COHORT OF ESES - PowerPoint Presentation

1. COHORT OF ESES Epilepsy team , Acute & Community Paediatrics, Colchester Hospital Dr. Manal Issa-Dr Manidipa Dutta-Dr Benjamin Marlow- Dr Angeliki Menounou -Dr Deepa Krishnakumar ( Addenbrookes Hospital)Nurse specialists-Jen vincent -Jennifer Beggy-Kayly Elmer-

2. Electrical status epilepticus during slow-wave sleep (ESES) is an epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behaviour. It is a particularly difficult-to-treat childhood epileptic syndrome.Currently no consensus on the treatment of ESES. No methodological consensus on EEG abnormality quantification and treatment efficacy evaluation.No completed RCT with blinded and standardized cognitive outcome assessment exists but benzodiazepines and corticosteroids are the mainstay of recommended treatment Small minority of patients whose ESES occurs in the setting of focal structural abnormalities and are favourable candidates for surgical resection.What do we know ?

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6. If there is concern about the school performance of a child or young person having antiseizure medication, seek guidance from an epilepsy specialist and consider:• sleep electroencephalogram (EEG) to exclude exacerbation of epileptic activity (electrical status epilepticus during sleep) and • neuropsychology assessment to review academic performance. ( NICE guidelines 2022 NG217)

7. Publications ….. CausesElectrical Status Epilepticus During Slow-wave Sleep (ESES): Current Perspectives- P. Arican et al, june 2021,J Paed Neurosci-Causes- structural anomalies -, early developmental lesions such as perinatal vascular lesions ,cortical malformations, abnormal myelination, early thalamic injury . -Genetic mutations noted in many patients especially GRIN2A mutations.Suggestion - Wide use of the genetic investigation including epilepsy gene panels, array-cGH, WES,WGS, may be capable of diagnosing etiologically well-known cases with ESES .RCT helping us with a more rationale approach to treatmentPooled data from different studies.

8. Frontiers in genetics , 2021

9. Studies….

10. Electrical Status Epilepticus During Slow-wave Sleep (ESES): Current Perspectives- P. Arican et al, june 2021,J Paed Neurosci-Treatment- Apart from BZD and steroids , Some retrospective studies suggest that sodium valproate, ethosuximide, levetiracetam, sulthiame, topiramate, amantadine, and immunomodulatory agents may be effective in the treatment of ESES.-ketogenic diet (KD) is an additional treatment option-Surgery -Jeong et al. reported that the patients with structural lesion and drug-resistant ESES should be evaluated for hemispherectomy as they may experience the cessation of seizures, termination of ESES, and improvement in neuropsychological status.Outcome- Majority of cognitive and behavioural deficits often remain, especially in verbal and attention abilities. 10–40% of children’s cognition &language becomes normal after ESES pattern has resolved. Poor prognosis for cognition - Longer duration of ESES, abnormal development before the onset of ESES, and severity of initial regressionPublications …..Treatment

11. Criteria- Patients under ESNEFT database ,(acute and community paediatrics team) known to have had evidence of ESES (electrical status epilepticus in slow wave sleep) on sleep EEG. Sleep EEG was ordered for poor seizure control or decline in behaviour/school performance .Duration of study – Patients 2010- 2022. Method- Data collected retrospectively from electronic records systemEEG criteria ESES when slow spike and wave discharges occupy >70% of sleep epochs.Materials and Methods

12. Total no of cases- 13Includes a pair of siblings

13. Age distribution (when diagnosed with ESES )YEARs

14. Epileptic activity pre CSWS ( at first presentation)..Centro-temp/centro tempo-parietal90%

15. Seizure types - through the journey …Number of patientsSome patients had 2 types of seizures

16. Manifestations during CSWS 54%39%23%

17. EEG Established sleep with CSWS ( R>L)Normalisation in wakefulnessCentro-temporal spikes in subsequent drowsiness

18. GENETICS 7q31-7q33 duplication

19. Neuroimaging findingsSlight rt sided thalamic volume loss withgliotic changes seen. Thalamic hemorrhage resolved

20. CaseSeizuresASMESES treatment1-LKSCECTSNaVSteroids high dose 6 weeks - maintenance 4 yr( 2mg/kg twice weekly)2CECTS- FocalNav /CMZ/ CMZ+LVT short courses of clobazam LMT only – short course of Clobazam3-LKSFocal onset-Bilateral TCMRI - positivePhenobarbitone as neonateNaV /NaV +LMT/ LMT+ Clob/ - only LMTClobazam , Steroids ( 6 weeks 2mg/kg- 12 months 1mg/kg alternate days)Ethosuxamide4CECTSCMZClobazam / Wean off CMZ5-LKSNO seizuresClobazam ( Steroids not tolerated)6FocalNavNaV - Clobazam7CECTSNaV/NaV + Keppra+ ClobazamKeppra + Clobazam +LMT LMT+Clobazam - 8CECTSClobazam / Steroids 1mg/kg for6 weeks9Vacant episodesCECTSClobazam ( Relapsed when stopped) restarted.weaning now. Keppra started10 LKSVacant - TCSNaV stopped- KeppraSteroids, Clobazam, Sulthiame Ethusoxamide11Focal-BlateralTCDrops-vacant?NaVNav ( Relapse and then resolved again)12Focal – TCSCMZ- stopped on KeppraClobazam13AbsencesClobazamMEDICATIONS

21. Time noted for improvement on EEGNumber of months No of cases

22. All patients received tertiary Paediatric neurology input.Documentation within 1-4 mthsTertiary input

23. Neuropsychology assessmentTime for Neuro psychology assessment from referral – 4 mths -3 yrs .Assessment done between 1-4 times38%

24. 2 patients were seen by clinical psychologist 1 patient awaiting assessment by EWMHS Psychology support

25. Development – Pre diagnosis

26. Outcome- currently on AED

27. Outcome- SequelaeSpeech/language /dyspraxiaLearning problems/Special needs schoolASD/special needs school

28. Sequelae ( no pre existing concerns)30%

29. 9/13 presented as focal seizures – CECTS spectrum semiology and on EEG11/13 patients in our cohort responded to Clobazam as monotherapy or combination with AED EEG improvement – resolution Performance at school +/- or speech improvementSteroids were given to 4 LKS patients .All except one patient had developmental sequelae.Timed/ Regular Neuropsychological assessment and psychology support are still a challenge for all patients.Conclusion-

30. 1) Diagnosis -Criteria for diagnosis including EEG criteria-Neuropsychology assessment-Investigations like genetics –WGS /EIEE panel?2) Treatment- Ideal drugs to start with? AED/clobazam/steroidsClobazam and Steroids dosage /duration3) Monitoring -EEG/clinical/ neuropsychological assessment4) Best practice guideline will be helpfulChallenges…

31. - 1) Survey through BPNA – Criteria for ESES diagnosis and treatment across UK2)Best practice paper – through a working group with EPEN( as lack of RCT)3)Present this to BPEG in 1 year Suggestions for EPEN ..

32. 1)Continuous spike wave during slow wave sleep –experience during 20 years. Laura e.Fernandez et al. www.analesdepediatria.org, Dec 20182)ILAE definition and classification and definition of epilepsy syndromes with onset in childhood . N.Spechhio et al, Epilepsia aug 20223) Corticosteroids vs clobazam in epileptic encephalopathy with ESES ( RESCUE ESES) B.Munchkof et al, BMC 20204)Treatment practices and outcomes in CSWS –a multicentre collaboration . F Baumer et al, J.Pediatr , May 20215) ESES –clinical and EEG characteristics and response to treatment. S Rosko et al, Archives of childhood diseases, Oct 2021, euro paeds conference abstract6) Clinical spectrum and treatment of children with ESES . U Kramer et al, Epilpeisa 2009 7) NICE guidelines, NG2178) ESES current perspectives – P.Arican et al. J paed neuroscience 20219)Electrical Status Epilepticus During Slow-wave Sleep (ESES): Current Perspectives- P. Arican et al, june 2021,J Paed Neurosci10) Genetic aetiologies in DEE with ESES – cohort study .P.Gong et al, frontiers in genetics , 2021References…

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