Consider meningitis in patients with headache and the classic triad of fever, altered mentation, and neck stiffness.19 The source of infection can be viral, bacterial, and less commonly, fungal or parasitic. Have a high index of suspicion for meningitis in those with immunosuppression (particularly acquired immunodeficiency syndrome, human immunodeficiency virus, cancer history, chemotherapy, chronic steroids), which may be associated with more insidious types of meningitis such as Cryptococcus. An LP is indicated for suspected meningitis. If the LP is delayed (e.g., CT, coagulopathy, thrombocytopenia, agitation) and meningitis is strongly suspected, administer antibiotics without delay.25,34 For many patients who are awake, are alert with no evidence of papilledema or focal neurologic deficit, and have no history to suggest immunocompromised state or new-onset seizure, the head CT can be delayed until after the LP.25
Subarachnoid hemorrhage resulting from rupture of an intracranial aneurysm carries only a 50% 30-day survival rate.35,36 Approximately half of survivors have some degree of neurologic impairment. Early detection and appropriate management lead to improved clinical outcome. Only 1% of patients presenting to the ED with headache have subarachnoid hemorrhage. However, 10% to 14% of those complaining of the "worst headache of their life" have subarachnoid hemorrhage.7,8 Acute onset of a severe headache is subarachnoid hemorrhage until proven otherwise.10,11 Inquire about a family history as outlined above.16 Obtain a noncontrast head CT as the first step in evaluation.37 With third–generation CT equipment, CT scan done within 6 hours of headache onset is reported to have a sensitivity of 93% and specificity of 100%, with a negative predictive value of 99.4% and positive predictive value of 100%.38 If head CT is negative for blood but suspicion for subarachnoid hemorrhage is strong, the next step is LP to detect blood or xanthochromia in the cerebrospinal fluid.39 For further discussion, see chapter 166, "Spontaneous Subarachnoid and Intracerebral Hemorrhage." Consultation with a neurologist or neurosurgeon may be appropriate if the history is highly suggestive of subarachnoid hemorrhage, because both the CT and LP can be normal.40,41,42 CT angiogram, magnetic resonance angiogram, MRI with fluid-attenuated inversion recovery/susceptibility-weighted images,43,44 or four-vessel cerebral angiogram may be reasonable.26
SUBDURAL HEMATOMA AND INTRACEREBRAL HEMORRHAGE
Intracranial hemorrhage may occur with or without a history of trauma, in the context of new or progressive headache, with or without associated neurologic deficit. This is particularly important in the elderly, those with chronic alcohol and substance abuse, and patients using antiplatelet and anticoagulant agents. The antiplatelet agent clopidogrel increases the risk of acute intracranial bleeding immediately after trauma, so patients receiving antiplatelet agents and anticoagulants should be screened using head CT, regardless of symptoms. In a prospective trial of patients with blunt head trauma, 12% of those taking clopidogrel and 5.1% of those taking warfarin had acute intracranial hemorrhage noted on their initial CT scan. The risk of delayed intracranial hemorrhage was small in both groups (0 of 296 patients taking clopidogrel and 4 of 687 patients taking warfarin).14
Acute headache with associated vestibular symptoms (vertigo or ataxia) should be considered a cerebellar hemorrhage until proven otherwise. Cerebellar hemorrhages make up approximately 10% of all intracerebral hemorrhages and may require prompt surgical evacuation of the hematoma in order to prevent the rapid progression to severe disability or death.45
Headache in the setting of brain tumor is caused, at least in part, by cerebrospinal fluid flow obstruction and intracranial hypertension.46
Clinical signs and symptoms suggesting brain tumor include abnormal neurologic examination, headache worsened by Valsalva maneuver, headache causing awakening from sleep, seizures, recent cancer diagnosis, or mental status change. Of course, the absence of these features does not exclude the possibility of a brain tumor. MRI with and without gadolinium is the study of choice for detecting brain tumors, but cost and limited access make it unfeasible in many settings. A noncontrast CT will identify large masses and edema associated with large masses, but may fail to identify smaller masses. Evaluate for potential barriers to access of medical care in clinical decision making, because additional imaging may be needed at follow-up.
CEREBRAL VENOUS THROMBOSIS
Cerebral venous thrombosis is a rare, but dangerous, cause of headache. Consider the diagnosis in patients presenting with new headache symptoms, especially in the presence of certain known risk factors. Cerebral venous thrombosis is more common in women, especially in the peripartum period, and in patients with a recent surgical history. It is associated with hypercoagulable states such as use of oral contraceptives, hematologic disorders, factor V Leiden homozygous mutation, protein S or protein C deficiency, and anti–thrombin III deficiency.47 The presentation can vary widely, from a progressive headache developing over days to weeks to, in some instances, a "thunderclap" headache. Similarly, the patient's clinical appearance can be quite benign, especially early on in the course of the illness, or in more severe cases, patients may present with seizures, stroke symptoms, and even coma.48,49
In the presence of abnormal imaging (CT, MRI), focal neurologic deficit, or altered mental status, the diagnosis is made definitively with magnetic resonance venography. Given the rare nature of this diagnosis, it is likely that patients suffering from cerebral venous thrombosis may be undergoing evaluation for other causes of severe headache. An elevated LP opening pressure should raise suspicion of central venous thrombosis in the appropriate clinical setting and prompt further imaging with magnetic resonance venography or consultation with a neurologist.50,51 LP can safely be performed in patients with central venous thrombosis.
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)
Patients with posterior reversible encephalopathy syndrome can present with severe headache, visual changes, seizures, and encephalopathy in the setting of marked blood pressure elevation (usually rapidly developing). It is most common in patients undergoing active treatment with immune-suppressing or modulating medications or chemotherapeutic agents, as well as in patients with end-stage renal disease. Imaging with MRI typically shows evidence of symmetrical vasogenic edema in the occipital area of the brain, although other areas of the brain can be involved. Treatment involves blood pressure control and supportive care.52
REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME
This condition is one of a short list of conditions that can mimic subarachnoid hemorrhage (Table 165-2). Characterized by the occurrence of one or more "thunderclap" headaches, the diagnosis should only be considered when the evaluation for subarachnoid hemorrhage has proven negative. The underlying pathophysiology of the syndrome is poorly understood, but it appears to coexist with a number of other cerebral angiopathies (including posterior reversible encephalopathy syndrome) that are characterized by diffuse cerebral vasospasm. The incidence is greater in women, and the peak age of onset is in the early 40s. Most patients will have more than one thunderclap headache over the course of a few weeks. Severe headache may be the only presenting feature, although some patients can present with seizure or focal neurologic deficit. The key diagnostic feature (multiple areas of cerebral vasoconstriction on cerebral angiography) is most commonly found on follow-up angiography between 2 and 3 weeks after symptom onset.15 In three published series, the rate of permanent neurologic disability was between 6% and 20%. Reversible cerebral vasoconstriction syndrome, although not widely known among nonneurologists, does not appear to be that rare. One prospective case series included 67 patients diagnosed at a single hospital over a 3-year period of data collection.53,54
Initial neuroimaging in these patients may show evidence of non-aneurysmal subarachnoid hemorrhage, ischemic stroke, or intracranial hemorrhage. However, head CT is most commonly normal in these patients. Ultimately, there will be magnetic resonance angiography evidence of cerebral vasoconstriction in all patients, but this may be delayed in appearance. As such, the clinical presentation of thunderclap headache without evidence of subarachnoid hemorrhage should be the main prompt to making this diagnosis or consulting with a neurologist.
Temporal arteritis, also known as giant cell arteritis, is an inflammatory condition affecting the small and medium-sized intracranial and extracranial vessels. Primarily a disease of those >50 years old, its incidence increases with age. In addition to headache, associated symptoms may include fatigue, fever, proximal muscle weakness, jaw claudication, or transient ischemic attack symptoms, especially transient visual loss. Sedimentation rate may be elevated. Check intraocular pressure to exclude glaucoma. Diagnosis is made by the presence of three of the five criteria listed in Table 165-6, with a sensitivity of 93.5% and a specificity of 91.2%.55 Begin treatment with prednisone, 60 milligrams PO daily, to minimize morbidity from visual impairment and stroke. Consult with an ophthalmologist to determine optic nerve function and a rheumatologist. It is important to ensure that there is rapid and appropriate follow-up for patients discharged from the ED, ideally with their primary care provider.
TABLE 165-6American College of Rheumatology Criteria for Diagnosis of Temporal Arteritis ||Download (.pdf) TABLE 165-6 American College of Rheumatology Criteria for Diagnosis of Temporal Arteritis
|Clinical Features ||Comments |
|Age at disease onset ≥50 years || |
|New headache ||Onset or type |
|Temporal artery abnormality || |
Tenderness to palpation of temporal arteries
Decreased pulsation of temporal arteries
|Erythrocyte sedimentation rate ≥50 mm/h ||Westergren method |
|Abnormal artery biopsy (can be done after initiating steroids) || |
Predominance of mononuclear cell infiltration or granulomatous inflammation
Multinucleated giant cells
The most common non–life-threatening headache in the ED is migraine (Table 165-3). Migraine is defined as a headache of moderate to severe intensity that lasts hours (4 to 72 hours on average) and is usually unilateral, pulsatile in quality, typically associated with both photophobia and phonophobia, and generally made worse with physical activity. Migraine can be episodic or chronic and can occur with or without aura. The characteristics of migraine aura vary widely. Among the most common aura symptoms are lightheadedness and visual changes (scotoma and scintillations). Migraines usually start in childhood and peak around age 40 years, with gradual decline thereafter. Prevalence is about 5% for males and 15% to 17% for females.9
Chronic migraine is defined as 5 or more migraine headache days per month over the past 3 months. Migraine sufferers who present to the ED are more likely to be chronic headache sufferers.56,57
There are many effective treatment options for management of migraine headache, based on randomized controlled trials. Triptans are considered first-line abortive therapy for migraine. However, in the ED setting, most patients have failed abortive therapy and require rescue therapy.
Initial treatment consists of IV hydration and repetitive IV treatment with nonsteroidal anti-inflammatory drugs and an antiemetic (Table 165-7). Many combinations are effective. Combination with antihistamine (usually diphenhydramine 25 to 50 milligrams IV) is helpful, because increased histamine levels correlate with migraine attacks, and diphenhydramine can also treat akathisias from antiemetics. Antihistamines alone are not helpful.58
TABLE 165-7Treatment Options for Migraine Headache ||Download (.pdf) TABLE 165-7 Treatment Options for Migraine Headache
|Drug ||Dosing ||Contraindications ||Precautions and Pregnancy Category ||Notes |
|Ketorolac ||30 milligrams IV or IM ||History of peptic ulcer disease (especially in elderly) || |
Pregnancy Category B
Avoid in third trimester
|Prochlorperazine ||5–10 milligrams IV or PR || || |
Pregnancy Category C
|Metoclopramide ||10 milligrams IV || || |
Pregnancy Category B
|Droperidol ||2.5 milligrams IV slow, or 2.5 milligrams IM || || |
Pregnancy Category C
QT interval prolongation and/or torsade de pointes
|Concurrent: diphenhydramine |
|Chlorpromazine ||7.5 milligrams IV || || |
Pregnancy not classified
Pretreat with: normal saline bolus to minimize hypotension
|Magnesium sulfate ||2 grams IV over 30 min || ||Pregnancy Category D but effective in pre-eclampsia and eclampsia ||Nonvalidated |
|Methylprednisolone ||125 milligrams IV or IM || ||Rescue therapy ||Nonvalidated |
|Dexamethasone ||6–10 milligrams IV || ||Rescue therapy ||Adjunctive therapy to reduce recurrence |
|Sumatriptan ||6 milligrams SC || |
Ischemic Heart Disease
Basilar or hemiplegic migraine
|Pregnancy Category C || |
|Dihydroergotamine (DHE) ||1 milligram IV over 3 min || |
Ischemic Heart Disease
Recent sumatriptan use (within 24 h)61
Basilar or hemiplegic migraine
Pregnancy Category X
|Pretreat with antiemetic |
|Valproate ||500 milligrams IV ||Pregnancy ||Pregnancy Category X ||Nonvalidated |
Steroids can be useful to reduce the risk for headache recurrence after ED discharge.59,60
Opiates and barbiturate-containing compounds should not be used routinely for abortive migraine therapy unless other standard treatments fail. Not recommended for routine use are ergotamine and codeine- and tramadol-containing medications, as well as butorphanol and butalbital-containing medications.62,63
In pregnancy, there is scant data on treatment of migraine. In general, triptans are contraindicated; acetaminophen, opioids, or corticosteroids can be used. Metoclopramide (U.S. Food and Drug Administration Category B) may be used. Nonsteroidal anti-inflammatory drugs may be also used until the third trimester. Ergotamines and combination agents with caffeine and isometheptene are absolutely contraindicated in pregnant women.
Upon discharge from the ED, more than half of patients will have some residual headache, and there is an increased rate of recurrence of headache within the first 3 days after discharge.59,60,64 Therefore, a prescription for abortive medications should form part of the discharge plan for patients being discharged from the ED with a diagnosis of migraine. Providers should be familiar with one or two fast-acting triptans (such as sumatriptan, sold as ImitrexTM in the United States, and rizatriptan, sold as MaxaltTM in the United States), as well as combinations of triptans, such as sumatriptan/naproxen (sold as TreximetTM in the United States), or combination drugs, such as MidrinTM (acetaminophen, 325 milligrams/dichloralphenazone, 100 milligrams/isometheptene, 65 milligrams).
Occipital neuralgia is characterized by paroxysms of lancinating pain at the back of the head, in the distribution of the greater and/or lesser occipital nerve. Patients describe the pain as stabbing or electric shock–like in quality, with hypersensitivity in the distribution of the affected nerve. Most cases are attributed to chronic neck tension or unknown causes. However, the condition can be associated with osteoarthritis or degenerative disease of the upper cervical spine. Occipital nerve block typically results in marked improvement of symptoms, and the results can persist for weeks after the injection. The procedure is both diagnostic and therapeutic. The procedure can be performed with ease in any setting and requires minimal expertise.
IDIOPATHIC INTRACRANIAL HYPERTENSION (PSEUDOTUMOR CEREBRI SYNDROME)
Idiopathic intracranial hypertension, also known as pseudotumor cerebri, is most common in obese women. The incidence is 19.3 per 100,000 obese women between the ages of 20 and 44 years and has increased along with the obesity epidemic. The most prominent symptoms include headache (84%), transient visual obscurations (68%), back pain (53%), and pulsatile tinnitus (52%). Only 32% of patients report visual loss. Untreated, idiopathic intracranial hypertension can lead to permanent visual impairment if not recognized and treated appropriately.65
The diagnostic criteria include papilledema with an otherwise normal neurologic examination and elevated opening pressure on LP (>25 cm H2O in adults and >28 cm H2O in children), in the setting of normal cerebrospinal fluid composition and normal imaging (having excluded other causes of raised intracranial pressure). Treatment is focused on preservation of vision. A variant of pseudotumor has been identified that does not present with papilledema but may present with the other clinical features of pseudotumor cerebri, along with abducens nerve palsy (unilateral or bilateral). In the absence of either papilledema or abducens nerve palsy, the diagnosis of pseudotumor without papilledema can be made if at least three of the following neuroimaging findings are present: empty sella, flattening of the posterior aspect of the globe, distention of the perioptic subarachnoid space with or without a tortuous optic nerve, and transverse venous sinus stenosis.66
LP is necessary to make the diagnosis of idiopathic intracranial hypertension, and concomitant removal of a volume of cerebrospinal fluid can provide temporary relief of symptoms. However, subjective improvement of symptoms after LP is not reliable in establishing the diagnosis.66 Perform the LP with the patient in the lateral decubitus position, without sedation (which may cause mild hypercapnia and, subsequently, an elevated cerebrospinal fluid pressure measurement). The knees should be extended for measurement of cerebrospinal fluid pressure, and the base of the manometer should be level with the right atrium. Elevated cerebrospinal fluid pressures can occur in the setting of the Valsalva maneuver, such as breath holding and crying, and if the pressure is measured in the sitting position. Cerebrospinal fluid can be removed in multiple aliquots, measuring cerebrospinal fluid pressure after each removal, until a target pressure of 15 to 20 cm H2O is achieved. Determine the opening pressure. In general, removal of 1 mL of cerebrospinal fluid will lower the cerebrospinal fluid pressure by about 1 cm H2O.67 To avoid lowering the pressure excessively, first remove 1 mL for every 1 cm H2O reduction desired, and then remeasure cerebrospinal fluid pressure. Excess cerebrospinal fluid removal can result in intracranial hypotension and a "low-pressure headache," which may require epidural blood patch for relief.
Oral acetazolamide can be effective in lowering intracranial pressure and decreasing the symptoms of idiopathic intracranial hypertension. Treatment is typically started at 250 to 500 milligrams twice a day.68 The dose can be increased to as much as 4 grams/d, but dose escalation is associated with significant side effects (paresthesias, fatigue, decreased libido, metallic taste) and should be done under the supervision of a neurologist or ophthalmologist for ongoing monitoring of papilledema and visual field testing to minimize the risk of visual loss.69 Long-term interventional management may include cerebrospinal fluid shunting and optic nerve sheath fenestration for failing vision. For obese patients, weight loss is recommended.69
The headache of intracranial hypotension (low-pressure headache) is most commonly associated with recent dural penetration, either during LP, epidural anesthesia, or any operative procedure that involves opening the dura. Using a noncutting needle reduces the risk of post-LP headache.70 Rarely, intracranial hypotension can occur spontaneously or in association with head or spine trauma.71,72,73 Clinical features include headache that increases in severity with upright posture but improves or resolves in the supine position. Associated symptoms, such as alterations in hearing or vision, nausea, vomiting, diplopia, and visual changes, may occur. MRI, with and without contrast, confirms the diagnosis by showing diffuse enhancement of the meninges. The LP, if performed, should have an opening pressure <6 cm H2O. Most patients experience spontaneous resolution of their symptoms. Evidence to support treatments, including IV fluid resuscitation and IV caffeine, is limited. The most effective therapy for low-pressure headache is an epidural blood patch, typically performed by anesthesiologists.71,74
About 5% to 10% of patients with cancer develop leptomeningeal metastases. In addition to headache, cranial nerve abnormalities (typically more than one) and other neurologic findings may be present. Risk factors for carcinomatous meningitis include aggressive lymphoma subtypes and uncontrolled systemic disease. In suspected patients, the appropriate testing would include MRI with and without contrast (to evaluate for meningeal enhancement). Obtain MRI before LP because MRI evidence of meningeal enhancement is common after LP and may confound the diagnosis. LP may reveal an elevated opening pressure (>20 cm H2O). Cerebrospinal fluid analysis should include cytology (solid tumors) or flow cytometry (hematologic tumors). Malignant cells degrade quickly, so timely review of cerebrospinal fluid is important.75
Cluster headaches (Table 165-4) occur in about 0.4% of the general population and can mimic dental pain. More common in men, cluster headaches typically start in adulthood and tend to occur in "clusters," with a circadian and circannual pattern, recurring daily for more than a week and remitting for at least 4 weeks. Episodes are typically unilateral and excruciating, but brief and self-limited. Up to 10% of patients will experience a more chronic form, with fewer episodes of remission. Associated ipsilateral symptoms are common (Table 165-4), and a distinguishing feature of this headache is the need for the patient to "pace," in contrast to the patient with migraine, who prefers to lie still in a quiet and dark room. Treatment consists of 100% oxygen administered at 12 L/min for 15 minutes through a nonrebreathing facemask.76,77 Sumatriptan, 6 milligrams SC, can also be used.
There is no compelling evidence linking mild to moderate hypertension with headache. Several studies using ambulatory blood pressure monitoring have found no association between mild to moderate high blood pressure (systolic blood pressure <180 mm Hg and/or diastolic blood pressure <120 mm Hg) and patient self-reported headache.78 Uncontrolled hypertension can be associated with headache, especially in conditions where there is a rapid and marked rise in blood pressure, such as pheochromocytoma, posterior reversible encephalopathy syndrome,20 hypertensive crisis, pre-eclampsia, and eclampsia.78
METABOLIC CAUSES OF HEADACHE
Metabolic headaches are hallmarked by deterioration in the setting of a disorder of homeostasis and typically improve after resolution of the disorder of homeostasis (Table 165-8).78
TABLE 165-8Metabolic Causes of Headache ||Download (.pdf) TABLE 165-8 Metabolic Causes of Headache
|History ||Examples ||Treatment |
|Hypoxia/hypercapnia || |
Congestive heart failure
Acetazolamide 125–250 milligrams twice a day
Prophylaxis: acetylsalicylic acid, 320 milligrams at 4-h intervals, starting 1 h prior to ascent; repeat 3 times
Nonsteroidal anti-inflammatory drugs (NSAIDs), pseudoephedrine, and nasal decongestants
|Dialysis || ||NSAIDs/analgesics during dialysis |
|Autonomic dysreflexia (typical in quadriplegia) || || |
Scrutinize for bladder distension/bowel impaction
|Other || |
Cardiac cephalgia (associated with myocardial ischemia)
Coital headache, also known as orgasmic headache, is a thunderclap headache that occurs at orgasm. Coital headache is considered benign with no specific treatment needed. Recovery is complete. However, the diagnosis is one of exclusion, to ensure that other causes of thunderclap headache are not missed, including subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome.79 The clinical diagnosis of coital headache is one of exclusion and cannot be made without imaging. If MRI is unavailable or not clinically feasible, consultation with radiology regarding other appropriate imaging modalities is prudent.26
Valsalva maneuver may trigger thunderclap headache, a diagnosis made when the headache is only associated with cough, straining, or a Valsalva maneuver, with normal neuroimaging. Symptomatic cough headache is the diagnosis made when an underlying pathology (usually a type I Chiari malformation) is likely to be the cause of the headache.80
Pituitary tumor apoplexy is a rare clinical diagnosis, that is usually due to spontaneous hemorrhage or infarction of a preexisting pituitary adenoma.81 The earliest symptom is sudden, severe headache. The headache location tends to be retro-orbital, bifrontal, or suboccipital. Between 63% and 100% of patients will experience headache.81 Associated symptoms may include ophthalmoplegia, reduced visual acuity, visual field defects, altered consciousness, meningismus, and nausea and vomiting. CT (noncontrast) and MRI may show a sellar mass and hemorrhage. In the first 1 to 2 hours, the hyperacute hemorrhage may be easier to see on CT than MRI. Pituitary adenomas and cerebral aneurysms have a co-occurrence rate of 7.4%.81 Pituitary tumor apoplexy requires immediate treatment with corticosteroids and urgent neurosurgical consultation. The treatment usually requires consultations from endocrinology, ophthalmology, and neurology with intensive care monitoring.
THIRD VENTRICLE COLLOID CYSTS
Colloid cysts of the third ventricle are a rare cause of acute neurologic deterioration and sudden death. The colloid cyst is usually congenital, slow growing, and benign, accounting for about 0.2% to 2% of all intracranial tumors, but it is the most common tumor of the third ventricle.82 The usual clinical presentation is a history of severe paroxysmal and episodic attacks of (typically frontal) headache associated with nausea and vomiting. The presumptive cause is the intermittent obstruction of cerebrospinal fluid flow through the foramina of Monro with associated rapid increase in intracranial pressure.83
Classic features of purulent nasal discharge, nasal or facial congestion, hyposomia, or anosmia with or without fever, along with headache, ear pain or fullness, halitosis, and dental pain, allow for clinical diagnosis of sinusitis,84 and treatment with antibiotics is warranted.