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A 38-year-old multigravid woman presents to the delivery suite with severe headache at 30 weeks gestation. She is type 2 diabetic and has a history of migraine. What must you not miss when assessing her and how would you manage a case of severe headache in the third trimester of pregnancy?
a Headache is extremely common during pregnancy. As many as ten per cent of cases of primary headache syndrome initially present, or are first diagnosed, during gestation.1 Among pregnant women with new or atypical headache: one-third have migraine, one-third have pre-eclampsia/eclampsia-related headache and the remaining one-third have a variety of other causes of headache, such as intracranial haemorrhage, cerebral venous thrombosis and so forth.2,3 The incidence of subarachnoid haemorrhage (SAH) is 1–5/10000 pregnancies. Maternal mortality is 30–40 per cent; however, rates as high as 80 per cent have been reported.4 Cerebral venous thrombosis is rare, but occurs more commonly in association with pregnancy.5
Even though headache is common in pregnancy, it could be the first manifestation of a life-threatening condition. Hence, very careful and prompt assessment to lead to proper diagnosis is of utmost importance in the management of these patients.
The aim of assessment of severe headache in third trimester is to rule out the uncommon, but potentially sinister, causes while establishing a diagnosis. One should be mindful of the so-called red flags6:
- sudden onset of severe headache;
- significant changes in the pattern of chronic headache;
- new-onset migrainous headaches;
- neurologic signs and symptoms;
- changes in patient’s level of consciousness, personality or cognition;
- headache precipitated or exacerbated by Valsalva’s manoeuvres;
- associated with fever;
- meningeal signs;
- history of recent trauma to head/neck;
- hypertension or endocrine disease; and
When assessing headache, as with any pain, the quality, location, severity, time, course and exacerbating or relieving factors should be fully evaluated. Ask for any associated neurological symptoms, such as numbness, tingling, loss or alteration in sensations or movements. Enquire about systemic disturbances, such as fever, nausea, vomiting, skin rash; and rule out medication overuse/withdrawal, any drug being given for pre-existing headache. Clinical examination should start with blood pressure, a complete neurological examination and a brief general physical examination, with particular attention paid to: throat and sinuses; stiffness of neck; fever; ear, nose and throat; and eye examination, including fundoscopy. The level of consciousness and cognitive ability should be assessed during history taking and examination. Evaluation should always include the clinical assessment of fetal wellbeing while investigating a cause for the mother.
With a history suggestive of migraine headaches, a normal neurological examination and resolution with simple measures, the patient may be followed clinically.4 The nature and extent of investigation is tailored to the clinical possibilities revealed during detailed history taking and clinical examination. Blood should be taken for complete blood count, renal and liver function tests and coagulation screening; and urine for protein creatinine ratio if clinical assessment points towards pre-eclampsia/eclampsia. An imaging study of the brain is an essential if an intracranial pathology is suspected. At this stage, simultaneous consultation with a neurophysician and a transfer to tertiary hospital either for diagnostic imaging facilities and/or for fetal consideration is essential. A noncontrast head computed tomography (CT) scan is typically the first diagnostic study. However, magnetic resonance imaging (MRI) is safe during pregnancy. In general, MRI is preferable to CT for assessing non-traumatic or non-hemorrhagic craniospinal pathology, such as oedema, vascular disease, mass lesions or local infection. MR venogram is the standard for detecting venous thrombosis. In a review of pregnant patients receiving neuroimaging, the most common imaging studies obtained were MR brain without contrast (87 per cent) and MR angiography head without contrast (73 per cent). The majority of patients (96 per cent) delivered in the third trimester without significant complications.7 Radiation exposure to the fetus with head CT, cerebral angiography and chest x-ray is approximately 50, 10, and 1mrad, respectively and these levels are considered safe.
Table 1. Causes of headache relevant in pregnancy from the international classification of headache disorder (ICHD-II).
|Primary headache||Migraine, tension headache|
|Secondary headache||Post head and neck injury|
|Vascular disorder (imminent eclampsia, SAH, acute ischaemic stroke)|
|Non-vascular intracranial disorders (idiopathic intracranial hypertension, tumours)|
|Drug withdrawal headache (substance abuse: alcohol, caffeine, cocaine, tobacco)|
|Disorder of homeostasis (hypoglycemia, hypoxia)|
|Disorders of cranial structures (toothache, jaw pain, sinusitis)|
|Psychiatric (anxiety, depression, insomnia)|
|Neuralgias (trigeminal, Bell’s palsy)|
A lumbar puncture should be performed following neuroimaging if increased intracranial pressure or infection is suspected. It may become necessary if a small subarachnoidal haemorrhage (SAH) is missed by CT/MRI brain. Further investigations that may be required are echocardiography, carotid doppler studies, peripheral blood smear, HIV screen, antinuclear antibody and laboratory evaluation for inherited or acquired thrombophilia.
Migraine is often unilateral, throbbing or pulsatile quality can be associated with nausea, vomiting, photophobia or phonophobia during attacks. Most women (60–70 per cent) with a history of migraine have improvement over the course of pregnancy, approximately five per cent describe worsening, and the remainder have no change. There is also increasing body of evidence supporting association of migraine, pregnancy induced hypertension and pre-eclampsia. When primary headache such as migraine presents as severe headache, pharmacological treatment generally includes use of simple agents such as acetaminophen, narcotics for severe cases or short course adjuvant glucocorticoids for refractory cases. Nonsteroidal anti-inflammatory drugs should generally be avoided in the third trimester. Although use of triptan is generally avoided, it can be given in severe cases not responding to other treatments. Human experience with triptan exposure during pregnancy has been generally reassuring.8
The cause of headache in severe pre-eclampsia/eclampsia is not known, but may be related to increased cerebral perfusion pressure (for example, hypertensive encephalopathy)9, cerebral ischemia from vasoconstriction, posterior reversible encephalopathy syndrome (PRES), cerebral oedema, or microhaemorrhages. Maternal mortality rates for eclamptic women have been reported to be 0–14 per cent in last few decades, and are higher in poor countries. The most common cause of death in eclamptic women is brain ischemia or haemorrhage.6 The goals of management of severe pre-eclampsia/eclampsia or HELLP syndrome are to stabilise the mother, prevent recurrent convulsions, treat severe hypertension to reduce or prevent cerebral oedema and haemorrhage, and initiate prompt delivery. Plasma exchange is the treatment of choice for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) occurring during pregnancy.
Stroke in pregnant or postpartum women is rare, however, risk is increased compared with non-pregnant age-matched controls, especially in late pregnancy and early puerperium. Recent evidence suggests that the rate of strokes occurring during pregnancy and postpartum are increasing, substantially for intracranial haemorrhage and cerebral venous sinus thrombosis.6 The primary cause of intracranial haemorrhage/SAH during gestation is ruptured cerebral aneurysms (most commonly occurs in the third trimester) or arteriovenous malformations.4,10 The classical presentation of SAH is the sudden onset of sever incapacitating headache, neck rigidity and collapse. Management is by interdisciplinary care with neurosurgeons and indications for neurosurgery are as for non-pregnant patients.
The incidence of pregnancy-associated ischemic stroke is 3–4/100,000/yr.4 Women with hypertension, diabetes mellitus, tobacco use, hyperlipidemia, sickle cell disease or antiphospholipid antibody syndrome are at risk. Management is by multidisciplinary team care, using aspirin and anticoagulation with heparin. The efficacy and safety of thrombolytic therapy for acute ischemic stroke in pregnant women is unknown.
The incidence of cerebral venous sinus thrombosis is 0.7– 24/100,000 deliveries6 and accounts for three to 57 per cent of pregnancy-related stroke reported by small retrospective studies. Clinical manifestations consist of diffuse, often severe headache, vomiting, focal or generalised seizure, confusion, blurred vision, focal neurologic deficits, and altered consciousness. The mainstay for the treatment is anticoagulation with heparin.
For women who have a stroke at between 28 and 32 weeks gestation, antenatal glucocorticoids can be administered to accelerate fetal lung maturation. A multidisciplinary approach in consultation with neurology, neurosurgery, anesthesia, neonatology and perinatology should be undertaken to stabilise the mother and assess fetal status. As long as maternal and fetal wellbeing are not deteriorating, plans can be made to continue the pregnancy with a scheduled controlled delivery between 34 and 39 weeks gestation to optimise fetal outcome.
Despite headache being a common symptom in pregnancy, in the case of severe headache in the third trimester potentially catastrophic medical conditions associated with maternal and perinatal mortality and morbidity always need to be excluded. The obstetric care providers need to be vigilant of red-flag signs to ensure prompt diagnosis and safe management of these patients.
- Melhado EM, Maciel JA Jr, Guerreiro CA. Headache during gestation: evaluation of 1101 women. Can J Neurol Sci 2007; 34:187.
- Contag SA, Bushnell C. Contemporary management of migrainous disorders in pregnancy. Curr Opin Obstet Gynecol 2010; 22:437.
- Marcus DA. Managing headache during pregnancy and lactation. Expert Rev Neurother 2008; 8:385.
- David K James, Philip J Steer, Carl P Weiner and Bernard Gonik High Risk Pregnancy, page 1061-1097, Elsevier 3rd edition.
- Jeng JS, Tang SC, Yip PK. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis 2004; 18:290.
- Jonathan A Edlow, Louis R Caplan, Karen O’Brien, Carrie D Tibbles. Diagnosis of acute neurological emergencies in pregnant and post-partum women, Lancet Neurol 2013; 12: 175–85.
- Semere LG, McElrath TF, Klein AM. Neuroimaging in pregnancy: A review of clinical indications and obstetric outcomes. J Matern Fetal Neonatal Med. August 6, 2012. (doi:10.3109/14767058.2012.713053).
- Belfort MA, Saade GR, Grunewald C, et al. Association of cerebral perfusion pressure with headache in women with pre-eclampsia. Br J Obstet Gynaecol 1999; 106:814.
- Michael A Belfort, George R Saade, Michael R Foley, Jeffrey P Phelan, Gary A Dildy Critical Care Obstetrics, Wiley Blackwell 5th edition.
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