Migraine headache
1. What every clinician should know
Migraine is a neurologic disorder with attacks that generally will include throbbing pain, activity intolerance, nausea, and light and sound sensitivity. In about 30% of individuals, attacks are preceded by an aura—most commonly visual phenomena that migrate across the visual field. Migraine affects roughly 12% of the U.S. population. However, it affects women three times more often than men and occurs most commonly in the years with childbearing potential. There is perhaps a 25% to 33% chance that a woman who becomes pregnant will have preexisting migraine.
Approximately 30% of persons with migraines have auras. Visual symptoms are the most common auras. Sensory symptoms are the second most common. The typical visual aura begins as a small area of scintillation (bright flashing light) partially surrounding an area of decreased vision, the scotoma, which may be dark, gray, or clear but blurred.
This perception grows in one or two visual fields over 5 to 60 minutes and is usually followed by a migraine headache. It may also be followed by a tension-type headache or no headache at all. Migraine with aura poses a small increased risk of stroke, particularly in women who smoke or take estrogen-containing birth control pills.
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Two percent of the population has chronic migraine, a much more disabling and impactful disease than episodic migraine. Unemployment due to chronic migraine is much more common than that due to episodic migraine, and quality of life in chronic migraine is substantially worse than in episodic migraine. Analgesic use more than 15 days per month, triptan (e.g., sumatriptan) use more than 8 days per month, and barbiturate or opioid use more than 4 days per month are risk factors for chronification of headaches. Other risks include obesity and stressful life events.
Migraine may develop for the first time during pregnancy, although this is not common. Rising or sustained high estrogen levels have been proposed as the mechanism of migraine relief that often occurs during pregnancy. This mechanism, however, cannot explain the worsening or new appearance of migraine that sometimes occurs.
The rapid fall of estrogen levels may be responsible for menstrual and postpartum migraine. Women with a prior history of migraine are more likely to develop postpartum migraine.
Migraine relief during pregnancy may be due to the differential effect of estrogen on neurons and glia. Although rising or sustained estrogen levels decrease headache in most women, these changes induce headache in some women.
Migraine pain may be due to increased reactivity of trigeminal nucleus caudalis glial cells, which may be dampened by high estrogen and progesterone levels. During late pregnancy, women have elevated pain thresholds. Estrogen levels do not differ in nonpregnant women with or without menstrual migraine.
Course of migraine during and after pregnancy
Approximately 60% to 70% of women with migraines will improve during pregnancy, while some women who have not had migraines will experience their first migraine headache. Migraine with aura probably improves less than migraine without aura.
Primiparous women may be more likely to improve. Case reports of migraines that occur for the first time during pregnancy emphasize the presence of focal neurologic symptoms (migraine with aura), probably because patients with these dramatic presentations are more likely to be referred to a specialist. In a series of 10 women with pregnancy-related headache and focal neurologic symptoms (visual or sensory aura, dysphasia, weakness, or a combination of these symptoms), two presented in the first trimester, six in the third trimester, and two postpartum.
Menstrually related migraine (a lack of headache improvement in the first and third trimesters), second-trimester hyperemesis, and a pathologic pregnancy course were associated with a lack of headache improvement in the second trimester.
Description:
Migraine is a disorder of recurrent headaches manifesting in attacks lasting 4 to 72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia.
The diagnostic criteria of the International Classification of Headache Disorders, 3rd edition (ICHD-3) are listed below. Note that migraine has a broad clinical spectrum. Two individuals may satisfy completely different pain criteria and have different associated symptoms—yet both will have migraine.
Diagnostic criteria:
A. At least five attacks fulfilling criteria B–D
B. Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated)
C. Headache has at least two of the following four characteristics:
- Unilateral location
- Pulsating quality
- Moderate or severe pain intensity
- Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
D. During headache at least one of the following:
- nausea and/or vomiting
- photophobia and phonophobia
E. Not attributed to another disorder
2. Diagnosis and differential diagnosis
The diagnosis of migraine is made clinically based on diagnostic criteria and the exclusion of a secondary cause to headache. To exclude secondary headache, assess for red flags and order subsequent diagnostic testing, if indicated (See Table I).
Table I.
| stands for… | for example… | think of… | |
| 2S | Secondary risk factorsSystemic symptoms | Fever, weight loss, fatigue,HIV, cancer, immune suppression | Infection, inflammation, metastatic cancer, carcinomatous meningitis |
| N | Neurologic symptoms/signs | Altered consciousness, focal deficits | Encephalitis, mass lesion, stroke |
| O | Onset | Split-second, thunderclap | Subarachnoid hemorrhage, and others |
| O | Older | New after age 50 | Temporal arteritis |
| P4 | Prior historyPositionalPapilledemaPrecipitants | First, newly progressive, or different from usualDramatic change upright vs. recumbentChange with neck positionVisual obscurationsDramatic, consistent triggering by cough, exertion, or first attack triggered by intercourse | Any secondary cause can lead to change in patternIntracranial hypotension, orthostatic dysautonomiaCervicogenic headacheIntracranial hypertensionPosterior fossa pathology, vasospasm, CSF obstruction or leakChiari malformationAneurysmal subarachnoid hemorrhage |
Adapted from Dodick DW. Pearls: Headache. Semin Neurol 2010;30(1):74-81.
There are numerous causes of secondary headache, but several deserve special consideration during pregnancy, as they may be confused with uncomplicated migraine. Headaches that are associated with pre-eclampsia may resemble migraine.
The headache of idiopathic intracranial hypertension (IIH, a.k.a., pseudotumor cerebri) is often indistinguishable from chronic migraine but may occur in the setting of excess weight and is often accompanied by papilledema, visual obscurations, and pulsatile tinnitus. Progressive visual loss, which is sometimes rapid, only occurs when there is papilledema. If IIH is suspected, an ophthalmologic consultation is appropriate.
Thunderclap headache, a severe headache reaching maximal intensity almost instantaneously (in less than one minute by definition), is not only concerning for aneurysmal rupture, but also of reversible cerebral vasoconstriction syndrome (RCVS). In fact, RCVS commonly manifests with multiple attacks of thunderclap headache in the first week.
Segmental, multifocal intracranial arterial constriction may be seen on angiogram, but these may not be discernible until days or weeks after the initial thunderclap headache. RCVS may be complicated by seizures, small cortical subarachnoid hemorrhages, intracranial hemorrhages, and infarcts. An overlap syndrome exists between eclampsia, posterior reversible encephalopathy syndrome, and RCVS.
In late pregnancy and early postpartum, women are at risk for venous sinus thrombosis. This may also present with a thunderclap headache, or more commonly, a relentless progressive severe headache that may resemble migraine.
Chronic migraine can be a complication of migraine. Headache frequency evolves to more than 15 days per month and is often daily and continuous. The headaches need not always have all the symptoms necessary to diagnose migraine. On many days the headache may resemble a tension-type headache.
Chronic migraine may be caused or complicated by the overuse of analgesics (acetaminophen, aspirin, nonsteroidal antiinflammatory drugs [NSAIDs]), opioids, barbiturate-containing medication, and triptans). In women, barbiturate-containing medications are the most potent for inducing the evolution of episodic to chronic migraine.
Medication-overuse headache (MOH)
Previously used terms: Rebound headache; drug-induced headache; medication-misuse headache
The diagnostic criteria of the International Classification of Headache Disorders,
3rd edition (ICHD-3) are listed below. Patients with a preexisting primary headache, who in association with medication overuse, develop a new type of headache or a marked worsening of their preexisting headache that, in either case, meets the criteria for “8.2 Medication-overuse headache” (or one of its subtypes), should be given both this diagnosis and the diagnosis of the preexisting headache. Patients who meet criteria for both “1.3 Chronic migraine” and “8.2 Medication-overuse headache” should be given both diagnoses.
Description:
Headache occurring on 15 or more days per month developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more, or 15 or more days per month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped.
General comment:
In the criteria set out below for the various subtypes, the specified numbers of days of medication use considered to constitute overuse are based on expert opinion rather than on formal evidence.
Diagnostic criteria:
A. Headache occurring 15 days per month in a patient with a preexisting headache disorder
B. Regular overuse for more than 3 months of one or more drugs that can be taken for acute and/or symptomatic treatment of headache
C. Not better accounted for by another ICHD-3 diagnosis
In most cases diagnostic testing is not needed. Diagnostic testing functions to exclude or diagnose other causes of headache, discover comorbid and coexistent disease that could complicate headache and its treatment, or help select and manage medications safely during and before initiating treatment.
To diagnose migraine without aura, one should ask specifically about severity, unilaterality, throbbing, and aggravation with activity, as well as nausea and light and sound sensitivity. To diagnose aura, ask about positive (flashing, shimmering, paresthesia) and negative (blurry, blank, dark, lack of feeling) sensory phenomena.
Also ask about growth of the involved area in the visual field or on the body, the duration of the symptoms, gradual movement of the symptoms across the visual field or body, and transition from one modality to the other (i.e., visual to sensory). For chronic migraine, pain should be present in more than 50% of days, and the headache should be associated with nausea or light and sound sensitivity in some of the days.
3. Management
Migraine management with medication can be construed as having three elements—acute, preventive, and “bridge” (a course of medications over a few days designed to break a cycle of intractable pain).
Antepartum
Many women with migraine use migraine preventives and abortives prior to pregnancy. In anticipation of pregnancy, it is our practice to modify treatment as the woman attempts to become pregnant. Preventive agents are weaned, except the woman is often started or maintained on oral magnesium supplementation, which appears to function as a preventive. The last dose of a preventive should be given at least five half-lives before fertilization might occur. We ask our patients to stop the other “natural” preventives, including vitamin B 2 and coenzyme Q-10 (which are given at supraphysiologic doses in migraine prophylaxis), feverfew, butterbur, and any other they may be taking because they have not been studied in pregnancy.
By preference we modify the abortive plan to one that is appropriate for pregnancy. For some this is not practical, so we have the patient meticulously check pregnancy tests while attempting to become pregnant, then switch to an acute plan more suitable for pregnancy as soon as she knows she is pregnant.
Intrapartum
The acute treatment of migraine consists of several classes of medication. Acetaminophen is probably the safest, but it is not very effective in migraine. NSAIDs are effective but are contraindicated in the third trimester. A patient may not recall instructions to stop using NSAIDs by the third trimester or other pregnant women in their third trimester may take NSAIDs because they observed their friend using during the first and second trimesters, but were never educated about the risks of third trimester use.
To date, no data have appeared indicating a concern for the use of triptans; sumatriptan has the greatest use and greatest experience favoring safety. Nonetheless, we rarely prescribe triptans during pregnancy given the relative lack of data. Virtually all dopamine blocking antiemetics are effective as acute migraine treatments and have an acceptable safety profile.
Opioids are effective and have a reasonable safety profile if used sparingly to avoid medication overuse headache, dependency, and maternal or infant withdrawal. Butalbital-containing drugs have a poor risk to benefit ratio. These drugs have the highest association with episodic migraine progression to chronic migraine.
Postpartum
Postpartum migraine treatment is resumed, as appropriate, for the patient’s migraine frequency and severity. The medication selection is influenced by whether the patient is breastfeeding.
Preventive medications are listed in Table II, along with the typical effective doses.
Table II.
| Medication | Caution | FDA Risk* |
| Preventive Therapy | ||
| Amitriptyline | Anticholinergic effects | C |
| Candesartan | Hypotension | D |
| Abortive Treatment | ||
| Acetaminophen | Hepatotoxicity with chronic use at >200 mg/kg/day | B |
| Butalbital | Dependence, medication overuse headache | C |
| Dihydroergotamine | Vasoconstriction | X |
| Metoclopramide | Sedation, diarrhea, extrapyramidal signs and symptoms | B |
| Nonsteroidal antiinflammatory drugs | Nausea, edema, GI bleed; premature closure of ductus arteriosus | B/C; D in third trimester |
| Ondansetron | Rare transient headache, constipation, dizziness | B |
| Opioids | Sedation, respiratory depression, constipation, dependence/addiction; neonatal withdrawal syndrome | B/C |
| Prochlorperazine | Sedation | c |
| Triptans** | Triptan sensation (neck and chest pressure, increase in headache) | C |
| Divalproex | Weight gain, hair loss, tremor | X† |
| Fluoxetine | May need dose increase during pregnancy (CYP2D6) | C |
| Lisinopril | Hypotension, cough | D |
| Nortriptyline | May need dose increase during pregnancy (CYP2D6) | D |
| Propranolol, Metoprolol, Nadolol | Hypotension, bradycardia, weakness, depression; possible fetal bradycardia, hypotension, and weakness in neonate | C |
| Topiramate | Tingling, metabolic acidosis (which should be monitored in pregnancy); 20-fold increase risk of cleft lip/palate | D |
| Venlafaxine | Some reports of neonates needing respiratory support and tube feeding | C |
| Butterbur, feverfew, vitamin B12 | No data available | N/A |
*Food and Drug Administration risk categories.
**Triptans approved by the Food and Drug Administration for treating migraine are sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan.
†For migraine indication, category D for epilepsy indication.
Adapted from; Lucas S. Medication use in the treatment of migraine during pregnancy and lactation. Curr Pain Headache Rep 2009;13:392-398.
4. Complications
Migraine is a fluctuating neurologic condition that can progress to a severe and disabling condition, leading to unemployment, affecting parenting ability, and causing irrevocable social harm. One concern is that during pregnancy, a time when abortive and preventive medications are often withheld, the migraine may progress to a debilitating and intractable stage. While this is not common, vigilance is appropriate.
The nausea and vomiting from migraine attacks may be so severe as to lead to weight loss and poor nutrition. We have seen many patients in whom the combined effect of severe chronic migraine and hyperemesis gravidarum requires aggressive intervention.
Migraine may be associated with low birth weight (odds ratio 3.0, confidence interval 1.3 to 7.0), but appears not to be associated with miscarriage, preeclampsia, or congenital anomalies.
Medication overuse is the principle complication of migraine that could lead to eventual worsening of the overall migraine or lead to use of medications that are harmful to the fetus.
5. Prognosis and outcome
Postnatal headache is common. While usually less severe than the patient’s typical migraine, often it is bifrontal, prolonged, and associated with photophobia, nausea, and anorexia. It occurs within 1 week of delivery in approximately 35% of women. Migraines decrease within the first month after delivery in around half of women with migraine. Bottle feeding is associated with the first month recurrence.
While poorly controlled migraines during pregnancy could theoretically promote an ongoing increase in migraine frequency, by and large migraines during pregnancy will not have a long-term health consequence for the mother or child.
6. What is the evidence for specific management and treatment recommendations
“Headache Classification Committee of the International Headache Society. The international classification of headache disorders”. Cephalalgia. vol. 33. 2013. pp. 679-808. (The pamphlet that defines how to classify headaches.)
Hoshiyama, E, Tatsumoto, M, Iwanami, H. “Postpartum migraines: a long-term prospective study”. Intern Med. vol. 51. 2012. pp. 3119-23. (The most comprehensive cohort study to assess headaches up to 12 months after delivery.)
Olesen, C, Steffensen, FH, Sorensen, HT, Nielsen, GL, Olsen, J. “Pregnancy outcome following prescription for sumatriptan”. Headache. vol. 40. 2000. pp. 20-4. (Imitrex was associated with preterm delivery and low birth weight. This could reflect drug exposure but disease severity or confounding factors are also possible.)
Sances, G, Granella, F, Nappi, RE. “Course of migraine during pregnancy and postpartum”. A prospective study. Cephalalgia. vol. 23. 2003. pp. 197-205. (Cohort study through each trimester of pregnancy.)
Stein, G, Morton, J, Marsh, A. “Headaches after childbirth”. Acta Neurol Scand. vol. 69. 1984. pp. 74-9. (Postpartum cohort study that characterizes headaches and migraine in a vigorous manner.)
Wainscott, G, Sullivan, FM, Volans, GN, Wilkinson, M. “The outcome of pregnancy in women suffering from migraine”. Postgrad Med J. vol. 54. 1978. pp. 98-102. (Large survey study in a migraine clinic showing no risk of adverse effects of a migraine in pregnancy.)
Lucas, S. “Medication use in the treatment of migraine during pregnancy and lactation”. Curr Pain Headache Rep. vol. 13. 2009. pp. 392-398. (Excellent review of known medication risks in pregnancy.)
Edlow, JA, Caplan, LR, O’Brien, K, Tibbles, CD. “Diagnosis of acute neurological emergencies in pregnant and post-partum women”. Lancet Neurol. vol. 12. 2013. pp. 175-185. (Up-to-date review of neurologic emergencies in pregnancy with discussions of emergencies presenting with a headache.)
Cunnington, M, Ephross, S, Churchill, P. “The safety of sumatriptan and naratriptan in pregnancy: what have we learned?”. Headache. vol. 49. 2009. pp. 1414-22. (Reassuring update in the sumatriptan pregnancy registry.)
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