A woman presenting with headache during pregnancy or postpartum/puerperium (the first 6 weeks after delivery) should be carefully evaluated, because this time period, in and of itself, is considered a “red flag” for secondary causes of headache.1 The physiologic, hormonal, and procedural factors of pregnancy and puerperium lead to increased risks for various underlying headache etiologies, including vascular and hypertensive disorders, derangements of intracranial pressure, and space-occupying lesions. This article summarizes data on the prevalence of secondary headache in pregnancy, discusses when a clinician should pursue further workup, and outlines the presentation of specific secondary headache etiologies.
Several studies have examined rates of secondary headache among women who are pregnant or in the postpartum period. A retrospective study in the Bronx, NY reviewed 140 women who presented to acute care with headache during pregnancy and received neurologic consultation.2 In this population, 35% of the women were ultimately diagnosed with secondary headache, and more than half of secondary headaches were caused by hypertensive disorders (51.0%), predominantly preeclampsia (38.8%). Another retrospective study in Berlin, Germany evaluated 151 women who received neurologic consultation for acute headache while pregnant and found that 42.4% were diagnosed with secondary headache, most commonly caused by an infectious etiology such as viral or acute sinusitis (29.7%), followed by hypertensive disorders (22%).3
For headache in the postpartum period, another study done in the Bronx, NY retrospectively reviewed cases of 63 women who presented with acute headache and received neurologic consultation. Nearly three-quarters of these postpartum women were diagnosed with secondary headache, most frequently from postdural puncture headache (45.7%).4 A retrospective study done in Cincinnati, OH of 95 women in their postpartum periods also found a high rate of secondary headache (51%), with 48% of secondary headache from preeclampsia/eclampsia.5 However, 2 prospective studies found much lower incidences of secondary headaches in the postpartum period—only 4.7%6 and 8.3%7 of women presenting with acute headache in the postpartum period were ultimately diagnosed with a secondary etiology. This discrepancy is likely reflective of differences in sampling across studies, since retrospective studies of women receiving neurologic consultation would have selected for more complex and concerning cases.
Neurologists evaluating acute headache in pregnancy and the postpartum period should maintain a high index of suspicion for secondary headache. Epidemiologic studies, however, also demonstrate that most women presenting with headache during pregnancy are ultimately diagnosed with a primary headache disorder, such as migraine or tension-type headache. Migraine is most common among women of child-bearing age, and although migraine typically improves as pregnancy progresses, up to one-third of all women experience migraine at some point during pregnancy,8 and some may even have their first migraine or migraine aura in pregnancy.2 During puerperium, migraine often worsens as a result of hormonal changes and sleep deprivation; just over 50% of women with migraine report recurrence within the first month after delivery.9
Considering the high rate of primary headache disorders in pregnancy and postpartum, it can be difficult to determine whether further workup should be pursued, particularly in a woman with a prior history of migraine. In general, a new headache or headache significantly different from prior headaches should be assessed for secondary causes. A history of migraine is not necessarily reassuring, because migraine is associated with higher risk of secondary headache etiologies such as preeclampsia/eclampsia.10
The Table presents typical signs and symptoms for secondary headache and demonstrates that many etiologies are likely to occur in late pregnancy and puerperium. Thus, a clinician should be especially vigilant for secondary headache as pregnancy progresses.
Some epidemiologic studies have examined which clinical features are associated with risk for secondary headache in pregnancy and postpartum. Risk factors identified include lack of headache history, history of secondary headache, elevated blood pressure, fever, abnormal laboratory results, and abnormal neurologic examination findings.2,3 A study found that brain imaging for acute headache in pregnancy was more likely to be abnormal when headache was severe or accompanied by seizures or change in consciousness.11 For postpartum headache, abnormal imaging findings and an orthostatic pattern were associated with risk for secondary headache.4 A headache during pregnancy or postpartum with new or unusual features or accompanied by systemic symptoms or acute neurologic deficits should prompt further workup with neuroimaging.
The preferred imaging modality during pregnancy is MRI because no maternal or fetal risks of 3 T or lower MRI have been identified. Gadolinium contrast, however, should be avoided during pregnancy, because it has been associated with risk for fetal developmental abnormalities, fetal inflammatory conditions, and spontaneous abortion. For venous imaging, MR venography (MRV) without gadolinium should be ordered.
Imaging with CT carries the risk of exposing the fetus to ionizing radiation, which could increase risk for fetal mutagenesis, malignancy, growth retardation, and congenital malformations, particularly if the fetus is exposed in early pregnancy. In an emergent situation, however, a noncontrast head CT should be obtained over an MRI because the estimated fetal radiation dose from a head CT is very low. Iodinated contrast should be avoided; it can suppress fetal thyroid function.
During puerperium, there are no specific limitations for neuroimaging. Use of iodinated contrast or gadolinium is considered safe during lactation and CT imaging including conventional angiography can be used. The Table provides specific imaging modalities recommended for each suspected secondary cause of headache.
The cardiovascular system undergoes many changes to meet the high metabolic demands of pregnancy. These changes include an increase in plasma volume, cardiac output, stroke volume, and heart rate. At the same time, systemic vascular resistance decreases, leading to increased venous capacitance and relative venous stasis. Venous stasis, an increase in procoagulant factors, and a decrease in coagulation inhibitors contribute to a state of hypercoagulability, which is greatest during the late third trimester and early puerperium. There may also be structural remodeling of arterial vessel walls, which creates more vulnerability to stress.12 These physiologic changes predispose a woman to many secondary causes of headache during pregnancy and postpartum.
Common Secondary Headaches of Pregnancy and Postpartum
Hypertensive and Homeostatic Disorders
Preeclampsia/eclampsia, reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) are causes of secondary headache characterized by increased vascular tone and endothelial dysfunction. Although these disorders can occur independently, preeclampsia/eclampsia, PRES, or RCVS often occur concurrently. For this reason, women with preeclampsia/eclampsia and headache should have neuroimaging to evaluate for RCVS or PRES, and likewise, the presence of RCVS or PRES should prompt workup for preeclampsia/eclampsia.
Preeclampsia/Eclampsia. Preeclampsia is diagnosed based on hypertension with evidence of end-organ damage (eg, thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, visual changes, or headache). If a generalized tonic-clonic seizure occurs, the diagnosis is eclampsia. Preeclampsia/eclampsia is present in 2% to 8% of pregnancies and can occur from gestational week 20 through the postpartum period. Of note, blood pressure may not appear elevated during the second and third trimesters because of decreased systemic resistance of pregnancy. Headache is a common symptom of preeclampsia and can precede seizures in 77% of women with eclampsia.13 The headache of preeclampsia/eclampsia is usually progressive and refractory to treatment and may have similar qualities as migraine.4 Even though the majority of preeclampsia/eclampsia cases will be ultimately diagnosed by obstetricians, careful attention to blood pressure and lab abnormalities is needed when evaluating a woman in late pregnancy or postpartum with refractory headache.
Reversible Cerebral Vasoconstriction. Reversible vasoconstriction of intracerebral arteries characterizes RCVS, which can be complicated by seizures, ischemic strokes, nonaneurysmal (convexity) subarachnoid hemorrhage (SAH), and reversible brain edema (ie, PRES). Usually, RCVS occurs in the postpartum period—typically the first week postpartum—and presents with a thunderclap headache, which is a headache that peaks in intensity within seconds. A woman in early postpartum with new or recurrent thunderclap headaches and fluctuating neurologic deficits or seizures should raise an alarm for this diagnosis. Segmental cerebral vessel narrowing on imaging that spontaneously resolves within 3 months confirms the diagnosis of RCVS. Vascular imaging can be negative, however, particularly early in the course of RCVS when smaller peripheral vessels are predominantly involved. In cases of high suspicion, imaging should be repeated in 2 to 4 weeks. During pregnancy, MR angiography (MRA) of the brain without contrast is the preferred imaging modality, but during postpartum, CT angiography (CTA) or conventional angiography are options. Serial intracranial Doppler ultrasounds can also be considered during pregnancy or postpartum.
Posterior Reversible Encephalopathy Syndrome. Loss of cerebral autoregulation and increased capillary leakage are caused by PRES and, in turn, lead to vasogenic edema, typically in the parietal and occipital lobes. During pregnancy and postpartum, PRES usually happens in the setting of preeclampsia/eclampsia but can occur in normotensive women. Headache is the most common symptom of PRES, and vision changes are also common owing to the involvement of occipital lobes. A retrospective study of women with eclampsia found 60% with concurrent PRES presented with headache and visual impairment.14 The headache of PRES is typically described as bilateral, occipital or holocephalic, and pressure-like.
The cardiovascular changes that occur during pregnancy and postpartum increase risk for ischemic and hemorrhagic strokes, which often present with headache. Stroke is the most common cause of serious disability in pregnancy, and rates of stroke during pregnancy and postpartum have risen over the past 20 years to 22 per 100,000 cases in the US, likely a result of rising rates of hypertension and cardiovascular disease.15 Preeclampsia/eclampsia is the strongest risk factor for stroke and plays a role in 25% to 50% of stroke cases during pregnancy and postpartum.16
Cerebral Venous Thrombosis. Typically, cerebral venous thrombosis (CVT) occurs in late pregnancy and postpartum when hypercoagulability risk is highest, and three-quarters of pregnancy-related CVT cases occur postpartum, when additional risk factors for thrombosis may be present (eg, traumatic delivery, cesarean section, cerebrospinal fluid (CSF) leak, dehydration, and anemia. The diagnosis of CVT is often delayed. A study found that the mean duration between symptom onset to diagnosis of CVT was almost 6 days.17 This delay is concerning, given the possibility of serious complications (eg, seizures or ischemic or hemorrhagic strokes). Headache is the most common symptom of CVT, reported as the presenting symptom in 86.1% of CVT cases.18 The headache of CVT typically has a slower onset, although it can be thunderclap in 10% of cases. Other clinical clues of CVT include signs of high intracranial pressure such as pulsatile tinnitus and papilledema or accompanying focal neurologic deficits that do not follow arterial distributions. The imaging modality of choice is MRI with MRV, which should be obtained with a new or unremitting headache during late pregnancy or postpartum.
Hemorrhagic Stroke. Hemorrhagic stroke is caused by multiple mechanisms throughout pregnancy and postpartum including arterial-venous malformation-related intracerebral hemorrhage (ICH), aneurysmal SAH, or RCVS with associated SAH or ICH. Studies on the course of vascular malformations and aneurysms are conflicting, but during the third trimester, aneurysm rupture risk may be higher due to rising blood pressure, increased plasma volume, and altered vascular reactivity. The risk of nonaneurysmal SAH is elevated only in the postpartum period because of the higher risk of RCVS. The presence of thrombocytopenia from preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome and thrombotic thrombocytopenic purpura during late pregnancy and postpartum can also increase risk of hemorrhagic stroke. Headache, particularly thunderclap headache, is a common symptom of hemorrhagic stroke, but there are often accompanying neurologic symptoms including a decreased level of consciousness. A suspicion for hemorrhagic stroke warrants emergent head CT, which if negative, should be followed by lumbar puncture in cases of suspected SAH.
Ischemic Stroke. There is an increased risk of ischemic stroke starting the first few days before delivery and extending into the postpartum period.19 Although the presenting symptoms of ischemic stroke are usually focal neurologic deficits, headache can be an accompanying symptom in up to one-third of cases, particularly for posterior fossa strokes. The headache is typically nonspecific and may be ipsilateral to the stroke. Infrequently, the headache can be thunderclap. Rare causes of stroke that can occur during pregnancy include trophoblastic embolism, amniotic fluid embolism, fat embolism, and cardioembolism from postpartum cardiomyopathy.
Arterial Dissection. Risk of arterial dissection may be higher in the peripartum because of mechanical forces of labor and delivery. High progesterone and decreased collagen synthesis in pregnancy may also weaken arterial walls. Reported rates of vertebral and cervical artery dissection, however, are not clearly higher during pregnancy than in the general population. Some cases have occurred in association with preeclampsia, possibly a result of surges in blood pressure. Arterial dissection often presents with headache and neck pain ipsilateral to the affected vessel as well as focal neurologic findings such as Horner syndrome. The headache can be thunderclap in onset, and cases of cluster-like headaches have been reported. If dissection is suspected, MRA of the head and neck should be obtained with the acquisition of T1 fat-saturated images.
Compared to hypertensive and cerebrovascular causes of secondary headache, intracranial masses are much rarer. During pregnancy, various types of benign and malignant neoplasms can grow because of hormonal and vascular changes, including pituitary adenomas, meningiomas, and primary glial tumors. Pituitary apoplexy can be caused by the rapid enlargement of either a normal pituitary gland or a pituitary adenoma, leading to pituitary gland hemorrhage or infarction. Pituitary apoplexy, hemorrhage, or infection presents with thunderclap headache and may have accompanying vision loss, ophthalmoplegia, or hypopituitarism; imaging with MRI or CT with pituitary protocols should be obtained for suspected cases. Nonneoplastic lesions (eg, colloid cysts or Chiari I malformations) can also cause headaches in pregnant women, specifically during the active labor phase because of Valsalva forces.
Disorders of Intracranial Pressure
Idiopathic Intracranial Hypertension. Commonly, idiopathic intracranial hypertension (IIH) occurs in women of childbearing age and has been reported in 5% of pregnant women. Pregnancy is not a risk factor for IIH in and of itself; however, rapid weight gain can predispose a woman to IIH, which can manifest throughout pregnancy. Headache is the most common presenting symptom of IIH and is typically accompanied by other symptoms and signs of increased intracranial pressure such as transient vision loss, pulsatile tinnitus, bilateral sixth nerve palsy, and papilledema. For a woman with suspected IIH, MRI and MRV should be obtained, and lumbar puncture can be performed to confirm elevated opening pressure. Typically, IIH is treated with acetazolamide. Although teratogenic effects of acetazolamide have been seen in rodents and rabbits; a small number of retrospective studies have not shown any adverse events of acetazolamide use in pregnancy after the first trimester.20 Other treatments for IIH that can be considered during pregnancy include serial lumbar punctures or optic nerve fenestration in cases of rapid or severe vision loss.
Postdural Puncture Headache. Headache during puerperium caused by low intracranial pressure is typically caused by an iatrogenic CSF leak caused by epidural anesthesia. Much more rarely, intracranial hypotension can be caused by the straining of labor. Approximately 1% of cases of epidural anesthesia are complicated by postdural puncture headache (PDPH), which usually occurs within 5 days of the procedure. The headache is almost always postural or orthostatic, with significant or complete resolution lying flat. Other common symptoms include photophobia, nausea, neck stiffness, tinnitus, and hyperacusis. PDPH can rarely be complicated by subdural hematomas, CVT, and PRES; thus, neuroimaging may be warranted in some cases. Most cases of PDPH resolve with conservative methods such as intravenous hydration and caffeine, but a blood patch may be necessary. Another rare cause of secondary headache related to epidural anesthesia is pneumocephalus caused by the introduction of air into the subarachnoid or subdural space, which presents with severe thunderclap headache immediately after epidural injection.21
Although most headaches during pregnancy and the puerperium are primary headaches, there are increased risks for many causes of secondary headache that may have high morbidity and mortality, such as cerebrovascular disease. For this reason, a woman presenting with a new or refractory headache or a headache significantly different from prior headaches should have neuroimaging, particularly if the headache is accompanied by neurologic deficits or abnormalities on physical or neurologic examination.
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KTH has served as a consultant for Guidepoint and received speaker fees from Springer-Neurodiem