Epilepsy in Children with Down Syndrome - PowerPoint Presentation

1. Epilepsy in Children with Down SyndromeDr Shpresa Pula, Clinical Research Fellow Dr Marian McGowan, Consultant PaediatricianNovember, 2019

2. Acknowledgments Dr Karine Lascelles, Consultant Paediatric Neurologist Dr Shan Tang, Consultant Paediatric Neurologist Dr Narad Mathura, Consultant Paediatrician Dr Anne Wright, Consultant Paediatrician Dr Veronica Kelly, Consultant in Paediatric Neurodisability

3. OutlineBackgroundObjective Materials and Methods ResultsConclusionAction Plan

4. Background Down Syndrome (DS) is the most common genetic condition The incidence of the DS in the U.K is 1:1000 live birthsBroadly the main clinical features of DS are as follows: -invariable: low muscle tone, distinctive features and cognitive difficulties -variable: cardiac, metabolic, respiratory, gastrointestinal, vascular, ENT, ophthalmologic, hematologic, neurologic including epilepsy

5. Epilepsy The reported incidence of epilepsy in this group varies from 1%-18%There is a bi-modal distribution of epilepsy in patients with Down Syndrome with Infantile spasms (2.5-5 %) in infancy and focal and generalized tonic-clonic during childhood during childhood and adolescence In the elderly the prevalence of epilepsy increases due to neurodegeneration. A particular type of epilepsy has been described which is called late onset myoclonic epilepsy

6. Epilepsy Seizure susceptibility in patients with DS is attributable both to inherited genetic differences in brain structure and to secondary complications such as hypoxic ischaemic brain injury, congenital heart diseases etcThe mechanisms responsible for epilepsy in DS remain unclear although neuronal structural abnormality, abnormal neuronal lamination, persistent foetal dendritic morphology have been considered

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8. Why service evaluation in this group?Improvement of the medical care for patients with DS has led to better medical care soon after the birth and to a substantial increase of their life expectancy Inconsistency of the data from the literature: “ seizures” or “epilepsy” , Partial definition given- some information (epilepsy diagnosis) Different inclusion criteria “active” or “life-long epilepsy”Follow-up period not always mentioned

9. Objective To assess the prevalence of epilepsy in three Child Development Centres in the South of London Those who have the diagnosis of epilepsy, what is the type of epilepsy? Occurrence of Epilepsy in specific genetic copy variants? Which investigations have been indicated? Antiepileptic Treatment and their response? How common was the misdiagnosis due to misinterpretation of behaviour, psychological events.

10. Materials and Methods Clinical information from 225 consecutive patients with genetically confirmed Down Syndrome was retrospectively reviewed as part of the service evaluation of three Child Development Centres based in South LondonThe data were extracted by two doctors independently The data were collected from: 1999-2018 Inclusion criteria -the diagnosis of DS and follow up in the District Neuro-disability Centres in South London Exclusion criteria -none

11. The study was registered and approved by the Hospital's internal review board/audit committeeAs this was a service evaluation, informed consent was not required All data were anonymised, and compiled to General Data Protection Regulation (GDPR)

12. ResultsStudy StST. GEORGE’S CENTRE N=79MARY- SHERIDANCENTREN=81 SUNSHINE CENTREN=65 STUDY GROUP N=225 Mean follow-up period 13.6 years (range 10-19 years)

13. Results2/225- ?infantile spasms referred to the tertiary neurology centre Extensive work up: -EEG, blood metabolic tests, CSF-Brain MRI- Infantile spasms excluded 1/225- Childhood absence seizures started on a conventional treatment with antiepileptic medication (Ethosuximide) No EEG correlate 2xNormal prolonged EEG The diagnose of epilepsy excludedTreatment discontinued

14. Results 121-males 104 females Mean cohort age: 8.75 yearsRange: 0-19 years Infantile spasms

15. E.T, DOB: 22/04/2015 Developmental history: fixing, following smiling good head, can roll to the rightHC 91st centile Admitted urgently to Evelina Children’s Hospital -had multiple spasms flexor spasms with extension of the arms and legs and axial jerk of the shoulders. The clusters would last 3-5 minutes. Abnormal EEG (features consistent with infantile spasms with hypsarrhythmia), 2-EEG no hypsarrythmia Full diagnostic work up (brain MRI, metabolic screening)Treatment: (Predisolone ICISS-protocol) 30 mg daily for five days, then20 mg daily for 5 days and finally 10 mg daily for 5 days Discontinued Paediatric Neurology follow up review: (2016)Seizure freeMaking good developmental progress, HC 91st centile Dg.: Down Syndrome (Trisomy 21) Infantile spasms (4- m) OSAS- st. post tonsillectomy PDA Anorectal anomaly-underwent surgery Born in London, postnatally diagnosed with Down Syndrome Since 4-months old parents observed abnormal movements often occurring when awakeLegs draw-up, turning hands, can be grumpy afterwards(referred by the community, when 5 months old, initially seen at A&E thought to have GE reflux)

16. P.A, DOB: 02/01/2016Developmental delay,Regression following IS (?details)Semiology: Brief 5-7 sec flexor spams of trunk, neck and limbs Abnormal EEG (features consistent with infantile spasms with hypsarrhythmia)Full diagnostic work up: -Blood investigations/metabolic -CSF Investigations -Brain MRI (no additional explanation for IS)Treatment (Prednisolone as per ICISS protocol)Continues on Sodium-Valproate (seizure free ~2 yr plan to wean off SV)Good developmental progress Dg.: Down Syndrome (Trisomy 21)Infantile Spasms (9-10months)Myoclonic jerks Originally from Africa

17. Comorbidities 40 %- cardiac issues (mainly AVSD)35%-respiratory difficultiesOther neurology problems: none Cognitive decline: none 40%

18. Limitations and ConclusionThe study was cross-sectional, although the case notes of those with possible diagnosis of epilepsy/syndrome were reviewed recently No availability of the DS patient database for natural history and prospective studies No clear outcome measures regarding comorbidities Co-occurrence of the mental health related problems?

19. 3/ 225 (1.3%) of patients were diagnosed with IS confirming this is the most frequent of all seizure types in infants with DS The findings might be due to decreased secondary complications, ?incidental No misdiagnosis of epilepsy amongst children with DS in comparison with the data from the literature No need to undertake an auditHowever, expanding the cohort by involving other Child Development Centres initially in the South London and later enrolling other centres might be of an importance as this would allow further research of the prevalence of epilepsy in this group

20. All children with DS and IS (SW/SE) are evaluated at Evelina Children’s HospitalThe EEG : through St George’s, Kings Hospital and Evelina

21. Questions and Suggestions? THANK YOU

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