Advances in Understanding Cognitive
Impairment of Epilepsy
December 2, 2011
David W. Loring, Ph.D., ABPP (Cn)
Departments of Neurology and Pediatrics
Emory University
Atlanta, GA 30322
American Epilepsy Society | Annual Meeting
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 comorbidities 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
80%
Percent Change
70%
60%
50%
40%
30%
20%
10%
0%
Controls
Epilepsy
Hermann et al.(2006). Ann Neurol, 60, 80-87
Age-related Practice Effects on
Memory
0.8
Salthouse (2010). Neuropsychology, 24(5), 563-572.
0.6
0.4
Z-Score
0.2
0
-0.2
-0.4
-0.6
-0.8
30
40
50
60
70
Chronological Age
80
Practice Effect Trajectories in
Location Learning “Epilepsy Only”
66
64
62
60
Patients
58
Controls
56
54
52
50
Dx
3 mos
12 mos
~ 42 mos
Oostrom et al. (2005). Brain, 128(7), 1546-1555.
Functioning
Cognitive Trajectory and Practice
Effects
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)
70
65
60
55
50
45
40
35
Controls
30
Epilepsy
25
20
15
10
5
0
Hermann et all (2006). Ann Neurol, 60, 80-87
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