Pediatric Epilepsy: Cognitive Problems, Medication Effects and Autism

1. Pediatric Epilepsy Cognition, Autism, Medication effects

2. Pediatric EpilepsyCognition Cognition Memory Perception Attention Organization Planning Problem solving abilities

3. Pediatric Epilepsy Cognition Children with epilepsy have a disproportionate share of problems with learning and behavior As a group they have an average IQ that is 10 points below normal There is a 3-fold increase in mental retardation Even those without mental retardation are at risk of academic underachievement or school failure

4. Pediatric Epilepsy Cognition On the bright side Half of children with epilepsy have normal academic records Two-thirds are in regular classes More than 80% are working at grade level A majority of children with epilepsy develop normally and have normal cognitive abilities

5. Pediatric Epilepsy Cognition Perception and attention have been found to be two of the major factors associated with learning difficulties in children with epilepsy Boys have more problems than girls It is difficult to determine the cause for academic difficulties in children with epilepsy

6. Pediatric Epilepsy Cognition Underlying factors in academic difficulties: Intrinsic developmental capability Associated brain disease Parent-child interactions Seizures Medications

7. Pediatric Epilepsy Cognition The underlying brain disease , not the seizures, is the most important factor contributing to subnormal intellect in children with epilepsy

8. Pediatric Epilepsy Cognition Epileptic syndrome and prognosis for cognitive function Unfavorable cognitive development West syndrome Lennox-Gastaut syndrome Doose’s syndrome Landau-Kleffner syndrome Rett syndrome

9. Pediatric Epilepsy Cognition Epileptic syndrome and prognosis for cognitive function Favorable cognitive development Febrile seizures Childhood absence epilepsy Benign partial epilepsy of childhood (Rolandic epilepsy) Juvenile myoclonic epilepsy

10. Pediatric EpilepsyAutism Neurodevelopmental disorder affecting primarily social communication but associated with language impairments and repetitive behaviors Autism spectrum disorders: a broader group of children including those with autism disorder, pervasive developmental disorders not otherwise specified, and those with Asperger’s syndrome

11. Pediatric EpilepsyAutism There is no clear evidence that epilepsy causes autism The contribution of epilepsy and interictal epileptiform discharges to ongoing cognitive deficits in children with autism remains poorly understood and controversial There is evidence that common shared anatomical and molecular mechanisms may account for both epilepsy and autism

12. Pediatric EpilepsyAutism Epilepsy and autism coexist in up to 20% of children with either disorder Intellectual disability show a very high prevalence in those with both autism and epilepsy Early onset seizures may be a factor in making infants at higher risk of autism

13. Pediatric EpilepsyAutism Epilepsy was noted in 21% of individuals with autism and intellectual disability versus 8% in individuals with autism without intellectual disability. There is consensus that there is a strong association between epilepsy, autism, intellectual and motor disability in infants with epileptic encephalopathy, the overall effect of both epilepsy and interictal epileptiform activity,

14. Pediatric EpilepsyAutism Mechanisms that lead to epilepsy may also affect the development of social cognition A recent study revealed malformations of cortical development in 12 of 13 autism brains and in only 1 of 14 control brains. Such malformations of cortical development are commonly found in children with epilepsy

15. Pediatric EpilepsyAutism Genome wide studies are demonstrating “copy number variants” or CNVs (deletions, duplications, and insertions) that are common to both epilepsy and autism.

16. Pediatric EpilepsyMedication Effects on Cognition Cognitive side effects are generally reported to be mild to moderate in magnitude compared with most of the other types of side effects. Some studies suggest such side effects have a greater impact on function and daily living than previously suspected.

17. Pediatric EpilepsyMedication Effects on Cognition Types of cognitive impairment Depressed capacity of the information-processing system by producing slowing Decreased the input of working memory Decreased mental flexibility

18. Pediatric EpilepsyMedication Effects on Cognition Many studies done only compare one agent with another that is thought to have a “favorable cognitive profile”

19. Pediatric EpilepsyMedication Effects on Cognition Phenobarbital Cognitive impairment including visual motor and memory tests Phenytoin (Dilantin) Attention, memory and memory speed Valproate (Depakote) Impairment of mental speed

20. Pediatric EpilepsyMedication Effects on Cognition Carbamazepine (Tegretol) Favorable compared with other “older” AED’s Lamotrigine (Lamictal) Does not impair cognition May benefit mental performance “Euphoria” secondary to impact of cognitive productivity Oxcarbazepine (Trileptal) No impairment/improved cognitive functioning

21. Pediatric EpilepsyMedication Effects on Cognition Topiramate Dose related slowing of mental speed and inattentiveness Word finding difficulty Felbatol (Felbamate) “Alerting” No formal studies have been done Gabapentin (Neurontin) Well tolerated cognitively

22. Pediatric EpilepsyMedication Effects on Cognition Vigabatrin (Sabril) Few cognitive side effects Zonisamide (Zonegran) Sedation Lacosamide (Vimpat) Sleepiness/fatigue Rufinamide (Banzel) Sleepiness/fatigue