This document discusses attention and working memory in pediatric epilepsy. It provides a brief history of ADHD and reviews the diagnostic criteria. Attention problems are common in epilepsy and may account for academic underachievement. While rates of ADHD in epilepsy vary, studies find prevalence is higher than the general population. Methylphenidate may be safely used to treat comorbid ADHD and epilepsy. Executive dysfunction, including problems with working memory, are seen in many children with epilepsy and can impact academic performance.

1. Pay Attention to This: Attention and Working Memory in Pediatric Epilepsy William S. MacAllister, Ph.D. Pediatric Neuropsychologist

2. To be discussed… Brief History of ADHD Review of the Diagnostic Criteria Associated Features / Comorbid Conditions Attention Problems in Epilepsy Treatment Considerations

3. History First descriptions of ADHD may have appeared 2500 years ago Hippocrates described a patient who had quickened responses to sensory experiences, but also less tenaciousness because the soul moves on quickly to the next impression Condition was attributed to an overbalance of fire over water

4. History Continued… George Frederick Still (1902) Defined chief characteristics in 43 kids “defects in moral control” “abnormal incapacity for sustained attention, restlessness, fidgetiness, violent outbursts, destructiveness, non-compliance” Demonstrate little “inhibitory volition”

5. Encephalitis outbreak of 1917 Called attention to the fact that these children showed similar deficits and allowed scientists of the day to draw parallels between these groups Gave rise to the concept of “minimal brain dysfunction”

6. DSM-IV Dx Criteria - Part 1

7. Inattentive Subtype

8. Diagnostic Criteria Part 2

9. ADHD is one of the most common psychiatric conditions of childhood Considered one of the best-researched disorders in medicine and the overall data on its validity are far more compelling than for many medical conditions (Goldman et al, 1998) In clinic samples, boys are 6-10x more likely to be referred for the d/o and 3-4x more likely to be dx May reflect biases - girls less likely to be disruptive

10. Several recent epidemiological studies of ADHD have been conducted Rowland et al, 2002; Harel & Brown, 2002; Barbaresi et al, 2002; CDC, 2005 Prevalence across these studies fairly consistent, with estimates between 6 and 10% Estimated to affect 4.4 million children in U.S. Interestingly, many identified a “treatment gap”

11. CDC Study For example, the CDC study indicated that 7.8% of children met criteria at some point in their lifetime But only 4.3% were treated with medications (only 55% of those with ADHD were treated pharmacologically)

12. In kids… Higher rates of ER admissions (Leibson et al 2001) More burns, TBI, fractures Driving accidents more common in adolescence More driving offenses (speeding, reckless driving -> suspended licenses) Higher rates of STD’s (4x higher; Fischer, 93) Higher teen pregnancy rates

13. Associated Disorders LD’s ODD Tic D/O’s Developmental Coordination Disorders

14. Learning Disabilities LD’s are comorbid in over 20% of cases Reading disorders (16-39%) Spelling problems (24-27%) Math disorders (13-33%)

15. DCD Approximately 6% of population with higher rates in ADHD Clumsiness, dysgraphia, articulation deficits Likely due to underlying neural substrates involving cortical-basal ganglia circuitry (see Delong 2002)

16. Milich et al, 2002; Coghill et al 2005 believe that ADHD-C and ADHD-I are actually “distinct disorders”

19. Cognition in Epilepsy Well established that inattention and hyperactivity are behavioral symptoms common in childhood onset epilepsy (Dunn & Austin, 1999) Such symptoms may, in large part, account for the degree of academic underachievement in these children

20. Prevalence of ADHD in epilepsy varies widely across samples studied and measures employed Epidemiological studies Rutter et al. (1970): Hyperactivity seen in 4/34 children with epilepsy (Isle of Wight Study: UK) McDermott et al (1995): Hyperactivity seen is 28% of children with epilepsy, versus 13% in cardiac patients, and 5% in control children Carlton-Ford et al (1995): Impulsivity seen in 39% of children with current OR past seizures, versus 11% in controls

21. Teacher Report Holdsworth and Whitmore (1974) – Teachers report inattention in 42% of children with seizures Sturniolo and Galletti (1994): Inattention or hyperactivity in 58% of children with seizures No standardized measures or diagnostic procedures

22. Dunn et al 2003 study Studied relations of ADHD Symptoms and: Seizure type Localization Study examined 175 children (85 boys, 90 girls) Mean age = 11y 10m Recruited from private practices and University Hospital samples

23. Measures CBCL (Achenbach) Dimensional instrument of symptoms CSI-4 / ASI-4 (Gadow and Sprafkin) Categorical and Dimensional Based on DSM-4 criteria

24. Sample characteristics

25. CBCL Results 42% of Adolescents and 58% of children were in the “at-risk” range for attention problems 25% adolescents and 37% of children were in the “clinical” range

26. Dunn Studies

27. ADHD by seizure type

28. ADHD Prevalence by Focus

29. Interesting findings of this study: In contrast to ADHD in non-epilepsy patients: Inattentive subtype ADHD was more common than Combined Girls were more likely to have ADHD than boys

30. Hermann et al (2007) Studied 75 children and adolescents with new onset epilepsy (ages 8 – 18) and 62 Controls KSADS Interview, Neuropsych ADHD was present in 31% of patients and only 6% of controls Inattentive subtype predominated, with symptoms of ADHD appearing before seizures Children with ADHD and epilepsy had higher rates of school interventions/services Neuropsych evaluation revealed prominent executive dysfunction ADHD was not associated with epilepsy characteristics or demographic variables

31. Executive Dysfunction Slick et al 2006 BRIEF as primary measure 80 children and adolescents with intractable epilepsy

32. Slick article

33. Treatment (Pharmacological) Methylphenidate (e.g., Ritalin; MPH) is commonly believed to lower seizure threshold PDR suggests that methylephenidate is contraindicated in children with epilepsy However, no controlled studies have proved this hypothesis Only isolated case studies seem to support MPH as analeptic

34. Safety Several publications indicate that MPH is safe in children with controlled epilepsy (Feldman et al, 1989) – 10 children with ADHD and Epilepsy – MPH effectively treated ADHD Symptoms and no seizures were seen during the 10 weeks of follow-up. All had abnormal EEG’s that were unchanged during the study

35. Gross-Tsur et al (1997) 30 Children with epilepsy and ADHD (25 were seizure free on AED’s, 5 with occasional seizures) Those that were seizure free prior to MPH remained so after MPH Those with ongoing seizures did not show an increase in seizure frequency

36. Gucuyener et al (2003) Followed two groups for one year one with ADHD and epilepsy, one with ADHD and EEG abnormalities (but no clinical seizures) MPH improved ADHD symptoms in both groups The epilepsy group experienced no change in seizure frequency AND EEG’s improved No patients in the abnormal EEG group experienced seizures

37. Summary of MPH studies Most agree that MPH is not contraindicated in children with ADHD No compelling evidence that MPH will increase risk of seizures in children with ADHD will cause seizures in those with ADHD and abnormal EEG or will increase seizure frequency in children with ADHD and epilepsy

38. Treatment with Amphetamines (e.g., Adderall, Dexedrine, Vyvanse) Effects of these agents in children with ADHD and Epilepsy has NOT been systematically studied Torres et al (2008) in their review of the evidence noted that: “Amphetamines might be proconvulsant, especially when abused; however there is some evidence that amphetamines may have an anticonvulsant effect in select patients.” “Case series for ADHD plus Epilepsy have reported disappointing response rates to amphetamine”

39. Atomoxetine (Strattera) No well-controlled trials of Atomoxetine in patients with ADHD and epilepsy Summarizing the results of available data “the rate of the positive response to atomoxetine was disappointing” (Torres et al, 2008) However, it was noted that almost all of the patients placed on Strattera had already had unsuccessful trials of stimulants

40. Summary of Medication studies suggest that MPH may be the best supported treatment in children with epilepsy and comorbid ADHD

41. Summary Points Rate of ADHD in children with epilepsy is several times higher than in general population (5 times higher?) Inattentive subtype more common Girls more affected than boys May be primary reason for school underachievement All seizure types at risk MPH may be treatment of choice

42. What is an Executive Function? Key elements: Anticipation and deployment of attention Impulse control/self-regulatory processes Initiation Working memory Mental flexibility Planning/organization Problem solving

43. What does executive dysfunction look like? Inability to focus or maintain attention Impulse control deficits Poor working memory Difficulties self-monitoring Inability to plan Disorganization Poor reasoning Perseveration

44. Neuroanatomy PFC (particularly dorsolateral PFC) are the last brain regions to myelinate PFC play a critical role in executive fx Region does not act in isolation Part of broader functional system Highly interconnected with other regions Damage to PFC is sufficient, but not necessary for executive dysfunction e.g., subcortical structures (basal ganglia) as well as the cerebellum are also crucial

45. Yeah… but what is workingmemory? Working Memory: A limited capacity memory system that provides temporary storage to manipulate complex cognitive tasks…

46. BaddeleyModel of Working Baddeley Model deals mainly with working memory Working memory – “a limited capacity system allowing the temporary storage and manipulation of information necessary for such complex tasks as comprehension, learning, and reasoning” (Baddeley, 2000) Holding information ‘On-line’ while operating on it.

47. Why is working memory important? Working memory deficits have the potential to adversely affect children in academic pursuits

48. School Note taking in class requires a tremendous amount of working memory Children must dual task as they listen to what the teacher is saying, while concurrently writing down what they have just said i.e., the ‘lag’ between the teacher’s real time speech and the child’s handwriting necessitates working memory for them to keep up with the demands of the classroom

49. Academic Achievement Several studies have linked executive function deficits (and particularly working memory deficits) to objective performance on academic tasks, even in children who do nothave primary learning disabilities…

50. Mathematics

51. Reading Comprehension

52. So now what? Can anything be done about this?

53. Adhd study

54. Stroke study

55. Holmes study

56. Klingberg ADHD Study

59. Interested? Call me! Let’s chat! 646-558-0852 Or Megan Marsh, Ph.D. 212-263-8304 OR just see me after this talk…