Persistent treatment resistance in genetic generalized epilepsy: A long-term outcome study in a tertiary epilepsy center.
Adult
Anticonvulsants
/ pharmacology
Cohort Studies
Drug Resistant Epilepsy
/ drug therapy
Electroencephalography
/ drug effects
Epilepsy, Generalized
/ drug therapy
Female
Humans
Longitudinal Studies
Male
Middle Aged
Myoclonic Epilepsy, Juvenile
/ drug therapy
Retrospective Studies
Time Factors
Treatment Outcome
Valproic Acid
/ pharmacology
generalized paroxysmal fast activity
genetic generalized epilepsy
idiopathic generalized epilepsy
prognostic factors
treatment resistance
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
20
05
2020
revised:
04
09
2020
accepted:
06
09
2020
entrez:
21
12
2020
pubmed:
22
12
2020
medline:
4
2
2021
Statut:
ppublish
Résumé
To assess prognostic patterns and investigate clinical and electroencephalography (EEG) variables associated with persistent treatment resistance in a population of genetic generalized epilepsy (GGE) patients with a long-term follow-up. Data from GGE patients followed from 1975 to 2019 were reviewed retrospectively. Subjects with a follow-up >10 years, starting from epilepsy diagnosis, were included. Persistent treatment resistance was defined as the absence of any period of remission ≥1 year despite treatment with two appropriate and adequate antiepileptic drugs (AEDs). One hundred ninety-nine patients were included. The median age was 39.5 years (interquartile range [IQR] 30-49) and the median follow-up was 27 years (IQR 18-35). The most common syndrome was juvenile myoclonic epilepsy (JME), diagnosed in 44.2% of patients. During follow-up, 163 subjects (81.9%) experienced 3-year remission from any seizure type, whereas 5- and 10-year remission occurred in 141 (70.8%) and 92 (46.2%) cases, respectively. The most common prognostic pattern was a relapsing-remitting course, observed in 80 patients (40.2%), whereas 29 (14.6%) displayed persistent treatment resistance. According to multivariable logistic regression analysis, febrile seizures (FS), specific EEG patterns (namely generalized paroxysmal fast activity, GPFA) and valproate (VPA) resistance were the only variables significantly associated with persistent treatment resistance. JME was the only epilepsy syndrome statistically associated with persistent treatment resistance in univariable logistic regression analysis. Persistent treatment resistance was observed in almost 15% of GGE patients followed in a tertiary epilepsy center. A worse outcome was associated with specific clinical variables (JME, FS) and EEG patterns (GPFA).
Substances chimiques
Anticonvulsants
0
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2452-2460Informations de copyright
© 2020 International League Against Epilepsy.
Références
Mullen SA, Berkovic SF. Genetic generalized epilepsies. Epilepsia. 2018;59:1148–53.
Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia. 2005;46:10–4.
Semah F, Picot M‐C, Adam C, Broglin D, Arzimanoglou A, Bazin B, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51:1256–62.
Mohanraj R, Brodie MJ. Outcomes of newly diagnosed idiopathic generalized epilepsy syndromes in a non‐pediatric setting. Acta Neurol Scand. 2007;115:204–8.
Berg AT, Shinnar S, Levy SR, Testa FM, Smith‐Rapaport S, Beckerman B, et al. Two‐year remission and subsequent relapse in children with newly diagnosed epilepsy. Epilepsia. 2001;42:553–62.
Seneviratne U, Cook M, D’Souza W. The prognosis of idiopathic generalized epilepsy. Epilepsia. 2012;53:2079–90.
Szaflarski JP. Can EEG predict outcomes in genetic generalized epilepsies? Clin Neurophysiol. 2014;125:215–6.
Geithner J, Schneider F, Wang Z, Berneiser J, Herzer R, Kessler C, et al. Predictors for long‐term seizure outcome in juvenile myoclonic epilepsy: 25–63 years of follow‐up. Epilepsia. 2012;53:1379–86.
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;18:61–3.
Geerts A, Arts WF, Stroink H, Peeters E, Brouwer O, Peters B, et al. Course and outcome of childhood epilepsy: A 15‐year follow‐up of the Dutch Study of Epilepsy in Childhood. Epilepsia. 2010;51:1189–97.
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–21.
Striano S, Striano P, Nocerino C, Boccella P, Bilo L, Meo R, et al. Eyelid myoclonia with absences: an overlooked epileptic syndrome? Neurophysiol Clin. 2002;32:287–96.
Brenner RP, Atkinson R. Generalized paroxysmal fast activity: electroencephalographic and clinical features. Ann Neurol. 1982;11:386–90.
Beghi E, Beretta S, Carone D, Zanchi C, Bianchi E, Pirovano M, et al. Prognostic patterns and predictors in epilepsy: a multicentre study (PRO‐LONG). J Neurol Neurosurg Psychiatry. 2019;90:1276–85.
Gesche J, Khanevski M, Solberg C, Beier CP. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies. Epilepsia. 2017;58:e64–e69.
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;58:1244–50.
Dragoumi P, Tzetzi O, Vargiami E, Pavlou E, Krikonis K, Kontopoulos E, et al. Clinical course and seizure outcome of idiopathic childhood epilepsy: determinants of early and long‐term prognosis. BMC Neurol. 2013;13:206.
Ashmawi A, Hosny H, Abdelalim A, Bianchi E, Beghi E. The long‐term prognosis of newly diagnosed epilepsy in Egypt: a retrospective cohort study from an epilepsy center in Greater Cairo. Seizure. 2016;41:86–95.
Nicolson A, Appleton RE, Chadwick DW, Smith DF. The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalised epilepsies. J Neurol Neurosurg Psychiatry. 2004;75:75–9.
Cerulli Irelli E, Morano A, Cocchi E, Casciato S, Fanella M, Albini M, et al. Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome. Epilepsia. 2020;61:107–14.
Cerulli Irelli E, Cocchi E, Morano A, Casciato S, Fanella M, Albini M, et al. Valproate impact and sex‐dependent seizure remission in patients with Idiopathic Generalized Epilepsy. J Neurol Sci. 2020;415:116940. https://doi.org/10.1016/j.jns.2020.116940
Cação G, Parra J, Mannan S, Sisodiya SM, Sander JW. Juvenile myoclonic epilepsy refractory to treatment in a tertiary referral center. Epilepsy Behav. 2018;82:81–6.
Myers KA, Scheffer IE, Berkovic SF. Genetic literacy series: genetic epilepsy with febrile seizures plus. Epileptic Disord. 2018;20:232–8.
Bonanni P, Malcarne M, Moro F, Veggiotti P, Buti D, Ferrari AR, et al. Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia. 2004;45:149–58.
Zhang Y‐H, Burgess R, Malone JP, Glubb GC, Helbig KL, Vadlamudi L, et al. Genetic epilepsy with febrile seizures plus: refining the spectrum. Neurology. 2017;89:1210–9.
Johannesen K, Marini C, Pfeffer S, Møller RS, Dorn T, Niturad CE, et al. Phenotypic spectrum of GABRA1: from generalized epilepsies to severe epileptic encephalopathies. Neurology. 2016;87:1140–51.
Marini C, Porro A, Rastetter A, Dalle C, Rivolta I, Bauer D, et al. HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond. Brain. 2018;141:3160–78.
Epi4K Consortium. De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am J Hum Genet. 2016;99:287–98.
Lachance‐Touchette P, Martin C, Poulin C, Gravel M, Carmant L, Cossette P. Screening of GABRB3 in French‐Canadian families with idiopathic generalized epilepsy. Epilepsia. 2010;51(9):1894–7.
Michelucci R, Rubboli G, Passarelli D, Riguzzi P, Volpi L, Parmeggiani L, et al. Electroclinical features of idiopathic generalised epilepsy with persisting absences in adult life. J Neurol Neurosurg Psychiatry. 1996;61:471–7.
Aydin‐Özemir Z, Matur Z, Bebek N, Gürses C, Gökyiğit A, Baykan B. Long‐term follow‐up of adult patients with genetic generalized epilepsy with typical absence seizures and generalized paroxysmal fast activity in their EEG. Seizure. 2014;23:607–15.
Guye M, Bartolomei F, Gastaut JL, Chauvel P, Dravet C. Absence epilepsy with fast rhythmic discharges during sleep: an intermediary form of generalized epilepsy? Epilepsia. 2001;42:351–6.
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:e1822–e1830.
Sagi V, Kim I, Bhatt AB, Sonmezturk H, Abou‐Khalil BW, Arain AM. Generalized paroxysmal fast activity in EEG: an unrecognized EEG finding in genetic generalized epilepsy. Epilepsy Behav. 2017;76:101–4.
Halász P. Runs of rapid spikes in sleep: a characteristic EEG expression of generalized malignant epileptic encephalopathies: a conceptual review with new pharmacological data. Epilepsy Res Suppl. 1991;2:49–71.
Badawy RA, Macdonell RA, Berkovic SF, Newton MR, Jackson GD. Predicting seizure control: cortical excitability and antiepileptic medication. Ann Neurol. 2010;67:64–73.
Pawley AD, Chowdhury FA, Tangwiriyasakul C, Ceronie B, Elwes RDC, Nashef L, et al. Cortical excitability correlates with seizure control and epilepsy duration in chronic epilepsy. Ann Clin Transl Neurol. 2017;4:87–97.
Badawy RA, Jackson GD, Berkovic SF, Macdonell RA. Cortical excitability and refractory epilepsy: a three‐year longitudinal transcranial magnetic stimulation study. Int J Neural Syst. 2013;23:1250030.
Syvertsen MR, Flogstad I, Enger U, Landmark CJ, Koht J. Antiepileptic drug withdrawal in juvenile myoclonic epilepsy. Acta Neurol Scand. 2019;139:192–8.
Syvertsen MR, Thuve S, Stordrange BS, Brodtkorb E. Clinical heterogeneity of juvenile myoclonic epilepsy: follow‐up after an interval of more than 20 years. Seizure. 2014;23:344–8.