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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

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






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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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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

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

https://www.researchgate.net/figure/268791949_fig5_Figure-5-Schematic-representation-of-the-hypothalamic-pituitary-gonadal-HPG-axes

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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

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

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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• 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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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.

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.

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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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






Thank you!

living with epilepsy - epilepsynorcal.org · •reward pathway has less input from frontal cortex

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