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EPIDEMIOLOGY

OF CHILDHOOD EPILEPSY Kari M Aaberg

MD PhD

Senior consultant

National Centre for Epilepsy

Oslo University Hospital

Norway

National Center for epilepsy

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EPIDEMIOLOGY

• «The study of what is upon the people»

• Epidemic – endemic

• The study and analysis of the distribution, patterns and determinants of diseases.

•What?

•Who?

•When?

•Where?

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CHILDHOOD EPILEPSY

• Definition

• Prevalence

• Incidence

• Seizure types, epilepsies and etiologies in childhood

• Comorbidities

• Seizure outcome

• Long-term outcome of childhood epilepsy

Definitions of epilepsy used in epidemiological studies:

- Registered epilepsy diagnoses

- Self-reported epilepsy

- Hospitalized for epilepsy

- …..

DIFFERENT DEFINITIONS – DIFFERENT OCCURRENCES OF EPILEPSY IN CHILDHOOD

Study population: The Norwegian Mother, Father and Child Cohort:

112 744 children (3-13 years, mean 7,4 years)

Aaberg KM et al. Pediatrics 2017

EPILEPSY CASE DEFINITIONS Number of

children

Population

proportion of

epilepsy

Children with any epilepsy diagnosis registered 838 0,74%

Children with any registered or reported epilepsy 896 0,79%

VALIDATION

Children with confirmed epilepsy after validation

according to the old epilepsy definition

587 0,52%

Children with confirmed epilepsy according to the new

epilepsy definition

606 0,54%

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PREVALENCE OF EPILEPSY

•Point prevalence

•Period prevalence - lifetime

•Prevalence of active epilepsy - definition

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PREVALENCE OF EPILEPSY IN CHILDHOOD

• The point prevalence of active epilepsy in childhood:

• 3.2 – 5.5 per 1000 children in high income countries

• 3.6 – 44 per 1000 children in low/medium income countries

Meta-analysis Fiest 2017:

Worldwide point prevalence of active epilepsy:

• 0-9 years old: 5.2 per 1000 (95% CI 3.5-7.6)

• 10-19 years old: 8.9 per 1000 (95% CI 6.6-11.9)

• All ages: 6.4 per 1000 (95% CI 5.6-7.3)

Worldwide lifetime prevalence epilepsy:

• <19y: 7.2 per 1000 (95% CI 5.7-9.1)

• 19+y: 8.6 per 1000 (95% CI 5.9-12.5)

• ALL ages: 7.6 per 1000 (95% CI 6.2-9.4)

Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epilepic Disord 2015

Fiest KM et al. Prevalence and incidence of epilepsy. A systematic review and meta-analysis. Neurology 2017

% 95%CI

Cumulativ incidence

1 year 0,21 0,19-0,24

5 years 0,45 0,41-0,49

10 years 0,66 0,53-0,78

Prevalence active epilepsy

(seizures last 5 years)

5 years 0,45 0,41-0,49

10 years 0,62 0,50-0,74

Childhood 0,47 0,43-0,50

Prevalence active epilepsy

(seizures last 2 years)

5 years 0,40 0,36-0,45

10 years 0,50 0,40-0,62

Childhood 0,39 0,35-0,43

Aaberg et al. Pediatrics 2017

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INCIDENCE RATE OF EPILEPSY - CHILDHOOD

• Incidence rate of epilepsy in childhood - range 41-187/100 000 person years.1,2

•Mostly 42-70 / 100 000 person years1,2

• Meta-analysis Fiest 20173: Worldwide incidence rate in childhood (<19 years): 47 per 100 000 person years (95% CI 42-52)

• Age differences

1Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children, Epileptic Disord 2015 2 Cowan L D. The epidemiology of the epilepsies in children. Ment Retard Dev Disabil Res Rev 2002 3 Fiest KM et al. Prevalence and incidence of epilepsy. A systematic review and meta-analysis. Neurology 2017

INCIDENCE RATES OF CHILDHOOD EPILEPSY BY AGE

Age-specific incidence rates per 100 000 persons per year of childhood epilepsy Modified table after table 2 in Okamoto et al 2018 Incidence of childhood epilepsy in Brain Dev 2018

Author Camfield1 Kurtz2 Zarrelli3 Freitag4

Durá-Travé 5 Wirrell6 Casetta7 Okamoto8 Aaberg9 MEAN

Country Canada UK US Germany Spain US Italy Japan Norway Publication year 1996 1998 1999 2001 2007 2011 2012 2018 2017 Age

0-1 year 118 90 57 146 95 102 109 144 107

1-4years 49 50 74 62 64 65 59 109 61 66

5-9 years 43 36 58 50 70 48 68 39 54 52

10-14 years 27 29 56 56 49 33 34 68 - 44

1-14 years 38 38 63 55 60 46 54 70 53

0-14 years 43 42 62 61 63 46 57 70 56

Population 1,464,000 213,946 55,820 55,907 281,86 522,735 307,811 41,193 112,744

1Camfield CS, et al. Incidence of epilepsy in childhood and adolescence. Epilepsia 1996 2Kurtz Z, et al. Epilepsy in young people. BMJ 1998 3Zarrelli MM,, et al. Incidence of epileptic syndromes in Rochester Minnesota. Epilepsia 1999 4Freitag CM, et al. Incidence of epilepsy and epileptic syndromes in children and adolescents. Epilepsia 2001 5Durá-Travé T, et al. Incidence of epilepsy in 0-15 year-olds An Pediart 2007 6Wirrell EC, et al. Incidence and classification of new-onset epilepsy syndromes in children in Olmsted County, Minnesota. Epilepsy Res 2011 7Casetta I, et al. Incidence of childhood and adulescence epilepsy. Eur J Neurol2012 8Okamoto K, et al Incidence of childhood epilepsy: A population-based study in rural Japan. Brain Dev 2018 9Aaberg KM, et al. Incidence and prevalence of childhood epilepsy. Pediatrics 2017

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INCIDENCE RATE OF CHILDHOOD EPILEPSY BY AGE

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1 2 3 4 5 6 7 8 9 10 11 12 13 14

Incid

en

ce

ra

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10

0 0

00

pe

rso

nye

ars

Age in years

Aaberg (Norway) 2017

Hauser (US) 1993

Camfield (Canada) 1996

Wirrell (US) 2011

Casetta (italy) 2012

Durá-Travé (Spain)2008

Olafsson (Iceland) 2005

Freitag (Germany) 2001

Kurtz (UK) 1998

Insidence rate Rate per

100,000

person-

year

95% CI

<1 year 144 122-

168

1-4 years 61 54-68

5-10 years 54 45-62

0-10 years old

epilepsy

definition

70 64-75

0-10 years

NEW epilepsy

definition

72 66-77

Aaberg KM, et al. Pediatrics 2017

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TYPES OF SEIZURES, EPILEPSIES AND ETIOLOGIES IN CHILDHOOD EPILEPSY

Figure based on Figure 1 in ILAE classification of the epilepsies: Position paper of the ILAE

Commission for Classification and Terminology by Scheffer I et al Epilepsia 2017

SEIZURE TYPES IN CHILDHOOD EPILEPSY BASED ON BUT MODIFIED AND EXTENDED AFTER TABLE 1 IN INCIDENCE, PREVALENCE AND AETIOLOGY OF SEIZURES AND EPILEPSY IN CHILDREN, CAMFIELD P, CAMFIELD C, EPILEPIC DISORD 2015

Area Turku,

Finland 1

Nova Scotia,

Canada2

Connecticut,

USA 3

Navarre,

Spain 4

Minnesota,

USA 5

MEAN

Children 245 693 631 365 359

Seizure type

Generalized 32% 40% 40% 43% 23% 36%

Focal 60% 53% 55% 54% 68% 58%

Unclassifiable 4% 2% 4% 4% 5% 4%

Spasms - 5% 3% 5% 3% 4%

Both focal and

generalized

4% - 1% 2% 0,5% 2%

1 Sillanpää M, et al. Epilepsy syndromes in patients with childhood-onset seizures in Finland. Pediatr. Neurol. 1999 2 Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disord 2015 3 Berg A, et al. Newly diagnosed epilepsy in children. Epilepsia 1999 4 Durá-Travé T, et al. Epilepsy in children in Navarre, Spain. J Child Neurol 2007 5 Wirrell EC, et al. Incidence and classification of new-onset epilepsy syndromes in children in Olmsted County, Minnesota. Epilepsy Res 2011

TYPE OF EPILEPSY IN CHILDHOOD TABLE MODIFIED AND EXTENDED AFTER TABLE 4 IN EPILEPSY IN CHILDREN IN NAVARRE, SPAIN, DURÉ-TRAVÉ ET AL J CHILD NEUROL 2007

Area Connecti

cut,

USA1

Turku,

Finland 2

Germany3 Navarre,

Spain 4

USA,

Minnesota 5

Norway 6 MEAN

Year 1999 1999 2001 2007 2011 2017

Children 613 235 36 365 359 606

Epilepsy type

Generalized 29% 25% 39% 44% 23% 35% 33%

Focal 59% 62% 58% 53% 68% 59% 60%

Other/

Undetermined

12% 4% - 0.5% 5% 6% 5%

Focal and

generalized

1% - 3% 3% 0.5% 4% 2%

1 Berg A, et al. Newly diagnosed epilepsy in children. Epilepsia 1999 2 Sillanpää M, et al. Epilepsy syndromes in patients with childhood-onset seizures in Finland. Pediatr. Neurol. 1999 3 Freitag CM, et al. Incidence of epilepsy and epileptic syndromes in children and adolescents. Epilepsia 2001 4 Durá-Travé T, et al. Epilepsy in children in Navarre, Spain. J Child Neurol 2007 5 Wirrell EC, et al. Incidence and classification of new-onset epilepsy syndromes in children in Olmsted County, Minnesota. Epilepsy Res 2011 6 Aaberg KM, et al. Seizures, syndromes, and etiologies in childhood epilepsy. Epilepsia 2017

ETIOLOGY OF CHILDHOOD EPILEPSY – OLD TERMINOLOGY MODIFIED AND EXTENDED AFTER TABLE 4 IN EPILEPSY IN CHILDREN IN NAVARRE, SPAIN, DURÉ-TRAVÉ ET AL J CHILD NEUROL 2007

Area Connecticut,

USA1

Turku,

Finland2

China3 Hong

Kong4

Navarre,

Spain5

Norway6 Mean over

studies

Year 1999 1999 2001 2004 2006 2017

Children 613 235 309 1103 365 606

Etiology

(Remote )

Symptomatic

18% 50% 41% 59% 25% 33% 38 %

Cryptogenic 52% 22% 17% 1% 29% 22% 24 %

Idiopathic 30% 28% 42% 40% 45% 45% 38 %

1 Berg AT,et al. Newly diagnosed epilepsy in children. Epilepsia 1999 2 Sillanpää M, et al. Epilepsy syndromes in patients with childhood-onset seizures in Finland. Pediatr. Neurol. 1999 3 Kwong KL et al. Epidemiology of childhood epilepsy in a cohort of 309 Chinese children. Pediatr Neurol 2001 4 Wong V. Study of seizure and epilepsy in Chinese children in Hong Kong. J Child Neurol 2004 5 Durá-Travé T, et al. Epilepsy in children in Navarre, Spain. J Child Neurol 2007 6 Aaberg KM, et al. Seizures, syndromes and etiologies in childhood epilepsy. Epilepsia 2017

ETIOLOGY OF CHILDHOOD EPILEPSY – NEW CLASSIFICATION

Area Minnesota,

USA1

Norway2 Buskerud,

Norway3

Berlin,

Germany4

Year 2011 2017 2019 2019

Number 606 370 371

Etiology

Structural/

metabolic

28% 27% 32% 33%

Genetic 22% 34% 31% 20%

Infectious 2% 2%

Immune 0% <1%

Unknown 50% 43% 37% 44%

1Wirrell EC, et al. Incidence and classification of new-onset epilepsy and epilepsy syndromes in Olmsted county, Minnesota.

Epilepsy Res 2011 2 Aaberg KM, et al. Seizures, syndromes and etiologies in childhood epilepsy. Epilepsia 2017 3 Dahl-Hansen E, et al. Epilepsy at different ages-Etiologies in a Norwegian population, Epilepsia Open 2019 4 Valova V, et al. Early onset, long illness duration, epilepsy type and polypharmacy have adverse effect on psychosocial

outcome in children with epilepsy. Neuropediatrics 2019

Aaberg KM, et al. Seizures, syndromes, and etiologies in childhood epilepsy. Epilepsia 2017

AGE DIFFERENCES IN ETIOLOGY OF CHILDHOOD EPILEPSY – OLD AND NEW CLASSIFICATION

Structural

26%

Genetic

34% (10% identified

genetic

24% presumed

genetic)

Unknown

43%

Immune

0%

Metabolic

1%

Infectious

2%

Co

mo

rbid

itie

s

Seizure types

Epilepsy types

Epilepsy syndromes

37%

Focal 69%

Generalized

43%

Unknown

24%

Focal

50%

Generalized

24%

Combined

focal and

generalized

18%

Unknown

7%

Etiology

The new ILAE classifications used in the Epilepsy in young children study

33%

identified

etiology

Median

2

seizure

types

54% Developmental/

neurological

impairments

Aaberg KM, et al. Seizures, syndromes, and etiologies in childhood epilepsy. Epilepsia 2017

COMORBIDITIES IN CHILDHOOD EPILEPSY • Children and adolescents with epilepsy (CWE) have increased risk of most comorbid

conditions compared to the general child population (GCP);

• Multiple comorbidities (medical, neurological, developmental/psychiatric)1: 13% of CWE, 0,3% of GCP

• Higher frequencies in hospital-based studies and directed studies

1 Aaberg KM, et al. Comorbidity and childhood epilepsy: A nationwide registry study. Pediatrics 2016 2 Jennum P, et al. Morbidity and mortality of childhood- and adolescent-onset epilepsy: A contolled national study. Epilepsy Behav 2017 3 Plioplys s, et al. 10-years update review: Psychiatric problems in children with epilepsy. J Am Acad Child Adolesc psychiatry 2007 4 Lin JJ et al. Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan. Lancet 2012 5 Auvin S et al. Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Epilepsia 2018 6 Strasser L et al. Prevalence and risk factors for autism spectrum disorder in epilepsy. Dev Med Child Neurol 2018

Condition Proportion

in CWE

Norwegian

study1

Proportion

in the GCP

Norwegian

study1

OR

Norwegian

study 1

Proportion

in CWE

Reviews

Increased

risk in

children

with

epilepsy

Any medical conditions 55% 25% 3,5

Any neurological condition 41% 2% 25

Cerebral palsy 14% 0,3% 56

Any developmental/

psychiatric condition

43% 7% 9,4 37-77%3

Intellectual disability 17% 0,4% 41 ~25%4

ADHD 12% 2% 5,4 12-15%5

30-40%5

2,5(-5,5) 5

Autism spectrum disorder 8% 0,6% 11 6%6 136

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COMORBIDITIES IN CHILDHOOD EPILEPSY – UNDERDIAGNOSED?

Only 1/3 previously diagnosed

Reilly C, et al. Pediatrics 2014

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AGE DIFFERENCES IN COMORBIDITIES

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BURDEN OF EPILEPSY

Long-term outcome

Burden of comorbidities

Seizure burden

Economic burden

Seizure outcome

Cognitive outcome

Psychiatric outcome

Social outcome

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ECONOMICS OF CHILDHOOD EPILEPSY

• Childhood epilepsy has several costs:

• Much of the costs related to:

• comorbidities - tripled costs with cognitive impairments

• frequent seizures - tripled costs with ≥ weekly seizures

• The educational and social costs were 4-times as high as the health care costs

• Need focus on the whole situation of the patient and family

Hunter RM, Reilly C, Atkinson P et al. The health, education and social care costs of school-

aged children with active epilepsy: A population-based study. Epilepsia 2015

Health care

Family Social care

Educational

support

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OUTCOME OF CHILDHOOD EPILEPSY - SEIZURES

• Around 2/3 of children with epilepsy reach seizure remission

• Around 30% continue to have active epilepsy

• Around 1/10 long-term intractable epilepsy

• Early onset epilepsy (<3year) 1/3 intractable

Berg A, et al. Complete remission of childhood –onset epilepsy. Brain 2014

Geerts A, et al. Course and outcome of childhood epilepsy. Epilepsia 2010

Wakamoto H et al Long-term medical, educational, and social prognoses of childhood-onset epilepsy Brain Dev 2000

Sillanpaa M , et al. Long-term prognisis of seizures with onset in childhood. N Engl J Med 1998

Wirrell E, et al. Predictors and course of medically intractable epilepsy in young children before 36 months of age. Epilepsia

2012

Berg A, et al. Immediate outcome in early life epilepsy. Epilepsy Behav 2019

Aaberg KM, et al. Short-term seizure outcome in childhood epilepsy. Pediatrics 2018

SEIZURE OUTCOME OF CHILDHOOD EPILEPSY – BY EPILEPSY SYNDROMES /TYPES

Figure based on table 2 In Camfield PR, Camfield CS. What happens to children

with epilepsy. Ped Neurol 2014

Intermediate prognoses

(30-75% remission) Childhood absence epilepsy (65% remission)

Doose syndrome (40% remission)

Focal «cryptogenic» epilepsies (65% remission)

Focal epilepsy with CPS +/- FTC (44% remission)

Epilepsy with GTC only (75% remission)

Nearly always remit

-Rolandic epilepsy

-Panayiotopoulos syndrome

-Familial neonatal infantile seizures

«Never» remit -Ohtahara syndrome

-Epilepsy of infancy with migrating focal seizures -Dravet syndrome -Lennox Gastaut syndrome

SEIZURE OUTCOME OF CHILDHOOD EPILEPSY

• Childhood epilepsy – variable courses

• Favorable course 48%

• Improving course 29%

• Varying 7%

• Poor/deteriorating course 16%

• Factors influencing prognosis

• Etiology (non-idiopathic)

• Type of epilepsy/seizures

• Seizure frequency

• Early remission or intractability

• Age of onset (early)

• Comorbidities

Berg AT, et al. Complete remission of childhood-onset epilepsy. Brain 2014

Wakamoto H et al Long-term medical, educational, and social prognoses of childhood-onset epilepsy Brain Dev 2000

Sillanpaa M, et al. Long-term prognosis of seizures with onset in

childhood. N Engl J Med 1998

Geerts A, et al. Course and outcome of childhood

epilepsy. Epilepsia 2010

OUTCOME OF CHILDHOOD EPILEPSY - PSYCHOSOCIAL

• Long term psychosocial outcome of children with epilepsy are worse than • Their siblings (Baca et al Epilepsia 2017)

• The general population

• Worse outcome in many aspects of life • Reduced school attends/employment rate

• Less driving license

• Less living independently

• Less married, less children

• Risk factors for worse outcome: • Complicated epilepsy/ Comorbidities (Cognitive impairments)

• No remission

• BUT children with normal cognition/uncomplicated epilepsy and seizure remission can have as good long-term outcomes as the general population.

→ We need to optimize seizure control BUT ALSO psychosocial support

Chin RF et al. Outcomes of childhood epilepsy at age 33 years. Epilepsia 2011

Geerts A et al Health perception and socioeconomic status following childhood-onset epilepsy. Epilepsia 2011

Sillanpaa M et al Long-term prognosis of seizures with onset in childhood. N Engl J Med 1998

Jennum P et al Long-term socioeconomic consequences and health care costs of childhood epilepsy. Epilepsia 2016

Puka K et al Social outcomes for adults with a history of childhood-onset epilepsy. Epilepsy Behav 2019

Baca et al Social outcomes of young adults with childhood-onset epilepsy. Epilepsia 2017

Berg AT et al Determinants of social outcomes in adults with childhood-onset epilepsy. Pediatrics 2016

Wakamoto H et al Long-term medical, educational, and social prognoses of childhood-onset epilepsy Brain Dev 2000

OUTCOME OF CHILDHOOD EPILEPSY - MORTALITY

• Children with epilepsy up to 5-10 times increased risk of death compared to the general child population

• Most deaths in childhood related to neurodisability with complications and not seizures

• SUDEP most common seizure-related cause – low in childhood, increasing in adolescence

• CWE with uncomplicated epilepsy and seizure control – similar mortality rate as the general population

• Increased mortality rates - mostly in symptomatic complicated epilepsy without remission → Need for individualized information

Berg A, et al. Mortality Risks in new-onset childhood epilepsy. Pediatrics 2013

Sillanpaa M, Shinnar S. SUDEP and other causes of mortality in childhood-onset epilepsy. Epilepsy Behav 2013

Donner EJ , et al. Understanding Deaths in Children With Epilepsy, Pediatr Neurol 2017

P Jennum P et al. Morbidity and mortality of childhood- and adolescent-onset epilepsy. Epilepsy Behav 2017

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CHILDHOOD EPILEPSY – SUM UP

• Epilepsy affects 7/1000 children world wide

• Differing data sources and definitions affects occurrences

• Differing types of seizures, epilepsies and etiologies

• Age-related differences in

• Types of seizures, epilepsies, etiologies, comorbidities and prognosis

• 6/10 children reach remission, but not all

• Burden of epilepsy for patient, families and society

• Burden - not only seizures:

• Comorbid medical, neurological, developmental and psychiatric conditions

• Long-term social consequences

• Mortality

• Multidisciplinary approach

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THANK YOU FOR LISTENING!

• Thanks to my collaborators in The epilepsy in young children study group

31 August, 2020 This presentation is owned by the ERN and may contain information that is confidential, proprietary or otherwise legally protected. 34

Pål Surén

MD, PhD

Richard

Chin

MD, PhD

Professor

Morten I

Lossius

MD, PhD

Professor

Camilla

Stoltenberg

MD, PhD

Professor

Inger

Johanne

Bakken

PhD

National Center for epilepsy