1. Epilepsy and Autism Stefanie Jean-Baptiste Berry, MD Pediatric Epileptologist Northeast Regional Epilepsy Group

2. What is Autism? Onset before 3 years of age Impairment in social interaction Impairment in communication Restricted, repetitive and stereotyped behavior, interests and activities

3. Prevalence 60 in 10,000 children (0.6%) Higher prevalence in males High genetic and metabolic contribution Some genetic syndromes have a high association with autism (Angelman and Fragile X)

4. Autism Spectrum Disorder Subtypes Autistic disorder Asperger’s syndrome Pervasive developmental disorder Disintegrative disorder Rett’s syndrome

5. Autistic Disorder (AD) Classic autism with incapacitating deficits in all 3 domains: 1. sociability 2. language and imagination 3. cognitive and behavior flexibility

6. Asperger’s syndrome Autism without mental retardation or delayed language development Pervasive Development Disorder Milder autism

7. Disintegrative Disorder Severe autism Acquired between ages 2 and 10 after entirely normal early development Regression is more profound

8. Rett’s Syndrome X-linked MeCP2 gene Postnatal brain growth affected Severe mental retardation and motor deficits

9. Clinical diagnosis Variable causes of autism Genetics plays a big role (high concordance in monozygotic twins, 4.5% increased risk in siblings) Epilepsy and autism may share common neurobiological basis ? Environmental factor

10. Natural history and outcome of autism is variable IQ less than 70% in most children with autism 1/3 with no communicative speech 75% who fail to show language skills by age 5 years fail to adjust personally or socially

11. Others make fairly adequate social adjust but retain peculiarities of personality, lack of humor and unawareness of social nuances Even with treatment programs, only some improve significantly (2 nd half of 1 st decade)

12. Best outcome in patients with normal intelligence and speak before 5 years old Applied behavior analyses (ABA) improve chances of functioning independently

13. What is Epilepsy? 2 or more unprovoked seizures Incidence <10 years old 5.2 to 8.1 per 1,000 (highest <1 year) Seizure types: Generalized Focal (Partial) Focal with secondary generalization

14. Generalized Seizures: 1.) Generalized tonic-clonic (grand mal)- Unconscious, whole body shaking; variable duration 2.) Absence (petit mal) – Staring, unawareness, brief (seconds) 3.) Myoclonic – Brief jerk of arm or leg 4.) Atonic – Sudden drop

15. Focal (Partial) Seizures: 1.) Simple – Consciousness preserved; twitching of one side of face or body, numbness, visual 2.) Complex – Impaired consciousness; twitching, head/eye deviation etc.

16. Epilepsy and Autism Prevalence of epilepsy among all children is 2-3% 5-38% autism with epilepsy Risk for epilepsy increased with greater intellectual disability, symptomatic vs. idiopathic, age and history of regression 35-65% with EEG abnormalities Epilepsy in autism increased mortality

17. Bimodal age distribution Peak infancy to age 5 years and adolescence Highest risk for epilepsy in those with severe mental retardation and cerebral palsy Epilepsy persists in the majority of patients into adult life (remission 16%)

18. Autistic Disorder - Clinical epilepsy by adolescence in more than 1/3 of patients Asperger’s syndrome - Estimated 5-10% likelihood of developing epilepsy in early childhood Pervasive Developmental Disorder - Risk for epilepsy linked to underlying brain dysfunction

19. Disintegrative Disorder - Risk for epilepsy as high as 70% Rett’s Syndrome - Risk for epilepsy is more than 90%

20. Diagnosis complicated because seizures may be mistaken for behaviors (not responding to name) Unusual repetitive behaviors, common in autism, hard to distinguish from seizures All seizure types may be seen

21. Prevalence of epilepsy and types of seizures vary Swedish study complex partial, atypical absence, myoclonic and tonic-clonic most common American study tonic clonic and atypical absence most common

22. Other studies state complex partial with centrotemporal spikes most common Some studies suggest that epileptiform discharges on EEG without seizures can cause behavioral and cognitive impairment Epilepsy more common in children who regressed in language after age 3.

23. Usually treat based on clinical seizures not just EEG findings. Should anti-epileptic medication be prescribed to children with autism, language regression and subclinical EEG abnormalities?

24. Long-duration EEGs that include slow wave sleep more likely to show epileptiform abnormalities Long-duration EEG of children with autism spectrum disorder and regression without clinical seizures – 46% with epileptiform activity Focal spikes - Centrotemporal spikes and temporoparietal spikes

28. Landau-Kleffner Syndrome Overlap with autistic regression Loss of language is prominent Language regression after age 3 Acquired aphasia associated with clinical seizures or an epileptiform EEG Clinical seizures not required for diagnosis No decline in sociability or repetitive behaviors

29. EEG abnormalities (spikes, sharp waves and spike wave discharges); mainly over temporoparietal regions 25% do not have clinical seizures Loss of language attributed to clinical or subclinical epilepsy in cortical areas responsible for language Children with severe and persistent language disorders at increased risk for seizures and epilepsy.

30. Medical treatment of seizures in autism similar to treating other children with epilepsy Limited data on response of children with epileptiform EEG without clinical seizures Same strategy as LKS – reduce epileptiform activity Reports that language of LKS and those with autism improved in response to anticonvulsants

31. Improvements have also been reported in patients treated with corticotropin, steroids, or immunoglobulins Clinical reports of the use of Depakote in children with autism with and without clinical seizures Most showed improvement in core symptoms of epilepsy

32. Absence of clinical trials, therefore no definite recommendations about treatment Surgical resection in children with autism and intractable epilepsy – may improve seizures +/- autistic symptoms 1 study subpial transections – language and behavior improved