Living with Epilepsy - epilepsynorcal.org · •Reward pathway has less input from frontal cortex
Transcript of Living with Epilepsy - epilepsynorcal.org · •Reward pathway has less input from frontal cortex
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Epilepsy Foundation of Northern California - 1736 Franklin Street, Suite 450 Oakland CA 94612 – 510-922-8687 www.epilepsynorcal.org – [email protected]
Puberty and EpilepsyJuly 22, 2017
Community Education ConferenceLiving with Epilepsy
Hill Physicians Medical Group
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Nilika Shah Singhal, MD
Assistant Professor,
Neurology & Pediatrics
July 2017
UCSF
DEPARTMENT OF
NEUROLOGY
Epilepsy and Puberty
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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
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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
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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; 2015
2.Yurgelun-Todd DA, Killgore WD. Fear-related activity in the prefrontal cortex
increases with age during adolescence: a preliminary fMRI study. Neurosci Lett
2006;406:194–9.
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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
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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;77:137–45
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Adrenarche
• Starts about 2 years prior to Gonadarche
– Maturation of the adrenal glands
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https://www.researchgate.net/figure/268791949_fig5_Figure-5-Schematic-representation-of-the-hypothalamic-pituitary-gonadal-HPG-axes
Rosciszewska D. Time course of epilepsy at the age of puberty ingirls. Nmrol Neiirochir Pol 1976; 19:597-602.
Diamantopoulos N, Crumrine PK. The effect of puberty on the course of epilepsy. Arch Neurol 1986;43:873-6.
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Gonadarche
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Menstrual disorders
Cramer et al. Reproductive Function in Epilepsy. Epilepsia 32(6):519-526, 1991.
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: 100-6.
• Anovulatory cycles
• Catamenial epilepsy
• Amenorrhea, oligomenorrhea, abnormal
cycle interval, PCOS
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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;202:379-82.
Mattson RH, Cramer JA. Epilepsy, sex hormones and antiepileptic drugs. Epilepsia 1985;26:S40-5 I
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Practical Approach to Contraception
• Reduces efficacy of OCPs
• Carbamazepine
• Oxcarbazepine
• Topiramate
• Phenobarbital
• Phenytoin
• Primidone
• Little Interaction
• Levetiracetam
• Pregabalin
• Gabapentin
• Zonisamide
• Lacosamide
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• AED Blood Levels affected by OCPs
• Lamotrigine
• Divalproex sodium
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Practical Approach to Contraception
• Other forms of contraception:
– Intrauterine device
• Hormone-releasing IUD, copper containing IUD
– Intramuscular medroxyprogesterone
– Nuva-ring
– Barrier methods
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Growth acceleration
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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
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• All youth ages 13-19 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;56:1–4.
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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
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Psychological stages of development
• Early stage – ages 10-13 years
• Middle stage – ages 14-17 years
• Late stage – ages 18-21 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;65:1415–28.
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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 6-20
– 3,280 also had epilepsy
– Mean age 15.9 years
– More likely to have coexisting sleep disorder
– Longer LOS
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Thibault, et al. Hospital Care for Mental Health and Substance Abuse in Children with Epilepsy. Epilepsy Behav 2016 Apr;57(Pt A):161-6.
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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
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Smith AW, et al. Rebellious Behaviors in Adolescents with Epilepsy. J Pediatr Psychol. 2017 May 30.
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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
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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: 550–4.
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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
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Thank you!