PAY ATTENTION TO THIS: ATTENTION AND WORKING MEMORY IN

PEDIATRIC EPILEPSY

William S. MacAllister, Ph.D.Pediatric Neuropsychologist

To be discussed…

Brief History of ADHD Review of the Diagnostic Criteria Associated Features / Comorbid Conditions Attention Problems in Epilepsy Treatment Considerations

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

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”

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”

DSM-IV Dx Criteria - Part 1

Inattentive Subtype

Diagnostic Criteria Part 2

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

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”

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)

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

Associated Disorders

LD’s ODD Tic D/O’s Developmental Coordination Disorders

Learning Disabilities

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

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)

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

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

Prevalence of ADHD in epilepsy varies widely across samples studied and measures employed

Epidemiological studiesRutter 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

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

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

Measures

CBCL (Achenbach) Dimensional instrument of symptoms

CSI-4 / ASI-4 (Gadow and Sprafkin) Categorical and Dimensional Based on DSM-4 criteria

Sample characteristics

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

Dunn Studies

ADHD by seizure type

ADHD Prevalence by Focus

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

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

Executive Dysfunction

Slick et al 2006 BRIEF as primary measure 80 children and adolescents with intractable

epilepsy

Slick article

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

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

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

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

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

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”

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

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

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

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

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

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

Yeah… but what is working memory?

Working Memory: A limited capacity memory system that provides temporary storage to manipulate complex cognitive tasks…

Baddeley Model 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.

Why is working memory important?

Working memory deficits have the potential to adversely affect children in academic pursuits

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

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 not have primary learning disabilities…

Mathematics

Reading Comprehension

So now what?

Can anything be done about this?

Adhd study

Stroke study

Holmes study

Klingberg ADHD Study

Interested?

Call me! Let’s chat! 646-558-0852

Or Megan Marsh, Ph.D. 212-263-8304

OR just see me after this talk…