Cognition in new onset epilepsy in children and adults

1. Cognition in new onset epilepsy in children and adults Nicole Taylor, PhD, C.Psych Antonina Omisade, PhD, R.Psych.

2. Faculty/Presenter Disclosure • Faculty: Nicole Taylor, Antonina Omisade • No conflicts to disclose

3. New Onset EpilepsyTerms and Definitions • New Onset (NOE) vs. Newly Diagnosed Epilepsy (NDE): • NOE is an subset of NDE – onset of seizures within the past year. • NDE is a broader category that may represent people who have had seizures for years, but were only recently diagnosed. Pohlmann-Eden, B (2011). Conceptual relevance of new onset epilepsy. Epilepsia 52(Suppl 4), 1-6.

4. Why is New Onset Epilepsy Special? • Most of what we know about cognitive dysfunction in epilepsy comes from studying people with chronic seizures; • Causes are multi-factorial, dynamic and interactive:

5. Why is New Onset Epilepsy Special? Witt, J.-A. & Helmstaedter, C. (2015). Cognition in the early stages of adult epilepsy. Seizure, 26, 65-68. (Review)

6. Why is New Onset Epilepsy Special? • It is impossible to attribute cognitive deficits to a specific cause without serial assessments, ideally starting prior to initiation of treatment. • Untreated NOE population is the key to understanding cognitive dysfunction and trajectories in epilepsy.

7. Why is New Onset Epilepsy Special? Witt, J.-A. & Helmstaedter, C. (2015). Cognition in the early stages of adult epilepsy. Seizure, 26, 65-68. (Review)

8. Goals of Presentation • Review what we know about cognition in NOE: • Cognitive profile at onset • Trajectory over time • Current recommendations regarding cognitive assessment of patients with NOE • Local practice • Unanswered questions

9. NOE in ChiLdren What do we know?

10. NOE and Cognition in Children:What do we know? Neuropsychological / Cognitive Findings in NOE • Attention, reaction time, visual memory • Mild generalized cognitive impairment in intelligence, language, attention, executive functioning, and psychomotor speed • Examination of new learning, memory, and attention revealed poor attention, visualmotor speed • Academic problems / use of educational services prior to epilepsy onset*

11. NOE and Cognition in Children:What do we know? Behavioral and Psychiatric Factors* • Higher than expected rates of behavior problems (32% in the clinical or at-risk range) in the 6 months before the first recognized seizure. • 45% with DSM-IV Axis I disorders before the first recognized seizure (ADHD, depression and anxiety). • Elevated rate of lifetime-to-date (DSM-IV) Axis I disorders (depressive disorders, anxiety disorders, ADHD). • In a population-based study, children with a spontaneous unprovoked seizure were 2.5 times more likely to meet DSM-IV criteria for ADHD before the first seizure.

12. NOE and Cognition in Children:What do we know? Neuroimaging • Baseline abnormalities in cortical and subcortical anatomy, white matter integrity, and ventricular volumes, suggestive of antecedent brain anomalies • Baseline abnormalities are related to cognitive and behavioral findings • Longitudinal findings show altered patterns of brain development after baseline (i.e. slowed white matter expansion and gray matter tissue loss)

13. NOE and Cognition in Children:What do we know? Cognitive Phenotypes in NOE • Associations between epileptic syndrome and specific cognitive dysfunctions • In NOE, unique cognitive phenotypes were identified representing variations in the presence, type, and degree of neuropsychological compromise. Hermann et al. (2016) • Cognitive phenotypes were independent of epilepsy syndrome • but were associated with neurobiological measures of brain structure (quantitative volumetrics) and features of family environment and early neurodevelopment

14. NOE and Cognition in Children:What do we know? Early Medical Risk Factors for Neuropsychological Deficit: • Multiple seizures • Use of AEDs • Epileptiform activity on the initial EEG • Symptomatic/cryptogenic etiology • Absence epilepsy • Unknown or unclassifiable epilepsy etiology • Genetic epilepsy • Unknown semiology of seizures • Idiopathic Generalized Epilepsy

15. NOE and Cognition in Children:What do we know? Early Neuropsychological Risk Factors for poor Outcomes: • Children having preexisting behavior / academic problems more likely to exhibit poor neuropsychological outcomes at 1 year • In FLE, worse neuropsychological outcomes at “Time 0” associated with poorer prognosis for epilepsy management as well as even poorer neuropsychological functioning at 1 year Matricardi et al (2016)

16. WISC Composite scores in: Group 1 (drug-resistant FLE at 1 year) Group 2 (good seizure control on monotherapy) A) Time 0 B) Time 1 S. Matricardi et al. (2016). Epilepsy & Behavior, 55, 79–83

17. NOE and Cognition in Adults What do we know?

18. NOE and Cognition in Adults:What do we know? • Subtle cognitive deficits are already present at the time of first seizure (Witt & Helmstaedter, 2015): • Psychomotor speed • Attention/ “Executive functions” • Memory • Deficits are present in absence of visible MRI lesions • People with “symptomatic” epilepsies tend to have more severe deficits than those with cryptogenic or idiopathic epilepsies. • Correlated with lower education and frequent GTC seizures (Witt & Helmstaedter, 2012).

19. NOE and Cognition in Adults:What do we know? • To date, only SANAD study has evaluated trajectory of cognitive dysfunction over time (12 months): Baker, G., Taylor, J., & Aldenkamp, A.P. (2011). Newly diagnosed epilepsy: Cognitive outcome after 12 months. Epilepsia 52(6), 1084-1091.

20. NOE and Cognition in Adults:What do we know? • To date, only SANAD study has evaluated trajectory of cognitive dysfunction over time (12 months): Baker, G., Taylor, J., & Aldenkamp, A.P. (2011). Newly diagnosed epilepsy: Cognitive outcome after 12 months. Epilepsia 52(6), 1084-1091.

21. NOE and Cognition in Adults:What do we know? • Cognitive problems are under-reported by NOE (seizures <12 months) and NDE patients: • Focus on controlling seizures and adjusting to diagnosis. Fig. 1 Prevalence of objective and subjective cognitive deficits in untreated patients with newly diagnosed epilepsy (n = 247) Witt & Helmsaedter, 2012.

22. Recommendations • Cognitive, behavioral, and academic problems should be screened at diagnosis, before initiation of medication treatment. • Consideration of a core uniform battery used across epilepsy centers to meet clinical and research goals. • Triplett & Asato (2015): pilot feasibility trial of a brief cognitive and behavioral screening (CNS Vital Signs computer-based screen, and Strengths & Difficulties parent questionnaire) in children with new-onset epilepsy • In pediatric cases, a history of academic problems and / or behavioral and psychiatric problems may indicate later cognitive impairment. Should consider increased prioritization in these cases.

23. Recommendations • Baseline cognitive screening : • Disentangle effects of pathology, seizures, AED’s and psychiatric comorbidities on cognition; • Identify potential biomarkers; • Help guide treatment decisions; • Provide counseling to patients to ameliorate any functional effects of cognitive problems; • Monitor the course of the disease and effects of treatment. • Screening should be offered regardless of subjective complaints.

24. Approach to NOE in Halifax • Brief (2-hour) baseline assessment is offered to: • All NOE patients within one month of initiation of AED’s; • Individuals after their first clearly-unprovoked seizure, • Patients who were seen after their first seizure are only seen again if they have another seizure • NOE patients are re-assessed after 2 years. • Individuals with major cognitive deficits or functional complaints are referred for a complete neuropsychological assessment.

25. Questions to be Addressed • The developmental course of epilepsy, including NOE needs further research in order to better understand the impact of factors such as : • Age of onset (are there critical stages of brain maturation that lead to specific alterations of brain organization impacting on developmental course?) • Seizure frequency and type, extension of epileptic focus, occurrence of secondarily generalized seizures, and duration of epilepsy • Trajectory of cognitive dysfunction and its clinical significance re: seizure management and functional outcomes

26. Questions to be Addressed • The cause of cognitive problems at (and even before) the time of the first seizure is unclear: • Underlying common pathology? • Some form of bi-directional relationship? • Cognition in new onset vs. newly diagnosed epilepsy: • SANAD study – mean duration of seizures prior to diagnosis was 5 years. • In adult studies, age ranges are large: • Implications for etiology of epilepsy, etc. • Elderly populations are under-represented • Role of “cognitive reserve” factors: • Current research: Whatley et al. (Halifax)

27. Acknowledgements Halifax First Seizure Clinic Winnipeg Epilepsy Surgery Group Dr. Fran Booth and Pediatric Neurology Team Kristi MacDonald (Psychometrist) • Dr. Bernhard Pohlmann-Eden • Karen Legg, RN-NP • Dr. Ben Whatley • Dawnette Benedict-Thomas (Psychometrist)