Sulthiame add-on treatment in children with epileptic encephalopathy with status epilepticus: an efficacy analysis in etiologic subgroups



Sulthiame (STM) has been recommended as an effective antiepileptic drug (AED) in children with epileptic encephalopathy with status epilepticus in sleep (ESES). The aim of this study is to evaluate the efficacy of STM add-on treatment in children with pattern of ESES with respect to the etiologic subgroup.


Twenty-nine children with ESES pattern with three different etiologic subgroups (epileptic syndromes: 14, structural/infectious: 9, unknown: 6) who were given STM as add-on treatment were included into the study. The efficacy of STM was evaluated in terms of seizure control, electroencephalography (EEG) findings, need of the new AEDs after add-on STM, and behavioral and cognitive improvement.


The range of the follow-up duration after add-on STM treatment was between 5 and 51 months. At the end of 1 year of STM treatment, the most successful electrophysiologic improvement was identified in the well-defined epileptic syndrome group; epileptic syndrome, 71.4% (10/14); structural/infectious, 33.3% (3/9); and unknown, 0% (0/6). Patients who had complete response or persistent ESES pattern at the 3rd month were still in the same condition at the 6th and 12th months. However, the ESES pattern reappeared in 35.2% of the patients who had partial electrophysiological improvement at the 3rd month. In the epilepsy syndrome group, eight out of ten patients who had either complete or partial EEG response after 1 year of STM treatment displayed behavioral and cognitive improvement.


Sulthiame might be a valid add-on treatment of ESES especially in children with epilepsy syndromes.

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  1. 1.

    Singhal NS, Sullivan JE (2014) Continuous spike-wave during slow wave sleep and related conditions. ISRN Neurology 2014:619079–619076.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Gencpinar P, Dundar NO, Tekgul H (2016) Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: an electroclinical evaluation according to the EEG patterns. Epilepsy Behav 61:107–111.

    Article  PubMed  Google Scholar 

  3. 3.

    Nickels K, Wirrell E (2008) Electrical status epilepticus in sleep. Semin Pediatr Neurol 15:50–60.

    Article  PubMed  Google Scholar 

  4. 4.

    Patry G, Lyagoubi S, Tassinari CA (1971) Subclinical electrical status epilepticus induced by sleep in children. A clinical and electroencephalographic study of six cases. Arch Neurol 24:242–252

    CAS  Article  Google Scholar 

  5. 5.

    Van Hirtum-Das M, Licht EA, Koh S, Wu JY, Donald Shields W, Sankar R (2006) Children with ESES: variability in the syndrome. Epilepsy Res 70:248–258.

    Article  Google Scholar 

  6. 6.

    Brazzo D, Pera MC, Fasce M, Papalia G, Balottin U, Veggiotti P (2012) Epileptic encephalopathies with status epilepticus during sleep: new techniques for understanding pathophysiology and therapeutic options. Epilepsy Res Treat 2012:1–6.

    Article  Google Scholar 

  7. 7.

    Arhan E, Serdaroglu A, Aydin K, Hırfanoglu T, Soysal AS (2015) Epileptic encephalopathy with electrical status epilepticus: an electroclinical study of 59 patients.

  8. 8.

    Rossi PG, Parmeggiani A, Posar A, Scaduto MC, Chiodo S, Vatti G (1999) Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical status epilepticus during sleep (ESES). Brain Dev 21:90–98

    CAS  Article  Google Scholar 

  9. 9.

    Inutsuka M, Kobayashi K, Oka M, Hattori J, Ohtsuka Y (2006) Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain Dev 28:281–286.

    Article  PubMed  Google Scholar 

  10. 10.

    Liukkonen E, Kantola-Sorsa E, Paetau R, Gaily E, Peltola M, Granström M-L (2010) Long-term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome. Epilepsia 51:2023–2032.

    Article  PubMed  Google Scholar 

  11. 11.

    Ben-Zeev B, Watemberg N, Lerman P, Barash I, Brand N, Lerman-Sagie T (2004) Sulthiame in childhood epilepsy. Pediatr Int 46:521–524.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Madeja M, Wolf C, Speckmann E-J (2001) Reduction of voltage-operated sodium currents by the anticonvulsant drug sulthiame. Brain Res 900:88–94.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Leniger T, Wiemann M, Bingmann D, Widman G, Hufnagel A, Bonnet U (2002) Carbonic anhydrase inhibitor sulthiame reduces intracellular pH and epileptiform activity of hippocampal CA3 neurons. Epilepsia 43:469–474.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Engler F, Maeder-Ingvar M, Roulet E, Deonna T (2003) Treatment with sulthiame (Ospolot®) in benign partial epilepsy of childhood and related syndromes: an open clinical and EEG study. Neuropediatrics 34:105–109.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Tacke M, Borggraefe I, Gerstl L, Heinen F, Vill K, Bonfert M, Bast T, HEAD Study group, Neubauer BA, Baumeister F, Baethmann M, Bentele K, Blank C, Blank HM, Bode H, Bosch F, Brandl U, Brockmann K, Dahlem P, Ernst JP, Feldmann E, Fiedler A, Gerigk M, Heß S, Hikel C, Hoffmann HG, Kieslich M, Klepper J, Kluger G, Koch H, Koch W, Korinthenberg R, Krois I, Kühne H, Kurlemann G, Mandl M, Mause U, Navratil P, Opp J, Penzien J, Prietsch V, Quattländer A, Rating D, Schara U, Shamdeen MG, Sprinz A, Wendker-Magrabi H, Stephani U, Muhle H, Straßburg HM, Töpke B, Trollmann R, Tuschen-Hofstätter E, Waltz S, Weber G, Wien FU, Wolff M, Polster T, Freitag H, Sönmez Ö, Reinhardt K, Traus M, Hoovey Z (2018) Effects of levetiracetam and sulthiame on EEG in benign epilepsy with centrotemporal spikes: a randomized controlled trial. Seizure 56:115–120.

    Article  PubMed  Google Scholar 

  16. 16.

    Uliel-Sibony S, Kramer U (2015) Benign childhood epilepsy with centro-temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be? Epilepsy Behav: E&B 44:117–120.

    Article  Google Scholar 

  17. 17.

    Shamdeen MG, Jost W, Frohnhöfer M, Gortner L, Meyer S (2012) Effect of sulthiame on EEG pathology, behavior and school performance in children with Rolandic epileptiform discharges. Pediatr Int 54:798–800.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Wirrell E, Ho AW-C, Hamiwka L (2006) Sulthiame therapy for continuous spike and wave in slow-wave sleep. Pediatr Neurol 35:204–208.

    Article  PubMed  Google Scholar 

  19. 19.

    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 58:512–521.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Aeby A, Poznanski N, Verheulpen D, Wetzburger C, Van Bogaert P (2005) Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases. Epilepsia 46:1937–1942.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Loddenkemper T, Fernandez IS, Peters JM (2011) Continuous spike and waves during sleep and electrical status epilepticus in sleep. J Clin Neurophysiol 28:154–164

    Article  Google Scholar 

  22. 22.

    Savaşır I, Şahin N. Wechsler Çocuklar İçin Zeka Ölçeği uygulama kitapçığı. 1995

  23. 23.

    Pera MC, Brazzo D, Altieri N, Balottin U, Veggiotti P (2013) Long-term evolution of neuropsychological competences in encephalopathy with status epilepticus during sleep: a variable prognosis. Epilepsia 54:77–85.

    Article  PubMed  Google Scholar 

  24. 24.

    Kramer U, Sagi L, Goldberg-Stern H, Zelnik N, Nissenkorn A, Ben-Zeev B (2009) Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia 50:1517–1524.

    Article  PubMed  Google Scholar 

  25. 25.

    Sánchez Fernández I, Chapman KE, Peters JM, Harini C, Rotenberg A, Loddenkemper T (2013) Continuous spikes and waves during sleep: electroclinical presentation and suggestions for management. Epilepsy Res Treat 2013:1–12.

    Article  Google Scholar 

  26. 26.

    Fortini S, Corredera L, Pastrana AL, Reyes G, Fasulo L, Caraballo RH (2013) Encephalopathy with hemi-status epilepticus during sleep or hemi-continuous spikes and waves during slow sleep syndrome: a study of 21 patients. Seizure 22:565–571.

    Article  PubMed  Google Scholar 

  27. 27.

    Caraballo RH, Veggiotti P, Kaltenmeier MC, Piazza E, Gamboni B, Avaria MFL, Noli D, Adi J, Cersosimo R (2013) Encephalopathy with status epilepticus during sleep or continuous spikes and waves during slow sleep syndrome: a multicenter, long-term follow-up study of 117 patients. Epilepsy Res 105:164–173.

    Article  PubMed  Google Scholar 

  28. 28.

    Fejerman N, Caraballo R, Cersósimo R, Ferraro SM, Galicchio S, Amartino H (2012) Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES). Epilepsia 53:1156–1161.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Bast T, Völp A, Wolf C, For The Sulthiame Study Group DR (2003) The influence of sulthiame on EEG in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Epilepsia 44:215–220.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Caraballo RH, Cejas N, Chamorro N, Kaltenmeier MC, Fortini S, Soprano AM (2014) Landau–Kleffner syndrome: a study of 29 patients. Seizure 23:98–104.

    Article  PubMed  Google Scholar 

  31. 31.

    Caraballo RH, Cersósimo RO, Fortini PS, Ornella L, Buompadre MC, Vilte C, Princich JP, Fejerman N (2013) Congenital hemiparesis, unilateral polymicrogyria and epilepsy with or without status epilepticus during sleep: a study of 66 patients with long-term follow-up. Epileptic Disord 15:417–427.

    Article  PubMed  Google Scholar 

  32. 32.

    Weissbach A, Tirosh I, Scheuerman O, Hoffer V, Garty BZ (2010) Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Pediatr Emerg Care 26:752–753.

    Article  PubMed  Google Scholar 

  33. 33.

    Miyajima T, Kumada T, Kimura N, Mikuni T, Fujii T (2009) Sulthiame treatment for patients with intractable epilepsy. No to Hattatsu = Brain Dev 41:17–20

    Google Scholar 

  34. 34.

    Swiderska N, Hawcutt D, Eaton V, Stockton F, Kumar R, Kneen R, Appleton R (2011) Sulthiame in refractory paediatric epilepsies: an experience of an ‘old’ antiepileptic drug in a tertiary paediatric neurology unit. Seizure 20:805–808.

    Article  PubMed  Google Scholar 

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Correspondence to Seda Kanmaz.

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This study was approved by the Ege University ethical committee.

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Kanmaz, S., Simsek, E., Serin, H.M. et al. Sulthiame add-on treatment in children with epileptic encephalopathy with status epilepticus: an efficacy analysis in etiologic subgroups. Neurol Sci (2020).

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  • Sulthiame
  • ESES
  • Epilepsy syndromes