Carolyn Bernstein1
(1)
Department of Neurology, Brigham and Womens Hospital, Boston, MA, USA
Carolyn Bernstein
Email: carolyn_bernstein@hms.harvard.edu
Keywords
MigraineVenous thrombosisHeadacheAuraIdiopathic intracranial hypertensionArteriovenous malformationBrain tumor
Clinicians are understandably concerned when a pregnant patient describes headache. Onset, duration, positional worsening, and accompanying features all figure into understanding the pathophysiology and making a determination for proper evaluation and subsequent treatment. Most concerning is the patient who has never had headache prior to the pregnancy who is now presenting with new and severe pain. Three illustrative actual cases will highlight salient features.
Neurologists approach a chief complaint of headache with meticulous wariness. The majority of headaches are benign, meaning that the pain is primary (without concerning secondary cause). Examples of primary headache include migraine and tension-type headache. Migraine is very common, affecting 18 % of American women. The condition is most common in women of childbearing age; migraine prevalence decreases postmenopause. It is genetic, with the predisposition running in families, and, often, patients can recall an elderly family member who had “sick headache” even if not formally diagnosed with migraine. The International Headache Society (IHS) has specific guidelines for making the diagnosis. A person must have at least five attacks lasting between 4 and 72 h of moderate to severe intensity, unilateral and throbbing in nature, accompanied by nausea or vomiting, or light and sound sensitivity. Patients often feel that if the headache is not excruciating, then it cannot be a migraine. An accurate diagnosis prior to pregnancy is helpful; migraine incidence decreases substantially during pregnancy. If a migraine patient who has been stable throughout the pregnancy describes a worsening in the third trimester, this should prompt a careful evaluation.
Tension-type headache, formally called “muscle contraction headache” or “hatband headache,” is quite common. IHS criteria define this phenotype as a headache, which is bilateral, squeezing, or pressing in description, mild to moderate intensity, with few other associated features. Fatigue, muscle spasm, and stress can certainly trigger a tension-type headache, and often rest alone is enough to let the pain improve. Patients are usually able to complete their regular tasks despite a tension-type headache; it is worth recognizing this description, as these headaches are far less worrisome.
A patient describing a new and different headache is concerning. Headaches that are explosive in onset may represent CNS bleeding, such as aneurysm rupture. These are the “thunderclap” headaches. If a patient describes an acute onset with any sort of change in consciousness, she should be directed to emergency evaluation at once. Headaches that are worse with bending over, positional, accompanied by focal numbness or weakness, vertigo, or diplopia (double vision) are also worrisome and should be promptly evaluated. “New and different” or “first or worst” are useful monikers.
Headache evaluation includes a detailed history with documentation of the start and frequency of the headaches, as well as any specific characteristics. Neurologic exam is essential; any focality or sign of increased intracranial pressure such as abnormal funduscopic exam requires further evaluation. Any concern for preeclampsia would of course prompt immediate evaluation.
During pregnancy, radiation should be avoided if possible especially during the first trimester although exposure to the fetus from a non-contrast head CT is less than 0.01 rad. The American College of Radiology states that pregnant women can undergo MRI imaging at any stage of pregnancy; it is a risk-benefit decision and should be performed only if absolutely necessary. There is very little data about gadolinium contrast safety, and contrast should be avoided if possible. MRI, MR angiogram, and MR venogram can all be performed without contrast. The neurologist and obstetrician should consult and make appropriate recommendations, explaining potential fetal risk, to the mother. If the evaluating neurologist has concern for a secondary cause of headache, it may well be necessary to image.
Once the patient has been diagnosed, treatment discussion should also be a joint process. Minimizing medication is important whenever possible, but if the mother’s disability from even a nonconcerning headache diagnosis such as migraine is great enough to impair her ability to function, medication may be necessary. Depending on the level of fetal development, there may be more options. Some of these will be discussed below. Acupuncture, biofeedback, and cognitive behavioral therapy are options for patients; some of these treatments are covered by health insurance. Massage may also help if the headache is considered secondary to muscle train; dry-needled trigger point injections can be an option as well.
Case One
Susan is a 31-year-old right-handed woman with a 10-year history of migraine with aura. She has two to three episodes each month of scintillating scotoma (visual obscuration surrounded by a glowing border), which last between 10 and 30 min. After the aura resolves, she develops a unilateral pain in one temple, right more commonly than left, which throbs and pulsates. She is photophobic and phonophobic and often becomes so nauseated that she will vomit. Untreated, the headache lasts about 6 h and may be so severe at times that she is unable to work or focus and must lie quietly in the dark. She has successfully treated with a combination of 10 mg of rizatriptan plus 500 mg of naproxen, which now will abort the entire process within an hour, and if she treats at the onset of the aura, the medication may entirely prevent the subsequent headache. She has been meticulously evaluated and her normal neurologic examination and the intermittent nature of her episodes have affirmed a clinical diagnosis of migraine with aura, meeting ICHD 3-beta diagnostic criteria.
Susan feels that her migraines became more severe when she completed her graduate studies and began working full time as a teacher. She manages her triggers carefully, focusing on regular sleep and hydration, but she credits topiramate, an antiepileptic medication that is also approved by the FDA for migraine prevention, as the most significant intervention in her migraine treatment. Prior to daily medication treatment, Susan experienced at least six migraines each month, and she found the episodes difficult to manage even with abortive medications. She worked diligently with her neurologist to tailor an individual plan for treatment and prevention and has felt well with a low disability scale score (MIDAS) for the past 3 years. Of note is that migraines are associated with an increased risk of preeclampsia.
Six months prior to becoming pregnant, Susan had her Mirena IUD removed and began taking prenatal vitamins; she had tapered off of the topiramate over 3 weeks. She was delighted to become pregnant after 3 months; her migraines have been quiet during the first trimester. Topiramate is class D during pregnancy; its use has been associated with increased risk of cleft lip/palate in a developing fetus [1]. The FDA reclassified this medication in 2011. This is the only malformation associated with topiramate; risk may be secondary to epilepsy as opposed to medication specifically. To date, there is no known association of migraine with fetal malformation. Statistically, migraine decreases with each successive trimester. The Norwegian MIGRA study was reported in 2011 [2]. Participants kept diaries throughout their pregnancies and reported a successive decrease in both the frequency and duration of headaches including self-reported migraine. When migraine patients, both with and without aura, are considering pregnancy, it is important to plan carefully and to minimize medications as much as possible, in particular those with known teratogenic effects [3].
Susan’s migraines increased slightly in frequency after her first trimester. She had four to five events per month, each of which was treated with acetaminophen. New data does not show increase in major congenital malformations in women who used triptans during pregnancy compared to healthy non-triptan using controls. A formulation of acetaminophen/caffeine/butalbital is sometimes offered to pregnant women as a migraine abortive. This medication is also class C. Obstetricians sometimes favor its use as it has been available for many years, and there are few adverse outcomes associated. However, both the caffeine and the barbiturate components may affect a developing fetus, and the combination of the three medications can cause or contribute to medication overuse headache. Susan’s obstetrician preferred that she avoid her prepregnancy abortive of rizatriptan and naproxen (note: there is more data for sumatriptan as it was the initial available molecule in this class) [4]. Susan had begun a course of cognitive behavioral therapy prior to her pregnancy and was often able to use meditation to decrease the pain when she did suffer a migraine. She stabilized with respect to the migraines and had a healthy baby girl at 37 weeks of gestation.
Ten days after the delivery, Susan developed a headache that was identical in description to her typical migraine although the pain was continuous. It was unilateral and throbbing. She had mild nausea and both photophobia and phonophobia. Both NSAIDs and some triptans are considered compatible with breast-feeding. Susan took 400 mg of ibuprofen with 100 mg of sumatriptan and the pain decreased slightly but persisted over the next 3 days. After 72 h, a continuous migraine is classified as status migrainosus. Susan presented to her neurologist and a thorough neurologic exam was normal. She was given an injection of ketorolac and felt better within 30 min.
The subsequent day, the pain returned. She had an MRI/MRV and was found to have a sagittal sinus thrombosis. Susan was admitted to the hospital and after a hypercoagulable screen was drawn, she was started on IV heparin and oral warfarin. Although warfarin is considered safe during breast-feeding, Susan felt more comfortable switching her daughter to formula, and a lactation consultant helped with the transition. Her hypercoagulable screen was negative, and the thrombosis was considered secondary to peripartum hypercoagulability. After 6 months of treatment with warfarin, Susan was able to stop the medication and has done well for 3 years. She was reimaged and the clot had canalized. Susan was counseled that she could have another CVT during a subsequent pregnancy and has chosen to limit her family to one child.
Pregnancy and puerperium are risk for CVT due to prothrombotic state independent of other factors such as infection and cesarean section [5]. Risk increases during the third trimester in particular. One study estimates 12 cases per 100,000 deliveries. During the pregnancy, patients may be treated with low molecular weight heparin; after delivery, the mother may be switched to warfarin [6].
This case illustrates a variation in the normal course of migraine during pregnancy and then a prolonged headache, which raised suspicion for other diagnostic possibilities. Understanding the typical course of migraine in pregnant patients, familiarity with safe treatment options including CBT, and quick recognition of a concerning change in headache duration were instrumental in managing this patient through a worrisome presentation* [7, 8].
Case Two
Barbara is a 28-year-old left-handed teacher with no neurologic history. She is pregnant with her second child and has had an uncomplicated course. Her first pregnancy was significant for hyperemesis gravidarum for which she was admitted to the hospital during the first trimester for intravenous fluids. At 35 weeks gestation, she develops headache, which is global and nonlocalized. She describes pressing throbbing sensation with brief bursts of more severe pain. Her vision is normal and she denies any focal numbness or weakness. The pain responds to acetaminophen. An intermittent headache persists over the next 2 weeks and she notes fatigue and mild nausea. Barbara goes into spontaneous labor at 37 weeks. Five hours into what has been an uncomplicated labor, she has a generalized convulsion, which lasts 60 s. She is treated with intravenous magnesium and lorazepam and a cesarean section is performed. The baby girl has Apgar scores of nine and nine; Barbara does well after the delivery. She has no further seizure activity.
A detailed neurologic exam is performed; examination is entirely normal. Barbara then has an MRI of her brain. She has a right temporal lobe AVM with a small amount of acute blood, and some hemosiderin product representing subacute bleeding as well. The neurologist reviews Barbara’s history. Barbara describes episodes during college of “spacing out” and occasional difficulty with word finding. Of note is that she is left-handed; left-handed people may have dominant right brain function with most speech function located in the right hemisphere, but it is more common for left-handed patients to have dominant left brains or dual brain speech control [9]. The nonspecific headaches that she experienced during the weeks leading up to birth were quite severe at times, but were not prolonged in duration. Again, Barbara had no headache history.
After several weeks postpartum, Barbara underwent resection of the AVM by a vascular neurosurgeon. She was treated with carbamazepine for seizure prophylaxis; of note is that this medication is considered safe during breast-feeding. Her headache had improved and she did not require pain medication. WADA testing was done prior to the surgery. Barbara had word finding difficulty postoperatively but this stabilized over 6 months and she did well.
AVMs are a tangle of arteries and veins connected by fistulas. There is a 3.5 % risk of hemorrhage during pregnancy due to the effects of estrogen. These malformations are most likely to hemorrhage in the fourth decade; they can rupture with devastating effect or hemorrhage in varying amounts [10]. If asymptomatic, the patient can be monitored throughout the pregnancy and surgically treated after. There is a 1–4 % risk of hemorrhage per year. Barbara’s lesion was relatively small and was fairly superficial (temporal tip) and therefore easily accessible. However, the blood products on imaging were consistent with repeat hemorrhage over the weeks leading up to diagnosis and support the theory that increased estrogen during the pregnancy was the most likely cause of bleeding as opposed to increased pressure during labor. Had the lesion been diagnosed earlier, there may have been discussion about treating prior to delivery.
Treatment options include surgery, embolization, and radiosurgery. AVMs are graded based on size, venous drainage, and location within the brain according to the Spetzler-Martin scale [11]. Grade I lesions are those which are small, easily surgically accessible and located in “non-eloquent cortex.” Barbara’s AVM is small and superficial, but, due to bilateral language influence, was a more complicated lesion to approach. Her lesion was discovered in the setting of a first-time seizure; in retrospect, her severe but short-lasting headaches may well have represented micro-hemorrhages.
There is not conclusive data about the risk of hemorrhage during pregnancy. The rate of rehemorrhage may be higher if a woman experiences a bleed during a pregnancy. Barbara’s presentation of seizure during delivery is quite concerning; data does not support higher risk of hemorrhage during vaginal delivery, and it is not clear whether Valsalva increases pressure in the AVM draining veins [12].
Case Three
Janine, a 24-year-old right-handed woman, has no history of headache. She is 10 weeks pregnant; the first trimester has been complicated by weight gain but otherwise normal. Janine had a BMI of 26 prior to the pregnancy. She had struggled to lose weight since she was a teenager. Her primary care physician had worked with her around improving nutrition and increasing exercise; Janine had worked hard to improve her health but despite her efforts, had difficulty consistently monitoring her caloric intake. She stopped using birth control (diaphragm and condoms) 4 months prior to becoming pregnant.
Janine had her first prenatal visit at 10 weeks and told her obstetrician that she was experiencing headaches, which did not respond to acetaminophen. This was a new complaint for her although her mother had migraines. The headaches were perhaps a little worse in the morning and she had global head pain, which improved over the course of the day. Her obstetrician gave her a prescription for butalbital/caffeine/acetaminophen and asked her to check back in 3 weeks. This prescription-only combination is an older formulation for headache. It is class C during pregnancy, and there have been few adverse effects documented on a developing fetus, although it can cause sedation of the baby if used close to the delivery. There are few animal reproductive studies of this formulation. There is a report of an infant who suffered withdrawal seizures after birth; traces of barbiturate were found in the bloodstream (reference here).
In 3 weeks, she returns to see for follow-up. She is having continuous pain and describes blurred vision as well. She is referred to neurology for a headache evaluation.
The neurologist learns that Janine wakes up each day with a severe holocranial headache that is pressing and occasionally throbbing. It remits during the day to some degree but gets worse as Janine become recumbent. She describes a gradual deterioration of her vision to the point where it is difficult for her to read text messages on her iPhone. Janine works on the computer at work, and looking at the screen makes her vision worse. She has some light sensitivity. She then describes a sound of “ocean waves” in her head; the neurologist elicits a description of pulsatile tinnitus with occasional horizontal diplopia with change in position. There is no numbness, weakness, vertigo, phonophobia, or osmophobia. Janine also describes some transient visual obscurations that fade in and out.
Examination in the office is significant only for mild crowding on the optic nerve head, with blurring of disk margins nasally greater than temporally. Otherwise, there is nothing focal or lateralizing, specifically no sixth nerve palsy. The neurologist sends Janine for a non-contrast brain MRI scan after consulting with the obstetrician; the study is normal other than a partially empty sella [13]. Janine then undergoes a lumbar puncture. Opening pressure in the recumbent position is 400. Thirty ccs of fluid are removed; closing pressure is 160. The CSF is sent for routine studies, all of which are normal other than a mildly elevated protein of 60. The subsequent day, Janine reports a greater than 50 % improvement in her headache although it still persists.
She then has a consultation with a neuro-ophthalmologist who finds grade one papilledema with constriction of the visual fields. Janine starts a calorie-restricted low-salt diet. She has gained 20 pounds in the first trimester and despite close follow-up with a dietician, she continues to gain weight at a rate of nearly 2 pounds per week for the next 6 weeks. Her headache worsens and she has a repeat spinal tap with opening pressure of 380. Again, 30 ccs of CSF are withdrawn and she improves. Her weight stabilizes, and she does well with respect to the headache until week 30 when she notes worsening of her vision, return of the pulsatile tinnitus, and increased headache severity. A third lumbar puncture shows opening pressure to be 400 [14].
At this point, the neurologist and obstetrician consult about acetazolamide. This medication is class D and is teratogenic in animal studies; however, there has been little documentation of actual risk and, in some instances, may be an appropriate option with an informed patient especially after 20 weeks [15]. When Janine learns of the potential risks, she declines although her fundi show increasing signs of increased pressure. The neuro-ophthalmologist monitors her carefully; fenestration of the optic nerve sheath can be safely done during pregnancy. A V-P shunt is another option although as the uterus enlarges, the shunt may obstruct. Janine stabilizes symptomatically with respect to the headache. Her vision does not deteriorate. Her weight gain decreases and she has a healthy baby girl at 38 weeks. The headache improves post-delivery, and she decides not to breast-feed the baby. She subsequently starts on acetazolamide at 500 mg twice/day and her vision stabilizes. She begins a supervised liquid diet under the care of the bariatric surgery clinic dietician and is able to lose about 4 pounds each month. The headache gradually resolves completely. Funduscopic examination and visual field tests are stable without requiring further intervention.
IIH is a misnomer in many cases. The name of this disorder has progressed from “pseudotumor cerebri” to “benign intracranial hypertension” to “idiopathic intracranial hypertension.” The patient describes symptoms of increased intracranial pressure without focal lesion on evaluation. Presenting complaint is often headache, which can be quite nonspecific. Pain is often worse in the morning after being recumbent during sleep and will improve with upright posture. The headache may remit for brief periods of time, but generally progresses as the pressure increases. The most concerning complication is visual loss, and it is essential to recognize this disorder prior to what may be permanent visual deterioration. Pulsatile tinnitus is often associated; patients describe the auditory rhythmic sound when asked but may not spontaneously comment on it. There can be transient visual obscurations that often sound much like migraine aura. There is no prodrome or buildup to the headache; rather, it is consistent and often quite severe. The headache may worsen concurrently with weight gain.
Workup includes a thorough evaluation for secondary causes of increased intracranial pressure such as tumor, hemorrhage, or vascular malformation. Classic imaging signs such as “slit-like ventricles” or empty sella are not pathognomic for IIH. There may be flattening of the posterior aspect of the globe that strongly suggests the diagnosis. Lumbar puncture is performed after imaging rules out a mass lesion, and the patient must be recumbent during the procedure. Opening pressure may be quite elevated, as in Janine’s case, and fluid is withdrawn after pressure recording to decrease to about 150–170 mm. There are no specific evidenced treatment protocols for IIH. Often, acetazolamide is used as a cerebral diuretic but a lack of safety evidence consensus during pregnancy exists. There is also debate about whether the diagnosis exists in the absence of papilledema. According to the IHS criteria, it is possible to make the diagnosis of IIH in the absence of papilledema based on CSF pressure in concordance with the headache description. The most serious outcome involves irreversible loss of vision. Steroids can usually safely be used during pregnancy in these patients as a short-term therapy to decrease intracranial pressure while preparing for shunt or optic nerve sheath fenestration. Disability from ongoing headache is concerning as well. Documented adverse effects from IIH on a developing fetus are not described. Weight loss and pain control are the key facets of treatment [16].
Other Secondary Causes of Headache
Although not common, a CNS tumor is another possibility for a headache that begins during pregnancy. While a new onset-seizure may be the presenting symptom, a progressive new and different headache should be carefully evaluated. There may be a focal deficit, such as weakness or clumsiness of a limb, signs of increased intracranial pressure, or seizure, both focal and generalized. One symptom of increased CNS pressure is persistent nausea and vomiting; this is often a component of an otherwise healthy pregnancy and care must be taken to look for other more ominous signs. Gliomas are a common type of CNS tumor and range from low grade (slowly developing) to high grade which are often more primitive and invasive. Studies have demonstrated that gliomas may increase during pregnancy as compared to prepregnancy states. Increased blood volume and fluid retention, as well as hormonal mechanisms, may all play a role.
Treatment depends in multiple factors. Surgery is an option, but may be reserved for tumors that are causing neurologic symptoms and are expanding rapidly on serial imaging. The gestational age of the fetus must also be considered, but a craniotomy and tumor resection can be performed. Radiation and chemotherapy are possible as well, although delaying until the fetus is more mature may minimize the development of teratogenicity.
Postpartum Headaches
Unfortunately, women who suffer from a primary headache disorder often revert to baseline postpartum. In particular, migraines which have improved or disappeared as the pregnancy progresses may recur starting as soon as a few days after delivery. This may be secondary to sleep deprivation or be directly associated with changing hormones. Lengthy labor may also predispose to muscle strain that can trigger tension-type headache. Low CSF pressure headache can be caused if there is an inadvertent dural puncture during epidural anesthesia placement; this can be corrected with a blood patch if necessary.
Secondary headache presenting postpartum should raise concerns of thrombotic events or cerebral hemorrhage. Any headache that is new and different or has focal neurologic features on examination must be promptly evaluated [13].
Headache and Breast-Feeding
Breast-feeding may prolong the decrease in frequency of migraine as it may suppress ovulation. It does not have similar effects on other types of primary headache, however. Triptans, sumatriptan, and zolmitriptan, in particular, are often compatible with breast-feeding; NSAIDs may be another option. LactMed maintains a database of medication risk during breast-feeding which is comprehensive and updated frequently [17].
In summary, most headaches experienced during pregnancy are benign and can be safely managed without fetal harm. The obstetrician must be aware of prepregnancy headache history and patterns and should monitor for increase in frequency and severity. Any change in presentation should prompt further evaluation. Migraineurs are delighted to learn that they may improve significantly during the pregnancy and possibly during breast-feeding as well [18]. Serious headaches may present during gestation and expert guidance is essential in management.
References
1.
Margulis A, Mitchell A, Gilboa S, WErler M, Mittleman M, Glynn R, Hernandez-Diaz S. Use of topiramate in pregnancy and risk of oral clefts. Presented, in abstract form, at the 27th international conference on Pharmacoepidemiology and Therapeutic Risk Management, organized by the International Society for Pharmacoepidemiology, Chicago, 14–17 Aug 2011. These findings were presented at a meeting of the Endocrinologic and Metabolic Drugs Advisory Committee, US Food and Drug Administration, Silver Spring, 22 Feb 2012.
2.
Kvisvik EV, Stovner LJ, Helde G, Bovim G, Linde M. Headache and migraine during p pregnancy and puerperium: the MIGRA-study. J Headache Pain. 2011;12(4):443–51.CrossRefPubMedPubMedCentral
3.
Dixit A, Bhardwaj M, Sharma B. Headache in pregnancy: a nuisance or a new sense? Obstet Gynecol Int. 2012(2012):697697, 11 p.
4.
Marchenko A, Etwel F, Olutunfese O, Nickel C, Koren G, Nulman I. Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis. Headache. 2015;55(4):490–501.CrossRefPubMed
5.
Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke. 2000;31:1274–82.CrossRefPubMed
6.
Piazza G. Cerebral venous thrombosis. Circulation. 2012;125:1704–9.CrossRefPubMed
7.
Kontogiorgi M, Kalodimou V, Kollias S, Exarchos D, Nanas S, Ghiatas A, Routs C. Postpartum fatal cerebral vein thrombosis: a case report and review. Open J Clin Diagnostics. 2012;2:1–3.CrossRef
8.
Gross BA, Du R. Hemorrhage from arteriovenous malformations during pregnancy. Neurosurgery. 2012;71(2):349–55; discussion 355–6.CrossRefPubMed
9.
Stewart CC, Swanson SJ, Sabsevitz DS, Rozman ME, Janecek JK, Binder JR. Predictors of language lateralization in temporal lobe epilepsy. Neuropsychologia. 2014;60:93–102.CrossRefPubMed
10.
Braksick SA, Fugate J. Management of brain arteriovenous malformations. Curr Treat Options Neurol. 2015;17:32.CrossRef
11.
Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg Special Suppl. 2010;112(2):476–83.
12.
Ogilvy CS, Stieg PE, Awad I, Brown Jr RD, Kondziolka D, Rosenwasser R, Young WL, Hademenos G. Recommendations for the management of intracranial arteriovenous malformations. Stroke. 2001;32:1458–71.CrossRefPubMed
13.
Kanal E, Borgstede JP, Barkovich AJ, Bradley WG, Etheridge S, Felmlee JP, et al. American college of radiology white paper on MR safety. AJR Am J Roentgenol. 2002;178:1335–47.CrossRefPubMed
14.
Huna-Baron R, Kupersmith M. Idiopathic intracranial hypertension in pregnancy. J Neurol. 2002;249(8):1078–81.CrossRefPubMed
15.
Lee A, Pless M, Falardeau J, Capozzoli T, Wall M, Kardon R. The use of acetazolamide in idiopathic intracranial hypertension during pregnancy. Am J Ophthalmol. 2005;139(5):855–9.CrossRefPubMed
16.
Dave SB, Subramanian PS. Pseudotumor cerebri: an update on treatment options. J Ophthalmol. 2014;62(10):996–8.
17.
Bar-Oz B, Nulman I, Koren G, Ito S. Anticonvulsants and breast feeding: a critical review. Paediatr Drugs. 2000;2(2):113–26.CrossRefPubMed
18.
Fact sheet. American Migraine Foundation.
19.
McGeeney BE, Friedman DI. Pseudotumor cerebri pathophysiology. Headache. 2014;54(3):445–58.CrossRefPubMed
20.
Agid R, Farb RI. Neuroimaging in the diagnosis of idiopathic intracranial hypertension. Minerva Med. 2006;97(4):365–70.PubMed
21.
Zwinkels H, Dörr J, Kloet F, Taphoorn MJB, Vecht CJ. Pregnancy in women with gliomas: a case-series and review of the literature. J Neurooncol. 2013;115:293–301.CrossRefPubMed
22.
Cady RK. Red flags and comfort signs for ominous secondary headaches. Otolaryngol Clin North Am. 2014;47(2):289–99.CrossRefPubMed
23.
Revell K, Morrish P. Headaches in pregnancy. Obstet Gynaecol. 2014. doi:10.1111/tog.12101.
24.
MacGregor EA. Headache in pregnancy. Neurol Clin. 2012;30(3):835–66, Copyright © 2012 Elsevier Inc.CrossRefPubMed