Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.
antiseizure medication (ASM)
drug resistance
idiopathic generalized epilepsy (IGE)
prognostic factors
withdrawal
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
23 Oct 2023
23 Oct 2023
Historique:
revised:
19
10
2023
received:
07
06
2023
accepted:
19
10
2023
pubmed:
24
10
2023
medline:
24
10
2023
entrez:
24
10
2023
Statut:
aheadofprint
Résumé
Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Research Foundation
Organisme : German Society of Epileptology
Informations de copyright
© 2023 International League Against Epilepsy.
Références
Hirsch E, French J, Scheffer IE, Bogacz A, Alsaadi T, Sperling MR, et al. ILAE definition of the idiopathic generalized epilepsy syndromes: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1475-1499. https://doi.org/10.1111/epi.17236
Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia. 2005;46(Suppl 9):10-14. https://doi.org/10.1111/j.1528-1167.2005.00309.x
Marini C, Scheffer IE, Crossland KM, Grinton BE, Phillips FL, McMahon JM, et al. Genetic architecture of idiopathic generalized epilepsy: clinical genetic analysis of 55 multiplex families. Epilepsia. 2004;45(5):467-478. https://doi.org/10.1111/j.0013-9580.2004.46803.x
Leu C, Stevelink R, Smith AW, Goleva SB, Kanai M, Ferguson L, et al. Polygenic burden in focal and generalized epilepsies. Brain. 2019;142(11):3473-3481.
Vorderwülbecke BJ, Wandschneider B, Weber Y, Holtkamp M. Genetic generalized epilepsies in adults - challenging assumptions and dogmas. Nat Rev Neurol. 2022;18(2):71-83.
Gesche J, Christensen J, Hjalgrim H, Rubboli G, Beier CP. Epidemiology and outcome of idiopathic generalized epilepsy in adults. Eur J Neurol. 2020;27(4):676-684.
Vorderwülbecke BJ, Kowski AB, Kirschbaum A, Merkle H, Senf P, Janz D, et al. Long-term outcome in adolescent-onset generalized genetic epilepsies. Epilepsia. 2017;58(7):1244-1250. https://doi.org/10.1111/epi.13761
Marini C, King MA, Archer JS, Newton MR, Berkovic SF. Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry. 2003;74(2):192-196. https://doi.org/10.1136/jnnp.74.2.192
Cerulli Irelli E, Orlando B, Salamone EM, Fisco G, Barone FA, Morano A, et al. High rates of early remission pattern in adult-onset compared with earlier-onset idiopathic generalized epilepsy: a long-term follow-up study. Seizure. 2022;94:52-56. https://doi.org/10.1016/j.seizure.2021.11.019
Gesche J, Beier CP. Drug resistance in idiopathic generalized epilepsies: evidence and concepts. Epilepsia. 2022;63(12):3007-3019. https://doi.org/10.1111/epi.17410
Loughman A, Bendrups NA, D'Souza WJ. A systematic review of psychiatric and psychosocial comorbidities of Genetic Generalised Epilepsies (GGE). Neuropsychol Rev. 2016;26(4):364-375. https://doi.org/10.1007/s11065-016-9333-1
Gesche J, Antonson S, Dreier JW, Christensen J, Beier CP. Social outcome and psychiatric comorbidity of generalized epilepsies - a case-control study. Epilepsia. 2021;62(5):1158-1169. https://doi.org/10.1111/epi.16870
Camfield P, Camfield C. Idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTC): a population-based cohort with >20 year follow up for medical and social outcome. Epilepsy Behav. 2010;18(1-2):61-63. https://doi.org/10.1016/j.yebeh.2010.02.01
Seneviratne U, Cook M, D'Souza W. The prognosis of idiopathic generalized epilepsy. Epilepsia. 2012;53(12):2079-2090. https://doi.org/10.1111/j.1528-1167.2012.03723.x
Reutens DC, Berkovic SF. Idiopathic generalized epilepsy of adolescence: are the syndromes clinically distinct? Neurology. 1995;45(8):1469-1476. https://doi.org/10.1212/wnl.45.8.1469
Ferrie CD. Idiopathic generalized epilepsies imitating focal epilepsies. Epilepsia. 2005;46(Suppl 9):91-95. https://doi.org/10.1111/j.1528-1167.2005.00319.x
Koutroumanidis M, Aggelakis K, Panayiotopoulos CP. Idiopathic epilepsy with generalized tonic-clonic seizures only versus idiopathic epilepsy with phantom absences and generalized tonic-clonic seizures: one or two syndromes? Epilepsia. 2008;49(12):2050-2062. https://doi.org/10.1111/j.1528-1167.2008.01702.x
Sun Y, Seneviratne U, Perucca P, Chen Z, Tan MK, O'Brien TJ, et al. Generalized polyspike train: an EEG biomarker of drug-resistant idiopathic generalized epilepsy. Neurology. 2018;91(19):e1822-e1830. https://doi.org/10.1212/WNL.0000000000006472
Cerulli Irelli E, Cocchi E, Ramantani G, Caraballo RH, Giuliano L, Yilmaz T, et al. Electroclinical features and long-term seizure outcome in patients with eyelid myoclonia with absences. Neurology. 2022;98(18):e1865-e1876. https://doi.org/10.1212/WNL.0000000000200165
Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-1077. https://doi.org/10.1111/j.1528-1167.2009.02397.x
Moons KG, Donders RA, Stijnen T, Harrell FE Jr. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol. 2006;59(10):1092-1101. https://doi.org/10.1016/j.jclinepi.2006.01.009
Caraballo R, Silva S, Beltran L, Calvo A, Caballero R. Childhood-only epilepsy with generalized tonic-clonic seizures: a well-defined epileptic syndrome. Epilepsy Res. 2019;153:28-33. https://doi.org/10.1016/j.eplepsyres.2019.03.017
Holtkamp M, Kowski AB, Merkle H, Janz D. Long-term outcome in epilepsy with grand mal on awakening: forty years of follow-up. Ann Neurol. 2014;75(2):298-302. https://doi.org/10.1002/ana.24103
Guaranha MS, Filho GM, Lin K, Guilhoto LM, Caboclo LO, Yacubian EM. Prognosis of juvenile myoclonic epilepsy is related to endophenotypes. Seizure. 2011;20(1):42-48. https://doi.org/10.1016/j.seizure.2010.10.004
Cerulli Irelli E, Morano A, Barone FA, Fisco G, Fanella M, Orlando B, et al. Persistent treatment resistance in genetic generalized epilepsy: a long-term outcome study in a tertiary epilepsy center. Epilepsia. 2020;61(11):2452-2460. https://doi.org/10.1111/epi.16708
Camfield CS, Striano P, Camfield PR. Epidemiology of juvenile myoclonic epilepsy. Epilepsy Behav. 2013;28(Suppl 1):S15-S17. https://doi.org/10.1016/j.yebeh.2012.06.024
Janz D. Epilepsy with grand mal on awakening and sleep-waking cycle. Clin Neurophysiol. 2000;111(Suppl 2):S103-S110. https://doi.org/10.1016/s1388-2457(00)00409-0
Jensen CD, Gesche J, Krøigård T, Beier CP. Prognostic value of generalized polyspike trains and prolonged epileptiform EEG runs. J Clin Neurophysiol. 2021;38(3):208-212. https://doi.org/10.1097/WNP.0000000000000679
Cerulli Irelli E, Barone FA, Mari L, Morano A, Orlando B, Salamone EM, et al. Generalized fast discharges along the genetic generalized epilepsy spectrum: clinical and prognostic significance. Front Neurol. 2022;13:844674. https://doi.org/10.3389/fneur.2022.844674
Kamitaki BK, Janmohamed M, Kandula P, Elder C, Mani R, Wong S, et al. Clinical and EEG factors associated with antiseizure medication resistance in idiopathic generalized epilepsy. Epilepsia. 2022;63(1):150-161. https://doi.org/10.1111/epi.17104
Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 2007;75(2-3):192-196. https://doi.org/10.1016/j.eplepsyres.2007.06.003
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319. https://doi.org/10.1056/NEJM200002033420503
Santana-Gomez CE, Engel J Jr, Staba R. Drug-resistant epilepsy and the hypothesis of intrinsic severity: what about the high-frequency oscillations? Epilepsia Open. 2022;7(Suppl 1):S59-S67. https://doi.org/10.1002/epi4.12565
Shakeshaft A, Panjwani N, Collingwood A, Crudgington H, Hall A, Andrade DM, et al. Sex-specific disease modifiers in juvenile myoclonic epilepsy. Sci Rep. 2022;12(1):2785. https://doi.org/10.1038/s41598-022-06324-2
Cerulli Irelli E, Morano A, Orlando B, Salamone EM, Fanella M, Fattouch J, et al. Seizure outcome trajectories in a well-defined cohort of newly diagnosed juvenile myoclonic epilepsy patients. Acta Neurol Scand. 2022;145(3):314-321. https://doi.org/10.1111/ane.13556
Choi H, Detyniecki K, Bazil C, Thornton S, Crosta P, Tolba H, et al. Development and validation of a predictive model of drug-resistant genetic generalized epilepsy. Neurology. 2020;95(15):e2150-e2160. https://doi.org/10.1212/WNL.0000000000010597
Herzog AG. Catamenial epilepsy: update on prevalence, pathophysiology and treatment from the findings of the NIH Progesterone Treatment Trial. Seizure. 2015;28:18-25. https://doi.org/10.1016/j.seizure.2015.02.024
May P, Girard S, Harrer M, Bobbili DR, Schubert J, Wolking S, et al. Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study. Lancet Neurol. 2018;17(8):699-708. https://doi.org/10.1016/S1474-4422(18)30215-1
Badawy RA, Vogrin SJ, Lai A, Cook MJ. Capturing the epileptic trait: cortical excitability measures in patients and their unaffected siblings. Brain. 2013;136(Pt 4):1177-1191. https://doi.org/10.1093/brain/awt047
Unterberger I, Trinka E, Luef G, Bauer G. Idiopathic generalized epilepsies with pure grand mal: clinical data and genetics. Epilepsy Res. 2001;44(1):19-25. https://doi.org/10.1016/s0920-1211(00)00210-2
Greenberg DA, Durner M, Resor S, Rosenbaum D, Shinnar S. The genetics of idiopathic generalized epilepsies of adolescent onset: differences between juvenile myoclonic epilepsy and epilepsy with random grand mal and with awakening grand mal. Neurology. 1995;45(5):942-946. https://doi.org/10.1212/wnl.45.5.942
Badawy RA, Macdonell RA, Jackson GD, Berkovic SF. Why do seizures in generalized epilepsy often occur in the morning? Neurology. 2009;73(3):218-222. https://doi.org/10.1212/WNL.0b013e3181ae7ca6
Hattemer K, Knake S, Reis J, Oertel WH, Rosenow F, Hamer HM. Cyclical excitability of the motor cortex in patients with catamenial epilepsy: a transcranial magnetic stimulation study. Seizure. 2006;15(8):653-657. https://doi.org/10.1016/j.seizure.2006.07.004
Manganotti P, Bongiovanni LG, Fuggetta G, Zanette G, Fiaschi A. Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy: a combined transcranial magnetic stimulation and EEG study. J Neurol Neurosurg Psychiatry. 2006;77(1):56-60. https://doi.org/10.1136/jnnp.2004.041137
Stevelink R, Al-Toma D, Jansen FE, Lamberink HJ, Asadi-Pooya AA, Farazdaghi M, et al. Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: a systematic review and individual participant data meta-analysis. EClinicalMedicine. 2022;53:101732. https://doi.org/10.1016/j.eclinm.2022.101732
Lamberink HJ, Otte WM, Geerts AT, Pavlovic M, Ramos-Lizana J, Marson AG, et al. Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis. Lancet Neurol. 2017;16(7):523-531. https://doi.org/10.1016/S1474-4422(17)30114-X
Syvertsen M, Fløgstad I, Enger U, Landmark CJ, Koht J. Antiepileptic drug withdrawal in juvenile myoclonic epilepsy. Acta Neurol Scand. 2019;139(2):192-198. https://doi.org/10.1111/ane.13042
Marson A, Burnside G, Appleton R, Smith D, Leach JP, Sills G, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. Lancet. 2021;397(10282):1375-1386. https://doi.org/10.1016/S0140-6736(21)00246-4
Tomson T, Marson A, Boon P, Canevini MP, Covanis A, Gaily E, et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia. 2015;56(7):1006-1019. https://doi.org/10.1111/epi.13021
Gesche J, Hjalgrim H, Rubboli G, Beier CP. Patterns and prognostic markers for treatment response in generalized epilepsies. Neurology. 2020;95(18):e2519-e2528. https://doi.org/10.1212/WNL.0000000000010644