Advances in Understanding Cognitive

Impairment of Epilepsy

David W. Loring, Ph.D., ABPP (Cn)

Departments of Neurology and Pediatrics

Emory University

Atlanta, GA 30322

American Epilepsy Society | Annual Meeting

December 2, 2011

Disclosures

NeuroPace

NINDS

UCB

NP and Wada testing

Consultant

Research Support

Research Support

Clinical Income

American Epilepsy Society | Annual Meeting

Learning Objectives

• Area III: Prevent, limit, and reverse the co-morbidities associated with epilepsy and its treatment.

– Recent advances in understanding cognitive comorbidities in epilepsy

– Methodological challenges studying neuropsychological change over time

– New directions

American Epilepsy Society | Annual Meeting

Historical Context

• Epilepsy considered degenerative brain

disease before AEDs (mid-19th century)

• Cognitive lifetime effects

(1471 patients) – 9% impaired < 10 convulsions

– 54% impaired 1000+ convulsions

Lennox WG, Lennox MA. (1960). Epilepsy and

Related Disorders. Boston, MA: Little, Brown. William G. Lennox (1884-1960)

Neuropsychology Impairments

• How often present?

• When do they emerge?

• What are associated factors?

– Underlying biologic substrate and syndrome

– Age of seizure onset or precipitating injury

– AED effects

– Direct seizure discharge effects

• Are cognitive impairments progressive?

Implications of Epilepsy Diagnosis

• Altered cognitive trajectory

– Slowed cognitive development?

– Loss of cognitive function/cognitive decline?

“Epilepsy Only” Findings in Pediatrics

Oostrom et al. (2003) Pediatrics, 112(6), 1338-1344.

New Onset Seizures in Pediatrics

• 282 epilepsy children with normal IQ – 48% idiopathic

– 48% symptomatic/cryptogenic

– 32% generalized

– 65% LRE

Fastenau et al (2009). Neurology, 73, 526-534.

Results by Syndrome

Fastenau et al (2009). Neurology, 73, 526-534.

Individual Results

• 27% with single seizure

• Cognitive impairment often precedes

seizure onset

• No group effects for academic

achievement measures

Fastenau et al (2009). Neurology, 73, 526-534.

Newly Diagnosed Adults

Taylor et al. (2010). Epilepsia, 51(1), 48-56.

Newly Diagnosed Adults

Taylor et al. (2010). Epilepsia, 51(1), 48-56.

Cognitive Progression - SANAD

Baker et al. (2011). Epilepsia, 52(6), 1084-1091.

Cognitive Progression - SANAD

Baker et al. (2011). Epilepsia, 52(6), 1084-1091.

Cognitive Progression - SANAD

Baker et al. (2011). Epilepsia, 52(6), 1084-1091.

SANAD Results

• Memory, psychomotor speed, executive

function were domains most likely to

decline

• Seizure freedom not strongly related to

change

• TPM related to change on 4/16 variables

• Measures changing typically different at

baseline

• Practice effect increases separation

Baker et al. (2011). Epilepsia, 52(6), 1084-1091.

Significant Test-Retest Improvements

4-yr TLE NP Outcome

%

%

%

%

%

%

%

%

%

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

Perc

ent C

han

ge

Controls Epilepsy

Hermann et al.(2006). Ann Neurol, 60, 80-87

Age-related Practice Effects on

Memory

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0.8

Z-S

co

re

Chronological Age

Salthouse (2010). Neuropsychology, 24(5), 563-572.

30 40 50 60 70 80

Practice Effect Trajectories in

Location Learning “Epilepsy Only”

50

52

54

56

58

60

62

64

66

Dx 3 mos 12 mos ~ 42 mos

Patients

Controls

Oostrom et al. (2005). Brain, 128(7), 1546-1555.

Cognitive Trajectory and Practice

Effects

Functionin

g

Time

Verbal Learning Age Regression

Helmstaedter and Elgar (2009). Brain, 132(Pt 10), 2822-2830.

Cross Sectional Design

• Avoids contamination with practice

effects

• Relies on retrospective seizure

characterization

• Difficult to identify individual

trajectories from single timepoint

Percent Abnormal Decline (Z < -2)

Hermann et all (2006). Ann Neurol, 60, 80-87

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

Controls

Epilepsy

Social Cognition

• Processing of social information and

cues

• Deficits seen in Asperger syndromes

• Often attributed to frontal lobe function

Social Cognition

• Theory of Mind- ability to attribute

mental states (e.g., intentions, beliefs,

desires) to others

• Theory of Mind: Faux Pas – Sally has short blonde hair. She was at her Aunt

Carol’s house. The doorbell rang. It was Mary, a

neighbor. Mary said “Hello”, then looked at Sally

and said “Oh, I don’t think I’ve met this little boy.

What’s your name?” Aunt Carol said “Who’d like

a cup of tea?”

Social Cognition: Faux Pas

• Decreased in epilepsy (FLE > TLE)

• Unrelated to age or number of AEDs

• Related to education, age of onset,

and executive function in NP

• Better ecological measure of

executive/non-verbal function?

• Related to QoL, employment, social

success?

Giovagnoli et al (2011). Epilepsia, 52(11), 1995-2002

Conclusions

• Cognitive function often predates

seizure onset – Altered cognitive trajectory

• Longitudinal and cross-sectional

designs have different strengths and

limitations

• Cognitive testing predicting complex

social behavior will increasingly be

studied