Current terminology, diagnosis and modern treatment options



Epilepsies, terminology, epileptic/developmental encephalopathies, Lennox-Gastaut syndrome, Dravet syndrome, antiseizure medications


Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes according to the age of onset from 2022, some terminologies are changed. Only Dravet syndrome, Lennox-Gastaut syndrome and Rasmussen syndrome remain with names of authors who described the syndromes. West syndrome becomes „Syndrome with epileptic infantile spasms”; Benign focal childhood epilepsies become „self-limited epilepsies”: Idiopathic epilepsy with centrotemporal spikes (Rolandic epilepsy becomes „Self-limited epilepsy with centrotemporal spikes”; Panayiotopoulos syndrome or early onset benign occipital epilepsy becomes „Self-limited epilepsy with autonomic seizures”; Occipital epilepsy Gastaut type (late onset benign occipital epilepsy) becomes „Childhood occipital visual epilepsy”. The new change in terminology classifies epilepsies according to age of onset. According to the new concept of developmental and/or epileptic encephalopathy and epileptic encephalopathy, epilepsy and delayed development are two conditions with a common etiology (structural and genetic causes), in which aggressive antiepileptic treatment is necessary. In epileptic encephalopathies that are pharmacoresistant, seizures and/or EEG discharges impair neuropsychic development and cognitive functions.
According to the age of onset, epileptic encephalopathies are: early infantile (Early-infantile developmental and epileptic encephalopathy, infantile epileptic spasms syndrome or West syndrome, migrating focal seizures, Dravet syndrome) and late (Lennox-Gastaut syndrome, epileptic encephalopathies with a sharp-slow wave activation in sleep, Landau Kleffner syndrome, atypical benign focal epilepsy in childhood, hemiconvulsion-hemiplegia-syndrome, febrile infection-related epilepsy syndrome; With onset at different ages are epileptic syndromes with progressive neurological damage, Rasmussen syndrome, progressive myoclonic epilepsy, febrile infection-related epilepsy syndrome. Neurocognitive and behavioral abnormalities may improve with seizure control and reduction of interictal epileptic activity. Developmental encephalopathies present with delayed neuropsychiatric development or intellectual deficit due to non-progressive brain damage, with or without epilepsy, and neurocognitive and behavioral deficits remain regardless of epilepsy control. Current algorithms for the treatment of epilepsies with monotherapy or rational polytherapy are presented, incl. with new antiseizure medications (ASM), emphasizing the treatment of epileptic encephalopathies.


Божинова, В. Диагностика и нови възможности за лечение на детските епилептични енцефалопатии – синдром на Dravet и синдром на Lennox-Gastaut. GP MEDIC. 2023, 5, 5, 10-16. [Bozhinova, V. Diagnostika i novi vazmozhnosti za lechenie na detskite epileptichni entsefalopatii – sindrom na Dravet i sindrom na Lennox-Gastaut. GP MEDIC. 2023, 5, 5, 10-16.]

Миланов, И, Божинова, В. Национален консенсус за диагностика и лечение на епилепсията. Българска неврология, 2022, 23, Suppl. 2, 1-30. [Milanov, I., Bozhinova, V. Natsionalen konsensus za diagnostika i lechenie na epilepsiata. Bulgarska nevrologia, 2022, 23, Suppl. 2, 1-30.]

Миланов, И., Божинова, В. Национален консенсус за диагностика и лечение на епилепсията, Българска неврология 2023, Suppl. 6, 1-38. [Milanov, I., Bozhinova, V. Natsionalen konsensus za diagnostika i lechenie na epilepsiata. Bulgarska nevrologia, 2023, Suppl. 6, 1-38.]

Arzimanoglou, A., French, J., Blume, W.T., Cross, J. H., Ernst, J. P., Feucht, M., Genton, P., Guerrini, R., Kluger, G., Pellock, J.M., Perucca, E., Wheless, J.W. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009, 8, 1, 82-93.

Asadi-Pooya, A. A. Lennox-Gastaut syndrome: a comprehensive review. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018, 39, 3, 403-414.

Bagdy, G., Riba, P., Jakus, R. et al. Serotonin and epilepsy. J Neurochem

, 100, 857-873.

Berkovic, S. F. Epileptic encephalopathies of infancy: welcome advances. Lancet.2019, 394, 10216, 2203-2204.

Bjørk, M. H., Zoega, H., Leinonen, M. K., Cohen, J. M., Dreier, J. W., Furu, K., Gilhus, N. E., Gissler, M., Hálfdánarson, Ó., Igland, J., Sun, Y., Tomson, T, Alvestad, S., Christensen, J. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA Neurol. 2022, 79, 7, 672-681.

Choen, J. M., Alvestad, S., Cesta, C. E. et al. Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations. Ann Neurol 2023, 93, 3, 551-562.

Ciranna, L. Serotonin as a modulator of glutamate- and GABAmediated neurotransmission: implications in physiological functions and in pathology. Curr Neuropharmacol. 2006, 4, 2, 101-114.

Cross, J. H., Auvin, S., Falip, M., Striano, P., Arzimanoglou, A. Expert Opinion on the Management of Lennox-Gastaut Syndrome: Treatment Algorithms and Practical Considerations. Front Neurol. 2017, 8, 505, doi: 10.3389/fneur.2017.00505. PMID: 29085326; PMCID: PMC5649136.

Devinsky, O., Patel, A.D., Cross, J.H., Villanueva, V. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. New England Journal of Medicine 2018, 378, 20, 1888-1897.

Devinsky, O., Cross, J. H., Laux, L. et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med 2017, 376, 2011-2021.

Dreier, J. W., Bjørk, M. H., Alvestad, S., Gissler, M., Igland, J., Leinonen, M. K., Sun, Y., Zoega, H., Cohen, J. M., Furu, K., Tomson, T., Christensen, J. Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders. JAMA Neurol. 2023, 80, 6, 568-577.

Gray, R.A, Whalley, B. J. The proposed mechanisms of action of CBD in epilepsy. Epileptic Disord. 2020, 22, suppl. 1, 10-15.

Hernández-Díaz, S., Mc Elrat, T. F., Pennell, P. B., Hauser, W. A., Yerby, M., Holmes, L.B., for the North American AED (Antiepileptic Drug) Pregnancy Registry. Fetal growth and premature delivery in pregnant women on antiepileptic drugs. Ann Neurol., 2017, 82, 457-465.

Hirsch, E., French, J., Scheffer, I. E., Bogacz, A., Alsaadi, T., Sperling, M. R., Abdulla, F., Zuberi, S. M., Trinka, E., Specchio, N., Somerville, E., Samia, P., Riney, K., Nabbout, R., Jain, S., Wilmshurst, J.M., Auvin, S., Wiebe, S., Perucca, E., Moshé, S.L., Tinuper, P., Wirrell, E.C. 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.

Kalser, J., Cross, J. H. The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies. Curr Opin Neurol. 2018, 31, 2, 216-222.

Knupp, K. G., Scheffer, I. E., Ceulemans, B., Sullivan, J. E., Nickels, K. C., Lagae, L., Guerrini R., Zuberi, S. M., Nabbout, R., Riney, K., Shore, S., Agarwal, A., Lock, M., Farfel, G. M., Galer, B. S., Gammaitoni, A. R., Davis, R., Gil-Nage, l. A. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox-Gastaut syndrome. A randomised controlled trial, JAMA Neurol. 2022; 79, 554-564.

Lagae, L., Sullivan, J., Knupp, K., Laux, L., Polster, T., Nikanorova, M., Devinsky, O., Cross, J. H., Guerrini, R., Talwar, D., Miller, I., Farfel, G., Galer, B.S., Gammaitoni, A., Mistry, A., Morrison, G., Lock, M., Agarwal, A., Lai, W. W., Ceulemans, B.; FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, doubleblind, placebo-controlled trial. Lancet. 2019, 394, 10216, 2243-2254.

Martin, P., de Witte, P.A.M., Maurice, T., Gammaitoni, A., Farfel, G., Galer, B. Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020, 105, 106989.

Nabbout, R., Mistry, A., Zuberi, S., Villeneuve, N., Gil-Nagel, A., Sanchez-Carpintero, R., Stephani, U., Laux, L., Wirrell, E., Knupp, K., Chiron, C., Farfel, G., Galer, B.S., Morrison, G., Lock, M., Agarwal, A., Auvin, S.; FAiRE, DS Study Group. Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. JAMA Neurol. 2020, 77, 3, 300-308.

Riney, K., Bogacz, A., Somerville, E., Hirsch, E., Nabbout, R., Scheffer, I.E., Zuberi S.M., Alsaadi, T., Jain, S., French, J., Specchio, N., Trinka, E., Wiebe, S,. Auvin, S., Cabral-Lim, L, Naidoo, A., Perucca, E., Moshe, S. L., Wirrell, E.C., Tinuper, P. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022, 63, 6, 1443-1474.

Riva, A., Coppola, A., Di Bonaventura, C., et al. An Italian consensus on the management of Lennox-Gastaut syndrome. Seizure 2022, 101, 134-140.

Ryskamp, D.A., Korban, S., Zhemkov, V., Kraskovskaya, N., Bezprozvanny, I. Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases. Front Neurosci. 2019, Aug 28;13:862. doi: 10.3389/fnins.2019.00862. PMID: 31551669; PMCID: PMC6736580.

Scheffer, I. E., Berkovic, S., Capovilla, G., et al. ILAE classification of the epilepsies: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017, 58, 512-521.

Shorvon, S.D., Guerrini, R., Cook, M., eds. Oxford textbook of epilepsy and epileptic seizures. 2013, Oxford: Oxford Univ. Press. p. 13. ISBN 978-0-19-965904-3

Sourbron, J., Smolders, I., de Witte, P., Lagae, L. Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in SCN1A Mutant Zebrafish. Front Pharmacol. 2017,8, 191.

Specchio, N., Curatolo, P. Developmental and epileptic encephalopathies: what we do and do not know. Brain, 2021, 144, 1, 32-43.

Specchio, N., Wirrell, E. C., Scheffer, I. E., Nabbout, R., Riney, K., Samia, P., Guerreiro, M., Gwer, S., Zuberi, S. M., Wilmshurst, J. M., Yozawitz, E., Pressler, R., Hirsch, E., Wiebe, S., Cross, H. J., Perucca, E., Moshé, S. L., Tinuper, P., Auvin, S. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022, 63, 6, 1398-1442.

Thiele, E. A., Marsh, E. D., French, J. A. et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018, 391, 10125.

Zuberi, S. M., Wirrell, E., Yozawitz, E., Wilmshurst, J. M., Specchio, N., Riney, K., Pressler, R., Auvin, S., Samia, P., Hirsch, E., Galicchio, S., Triki, C., Snead, O.C., Wiebe, S., Cross, J. H., Tinuper, P., Scheffer, I. E., Perucca, E., Moshé, S. L., Nabbout R. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022, 63, 6, 1349-1397.



How to Cite

Bojinova, V., & Milanov, I. (2023). Current terminology, diagnosis and modern treatment options. Bulgarian Neurology, 24(3), 91–100. Retrieved from