Advances in Understanding Cognitive Impairment of...

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