Advances in Understanding Cognitive Impairment of Epilepsy

Transcription

1 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 American Epilepsy Society Annual Meeting

2 Disclosures NeuroPace NINDS UCB NP and Wada testing Consultant Research Support Research Support Clinical Income American Epilepsy Society Annual Meeting

3 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

4 Historical Context Epilepsy considered degenerative brain disease before AEDs (mid-19th century) Cognitive lifetime effects (1471 patients) 9% impaired < 10 convulsions 54% impaired convulsions Lennox WG, Lennox MA. (1960). Epilepsy and Related Disorders. Boston, MA: Little, Brown. William G. Lennox ( )

5 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?

6 Implications of Epilepsy Diagnosis Altered cognitive trajectory Slowed cognitive development? Loss of cognitive function/cognitive decline?

7 Epilepsy Only Findings in Pediatrics Oostrom et al. (2003) Pediatrics, 112(6),

8 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,

9 Results by Syndrome Fastenau et al (2009). Neurology, 73,

10 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,

11 Newly Diagnosed Adults Taylor et al. (2010). Epilepsia, 51(1),

12 Newly Diagnosed Adults Taylor et al. (2010). Epilepsia, 51(1),

13 Cognitive Progression - SANAD Baker et al. (2011). Epilepsia, 52(6),

14 Cognitive Progression - SANAD Baker et al. (2011). Epilepsia, 52(6),

15 Cognitive Progression - SANAD Baker et al. (2011). Epilepsia, 52(6),

16 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),

17 Percent Change Significant Test-Retest Improvements 4-yr TLE NP Outcome 80 % 70 % 60 % 50 % 40 % 30 % 20 % 10 % 0 % Controls Epilepsy Hermann et al.(2006). Ann Neurol, 60, 80-87

18 Z-Score Age-related Practice Effects on Memory Salthouse (2010). Neuropsychology, 24(5), Chronological Age

19 Practice Effect Trajectories in Location Learning Epilepsy Only Patients Controls Dx 3 mos 12 mos ~ 42 mos Oostrom et al. (2005). Brain, 128(7),

20 Functioning Cognitive Trajectory and Practice Effects Time

21 Verbal Learning Age Regression Helmstaedter and Elgar (2009). Brain, 132(Pt 10),

22 Cross Sectional Design Avoids contamination with practice effects Relies on retrospective seizure characterization Difficult to identify individual trajectories from single timepoint

23 Percent Abnormal Decline (Z < -2) Controls Epilepsy Hermann et all (2006). Ann Neurol, 60, 80-87

24 Social Cognition Processing of social information and cues Deficits seen in Asperger syndromes Often attributed to frontal lobe function

25 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?

26 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),

27 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