONG). J Neurol Neurosurg Psychiatry. 90:1276–1285PubMedCrossRefPubMedCentralGoogle Scholar
- 57.Aguglia U, Beghi E, Labate A, Condino F, Cianci V, Mumoli L, Gasparini S, Quattrone A, Gambardella A (2011) Age at onset predicts good seizure outcome in sporadic non-lesional and mesial temporal sclerosis based temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 82:555–559PubMedCrossRefPubMedCentralGoogle Scholar
- 64.Afawi Z, Oliver KL, Kivity S, Mazarib A, Blatt I, Neufeld MY, Helbig KL, Goldberg-Stern H, Misk AJ, Straussberg R, Walid S, Mahajnah M, Lerman-Sagie T, Ben-Zeev B, Kahana E, Masalha R, Kramer U, Ekstein D, Shorer Z, Wallace RH, Mangelsdorf M, MacPherson JN, Carvill GL, Mefford HC, Jackson GD, Scheffer IE, Bahlo M, Gecz J, Heron SE, Corbett M, Mulley JC, Dibbens LM, Korczyn AD, Berkovic SF (2016) Multiplex families with epilepsy: success of clinical and molecular genetic characterization. Neurology 86:713–722PubMedPubMedCentralCrossRefGoogle Scholar