85b - Neurological Diseases in Women

Question 1

Which hormonal fluctuations are likely to affect seizure frequency in women with epilepsy?

Answer 1

More estrogen + less progesterone -> more seizures

(Increased estrogen:progesterone ratio)

Question 2

An abrupt drop in estorgen levels may trigger…

1. Epileptic seizures
2. MS flares
3. Menstrually related migraines

Answer 2

Menstrually related migraines

• Rapid withdrawal of estrogen may trigger migraine
• May happen just before menstrual period, postpartum, or perimenopause

Question 3

How do sex hormones influence the course of MS?

Answer 3

Estrogen (E2) -> Th1 phenotype -> Inflammatory -> MS predisposition

Note: E3 estrogen released in pregnancy leads to Th2 phenotype, MS remission

Question 4

How does progesterone influence epilepsy?

Answer 4

Progesterone increases seizure threshold

• Potentiates GABA
  
  • -> Increased general inhibition

Question 5

What happens to migraine in pregnancy?

Answer 5

• Migraines unusual in 1st and 2nd trimester
  
  • Estrogen slowly increasing
• Increase during 3rd trimester, postpartum
  
  • Rapid withdrawal of estrogen

Question 6

Valproic acid should be avoided in which population

Answer 6

Women of childbearing age

Find soemthing else to treat migraine or epilepsy in anyone who might have a child!!

Question 7

Which AED is most affected by changes in drug metabolism during pregnancy?

Answer 7

Lamotrigine

• Glucuronidation is facilitated by estrogen
• -> Faster drug metabolism during pregnancy

Question 8

Rapid withdrawal of which hormone is might trigger a migraine in a suceptible individual?

Answer 8

Estrogen

Question 9

If a patient with MS needs a disease-modifying agent during pregnancy, which one should you use?

Answer 9

Glatimer acetate

BUT, avoid DMAs in pregnancy if possible; MS flares are liekly to decrease due to increased E3 estrogen

Question 10

If a patient is having higher estrogen and lower progesterone, are they more or less likely to have seizures?

Answer 10

More likely

(More estrogen + less progesterone -> more seizures)

• Estrogen (E2) -> more seizures
• Progesterone -> fewer seizures

Question 11

How does pregnancy affect MS?

Answer 11

Women with MS are likely to remit during pregnancy

• E3 estrogen released in pregnancy
  
  • -> Th2 phenotype (less inflammatory, increased immune tolerance)
  • Fewer MS flares

Question 12

What is the best mode of contraception for a young woman with migrain with aura?

Answer 12

IUD

(In general, seems like the best option for all people discussed in this lecture)

• Combined oral contraceptive pills and migraine with aura both increase risk of stroke; together, result in 7x increased risk

Question 13

What happens to migraine frequency during menopause?

Answer 13

• More migraines during menopause as estrogen levels rapidly fall
• Much lower frequency of migraines after menopause
  
  • Estrogen is lower, but at a steady state

Question 14

Many AEDs are enzyme inducers - what are the implications for patients taking oral contraceptive pills?

Answer 14

Less bioavailability of OCPs

Notably, OCPs also decrease bioavailability of lamotrigine

• Recommend IUD, depo-provera, or condoms

Question 15

Which hormone is associated with decreased MS flares during pregnancy?

Answer 15

Estriol (E3)

Most acitve during 3rd trimester

Question 16

How does seizure frequency change during pregnancy?

Post-partum period?

Answer 16

• Stays the same in pregnancy
• Increases post-partum

Question 17

Which agents are used for abortive migraine management during pregnancy?

Answer 17

• 1st line
  
  • Non-pharmacologic (cold compress)
  • Acetaminophin
• 2nd line
  
  • NSAID - 1st and 2nd trimester only!!
  • Metoclopramide
• 3rd line
  
  • Sumatriptan (1st line when not pregnant!)
• DO NOT USE BARBITUATES, ERGOT, DHE

Question 18

What agents are used for prophylactic migraine treatment in pregnancy?

Answer 18

Usually not indicated during pregnacy - migraine frequencey decreases due to steadily inreasing estogen

If anything, use:

• 1st line: Mg
• 2nd line: Metoprolol, propranolol
  
  • Stop a few days before delivery
• 3rd line: verapamil, TCAs, SSRI, SNRI
• DO NOT GIVE VALPROIC ACID OR TOPIRAMATE

Question 19

How does estrogen (E2) influence epilepsy?

Answer 19

Estrogen (E2) lowers the seizure threshold

• Potentiates Glutamate
  
  • -> Excitation
• Inhibits GABA
  
  • -> Decreased inhibiton

Question 20

Which anti-seizure drug carries the highest risk of major congenital malformation?

Answer 20

Valproic acid

Also associated with lower IQ, increased risk of Autism

Better option = Lamotrigine

Question 21

Which medication for MS takes up to 2 years to wash out and is FDA pregnancy class X?

Answer 21

Teriflunamide

• Persists in sperm too!