neurologist iranian headache association€¦ · •headache is a common complaint in females of...
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Neurologist
Iranian headache association
• Headache is a common complaint in females of childbearing age.
• Primary headaches, such as migraine and tension headache, account for most headaches in pregnancy.
• Consider secondary causes in the differential diagnosis:oPre-eclampsia, eclampsia
oCVT, certain types of ischemic and hemorrhagic stroke, SAH
oRCVS, PRES
oPituitary apoplexy
Warning symptoms and signs
Signs and symptoms Possible diagnosis
Thunderclap headache SAH Postpartum angiopathyPituitary apoplexy
Headache with atypical aura(aura >1 h or including motor weakness)
TIAIschemic stroke
Fever Meningitis
History of HIV or Syphilis Meningoencephalitis
History of cancer Secondary brain metastases
Postural headache SAH , CVT, intracranial hypotension
Progressive headache, cognitive change, symptoms of raised ICP, new- onset seizure, progressive neurologicdeficit
Intracranial SOL, IIH, CVT, eclampsia
Visual disturbance Preeclampsia, IIH
Migraine in pregnancy
• Migraine incidence: 18% among women and 6% among men.
• Incidence in women aged between 30 and 39 years: 25%.
• First presentation during pregnancy : 1 up to 16%
➢ 1st trimester
➢ Migraine with aura
Worsening Improvement
Impact of pregnancy on migraine
• Improvement: 50-75 %
✓ Menstrual migraine:60 to 87% of women with MRM
improve in the second or third trimester.
✓ Migraine without aura
✓ 2nd and 3rd trimesters
• Aggravation: 5-10 %
• No change : 5-30 %
improvement
no change
aggrevation
improvement no change aggrevation
Impact of migraine on pregnancy
• No congenital malformation
• Pregnancy-associated hypertensive disorders: 1.3-5.6-fold
• Increased risk of preeclampsia in migraineurs, especially in those with worsening of migraine during pregnancy.
• Low birth weight: 1.2-3.2-fold
• Preterm birth: 0.6-2.7-fold
• Arterial and venous thrombosis: ischemic stroke, myocardial infarct, VTE, pulmonary embolism.
• Sleep disturbance and depression
• ICU stays, hospitalizations, respiratory distress syndrome, and febrile seizures slightly more common in infants.
• Cesarean delivery
Migraine treatment during pregnancy
Treatment options
Non-pharmacological optionsHealthy lifestyle habitsBehavioral treatments
Mind-body treatments
Good nutrition, trigger avoidanceRelaxation training, cognitive behavioral therapy, biofeedback, stress management
Meditation , yoga
Pharmacological options Acute medicationsPreventive drugs
Dietary supplements CoQ10, magnesium, vit B2,vit D
Procedure-based interventions Physical therapyAcupunctureNerve blocks
• Lifestyle factors, such as a healthy diet and regular sleep, maintaining good hydration,
minimizing caffeine, and avoiding triggers.
• Biofeedback, acupuncture, meditation, icepacks or heat.
• Moderate exercise as tolerated.
• These measures may be sufficient to get the patient through the first trimester, after
which migraines tend to improve.
• Undermanaged headache can lead to stress, dehydration, sleep deprivation,
depression, poor nutritional intake and electrolyte imbalances due to vomiting, which
in turn can have negative consequences for mother and baby.
Non-Pharmacological treatments
Pharmacologic treatments
Analgesics Notes
Acetaminophen/ paracetamol First line; association with ADHD with longer use and use in T3.Increased risk of early childhood respiratory disorders with frequent maternal use.
NSAIDs
non-selective COX2inhibitors
Second line; safe in T2: ibuprofen, naproxen, ketorolac and diclofenac.Ibuprofen has the best safety data. Poor evidence for indomethacin.Avoid during T1 due to increased risk of miscarriage when used close to conceptionand probable risk of congenital malformations.Not recommended in T3 due to increased risk of PDA, impaired renal function, oligohydraminous, cerebral palsy and neonatal IVH.Limit their use to < 48 hours in T3.
Selective COX2-inhibitors Contraindicated based on the few available prenatal data.
Caffeine low doses(<200mg/day) are safe. Moderate-to high daily doses might be associated with miscarriage, low birth weight and preterm delivery.Combined preparations containing caffeine should be avoided.
Aspirin Use in T1 and T2 only in low doses (<100 mg/day).Teratogenic effects with chronic medium to high doses.Avoid for migraine treatment indication. Avoid near term: risk of prolonged labor , postpartum and neonatal bleeding, PDA and oligohydramnios.
Antiemetics
Antiemetics Dose Notes
Diphenhydramin 25-50 mg PO10-50 mg IM,IV
Sedation and apnea after delivery are possible.Possible neonatal withdrawal with prolonged maternal use in T3.
Promethazine 12.5-25 mg IM May cause platelet aggregation inhibition, irritability, or extrapyramidal effects in infants after maternal use within 2 weeks prior to delivery.
Metoclopramide 10mg PO,IM , IV Safe; extrapyramidal signs and methemoglobinemia in neonates with maternal exposure during delivery.
Prochlorperazine 10 mg IM Increased risk for neonatal extrapyramidal or withdrawal symptoms if taken during T3.
Chlorpromazine 25-50 mg IM
Domperidon 10mg PO Might lead to long QT syndrome.
Ondansetron 4-8 mg PO,IV Possible teratogenic effect: increased risk of cleft palate and cardiac anomalies. serotonin syndrome and QT prolongation.
Triptans Triptans
Sumatriptan 15% of maternal dose reach the fetus after 4 h.Risk rates for major birth defects and prematurity are similar to general population.Elevated rates of spontaneous abortions compared to healthy controls but not with untreated migraineurs.Increased risk of behavioral problems like attention deficit and aggression disorders after exposure in T1.Increased risk of atonic uterus and postpartum hemorrhage with exposure in late pregnancy.
Rizatriptan In the rizatriptan registry 4 major birth malformations occurred in 56 pregnancies (7.1%).
Frovatriptan Less desirable because of longer half-life.
Naratriptan Less desirable because of longer half-life and less effectiveness.
Triptans
• May be appropriate as a third-line treatment, especially for moderate
to severe unresponsive attacks and in patients who are known to
respond well to triptans.
• Fewer doses of acute medication may be required and the overall
burden of medication may be lower.
Acute medications: Ergots
• contraindicated in pregnancy
• Uterine hypertonicity, miscarriage
Acute medications: Opioids
• Treatment of moderate to severe pain in T2 and early T3.
• Inappropriate for migraine: worsening of N/V and constipation.
• A slightly higher risk for cardiac defects or spina bifida after opioid exposure in T1.
• Risk of MOH in mother and neonatal withdrawal syndrome with prolonged use.
• Weak opioids like tramadol, oxycodone and codeine can be considered when non-
opioid medication brings no relief.
• If necessary as a rescue therapy, oxycodone may be the safest one.
Corticosteroids
• If steroids are indicated, prednisone is preferred to dexamethasone.
• Avoid during T1: increased risk of cleft lip or cleft palate, low birth weight.
• Risks more strongly associated with chronic rather than episodic use;
monitor infants for hypoadrenalism with chronic maternal use.
• Early lung maturation
• In status migrainosus, prednisone and prednisolone remain a reasonable
alternative.
Treatment of refractory migraine
• Intravenous hydration
• Antiemetics:
o Metoclopramide 10 mg IM/IV
o Chlorpromazine 25-50 mg IM
• MgSO4 1 gr IV in 15 min
• IV opioids
• Corticosteroids: prednisolone (60 mg for 2 days, 40 mg for 2 days, 20 mg for 2 days) or methylprednisolone (4 mg, 21 tablets) for 6 days
• Peripheral nerve blocks
Treatment of acute migraine attackNon- Pharmacological treatments
Acetaminophen 650-1000 mg +/- metoclopramide 10 mg
NSAIDs: Ibuprofen, Naproxen and Ketorolac
Sumatriptan, weak opioids
IV fluids
Metoclopramide 10 mg or chlorpromazine 25-50 mg IM +/- Diphenhydramine12.5 mg
IV Opioid
Magnesium sulfate 1 g over 15 min ; Glucocorticoids;
Peripheral nerve blocks
Preventive treatments
Preventive treatment
• Frequent, moderate to severe attacks that do not respond well to acute treatment.
• Continue treatments with lower risk profiles if the baseline headache burden was high and a patient believes that managing without prevention would be intolerable.
• Whenever possible, medications with a higher risk burden should be converted to lower-risk medications if prevention is continued.
• No need for a prolonged oral preventive washout period prior to attempting pregnancy.
Beta blockers
✓ Choice : metoprolol and propranolol.
✓ First line options in pregnancy and breast feeding.
✓ IUGR (atenolol), preterm birth, transient neonatal bradycardia, respiratory
suppression, hypoglycemia and hypotension, decrease uterine contraction.
✓ Gradual taper 4 weeks before delivery and stop 2-3 days before childbirth.
✓ Monitor the neonate for bradycardia, hypotension, and hypoglycemia.
TCAs
➢ Choice : Amitriptyline > Nortriptyline : 10-25 mg.
➢ The safest second-line option when β-blockers are contraindicated or
ineffective.
➢ No clear teratogenic effect with low doses (10-50 mg per day).
➢ Taper 3-4 week before delivery.
➢ Monitor the neonate for side effects like drowsiness, irritability, and
sucking problems, urinary retention or constipation with late term
exposure.
SSRIs
• Cardiovascular malformations.
• Use of SSRIs at the end of pregnancy may lead to transient
withdrawal syndrome in the neonate manifested by persistent crying,
irritability, chills, fever, hypertonia or rigidity, tachypnea or respiratory
distress, hypoglycemia, and seizures.
• Use of SSRIs after 20 weeks’ gestation is associated with persistent
pulmonary hypertension.
SNRIs
• Venlafaxine should be avoided during pregnancy.
• Possible increased risk of spontaneous abortion; neonatal seizures,
neonatal abstinence syndrome, or serotonergic toxicity possible with
maternal use in third trimester.
• No clear indication of a possible teratogenic or abortifacient effect of
duloxetine.
Antiepileptics
❑ Sodium valproate:
✓ Contraindicated in pregnancy, in the absence of epilepsy.
✓ Devastating fetal side-effects like neural tube defects and other major
malformations such as cleft palate, cardiac or genitourinary tract defects
and developmental delay .
❑ Topiramate :
o Increased risk of cleft lip/palate, hypospadias and low birth weight,
especially if used during T1.
o Should be avoided during pregnancy.
Antiepileptics
❑ Gabapentin :
✓ A link with osteological deformities; possible increased risk of
preterm birth.
✓ Is not recommended during pregnancy.
✓ Third line in refractory cases.
❑ Lamotrigine has a good safety profile.
Calcium channel blockers
▪ Verapamil : No increase in fetal congenital malformations; may
cause fetal bradycardia, hypotension, heart block; tocolytic;
avoid in late pregnancy.
▪ Flunarizine should be avoided in pregnancy and breastfeeding,
since there are not enough safety data.
❖Angiotensin receptor blockers:
✓ Congenital malformations, renal damage, skull ossification defects and death.
✓ Avoid
❖ACE inhibitors:
❑ Lisinopril : no risk in T1; toxic and teratogenic in T2 and T3
❑ Prematurity, IUGR, renal tubular dysplasia, lung hypoplasia, skull hypoplasia, limb contracture, and neonatal hypotension.
❑ Avoid
Other drugs
❑ Cyproheptadine : group B
❑ Memantin : group B
❑ Melatonin: There is no clear evidence of harmful adverse
events; can interfere with the development of the postnatal
circadian rhythm.
Procedure based interventions
• Acupuncture : safe in pregnancy.
• Chiropractic : avoid.
• Supraorbital nerve stimulator and transcranial magnetic stimulators.
❑Peripheral nerve blocks:
✓Safe.
✓Use lidocaine or ropivacaine.
✓Bupivacaine may be associated with fetal cardiotoxicity.
✓Steroids should be avoided because of the risk of accelerated fetal lung maturity.
Botulinum toxin type A
• Probably safe during pregnancy due to its local mechanisms of action.
• Only very few data are available and mainly for its use as cosmetic
treatment.
• It should only be reserved for severe refractory chronic migraine
patients.
• Due to a long duration of action, pregnancy should not be attempted
until 12 weeks after the last exposure.
CGRP mAbs
• No data in humans; animal studies showed no teratogenic effects.
• CGRP levels may affect the development of preeclampsia.
• These treatments have a long half- life, and the current
recommendation is to withhold CGRP mAbs 4-6 months prior to
attempted conception.
• Women of childbearing age should receive counseling on the
appropriate use of methods of birth control.
Dietary supplements
Magnesium sulfate
• Magnesium (up to 350 mg/day) can be used during pregnancy.
• Transient neurological symptoms in newborns and hypotonia have
been reported.
• Prolonged IV treatment (more than 5 consecutive days) may be
associated with fetal skeletal abnormalities.
Dietary supplements
• Coenzyme Q10: 100 mg Bid
• Magnesium sulfate: 350 mg/day
• Vitamin B2: 400 mg/day
• Vitamin D: 10 mcg/day
Postpartum migraine
Postpartum headache
• Postpartum headache occurs in about 30–40% of all women.
✓Abrupt fall in the level of estrogen levels immediately after childbirth with an over 95% reduction .
✓Postpartum depression
✓New parental role and psychological adaptation
✓Sleep deprivation
✓Fatigue
✓Multiparity and age over 30 years?
Postpartum migraine
• Reoccurrence of migraine within 72 h after childbirth in about 4% of women; increases to 30–40% during the first week and 50–60%during the first month.
• Apparent sparing of the day of birth.
• Decline in attacks frequency starting five weeks after delivery.
• Pre-pregnancy headache pattern restores within 1 month from delivery in 55% of patients.
• Secondary headaches like preeclampsia, postpartum stroke, RCVS, cerebral venous thrombosis, postdural puncture headache, subdural hematoma, meningitis and pituitary tumors should be considered.
Post partum headache
• Breast-feeding exerts a protective effect against migraine.
• The regular secretion of prolactin can inhibit ovulation, plasma fluctuation
of estrogen levels, and menses.
• In women who breastfeed exclusively, ovulation returns about 27 weeks
after childbirth, whereas it returns within about 6 weeks after childbirth in
women who do not breastfeed.
• A rise in vasopressin and oxytocin levels could exert a protective effect
against migraine due to their antinociceptive activity.
Treatment of migraine during lactation
• Non pharmacological treatments during pregnancy should be continued during lactation.
• There are more options for treatment during lactation than during pregnancy
• Migraine is almost never a reason to withhold breastfeeding, except a woman whose migraines are refractory to typical oral treatments and who is dependent on Onabotulinum toxin or a CGRP monoclonal antibody.
• Medication is considered safe during breastfeeding if the relative infant dose is <10%.
• Delay feeding, substitute formula, pump and dump the milk for at least 4 hours after drug use.
Analgesics
• Acetaminophen is the preferred acute treatment.
• NSAIDs:✓Ibuprofen, and diclofenac are considered safe; there is less evidence for
naproxen and indomethacin.
✓Ibuprofen is preferred because of its short elimination half-life and low excretion in milk.
✓Avoid in mothers of infants with platelet dysfunction or thrombocytopenia.
✓Exacerbation of jaundice in newborns by NSAIDs
• Aspirin:o should be avoided as a first-line treatment due to risk of hemolysis and
bleeding conditions in the newborn.
oCaution should be exercised when using aspirin due to the risk of Reye’s syndrome.
Antiemetics
• Metoclopramide :✓May increase milk supply.
✓ Infants may experience intestinal discomfort; monitor infants for extrapyramidal symptoms and methemoglobinemia.
• Prochlorperazine: Sedation or irritability, also apnea and extrapyramidal symptoms in child; may increase milk supply.
• Diphenhydramine: Other agents preferred; monitor for drowsiness or irritability; may reduce milk supply.
• Promethazine: Other agents preferred. May cause sedation or irritability in infants. May lower milk production. Could be used after milk supply is well established.
• Ondansetron: No evidence.
Triptans
• Sumatriptan is compatible with breastfeeding without the need to pump and dump.
• The infant exposure is very low corresponding to 0.5% of maternal dose.
• Eletriptan is the highest protein bound and the dose in breast milk is only 0.002% after 24 h; may be safer.
• Avoid long-acting triptans: naratriptan and frovatriptan
• As an extra safety measure it can be advised to avoid breastfeeding for 12 h after their use, particularly if an infant is young or low in weight.
Other acute medications
• Sporadic use of weak opioids is compatible with breastfeeding.
• Moderate intake of caffeine seems safe for mother and child.
• Ergots should not be used.
Corticosteroids
• Oral prednisone and prednisolone are compatible with breastfeeding
as only about 1–2% of the mother dose transfers to the fetus.
• Prolonged high-dosed therapy should be avoided since infant growth
and development could be affected.
• When administered intravenously, breastfeeding should be delayed
until 2 to 8 h after administration.
Preventive therapy
Recommended drugs:
Beta blockers:
✓Are excreted in breast milk in very low doses.
✓Metoprolol is preferred over propranolol.
✓Possible side effects: drowsiness, neonatal hypoglycemia,
hypotension, weakness and bradycardia.
✓ Compatible with breastfeeding.
✓Monitor infant for bradycardia, hypoglycemia.
✓Caution has to be paid in infants with asthma.
TCAs
➢Second-line treatment due to concerns about sedation in infants. This
concern generally decreases as the infant grows older.
➢Amitriptyline is relatively safe during breastfeeding.
➢Infants are exposed to about 1–2% of maternal dose.
➢Drowsiness and anticholinergic symptoms like dry mouth or
constipation might occur.
SNRIs
oVenlafaxine:
✓No adverse pediatric effects have been reported in the little data on
nursing infants.
✓Use during lactation generally restricted to migraine with psychiatric
comorbidity.
Antiepileptic drugs
• Valproate:
✓Transfers to breast milk in very low doses and is unlikely to affect the child seriously.
✓Should be avoided in women of childbearing age because of its teratogenic effect.
✓When nursing on valproate can not be avoided, monitoring for liver and platelet
function in the child is advised.
Antiepileptic drugs
oTopiramate:✓Reaches infant plasma level up to 25% of maternal levels and newborns
should be monitored for sedation, irritability, poor suckling, weight loss and diarrhea.
✓Good tolerability.
➢Gabapentin seems compatible with breastfeeding.
• Lamotrigine is safe and no serious adverse effects or cognitive and development alterations have been reported.
ARBs and ACE inhibitors:
• Candesartan is probably compatible with breastfeeding with special
attention for kidney development.
• Lisinopril seems probably compatible as well, but there is no specific
breastfeeding data available.
Other treatments
• Verapamil is compatible with breastfeeding.
• Citalopram, Fluoxetine are not recommended.
• Atenolol, and Tizanidine should be used with caution.
• Ergotamine, and Lithium should be avoided.
• Melatonin in low doses seems compatible with breastfeeding.
• Both magnesium and riboflavin are compatible with breastfeeding.
• Safety of CGRP mAbs during breastfeeding has not been studied; recommendation is to withhold CGRP mAbs during lactation.
• Botulinum toxin type A is probably compatible with breast-feeding since a
transfer to breast milk is not probable due to its high molecular weight.
• Peripheral nerve blocks are safe.
• Lidocaine, ropivacaine, and bupivacaine are not excreted into breastmilk at
high levels.
• Noninvasive devices including nerve stimulators and transcranial magnetic
stimulators are compatible with breastfeeding.
Procedure based interventions
Primary headaches, such as migraine and tension headache, account for most headaches in pregnancy.
Consider important secondary causes in the differential diagnosis.
Acetaminophen is safe and ibuprofen can be prescribed for short-term use in T1 and T2
Metoprolol and propranolol are the first choice for migraine prevention, followed by amitriptyline.
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