Epilepsy and Puberty UCSF DEPARTMENT OF NEUROLOGY. Nilika Shah Singhal, MD Assistant Professor, Neurology & Pediatrics

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1 Li v i ngwi t hepi l e ps y Communi t yeducat i onconf er ence J ul y22,2017 Puber t yandepi l eps y Hi l lphysi ci ansmedi calgroup Epi l eps yf oundat i onofnor t her ncal i f or ni a-1736f r ankl i ns t r eet,s ui t e450oakl andca www. epi l eps ynor cal. or g epnca@epi l eps ynor cal. or g

2 Epilepsy and Puberty UCSF DEPARTMENT OF NEUROLOGY Nilika Shah Singhal, MD Assistant Professor, Neurology & Pediatrics July 2017

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4 Road Map Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 3

5 Adolescence Transitions Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 4

6 Brain changes in adolescence: risk-taking vs pleasure-seeking Grey matter loses density Synaptic pruning, increased myelination, increasing axonal diameter Posterior to anterior maturation White matter connectivity changes Different brain areas are activated on fmri in adolescents and adults on tasks involving recognition of emotion Impact on social interaction and decision making Dopamine increases Reward pathway has less input from frontal cortex Emotions and pleasure seeking are less inhibited 1.Jensen FE. The teenage brain. Toronto: Harper Collins; Yurgelun-Todd DA, Killgore WD. Fear-related activity in the prefrontal cortex increases with age during adolescence: a preliminary fmri study. Neurosci Lett 2006;406:

7 Adolescence Transitions Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 6

8 Puberty: Endocrine changes Onset of Puberty = Tanner stage 2 Breast and testicular development Around age 10 years for girls and 12 years for boys Activation of 3 axes: Hypothalamic-Pituitary-Adrenal axis Hypothalamic-Pituitary-Gonadal axis Growth hormone-insulin like growth factor axis Seizures and AEDs may affect endocrine function 3. Sørensen K, Mouritsen A, Aksglaede L, Hagen CP, Mogensen SS, Juul A. Recent secular trends in pubertal timing: implications for evaluation and diagnosis of precocious puberty. Horm Res Paediatr 2012;77:

9 Adrenarche Starts about 2 years prior to Gonadarche Maturation of the adrenal glands 8

10 Gonadarche Rosciszewska D. Time course of epilepsy at the age of puberty ingirls. Nmrol Neiirochir Pol 1976; 19: Diamantopoulos N, Crumrine PK. The effect of puberty on the course of epilepsy. Arch Neurol 1986;43:

11 Menstrual disorders Anovulatory cycles Catamenial epilepsy Amenorrhea, oligomenorrhea, abnormal cycle interval, PCOS Cramer et al. Reproductive Function in Epilepsy. Epilepsia 32(6): , Mattson RH, Kramer JA, Caldwell BV, Cramer JA. Seizure frequency and the menstrual cycle: a clinical study. Epilepsia 198 1;22:242 Bonuccelli U, Melis GB, Paoletti AM, Fioretti P, Mum L, Muratorio A. Unbalanced progesterone and estradiol secretion in catamenid epilepsy. Epilepsy Res 1989;3:

12 Hormone pathways AEDs Martin JB, Reichlin S, Brown GM. Clinical neuroendocrinology. Philadelphia: FA Davis, 1977 Wooley DE, Timiras PS. Estrous and circadian periodicity and electroshock convulsions in rats. Am J Physiol 1962a;202: Mattson RH, Cramer JA. Epilepsy, sex hormones and antiepileptic drugs. Epilepsia 1985;26:S40-5 I 11

13 Practical Approach to Contraception Reduces efficacy of OCPs AED Blood Levels affected by OCPs Little Interaction Carbamazepine Oxcarbazepine Topiramate Phenobarbital Phenytoin Primidone Lamotrigine Divalproex sodium Levetiracetam Pregabalin Gabapentin Zonisamide Lacosamide 12

14 Practical Approach to Contraception Other forms of contraception: Intrauterine device Hormone-releasing IUD, copper containing IUD Intramuscular medroxyprogesterone Nuva-ring Barrier methods 13

15 Growth acceleration 14

16 Adolescence Transitions Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 15

17 All youth ages years studied in 1 country (Norway) 85% responder rate Lossius MI, Alfstad KÅ, Van Roy B, Mowinckel P, Clench-Aas J, Gjerstad L, et al. Early sexual debut in Norwegian youth with epilepsy: a population-based study. Epilepsy Behav 2016;56:

18 Adolescence Transitions Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 17

19 Psychological stages of development Early stage ages years Middle stage ages years Late stage ages years Epilepsy onset in childhood vs adolescence FAMILY /Parental coping predicts coping to chronic disease Erikson EH. Youth identity and crisis. New York: Norton; 1968 Pianta RC, Lothman DJ. Predicting behavior problems in children with epilepsy: child factors, disease factors, family stress, and child-mother interaction. Child Dev 1994;65:

20 Mental Health and Substance Abuse Mental illness is common in children Psychiatric co-morbidities in YWE can impact QOL Independent of seizures ALL YWE should be screened for depression, anxiety, suicidality 353,319 hospitalizations of children ages ,280 also had epilepsy Mean age 15.9 years More likely to have coexisting sleep disorder Longer LOS Thibault, et al. Hospital Care for Mental Health and Substance Abuse in Children with Epilepsy. Epilepsy Behav 2016 Apr;57(Pt A):

21 Rebellious Behaviors in YWE Co-morbid: depression, executive function deficits, ADHD Impulsivity, poor decision making perfect storm Predictors of Rebelliousness Age at baseline Clinical implications: All YWE at risk Screen all youth Pay attention to Memory Smith AW, et al. Rebellious Behaviors in Adolescents with Epilepsy. J Pediatr Psychol May

22 Adolescence Transitions Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 21

23 Bone health Peak bone mass achieved in adolescence Youth with Epilepsy increased risk for fracture Reduced bone mineral density Abnormalities in bone/ mineral metabolism Biochemical changes with AEDs: CBZ, OXC, PHT, VPA, GBP, PHB and KD increased risk fx Hahn TJH, Scharp CR, Boisseau VC, Haddad JG. Serum 25-hydroxycalciferol levels and bone mass in children on chronic anticonvulsant therapy. NEJM 1975;292:

24 Road Map Brain changes in adolescence leave an imbalance between risk-taking and pleasure-seeking behaviors Puberty is a major change Sexual development occurs Psychological stages of development Impacts of treatment on Bone health 23

25 Thank you!