Stefanie Jean-Baptiste Berry, MD
Pediatric Epileptologist
Northeast Regional Epilepsy Group

 Onset before 3 years of age
 Impairment in social interaction
 Impairment in communication
 Restricted, repetitive and stereotyped behavior, interests and activities

 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)

 Autistic disorder

Asperger’s syndrome
 Pervasive developmental disorder
 Disintegrative disorder

Rett’s syndrome

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

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

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

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

 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

 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

 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)

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

 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

 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

 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.

 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

 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%)

 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

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

 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

 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

 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.

 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?

 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

 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

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.

 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

 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

 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