Review Article Address correspondence to Dr Todd J. Schwedt, Mayo Clinic Arizona, 5777 East Mayo Boulevard #5E, Phoenix, AZ 85054, [email protected]. Relationship Disclosure: Dr Schwedt has served as a consultant for Allergan, Inc; Pfizer Inc; Supernus Pharmaceuticals, Inc; and Zogenix, Inc, and received paid travel accommodations/ meeting expenses from the American Headache Society. Dr Schwedt receives royalties from Cambridge University Press and UpToDate, Inc. Unlabeled Use of Products/Investigational Use Disclosure: Dr Schwedt reports no disclosure. * 2015, American Academy of Neurology.
Thunderclap Headache Todd J. Schwedt, MD, FAAN ABSTRACT Purpose of Review: A thunderclap headache is a very severe headache that reaches its maximum intensity within 1 minute. Patients with thunderclap headache must be evaluated emergently and comprehensively to rule out underlying disorders that can be associated with high mortality and morbidity, determine the cause for the thunderclap headache, and initiate targeted therapy. This review presents an up-to-date summary on the clinical presentation, diagnostic evaluation, and causes of thunderclap headache. Recent Findings: Numerous etiologies for thunderclap headaches have been identified, with the most common causes being subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome. Other relatively common causes include cervical artery dissection, cerebral venous sinus thrombosis, and spontaneous intracranial hypotension. Although ‘‘primary’’ thunderclap headache is typically accepted to exist, it may be that such cases represent missed diagnoses of underlying causes. The urgent evaluation of the patient with thunderclap headache includes brain CT, followed by lumbar puncture if the brain CT is nondiagnostic. If a diagnosis is not reached following brain CT and lumbar puncture, brain MRI and imaging of the brain and cervical vasculature are indicated. Summary: Patients with thunderclap headache require an emergent and comprehensive evaluation to identify the underlying cause and to initiate appropriate therapy. Continuum (Minneap Minn) 2015;21(4):1058–1071.
INTRODUCTION ‘‘Thunderclap headache’’ refers to a headache that is very severe and has abrupt onset, reaching maximum intensity in less than 1 minute.1 A thunderclap headache is typically described by patients as an apoplectic event, one that clearly stands out from other types of headaches they may have previously experienced. Patients with thunderclap headache often liken the sensation to an explosion in their head or being struck in the head. It is essential to recognize that a thunderclap headache is not defined solely by its high-intensity pain, but also by the rapidity with which it reaches maximum intensity. A thunderclap headache is a medical emergency that requires urgent evaluation for its underlying cause. Because it is associated with high rates of morbidity and mortality, subarachnoid hemorrhage (SAH) must be the foremost consideration. However, if SAH is not
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present, other causes of the thunderclap headache must be sought (Table 8-1). This article discusses the clinical presentation of patients with thunderclap headache, the diagnostic approach to the patient with thunderclap headache, and causes for thunderclap headache. CLINICAL PRESENTATION Differentiation of a thunderclap headache from other headache types is essential for the appropriate diagnostic evaluation to be initiated. Although missed diagnoses of thunderclap headaches likely pose the greatest threat, overdiagnoses can lead to unnecessary tests, adverse effects from such tests, and unnecessary patient worry. Thunderclap headaches can be differentiated from other severe headaches, such as migraine or cluster, by the rapidity with which they reach their maximum intensity. However, thunderclap headaches cannot be differentiated from
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KEY POINTS a TABLE 8-1 Causes of Thunderclap Headache
h ‘‘Thunderclap headache’’ refers to a headache that is very severe and has abrupt onset, reaching maximum intensity in less than 1 minute.
b Most Common Causes of Thunderclap Headache Reversible cerebral vasoconstriction syndrome Subarachnoid hemorrhage
h A thunderclap headache
b Less Common Causes of Thunderclap Headache
is a medical emergency that requires urgent evaluation for its underlying cause.
Cerebral infection Cerebral venous sinus thrombosis Cervical artery dissection Complicated sinusitis Hypertensive crisis Intracerebral hemorrhage Ischemic stroke Spontaneous intracranial hypotension Subdural hematoma b Uncommon Causes of Thunderclap Headache Aqueductal stenosis Brain tumor Cardiac cephalgia Giant cell arteritis Pituitary apoplexy Pheochromocytoma Retroclival hematoma Spontaneous spinal epidural hematoma Third ventricle colloid cyst b Possible Causes of Thunderclap Headacheb Primary or idiopathic thunderclap headache Unruptured intracranial aneurysm a
b
Although the exact incidence of each cause of thunderclap headache is not well defined, certain causes of thunderclap headache are more common than others based upon how often they present with thunderclap headache and the incidence of the condition itself. For example, although pituitary apoplexy might commonly present with thunderclap headache, as pituitary apoplexy is an uncommon condition, it is an unlikely cause of a patient’s thunderclap headache. Controversy exists as to whether unruptured intracranial aneurysms can cause thunderclap headache and whether a truly primary or idiopathic thunderclap headache exists.
other headache types based solely upon the intensity of the headache. Although any headache that stands out from previously experienced headaches because of its greater severity is worrisome and might Continuum (Minneap Minn) 2015;21(4):1058–1071
trigger diagnostic testing, unless the headache reached maximum intensity quite quickly, it is not a thunderclap headache. Regardless of the cause of a thunderclap headache, patients can present www.ContinuumJournal.com
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Thunderclap Headache KEY POINTS
h Recurrent thunderclap headaches over several days to weeks are suggestive of reversible cerebral vasoconstriction syndrome.
h Following the history, a general physical examination and neurologic examination, all patients with thunderclap headache should have brain CT without contrast.
h The sensitivity of brain CT for detecting subarachnoid hemorrhage declines as the interval between the hemorrhage and the CT lengthens.
h If brain CT does not reveal the etiology for the thunderclap headache, lumbar puncture is indicated.
with thunderclap headache alone or with additional symptoms or signs. Through the clinical interview, physical examination, and neurologic examination, the clinician should assess for altered level of consciousness, visual symptoms, papilledema, meningismus, fever, tinnitus, auditory muffling, Horner syndrome, hypertension, orthostatic worsening of the headache, seizures, and focal neurologic deficits such as focal weakness and sensory disturbance. Certain historical features, symptoms, and signs that are present in a patient with thunderclap headache might raise the clinician’s level of suspicion for certain underlying causes. For example, a thunderclap headache associated with altered level of consciousness, seizures, or focal neurologic symptoms and signs could suggest an SAH, other intracranial hemorrhages, hypertensive crisis, cervical artery dissection, ischemic stroke, reversible cerebral vasoconstriction syndrome (RCVS) associated with posterior reversible encephalopathy syndrome (PRES), or cerebral venous sinus thrombosis. Recurrent thunderclap headaches over several days to weeks are suggestive of RCVS. Some patients with aneurysmal SAH might experience what has been referred to as a sentinel headache, a thunderclap headache days or weeks prior to their diagnosed SAH, while a thunderclap headache followed by orthostatic headaches and auditory muffling is consistent with spontaneous intracranial hypotension. However, it is not possible to determine the cause of a thunderclap headache with certainty based on clinical symptoms alone. DIAGNOSTIC EVALUATION OF THE PATIENT WITH THUNDERCLAP HEADACHE All patients with thunderclap headache need to be evaluated emergently, beginning with the patient’s history, a general physical examination, and a neurologic examination.
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General Evaluation of the Patient With Thunderclap Headache Following history, physical examination, and neurologic examination, all patients with thunderclap headache should have brain CT without contrast. Brain CT may detect several potential causes of thunderclap headache and is an essential component of the evaluation for SAH. Brain CT should be performed as soon as possible after the onset of a thunderclap headache, as its sensitivity for detecting an SAH declines as the interval between the hemorrhage and the CT lengthens. Using modern-day CT scanners and with images interpreted by highly trained radiologists, published studies have reported that the sensitivity of CT for detecting an aneurysmal SAH when the CT is performed within 6 hours of symptom onset is between 92% and 100%.2Y6 However, the sensitivity of CT for detecting SAH falls relatively rapidly as the interval between symptom onset and CT lengthens: about 85% to 95% on day 2, about 75% on day 3, and about 50% after 5 days.2,7 In addition to evaluating for SAH, brain CT might identify findings associated with other causes of thunderclap headache, including other intracranial hemorrhages, ischemic stroke, cerebral venous sinus thrombosis, brain tumor, complicated sinusitis, and third ventricle colloid cyst. If brain CT does not reveal the etiology for the thunderclap headache, lumbar puncture (LP) is indicated. Although brain CT has very high sensitivity for detecting SAH when performed early after the onset of thunderclap headache, its sensitivity is not 100%. A diagnosis of SAH cannot be overlooked, and the LP helps to evaluate for SAH and other causes of thunderclap headache. To expedite the evaluation of a patient with thunderclap headache, LP should be performed as soon as possible after the brain CT. However, the sensitivity of CSF analyses for detection of an SAH is higher if the
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LP is performed at least 6 hours, preferably 12 hours, after SAH onset.8 This relationship between timing and sensitivity must be considered when interpreting results. However, LP should not be delayed, because of the risk of a second aneurysmal rupture within 24 hours. In addition, even if an LP is done early and found to be unremarkable, noninvasive neurovascular imaging will be required and should exclude the presence of a symptomatic intracranial saccular aneurysm. LP should include measurement of opening pressure, cell counts with differential in tube 1 and tube 4, protein, glucose, closing pressure, and visual inspection for xanthochromia. Other studies, such as testing for CNS infections, should be ordered when indicated. Spectrophotometry for xanthochromia, if available, has high sensitivity for detection of SAH when CSF is obtained between 12 hours and 2 weeks after the SAH.9,10 Patients who have thunderclap headache with nondiagnostic brain CT and LP should be further evaluated with contrast-enhanced brain MRI and noninvasive vascular imaging of the head and neck (eg, magnetic resonance angiography [MRA], CT angiography [CTA]). Venoussinus imaging via magnetic resonance venography or CT venography might be indicated depending upon the clinical suspicion for an underlying cerebral venous sinus thrombosis. Specific Findings With the Most Common Causes of Thunderclap Headache Table 8-2 lists specific diagnostic findings for the most common causes of thunderclap headache. Aneurysmal subarachnoid hemorrhage. Given the very high rates of mortality and morbidity associated with aneurysmal SAH, SAH is the diagnosis of first consideration in a patient with a thunderclap headache. Approximately 70% of patients with SAH present with Continuum (Minneap Minn) 2015;21(4):1058–1071
headache as a main symptom; 50% present with thunderclap headache, and SAH is found in up to 25% of patients with thunderclap headache.11 Although no symptoms or signs are highly specific for an eventual diagnosis of SAH, the absence of certain symptoms in patients with normal neurologic examinations does highly suggest that an SAH has not occurred. In a multicenter Canadian emergency department study of 132 patients with SAH who had headache peaking within 1 hour (not the definition for a thunderclap headache) and normal neurologic examinations, the following features yielded a sensitivity of 98.5% (95% confidence interval of 94.6% to 99.6%) for an eventual diagnosis of SAH: age 40 years or older, neck pain or stiffness, witnessed loss of consciousness, or onset during exertion.12 However, the presence of these features were not specific for SAH (27.5% specificity, 95% confidence interval of 25.6% to 29.5%). Adding thunderclap headache and limited neck flexion on examination increased the sensitivity for SAH to 100% (95% confidence interval of 97.2% to 100%), while decreasing the specificity to 15.3% (95% confidence interval of 13.8% to 16.9%). Brain CT typically reveals the location and severity of the SAH and associated complications, such as intraparenchymal extension, hydrocephalus, and brain edema.13 SAH from aneurysmal rupture must be differentiated from a cortical SAH that can be seen with RCVS. Aneurysmal SAH is typically seen within the sylvian fissures and basal cisterns, while SAH from RCVS is seen in the hemispheric convexities (Figure 8-1).14 The cortical SAH from RCVS is associated with less severe neurologic presentations than aneurysmal SAH.14 In patients with thunderclap headache, CSF analysis is performed following a nondiagnostic brain CT. Approximately 2% to 15% of patients with thunderclap headache with normal brain CT scans
KEY POINTS
h Patients who have thunderclap headache with nondiagnostic brain CT and lumbar puncture should be further evaluated with contrast-enhanced brain MRI and noninvasive vascular imaging of the head and neck.
h Approximately 70% of patients with subarachnoid hemorrhage present with headache as a main symptom; 50% present with thunderclap headache, and subarachnoid hemorrhage is found in up to 25% of patients with thunderclap headache.
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TABLE 8-2 Diagnostic Findings for the More Common Causes of Thunderclap Headache Clinical Features
Cause Aneurysmal subarachnoid hemorrhage
Brain CT
Altered consciousness, Subarachnoid seizures, meningismus blood in basilar cisterns and sylvian fissures
Reversible cerebral Recurrent thunderclap Normal, headaches subarachnoid vasoconstriction blood along syndrome cortical surface/sulci
Lumbar Puncture
Angiography
Brain MRI
Elevated red blood cells, xanthochromia
Ruptured aneurysm, vasospasm
Subarachnoid blood in basilar cisterns and sylvian fissures
Multifocal Normal, mild white blood cell multivessel vasoconstriction elevation, mild protein elevation
Normal
Normal, subarachnoid blood along cortical surface/sulci, ischemic stroke, cerebral edema, intracerebral hemorrhage
Dissected artery, Normal, ischemic stroke multifocal, segmental vasoconstriction if associated with reversible cerebral vasoconstriction syndrome
Carotid and vertebral artery dissection
Neck pain, symptoms related to cerebral ischemia, Horner syndrome (carotid dissection)
Normal, ischemic stroke
Cerebral venous sinus thrombosis
Focal neurologic deficits, altered mental status, visual changes
Elevated opening Venous sinus Dense triangle thrombosis sign (clot inside pressure, high protein the sinus), cord sign (thrombosed cortical or deep vein), venous hemorrhages
Spontaneous intracranial hypotension
Orthostatic headache, Normal, subdural Low opening auditory muffling collections pressure
Normal
Normal, venous infarctions with hemorrhage; MRI evidence of intraluminal thrombus on T1, T2, and susceptibilityweighted imaging sequences Pachymeningeal enhancement, sagging brain, subdural collections
CT = computed tomography; MRI = magnetic resonance imaging.
who are ultimately diagnosed with aneurysmal SAH have evidence for SAH on CSF analysis.15 The CSF diagnosis of SAH is made via measurement of red blood cells in tube 1 and tube 4, visual inspection of the CSF for xanthochromia, and spectrophotometry (if available). In contrast to a traumatic LP, red blood cell counts in
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tube 4 should be similar to or higher than tube 1 in patients with SAH. Spectrophotometry is useful, when available, as it has a sensitivity of 98% for detecting SAH when performed between 12 hours and 2 weeks after symptom onset.16 Brain MRI fluid-attenuated inversion recovery (FLAIR) and gradient echo/
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KEY POINT
h Brain MRI is an important tool for the evaluation of patients suspected to have SAH who present for evaluation several days after symptom onset.
Axial noncontrast CTs showing aneurysmal subarachnoid hemorrhage versus cortical subarachnoid hemorrhage. A, Extensive blood within the basilar cisterns, a typical finding of aneurysmal subarachnoid hemorrhage. B, A small amount of subarachnoid blood (arrows) along the cortex of the postcentral gyrus, a finding that can be consistent with the nonaneurysmal cortical subarachnoid hemorrhage seen in up to one-third of patients with reversible cerebral vasoconstriction syndrome.
FIGURE 8-1
susceptibility-weighted images are very sensitive for detecting SAH.17,18 Brain MRI is considered to be equally as sensitive as brain CT for detecting SAH within the acute phase and more sensitive than CT after the acute phase.19 Thus, brain MRI is an important tool for the evaluation of patients suspected to have SAH who present for evaluation several days after symptom onset. Angiography is required in patients with aneurysmal SAH to determine the site and morphology of the aneurysm and guide treatment. Although catheter angiography is still considered the gold standard, MRA or CTA may be considered for the initial angiographic evaluation. MRA and CTA on modern scanners have high sensitivity for detecting aneurysms, especially those larger than 3 mm.20,21 If the site of the aneurysm is not detected by noninvasive angiography in a patient with aneurysmal SAH, intra-arterial catheter angiography is indicated. Angiography is also useful for detecting vasospasm that might occur secondary to SAH. The vasospasm of SAH must be differentiated Continuum (Minneap Minn) 2015;21(4):1058–1071
from the vasoconstriction of RCVS. Both the vasoconstriction of RCVS and the vasospasm of aneurysmal SAH can be delayed findings, being maximal several days to 1 week after aneurysmal SAH and up to 3 weeks following onset of RCVS. The vasospasm of aneurysmal SAH is confined to the blood vessels in the area of the SAH, while the vasoconstriction of RCVS involves multiple arteries, often including vessels in both hemispheres and in both the anterior and posterior circulation.14 Reversible cerebral vasoconstriction syndrome. RCVS presents with thunderclap headache(s) with or without other symptoms, no aneurysmal SAH, normal or near-normal CSF, and multifocal vasoconstriction of cerebral arteries that normalizes within 12 weeks of onset.22 Table 8-3 lists diagnostic criteria for RCVS.22,23 A pattern of recurrent thunderclap headaches (between 2 and 10 thunderclap headaches) over approximately 1 to 2 weeks is very suggestive of RCVS.23Y25 Individual thunderclap headaches are often provoked by activities such as www.ContinuumJournal.com
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Thunderclap Headache KEY POINT
h Reversible cerebral vasoconstriction syndrome may be associated with cortical subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, cerebral edema, and cervical artery dissection.
Cerebral TABLE 8-3 Diagnostic Criteria for Reversible Vasoconstriction Syndromesa b Thunderclap headache(s) with or without focal neurologic deficits or seizures b Monophasic course without new symptoms more than 1 month after initial onset of symptoms b Multifocal, multivessel, segmental vasoconstriction of cerebral arteries b Absence of aneurysmal subarachnoid hemorrhage b Normal or near-normal CSF Protein less than 100 mg/dL White blood cells less than 15 per mm3 Glucose normal b Complete or substantial normalization of cerebral arteries within 12 weeks of symptom onset CSF = cerebrospinal fluid. a Data from Calabrese LH, et al, Ann Intern Med,22 annals.org/article.aspx?articleid=477594, Ducros A, Lancet Neurol. 23 www.thelancet.com/journals/laneur/article/PIIS14744422(12)70135-7/fulltext.
urinating, bathing/showering, bending, Valsalva, and sexual activity and by strong emotions (eg, anger).26,27 However, since patients with thunderclap headache are often evaluated after their first thunderclap headache, a high index of suspicion for RCVS should be present after a single thunderclap headache. RCVS can present with thunderclap headache only or may be accompanied by other symptoms, such as a continuous mild to moderate headache, nausea, vomiting, photophobia, phonophobia, cognitive dysfunction, alterations in consciousness, seizures, transient focal neurologic deficits, and permanent neurologic deficits from ischemic or hemorrhagic stroke. As illustrated in Case 8-1, RCVS tends to affect women who are in their fourth and fifth decades of life. Risk factors for development of RCVS may include female sex, being postpartum, use of marijuana, binge alcohol drinking, use of serotonergic and sympathomimetic substances (eg, antidepressants, stimulants, cold medicines), and migraine.
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Brain CT and brain MRI are normal in 30% to 70% of patients with RCVS.27 RCVS is associated with brain imaging abnormalities such as cortical SAH in 22% to 34%, intracerebral hemorrhage in 6% to 20%, ischemic stroke in 4% to 39%, and cerebral edema such as that seen in PRES in 9% to 38%.25,28,29 As discussed in the SAH section earlier in this article, it is important to differentiate a cortical SAH related to RCVS from an aneurysmal SAH. LP is normal or near normal in RCVS. Mild elevations in white blood cell counts (less than 15 per mm3) and protein (less than 100 mg/dL) are possible with RCVS. Other CSF measurements should be normal. Angiography reveals multifocal vasoconstrictions of multiple intracranial arteries in a ‘‘string of beads’’ appearance (Figure 8-2). Vasoconstrictions are maximal at about 2 to 3 weeks after symptom onset.28 Since vasoconstriction might start distally and move more proximally during the first several weeks after symptom onset, vascular imaging performed early
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Case 8-1 A 45-year-old woman presented to the emergency department after she developed a very severe, 10/10 intensity occipital headache that started and reached maximal intensity instantaneously. She stated that the headache felt like a bomb went off in her head. The very intense pain lasted for about 5 minutes, and since that time she had a moderate 5/10 intensity holocephalic aching headache. The patient reported that she had two headaches quite similar to her current one within the last week, but she did not previously seek medical attention. She had otherwise felt in her usual state of health. The patient had a history of episodic migraine and depression. She stated that her current headaches were not similar to her usual migraine attacks as her current headaches were more severe and peaked very quickly. The patient had been on a selective serotonin reuptake inhibitor (SSRI) for the previous 6 months for treatment of mild depression, and she had taken over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) intermittently over the last week for treatment of her current headaches. She occasionally smoked marijuana, did not use any other illicit drugs, and infrequently drank alcohol. Her vital signs were normal other than a mildly elevated blood pressure at 145/92, and her physical and neurologic examinations were normal. Brain CT without contrast was normal. Lumbar puncture was normal other than a mildly elevated white blood cell count at 8 per mm3 and a mildly elevated protein at 60 mg/dL. Brain MRI with gadolinium was normal. Brain magnetic resonance angiogram (MRA) showed multifocal areas of vasoconstriction in bilateral cerebral arteries including the middle cerebral arteries, anterior cerebral arteries, and posterior cerebral arteries. Cervical MRA was normal. The patient was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS), started on verapamil 80 mg 3 times a day, and instructed to discontinue the SSRI and marijuana use. With this therapy, she did not have any recurrent thunderclap headaches, and her MRA showed resolution of the vasoconstriction 12 weeks after symptom onset. Comment. This patient with thunderclap headache has several features that increase the suspicion for RCVS, including: (1) presenting with recurrent thunderclap headaches; (2) personal history of migraine; (3) use of a serotonergic medication; (4) use of marijuana; (5) normal brain CT and brain MRI; (6) mild elevation in CSF white blood cell count and protein; and (7) angiography showing vasoconstriction that is multifocal and bilateral. Normalization of the intracranial vasoconstriction is required before a definite diagnosis of RCVS can be assigned.
after the onset of symptoms might be normal. When clinical suspicion for RCVS is high despite normal vasculature on angiography performed early after the onset of symptoms, repeat vascular imaging after several weeks is indicated in search of vasoconstriction. Of note, the angiographic appearance of RCVS is similar to that of primary angiitis of the CNS (also known as primary CNS vasculitis). However, primary angiitis of the CNS has more of an indolent clinical presentation (not presenting with thunderclap headache); CSF analysis reveals greater elevations in white blood cell count and protein than those seen in Continuum (Minneap Minn) 2015;21(4):1058–1071
RCVS, and brain MRI is nearly always abnormal, showing multiple white matter hyperintensities on T2 and FLAIR sequences and ischemic strokes of different ages and in different vascular territories.30 Internal carotid and vertebral artery dissections. Internal carotid artery and vertebral artery dissections can present with thunderclap headache. In a large series of patients with spontaneous internal carotid or vertebral artery dissections, headache was present at clinical presentation in about 70% of patients.31,32 Thunderclap headaches are present in 9.2% of patients with vertebral artery dissections and 3.6% of patients with
KEY POINT
h When clinical suspicion for reversible cerebral vasoconstriction syndrome is high despite normal vasculature on angiography performed early after the onset of symptoms, repeat vascular imaging after several weeks is indicated in search of vasoconstriction.
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FIGURE 8-2
Angiographic appearance of reversible cerebral vasoconstriction syndrome. Numerous areas of vasoconstriction (arrows) are apparent within the anterior (A) and posterior (B) circulation on magnetic resonance angiography. Normalization of the intracranial arteries is seen 10 weeks later (C, D).
internal carotid artery dissections.32 Patients typically have symptoms and signs in addition to headache. Neck pain is present in about 66% of those with vertebral artery dissection and 33% of those with internal carotid artery dis-
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section.31,32 Symptoms related to cerebral ischemia (eg, stroke, transient ischemic attack) are present in 84% to 90% of patients with vertebral artery dissection, and symptoms related to cerebral or retinal ischemia (eg, stroke, transient
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ischemic attack, amaurosis fugax) are present in 70% to 73% of patients with internal carotid artery dissection. Horner syndrome is present in 47.2% of patients with internal carotid dissection. Some patients with cervical artery dissections also have RCVS. In a single institution’s experience with 173 patients with RCVS and 285 patients with cervical artery dissection, 20 of the patients were found to have both.33 Other cases of RCVS and carotid or vertebral artery dissection are reported in the literature. The nature of the relationship between RCVS and cervical artery dissection is not clear. It is possible that one condition leads to the other or that they have a shared underlying etiology. Brain CT and LP will often be normal in the patient presenting with thunderclap headache due to internal carotid or vertebral artery dissection. It is possible that ischemic stroke secondary to the dissection may be seen on CT, and SAH associated with the dissection should be detected on brain CT or CSF analysis. MRI of the brain, MRI of the neck with fat saturation technique, and MRA are often necessary for detecting the dissection and secondary complications. Cerebral venous sinus thrombosis. At least two-thirds of patients with cerebral venous sinus thrombosis present with headaches.34 Cerebral venous sinus thrombosis most commonly presents with a subacute onset of chronic daily headache. However, about 5% of patients with cerebral venous sinus thrombosis present with a thunderclap headache.34 Although 25% of patients with cerebral venous sinus thrombosis present with headache alone, the majority of patients present with additional features such as abnormal neurologic examinations, papilledema, altered mental status, seizures, and focal neurologic deficits.35Y37 Some patients may present with the clinical features of idiopathic intracranial hypertension Continuum (Minneap Minn) 2015;21(4):1058–1071
(ie, headache, papilledema, visual field loss). The diagnosis of cerebral venous sinus thrombosis is made by imaging of the cerebral venous sinus system, typically via magnetic resonance venography or computed tomographic venography. However, there may be clues for the diagnosis on brain CT (eg, dense triangle sign, cord sign, venous infarctions with hemorrhages), LP (eg, elevated opening pressure, high protein), and brain MRI (eg, suggestion of clot on T1-weighted, T2weighted, and susceptibility-weighted imaging sequences; venous infarctions with hemorrhage).38 Spontaneous intracranial hypotension. The hallmark feature of spontaneous intracranial hypotension is an orthostatic headache, a headache that is worsened when a person is upright (standing or sitting) and relieved when lying down (Case 8-2). However, about 15% of patients with spontaneous intracranial hypotension initially present with a thunderclap headache.39 In addition to headache, common symptoms of spontaneous intracranial hypotension include auditory muffling, tinnitus, nausea, vomiting, neck stiffness, dizziness, and visual changes. Brain MRI with contrast reveals diffuse, smooth, and continuous pachymeningeal enhancement in patients with spontaneous intracranial hypotension. Other brain MRI findings include cerebellar tonsil and optic chiasmal descent, flattening of the anterior pons and tectum, pituitary enlargement, and dilation/engorgement of the cerebral venous sinuses. Subdural fluid collections (hematomas or hygromas), easily identified on CT or brain MRI, may be found in some patients with spontaneous intracranial hypotension.40 Spine MRI might show extra-arachnoid spinal fluid collections coursing along the cervical, thoracic, or lumbar spine; venous engorgement; and nerve root sleeve diverticula.
KEY POINTS
h Although cerebral venous sinus thrombosis most commonly presents with a subacute onset of chronic daily headache, about 5% of patients present with a thunderclap headache.
h The hallmark feature of spontaneous intracranial hypotension is an orthostatic headache, a headache that is worsened when a person is upright and relieved when lying down. However, about 15% of patients with spontaneous intracranial hypotension initially present with a thunderclap headache.
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Case 8-2 A 50-year-old man presented to the outpatient clinic reporting a very severe headache that had started 3 days prior. He reported that he was in his usual state of health that day until he had the sudden onset of a very intense headache that felt like he was ‘‘hit over the head.’’ He stated that he had never felt such severe pain. The most intense pain lasted for about 10 minutes and then slowly lessened. He presented to an emergency department, where he had a normal examination, a normal brain CT, and normal CSF studies. Opening and closing pressures were not measured. He was treated with pain medications and discharged from the emergency department. Since his discharge, he had continued to have a headache that was continuous but substantially worse when he was upright and relieved somewhat when he lay down. Because of the orthostatic component to his headache, he had spent most of his time in bed. In addition to headache, he reported a muffled sensation in the ears as if he were underwater. The patient had no pertinent past medical history and did not take any medications. His vital signs, physical examination, and neurologic examination were normal. The patient’s symptoms were felt to be most consistent with intracranial hypotension. However, it was not clear if the intracranial hypotension was spontaneous, initially presenting with a thunderclap headache, or if the intracranial hypotension was due to the lumbar puncture (LP) and the thunderclap headache had a different cause. Thus, contrast-enhanced MRI of the brain and magnetic resonance angiogram (MRA) of the brain and neck were ordered to evaluate for other causes of the thunderclap headache. MRA of the brain and neck were normal. Brain MRI showed diffuse pachymeningeal enhancement, low-lying cerebellar tonsils, and flattening of the anterior pons (Figure 8-3). The patient was successfully treated with an autologous lumbar epidural blood patch without recurrence of symptoms.
FIGURE 8-3
MRI appearance of intracranial hypotension. A, Sagittal noncontrast T1-weighted image showing cerebellar tonsillar descent (arrowhead) and flattening of the anterior pons (arrows). B, Axial postgadolinium T1-weighted image showing diffuse pachymeningeal enhancement (arrows).
Comment. This patient with thunderclap headache has several features that are consistent with a diagnosis of intracranial hypotension: (1) orthostatic headache; (2) auditory muffling; and (3) brain MRI showing pachymeningeal enhancement, cerebellar tonsil descent, and flattening of the anterior pons. However, since LP is part of the routine initial evaluation of patients with thunderclap headache, it will often be unclear if the thunderclap headache was due to spontaneous intracranial hypotension or if the intracranial hypotension is secondary to the LP. In this situation, other causes for the thunderclap headache must be considered prior to attributing the thunderclap headache to spontaneous intracranial hypotension.
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For more information, refer to the article ‘‘Spontaneous Intracranial Hypotension’’ by Bahram Mokri, MD, FAAN, . in this issue of Other Causes of Thunderclap Headache Numerous other causes of thunderclap headache exist (Table 8-1). When evaluating the patient with thunderclap headache, the clinician must initially consider the possible causes associated with the greatest risk to the patient (eg, SAH, intracerebral hemorrhage). The prevalence of each disorder and how often each one presents with thunderclap headache should also be considered. Aneurysmal SAH and RCVS account for the majority of secondary thunderclap headache cases. Other conditions rarely present with thunderclap headache but are relatively common conditions, such as cerebral infections and hypertensive crisis. Others commonly present with thunderclap headache but are quite rare, such as pituitary apoplexy. Finally, the headaches associated with cough, exercise, and sexual activity might initially be indistinguishable from a thunderclap headache and thus necessitate the thunderclap headache evaluation. Although headaches provoked by cough, exercise, and sexual activity might be primary headaches, typically it is not possible to differentiate primary cough headache, primary exercise headache, and primary headache associated with sexual activity from secondary headaches based upon clinical symptoms alone.41,42 Therefore, diagnostic evaluations are needed to rule out underlying causes, including, but not limited to, SAH, RCVS, arterial dissection, intracranial hypotension, Chiari malformation, middle cranial fossa tumors, and posterior fossa tumors.41,42 Once determined to be primary in nature, headaches associated with cough, exercise, and sexual activity are comContinuum (Minneap Minn) 2015;21(4):1058–1071
monly responsive to treatment with indomethacin. An evaluation that includes efficient collection of clinical history, vital signs, physical and neurologic examination, brain CT, and LP will adequately investigate for the potential causes of thunderclap headache that require emergent treatment. However, if a diagnosis is not reached after this initial investigation, additional testing with contrast-enhanced brain MRI and noninvasive vascular imaging is necessary to investigate for other causes of thunderclap headache.
KEY POINT
h Aneurysmal subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome account for the majority of secondary thunderclap headache cases.
Unruptured Aneurysms and Thunderclap Headache It is not uncommon to encounter a patient with thunderclap headache and an unruptured intracranial aneurysm. This might be by chance alone, since unruptured intracranial aneurysms are found in 3% to 6% of the general population, or might be due to a causal relationship.43 Of patients who have an aneurysmal SAH, 10% to 43% retrospectively report having had a thunderclap headache within days to weeks prior to their SAH, a headache that has been termed a warning or sentinel headache.44 A sentinel headache might be due to a small amount of blood seepage from the aneurysm or due to structural changes (eg, stretching or thinning) in the aneurysm wall or the wall of the artery adjacent to the aneurysm. Since the nature of the relationship between thunderclap headache and an unruptured intracranial aneurysm is difficult to determine, patients with thunderclap headaches with unruptured intracranial aneurysms should be evaluated for other potential causes of the thunderclap headache. The decision of whether to treat the unruptured aneurysm should be based on current guidelines for the management of unruptured intracranial aneurysms. For patients who do not undergo aneurysm treatment, close follow-up is indicated. www.ContinuumJournal.com
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CONCLUSION A thunderclap headache is a very severe headache that reaches maximum intensity in less than 1 minute, often nearly instantaneously. Although numerous causes for thunderclap headache exist, SAH and RCVS seem to be the most common. Patients with thunderclap headache need to be evaluated emergently. Following efficient collection of the medical history, vital signs, and general physical and neurologic examinations, noncontrast brain CT should be performed. If the CT is nondiagnostic, LP is required. If a diagnosis cannot be reached after CT and LP, brain MRI with contrast and imaging of the cerebral and cervical arteries is recommended. REFERENCES 1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33(9):629Y808. doi:10.1177/0333102413485658. 2. Backes D, Rinkel GJ, Kemperman H, et al. Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage. Stroke 2012;43(8):2115Y2119. doi:10.1161/ STROKEAHA.112.658880. 3. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage? J Emerg Med 2005;29(1):23Y27. 4. Byyny RL, Mower WR, Shum N, et al. Sensitivity of noncontrast cranial computed tomography for the emergency department diagnosis of subarachnoid hemorrhage. Ann Emerg Med 2008;51(6):697Y703. doi:10.1016/j.annemergmed.2007.10.007. 5. Gee C, Dawson M, Bledsoe J, et al. Sensitivity of newer-generation computed tomography scanners for subarachnoid hemorrhage: a Bayesian analysis. J Emerg Med 2012;43(1):13Y18. doi:10.1016/ j.jemermed.2011.09.012. 6. Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid
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haemorrhage: prospective cohort study. BMJ 2011;343:d4277. doi:10.1136/bmj.d4277. 7. van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology 1982;23(3):153Y156. 8. van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;124(pt 2):249Y278. 9. Cruickshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45(pt 3):238Y244. doi:10.1258/acb.2008.007257. 10. Wood MJ, Dimeski G, Nowitzke AM. CSF spectrophotometry in the diagnosis and exclusion of spontaneous subarachnoid haemorrhage. J Clin Neurosci 2005;12(2):142Y146. 11. Ducros A, Bousser MG. Thunderclap headache. BMJ 2013;346:e8557. doi:10.1136/bmj.e8557. 12. Perry JJ, Stiell IG, Sivilotti ML, et al. Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA 2013;310(12):1248Y1255. doi:10.1001/jama.2013.278018. 13. Moore SA, Rabinstein AA, Stewart MW, et al. Recognizing the signs and symptoms of aneurysmal subarachnoid hemorrhage. Expert Rev Neurother 2014;14(7):757Y768. doi:10.1586/14737175.2014.922414. 14. Muehlschlegel S, Kursun O, Topcuoglu MA, et al. Differentiating reversible cerebral vasoconstriction syndrome with subarachnoid hemorrhage from other causes of subarachnoid hemorrhage. JAMA Neurol 2013;70(10):1254Y1260. 15. Schwedt TJ. Thunderclap headaches: a focus on etiology and diagnostic evaluation. Headache 2013;53(3):563Y569. doi:10.1111/ head.12041. 16. Vermeulen M, Hasan D, Blijenberg BG, et al. Xanthochromia after subarachnoid hemorrhage needs no revisitation. J Neurol Neurosurg Psychiatry 1989;52(7):826Y828. 17. Mitchell P, Wilkinson ID, Hoggard N, et al. Detection of subarachnoid haemorrhage with magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2001;70(2):205Y211. 18. Verma RK, Kottke R, Andereggen L, et al. Detecting subarachnoid hemorrhage: comparison of combined FLAIR/SWI versus CT. Eur J Radiol 2013;82(9):1539Y1545. doi:10.1016/j.ejrad.2013.03.021.
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19. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet 2007;369(9558):306Y318.
the vertebral artery. Stroke. 2013;44(6): 1537Y1542. doi:10.1161/STROKEAHA.113.001057.
20. Li MH, Li YD, Tan HQ, et al. Contrast-free MRA at 3.0 T for the detection of intracranial aneurysms. Neurology 2011;77(7):667Y676. doi:10.1212/WNL.0b013e3182299f5a.
33. Mawet J, Boukobza M, Franc J, et al. Reversible cerebral vasoconstriction syndrome and cervical artery dissection in 20 patients. Neurology 2013;81(9):821Y824. doi:10.1212/WNL.0b013e3182a2cbe2.
21. Westerlaan HE, van Dijk JM, Jansen-van der Weide MC, et al. Intracranial aneurysms in patients with subarachnoid hemorrhage: CT angiography as a primary examination tool for diagnosisVsystematic review and meta-analysis. Radiology 2011;258(1):134Y145. doi:10.1148/radiol.10092373. 22. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med 2007;146(1):34Y44. 23. Ducros A. Reversible cerebral vasoconstriction syndrome. Lancet Neurol 2012;11(10):906Y917. doi:10.1016/S1474-4422(12)70135-7. 24. Chen SP, Fuh JL, Lirng JF, et al. Recurrent primary thunderclap headache and benign CNS angiopathy: spectra of the same disorder? Neurology 2006;67(12):2164Y2169. 25. Ducros A, Boukobza M, Porcher R, et al. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain 2007;130(pt 12):3091Y3101. 26. Ducros A. L37. Reversible cerebral vasoconstriction syndrome: distinction from CNS vasculitis. Presse Med 2013;42(4 pt 2): 602Y604. doi:10.1016/j.lpm.2013.01.037. 27. Ducros A. Reversible cerebral vasoconstriction syndrome. Handb Clin Neurol 2014;121:1725Y1741. doi:10.1016/B978-0-7020-4088-7.00111-5. 28. Chen SP, Fuh JL, Wang SJ, et al. Magnetic resonance angiography in reversible cerebral vasoconstriction syndromes. Ann Neurol 2010;67(5):648Y656. doi:10.1002/ana.21951. 29. Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction syndromes analysis of 139 cases. Arch Neurol 2011;68(8): 1005Y1012. doi:10.1001/archneurol.2011.68. 30. Singhal AB, Topcuoglu MA, Caviness VS, et al. Call-fleming syndrome versus isolated cerebral vasculitis: MRI lesion patterns. Stroke 2003;34:264. 31. Debette S, Grond-Ginsbach C, Bodenant M, et al. Differential features of carotid and vertebral artery dissections: the CADISP Study. Neurology 2011;77(12):1174Y1181. doi:10.1212/WNL.0b013e31822f03fc. 32. von Babo M, De Marchis GM, Sarikaya H, et al. Differences and similarities between spontaneous dissections of the internal carotid artery and Continuum (Minneap Minn) 2015;21(4):1058–1071
34. Wasay M, Kojan S, Dai AI, et al. Headache in cerebral venous thrombosis: incidence, pattern and location in 200 consecutive patients. J Headache Pain 2010;11(2):137Y139. doi:10.1007/s10194-010-0186-3. 35. Cumurciuc R, Crassard I, Sarov M, et al. Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J Neurol Neurosurg Psyschiatry 2005;76(8):1084Y1087. 36. de Bruijn SF, de Haan RJ, Stam J. Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients. For the Cerebral Venous Sinus Thrombosis Study Group. J Neurol Neurosurg Psyschiatry 2001;70(1):105Y108. 37. Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42(4):1158Y1192. doi:10.1161/STR.0b013e31820a8364. 38. Ferro JM, Canh~ ao P. Cerebral venous sinus thrombosis: update on diagnosis and management. Curr Cardiol Rep 2014; 16(9):523. doi:10.1007/s11886-014-0523-2. 39. Schievink WI, Wijdicks EF, Meyer FB, Sonntag VK. Spontaneous intracranial hypotension mimicking aneurysmal subarachnoid hemorrhage. Neurosurgery 2001;48(3):513Y516. 40. Lai TH, Fuh JL, Lirng JF, et al. Subdural haematoma in patients with spontaneous intracranial hypotension. Cephalalgia 2007;27(2):133Y138. 41. Alvarez R, Ramon C, Pascual J. Clues in the differential diagnosis of primary vs. secondary cough, exercise, and sexual headaches. Headache 2014;54(9):1560Y1562. doi:10.1111/head. 42. Halker RB, Vargas BB. Primary exertional headache: updates in the literature. Curr Pain Headache Rep 2013;17(6):337. doi:10.1007/s11916-013-0337-8. 43. Wardlaw JM, White PM. The detection and management of unruptured intracranial aneurysms. Brain 2000;123(pt 2):205Y221. 44. Polmear A. Sentinel headaches in aneurysmal subarachnoid haemorrhage: what is the true incidence? A systematic review. Cephalalgia 2003;23(10):935Y941. www.ContinuumJournal.com
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Thunderclap Headache Todd J. Schwedt, MD, FAAN ABSTRACT Purpose of Review: A thunderclap headache is a very severe headache that reaches its maximum intensity within 1 minute. Patients with thunderclap headache must be evaluated emergently and comprehensively to rule out underlying disorders that can be associated with high mortality and morbidity, determine the cause for the thunderclap headache, and initiate targeted therapy. This review presents an up-to-date summary on the clinical presentation, diagnostic evaluation, and causes of thunderclap headache. Recent Findings: Numerous etiologies for thunderclap headaches have been identified, with the most common causes being subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome. Other relatively common causes include cervical artery dissection, cerebral venous sinus thrombosis, and spontaneous intracranial hypotension. Although ‘‘primary’’ thunderclap headache is typically accepted to exist, it may be that such cases represent missed diagnoses of underlying causes. The urgent evaluation of the patient with thunderclap headache includes brain CT, followed by lumbar puncture if the brain CT is nondiagnostic. If a diagnosis is not reached following brain CT and lumbar puncture, brain MRI and imaging of the brain and cervical vasculature are indicated. Summary: Patients with thunderclap headache require an emergent and comprehensive evaluation to identify the underlying cause and to initiate appropriate therapy. Continuum (Minneap Minn) 2015;21(4):1058–1071.
INTRODUCTION ‘‘Thunderclap headache’’ refers to a headache that is very severe and has abrupt onset, reaching maximum intensity in less than 1 minute.1 A thunderclap headache is typically described by patients as an apoplectic event, one that clearly stands out from other types of headaches they may have previously experienced. Patients with thunderclap headache often liken the sensation to an explosion in their head or being struck in the head. It is essential to recognize that a thunderclap headache is not defined solely by its high-intensity pain, but also by the rapidity with which it reaches maximum intensity. A thunderclap headache is a medical emergency that requires urgent evaluation for its underlying cause. Because it is associated with high rates of morbidity and mortality, subarachnoid hemorrhage (SAH) must be the foremost consideration. However, if SAH is not
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present, other causes of the thunderclap headache must be sought (Table 8-1). This article discusses the clinical presentation of patients with thunderclap headache, the diagnostic approach to the patient with thunderclap headache, and causes for thunderclap headache. CLINICAL PRESENTATION Differentiation of a thunderclap headache from other headache types is essential for the appropriate diagnostic evaluation to be initiated. Although missed diagnoses of thunderclap headaches likely pose the greatest threat, overdiagnoses can lead to unnecessary tests, adverse effects from such tests, and unnecessary patient worry. Thunderclap headaches can be differentiated from other severe headaches, such as migraine or cluster, by the rapidity with which they reach their maximum intensity. However, thunderclap headaches cannot be differentiated from
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KEY POINTS a TABLE 8-1 Causes of Thunderclap Headache
h ‘‘Thunderclap headache’’ refers to a headache that is very severe and has abrupt onset, reaching maximum intensity in less than 1 minute.
b Most Common Causes of Thunderclap Headache Reversible cerebral vasoconstriction syndrome Subarachnoid hemorrhage
h A thunderclap headache
b Less Common Causes of Thunderclap Headache
is a medical emergency that requires urgent evaluation for its underlying cause.
Cerebral infection Cerebral venous sinus thrombosis Cervical artery dissection Complicated sinusitis Hypertensive crisis Intracerebral hemorrhage Ischemic stroke Spontaneous intracranial hypotension Subdural hematoma b Uncommon Causes of Thunderclap Headache Aqueductal stenosis Brain tumor Cardiac cephalgia Giant cell arteritis Pituitary apoplexy Pheochromocytoma Retroclival hematoma Spontaneous spinal epidural hematoma Third ventricle colloid cyst b Possible Causes of Thunderclap Headacheb Primary or idiopathic thunderclap headache Unruptured intracranial aneurysm a
b
Although the exact incidence of each cause of thunderclap headache is not well defined, certain causes of thunderclap headache are more common than others based upon how often they present with thunderclap headache and the incidence of the condition itself. For example, although pituitary apoplexy might commonly present with thunderclap headache, as pituitary apoplexy is an uncommon condition, it is an unlikely cause of a patient’s thunderclap headache. Controversy exists as to whether unruptured intracranial aneurysms can cause thunderclap headache and whether a truly primary or idiopathic thunderclap headache exists.
other headache types based solely upon the intensity of the headache. Although any headache that stands out from previously experienced headaches because of its greater severity is worrisome and might Continuum (Minneap Minn) 2015;21(4):1058–1071
trigger diagnostic testing, unless the headache reached maximum intensity quite quickly, it is not a thunderclap headache. Regardless of the cause of a thunderclap headache, patients can present www.ContinuumJournal.com
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Thunderclap Headache KEY POINTS
h Recurrent thunderclap headaches over several days to weeks are suggestive of reversible cerebral vasoconstriction syndrome.
h Following the history, a general physical examination and neurologic examination, all patients with thunderclap headache should have brain CT without contrast.
h The sensitivity of brain CT for detecting subarachnoid hemorrhage declines as the interval between the hemorrhage and the CT lengthens.
h If brain CT does not reveal the etiology for the thunderclap headache, lumbar puncture is indicated.
with thunderclap headache alone or with additional symptoms or signs. Through the clinical interview, physical examination, and neurologic examination, the clinician should assess for altered level of consciousness, visual symptoms, papilledema, meningismus, fever, tinnitus, auditory muffling, Horner syndrome, hypertension, orthostatic worsening of the headache, seizures, and focal neurologic deficits such as focal weakness and sensory disturbance. Certain historical features, symptoms, and signs that are present in a patient with thunderclap headache might raise the clinician’s level of suspicion for certain underlying causes. For example, a thunderclap headache associated with altered level of consciousness, seizures, or focal neurologic symptoms and signs could suggest an SAH, other intracranial hemorrhages, hypertensive crisis, cervical artery dissection, ischemic stroke, reversible cerebral vasoconstriction syndrome (RCVS) associated with posterior reversible encephalopathy syndrome (PRES), or cerebral venous sinus thrombosis. Recurrent thunderclap headaches over several days to weeks are suggestive of RCVS. Some patients with aneurysmal SAH might experience what has been referred to as a sentinel headache, a thunderclap headache days or weeks prior to their diagnosed SAH, while a thunderclap headache followed by orthostatic headaches and auditory muffling is consistent with spontaneous intracranial hypotension. However, it is not possible to determine the cause of a thunderclap headache with certainty based on clinical symptoms alone. DIAGNOSTIC EVALUATION OF THE PATIENT WITH THUNDERCLAP HEADACHE All patients with thunderclap headache need to be evaluated emergently, beginning with the patient’s history, a general physical examination, and a neurologic examination.
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General Evaluation of the Patient With Thunderclap Headache Following history, physical examination, and neurologic examination, all patients with thunderclap headache should have brain CT without contrast. Brain CT may detect several potential causes of thunderclap headache and is an essential component of the evaluation for SAH. Brain CT should be performed as soon as possible after the onset of a thunderclap headache, as its sensitivity for detecting an SAH declines as the interval between the hemorrhage and the CT lengthens. Using modern-day CT scanners and with images interpreted by highly trained radiologists, published studies have reported that the sensitivity of CT for detecting an aneurysmal SAH when the CT is performed within 6 hours of symptom onset is between 92% and 100%.2Y6 However, the sensitivity of CT for detecting SAH falls relatively rapidly as the interval between symptom onset and CT lengthens: about 85% to 95% on day 2, about 75% on day 3, and about 50% after 5 days.2,7 In addition to evaluating for SAH, brain CT might identify findings associated with other causes of thunderclap headache, including other intracranial hemorrhages, ischemic stroke, cerebral venous sinus thrombosis, brain tumor, complicated sinusitis, and third ventricle colloid cyst. If brain CT does not reveal the etiology for the thunderclap headache, lumbar puncture (LP) is indicated. Although brain CT has very high sensitivity for detecting SAH when performed early after the onset of thunderclap headache, its sensitivity is not 100%. A diagnosis of SAH cannot be overlooked, and the LP helps to evaluate for SAH and other causes of thunderclap headache. To expedite the evaluation of a patient with thunderclap headache, LP should be performed as soon as possible after the brain CT. However, the sensitivity of CSF analyses for detection of an SAH is higher if the
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LP is performed at least 6 hours, preferably 12 hours, after SAH onset.8 This relationship between timing and sensitivity must be considered when interpreting results. However, LP should not be delayed, because of the risk of a second aneurysmal rupture within 24 hours. In addition, even if an LP is done early and found to be unremarkable, noninvasive neurovascular imaging will be required and should exclude the presence of a symptomatic intracranial saccular aneurysm. LP should include measurement of opening pressure, cell counts with differential in tube 1 and tube 4, protein, glucose, closing pressure, and visual inspection for xanthochromia. Other studies, such as testing for CNS infections, should be ordered when indicated. Spectrophotometry for xanthochromia, if available, has high sensitivity for detection of SAH when CSF is obtained between 12 hours and 2 weeks after the SAH.9,10 Patients who have thunderclap headache with nondiagnostic brain CT and LP should be further evaluated with contrast-enhanced brain MRI and noninvasive vascular imaging of the head and neck (eg, magnetic resonance angiography [MRA], CT angiography [CTA]). Venoussinus imaging via magnetic resonance venography or CT venography might be indicated depending upon the clinical suspicion for an underlying cerebral venous sinus thrombosis. Specific Findings With the Most Common Causes of Thunderclap Headache Table 8-2 lists specific diagnostic findings for the most common causes of thunderclap headache. Aneurysmal subarachnoid hemorrhage. Given the very high rates of mortality and morbidity associated with aneurysmal SAH, SAH is the diagnosis of first consideration in a patient with a thunderclap headache. Approximately 70% of patients with SAH present with Continuum (Minneap Minn) 2015;21(4):1058–1071
headache as a main symptom; 50% present with thunderclap headache, and SAH is found in up to 25% of patients with thunderclap headache.11 Although no symptoms or signs are highly specific for an eventual diagnosis of SAH, the absence of certain symptoms in patients with normal neurologic examinations does highly suggest that an SAH has not occurred. In a multicenter Canadian emergency department study of 132 patients with SAH who had headache peaking within 1 hour (not the definition for a thunderclap headache) and normal neurologic examinations, the following features yielded a sensitivity of 98.5% (95% confidence interval of 94.6% to 99.6%) for an eventual diagnosis of SAH: age 40 years or older, neck pain or stiffness, witnessed loss of consciousness, or onset during exertion.12 However, the presence of these features were not specific for SAH (27.5% specificity, 95% confidence interval of 25.6% to 29.5%). Adding thunderclap headache and limited neck flexion on examination increased the sensitivity for SAH to 100% (95% confidence interval of 97.2% to 100%), while decreasing the specificity to 15.3% (95% confidence interval of 13.8% to 16.9%). Brain CT typically reveals the location and severity of the SAH and associated complications, such as intraparenchymal extension, hydrocephalus, and brain edema.13 SAH from aneurysmal rupture must be differentiated from a cortical SAH that can be seen with RCVS. Aneurysmal SAH is typically seen within the sylvian fissures and basal cisterns, while SAH from RCVS is seen in the hemispheric convexities (Figure 8-1).14 The cortical SAH from RCVS is associated with less severe neurologic presentations than aneurysmal SAH.14 In patients with thunderclap headache, CSF analysis is performed following a nondiagnostic brain CT. Approximately 2% to 15% of patients with thunderclap headache with normal brain CT scans
KEY POINTS
h Patients who have thunderclap headache with nondiagnostic brain CT and lumbar puncture should be further evaluated with contrast-enhanced brain MRI and noninvasive vascular imaging of the head and neck.
h Approximately 70% of patients with subarachnoid hemorrhage present with headache as a main symptom; 50% present with thunderclap headache, and subarachnoid hemorrhage is found in up to 25% of patients with thunderclap headache.
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TABLE 8-2 Diagnostic Findings for the More Common Causes of Thunderclap Headache Clinical Features
Cause Aneurysmal subarachnoid hemorrhage
Brain CT
Altered consciousness, Subarachnoid seizures, meningismus blood in basilar cisterns and sylvian fissures
Reversible cerebral Recurrent thunderclap Normal, headaches subarachnoid vasoconstriction blood along syndrome cortical surface/sulci
Lumbar Puncture
Angiography
Brain MRI
Elevated red blood cells, xanthochromia
Ruptured aneurysm, vasospasm
Subarachnoid blood in basilar cisterns and sylvian fissures
Multifocal Normal, mild white blood cell multivessel vasoconstriction elevation, mild protein elevation
Normal
Normal, subarachnoid blood along cortical surface/sulci, ischemic stroke, cerebral edema, intracerebral hemorrhage
Dissected artery, Normal, ischemic stroke multifocal, segmental vasoconstriction if associated with reversible cerebral vasoconstriction syndrome
Carotid and vertebral artery dissection
Neck pain, symptoms related to cerebral ischemia, Horner syndrome (carotid dissection)
Normal, ischemic stroke
Cerebral venous sinus thrombosis
Focal neurologic deficits, altered mental status, visual changes
Elevated opening Venous sinus Dense triangle thrombosis sign (clot inside pressure, high protein the sinus), cord sign (thrombosed cortical or deep vein), venous hemorrhages
Spontaneous intracranial hypotension
Orthostatic headache, Normal, subdural Low opening auditory muffling collections pressure
Normal
Normal, venous infarctions with hemorrhage; MRI evidence of intraluminal thrombus on T1, T2, and susceptibilityweighted imaging sequences Pachymeningeal enhancement, sagging brain, subdural collections
CT = computed tomography; MRI = magnetic resonance imaging.
who are ultimately diagnosed with aneurysmal SAH have evidence for SAH on CSF analysis.15 The CSF diagnosis of SAH is made via measurement of red blood cells in tube 1 and tube 4, visual inspection of the CSF for xanthochromia, and spectrophotometry (if available). In contrast to a traumatic LP, red blood cell counts in
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tube 4 should be similar to or higher than tube 1 in patients with SAH. Spectrophotometry is useful, when available, as it has a sensitivity of 98% for detecting SAH when performed between 12 hours and 2 weeks after symptom onset.16 Brain MRI fluid-attenuated inversion recovery (FLAIR) and gradient echo/
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KEY POINT
h Brain MRI is an important tool for the evaluation of patients suspected to have SAH who present for evaluation several days after symptom onset.
Axial noncontrast CTs showing aneurysmal subarachnoid hemorrhage versus cortical subarachnoid hemorrhage. A, Extensive blood within the basilar cisterns, a typical finding of aneurysmal subarachnoid hemorrhage. B, A small amount of subarachnoid blood (arrows) along the cortex of the postcentral gyrus, a finding that can be consistent with the nonaneurysmal cortical subarachnoid hemorrhage seen in up to one-third of patients with reversible cerebral vasoconstriction syndrome.
FIGURE 8-1
susceptibility-weighted images are very sensitive for detecting SAH.17,18 Brain MRI is considered to be equally as sensitive as brain CT for detecting SAH within the acute phase and more sensitive than CT after the acute phase.19 Thus, brain MRI is an important tool for the evaluation of patients suspected to have SAH who present for evaluation several days after symptom onset. Angiography is required in patients with aneurysmal SAH to determine the site and morphology of the aneurysm and guide treatment. Although catheter angiography is still considered the gold standard, MRA or CTA may be considered for the initial angiographic evaluation. MRA and CTA on modern scanners have high sensitivity for detecting aneurysms, especially those larger than 3 mm.20,21 If the site of the aneurysm is not detected by noninvasive angiography in a patient with aneurysmal SAH, intra-arterial catheter angiography is indicated. Angiography is also useful for detecting vasospasm that might occur secondary to SAH. The vasospasm of SAH must be differentiated Continuum (Minneap Minn) 2015;21(4):1058–1071
from the vasoconstriction of RCVS. Both the vasoconstriction of RCVS and the vasospasm of aneurysmal SAH can be delayed findings, being maximal several days to 1 week after aneurysmal SAH and up to 3 weeks following onset of RCVS. The vasospasm of aneurysmal SAH is confined to the blood vessels in the area of the SAH, while the vasoconstriction of RCVS involves multiple arteries, often including vessels in both hemispheres and in both the anterior and posterior circulation.14 Reversible cerebral vasoconstriction syndrome. RCVS presents with thunderclap headache(s) with or without other symptoms, no aneurysmal SAH, normal or near-normal CSF, and multifocal vasoconstriction of cerebral arteries that normalizes within 12 weeks of onset.22 Table 8-3 lists diagnostic criteria for RCVS.22,23 A pattern of recurrent thunderclap headaches (between 2 and 10 thunderclap headaches) over approximately 1 to 2 weeks is very suggestive of RCVS.23Y25 Individual thunderclap headaches are often provoked by activities such as www.ContinuumJournal.com
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Thunderclap Headache KEY POINT
h Reversible cerebral vasoconstriction syndrome may be associated with cortical subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, cerebral edema, and cervical artery dissection.
Cerebral TABLE 8-3 Diagnostic Criteria for Reversible Vasoconstriction Syndromesa b Thunderclap headache(s) with or without focal neurologic deficits or seizures b Monophasic course without new symptoms more than 1 month after initial onset of symptoms b Multifocal, multivessel, segmental vasoconstriction of cerebral arteries b Absence of aneurysmal subarachnoid hemorrhage b Normal or near-normal CSF Protein less than 100 mg/dL White blood cells less than 15 per mm3 Glucose normal b Complete or substantial normalization of cerebral arteries within 12 weeks of symptom onset CSF = cerebrospinal fluid. a Data from Calabrese LH, et al, Ann Intern Med,22 annals.org/article.aspx?articleid=477594, Ducros A, Lancet Neurol. 23 www.thelancet.com/journals/laneur/article/PIIS14744422(12)70135-7/fulltext.
urinating, bathing/showering, bending, Valsalva, and sexual activity and by strong emotions (eg, anger).26,27 However, since patients with thunderclap headache are often evaluated after their first thunderclap headache, a high index of suspicion for RCVS should be present after a single thunderclap headache. RCVS can present with thunderclap headache only or may be accompanied by other symptoms, such as a continuous mild to moderate headache, nausea, vomiting, photophobia, phonophobia, cognitive dysfunction, alterations in consciousness, seizures, transient focal neurologic deficits, and permanent neurologic deficits from ischemic or hemorrhagic stroke. As illustrated in Case 8-1, RCVS tends to affect women who are in their fourth and fifth decades of life. Risk factors for development of RCVS may include female sex, being postpartum, use of marijuana, binge alcohol drinking, use of serotonergic and sympathomimetic substances (eg, antidepressants, stimulants, cold medicines), and migraine.
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Brain CT and brain MRI are normal in 30% to 70% of patients with RCVS.27 RCVS is associated with brain imaging abnormalities such as cortical SAH in 22% to 34%, intracerebral hemorrhage in 6% to 20%, ischemic stroke in 4% to 39%, and cerebral edema such as that seen in PRES in 9% to 38%.25,28,29 As discussed in the SAH section earlier in this article, it is important to differentiate a cortical SAH related to RCVS from an aneurysmal SAH. LP is normal or near normal in RCVS. Mild elevations in white blood cell counts (less than 15 per mm3) and protein (less than 100 mg/dL) are possible with RCVS. Other CSF measurements should be normal. Angiography reveals multifocal vasoconstrictions of multiple intracranial arteries in a ‘‘string of beads’’ appearance (Figure 8-2). Vasoconstrictions are maximal at about 2 to 3 weeks after symptom onset.28 Since vasoconstriction might start distally and move more proximally during the first several weeks after symptom onset, vascular imaging performed early
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Case 8-1 A 45-year-old woman presented to the emergency department after she developed a very severe, 10/10 intensity occipital headache that started and reached maximal intensity instantaneously. She stated that the headache felt like a bomb went off in her head. The very intense pain lasted for about 5 minutes, and since that time she had a moderate 5/10 intensity holocephalic aching headache. The patient reported that she had two headaches quite similar to her current one within the last week, but she did not previously seek medical attention. She had otherwise felt in her usual state of health. The patient had a history of episodic migraine and depression. She stated that her current headaches were not similar to her usual migraine attacks as her current headaches were more severe and peaked very quickly. The patient had been on a selective serotonin reuptake inhibitor (SSRI) for the previous 6 months for treatment of mild depression, and she had taken over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) intermittently over the last week for treatment of her current headaches. She occasionally smoked marijuana, did not use any other illicit drugs, and infrequently drank alcohol. Her vital signs were normal other than a mildly elevated blood pressure at 145/92, and her physical and neurologic examinations were normal. Brain CT without contrast was normal. Lumbar puncture was normal other than a mildly elevated white blood cell count at 8 per mm3 and a mildly elevated protein at 60 mg/dL. Brain MRI with gadolinium was normal. Brain magnetic resonance angiogram (MRA) showed multifocal areas of vasoconstriction in bilateral cerebral arteries including the middle cerebral arteries, anterior cerebral arteries, and posterior cerebral arteries. Cervical MRA was normal. The patient was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS), started on verapamil 80 mg 3 times a day, and instructed to discontinue the SSRI and marijuana use. With this therapy, she did not have any recurrent thunderclap headaches, and her MRA showed resolution of the vasoconstriction 12 weeks after symptom onset. Comment. This patient with thunderclap headache has several features that increase the suspicion for RCVS, including: (1) presenting with recurrent thunderclap headaches; (2) personal history of migraine; (3) use of a serotonergic medication; (4) use of marijuana; (5) normal brain CT and brain MRI; (6) mild elevation in CSF white blood cell count and protein; and (7) angiography showing vasoconstriction that is multifocal and bilateral. Normalization of the intracranial vasoconstriction is required before a definite diagnosis of RCVS can be assigned.
after the onset of symptoms might be normal. When clinical suspicion for RCVS is high despite normal vasculature on angiography performed early after the onset of symptoms, repeat vascular imaging after several weeks is indicated in search of vasoconstriction. Of note, the angiographic appearance of RCVS is similar to that of primary angiitis of the CNS (also known as primary CNS vasculitis). However, primary angiitis of the CNS has more of an indolent clinical presentation (not presenting with thunderclap headache); CSF analysis reveals greater elevations in white blood cell count and protein than those seen in Continuum (Minneap Minn) 2015;21(4):1058–1071
RCVS, and brain MRI is nearly always abnormal, showing multiple white matter hyperintensities on T2 and FLAIR sequences and ischemic strokes of different ages and in different vascular territories.30 Internal carotid and vertebral artery dissections. Internal carotid artery and vertebral artery dissections can present with thunderclap headache. In a large series of patients with spontaneous internal carotid or vertebral artery dissections, headache was present at clinical presentation in about 70% of patients.31,32 Thunderclap headaches are present in 9.2% of patients with vertebral artery dissections and 3.6% of patients with
KEY POINT
h When clinical suspicion for reversible cerebral vasoconstriction syndrome is high despite normal vasculature on angiography performed early after the onset of symptoms, repeat vascular imaging after several weeks is indicated in search of vasoconstriction.
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FIGURE 8-2
Angiographic appearance of reversible cerebral vasoconstriction syndrome. Numerous areas of vasoconstriction (arrows) are apparent within the anterior (A) and posterior (B) circulation on magnetic resonance angiography. Normalization of the intracranial arteries is seen 10 weeks later (C, D).
internal carotid artery dissections.32 Patients typically have symptoms and signs in addition to headache. Neck pain is present in about 66% of those with vertebral artery dissection and 33% of those with internal carotid artery dis-
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section.31,32 Symptoms related to cerebral ischemia (eg, stroke, transient ischemic attack) are present in 84% to 90% of patients with vertebral artery dissection, and symptoms related to cerebral or retinal ischemia (eg, stroke, transient
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ischemic attack, amaurosis fugax) are present in 70% to 73% of patients with internal carotid artery dissection. Horner syndrome is present in 47.2% of patients with internal carotid dissection. Some patients with cervical artery dissections also have RCVS. In a single institution’s experience with 173 patients with RCVS and 285 patients with cervical artery dissection, 20 of the patients were found to have both.33 Other cases of RCVS and carotid or vertebral artery dissection are reported in the literature. The nature of the relationship between RCVS and cervical artery dissection is not clear. It is possible that one condition leads to the other or that they have a shared underlying etiology. Brain CT and LP will often be normal in the patient presenting with thunderclap headache due to internal carotid or vertebral artery dissection. It is possible that ischemic stroke secondary to the dissection may be seen on CT, and SAH associated with the dissection should be detected on brain CT or CSF analysis. MRI of the brain, MRI of the neck with fat saturation technique, and MRA are often necessary for detecting the dissection and secondary complications. Cerebral venous sinus thrombosis. At least two-thirds of patients with cerebral venous sinus thrombosis present with headaches.34 Cerebral venous sinus thrombosis most commonly presents with a subacute onset of chronic daily headache. However, about 5% of patients with cerebral venous sinus thrombosis present with a thunderclap headache.34 Although 25% of patients with cerebral venous sinus thrombosis present with headache alone, the majority of patients present with additional features such as abnormal neurologic examinations, papilledema, altered mental status, seizures, and focal neurologic deficits.35Y37 Some patients may present with the clinical features of idiopathic intracranial hypertension Continuum (Minneap Minn) 2015;21(4):1058–1071
(ie, headache, papilledema, visual field loss). The diagnosis of cerebral venous sinus thrombosis is made by imaging of the cerebral venous sinus system, typically via magnetic resonance venography or computed tomographic venography. However, there may be clues for the diagnosis on brain CT (eg, dense triangle sign, cord sign, venous infarctions with hemorrhages), LP (eg, elevated opening pressure, high protein), and brain MRI (eg, suggestion of clot on T1-weighted, T2weighted, and susceptibility-weighted imaging sequences; venous infarctions with hemorrhage).38 Spontaneous intracranial hypotension. The hallmark feature of spontaneous intracranial hypotension is an orthostatic headache, a headache that is worsened when a person is upright (standing or sitting) and relieved when lying down (Case 8-2). However, about 15% of patients with spontaneous intracranial hypotension initially present with a thunderclap headache.39 In addition to headache, common symptoms of spontaneous intracranial hypotension include auditory muffling, tinnitus, nausea, vomiting, neck stiffness, dizziness, and visual changes. Brain MRI with contrast reveals diffuse, smooth, and continuous pachymeningeal enhancement in patients with spontaneous intracranial hypotension. Other brain MRI findings include cerebellar tonsil and optic chiasmal descent, flattening of the anterior pons and tectum, pituitary enlargement, and dilation/engorgement of the cerebral venous sinuses. Subdural fluid collections (hematomas or hygromas), easily identified on CT or brain MRI, may be found in some patients with spontaneous intracranial hypotension.40 Spine MRI might show extra-arachnoid spinal fluid collections coursing along the cervical, thoracic, or lumbar spine; venous engorgement; and nerve root sleeve diverticula.
KEY POINTS
h Although cerebral venous sinus thrombosis most commonly presents with a subacute onset of chronic daily headache, about 5% of patients present with a thunderclap headache.
h The hallmark feature of spontaneous intracranial hypotension is an orthostatic headache, a headache that is worsened when a person is upright and relieved when lying down. However, about 15% of patients with spontaneous intracranial hypotension initially present with a thunderclap headache.
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Case 8-2 A 50-year-old man presented to the outpatient clinic reporting a very severe headache that had started 3 days prior. He reported that he was in his usual state of health that day until he had the sudden onset of a very intense headache that felt like he was ‘‘hit over the head.’’ He stated that he had never felt such severe pain. The most intense pain lasted for about 10 minutes and then slowly lessened. He presented to an emergency department, where he had a normal examination, a normal brain CT, and normal CSF studies. Opening and closing pressures were not measured. He was treated with pain medications and discharged from the emergency department. Since his discharge, he had continued to have a headache that was continuous but substantially worse when he was upright and relieved somewhat when he lay down. Because of the orthostatic component to his headache, he had spent most of his time in bed. In addition to headache, he reported a muffled sensation in the ears as if he were underwater. The patient had no pertinent past medical history and did not take any medications. His vital signs, physical examination, and neurologic examination were normal. The patient’s symptoms were felt to be most consistent with intracranial hypotension. However, it was not clear if the intracranial hypotension was spontaneous, initially presenting with a thunderclap headache, or if the intracranial hypotension was due to the lumbar puncture (LP) and the thunderclap headache had a different cause. Thus, contrast-enhanced MRI of the brain and magnetic resonance angiogram (MRA) of the brain and neck were ordered to evaluate for other causes of the thunderclap headache. MRA of the brain and neck were normal. Brain MRI showed diffuse pachymeningeal enhancement, low-lying cerebellar tonsils, and flattening of the anterior pons (Figure 8-3). The patient was successfully treated with an autologous lumbar epidural blood patch without recurrence of symptoms.
FIGURE 8-3
MRI appearance of intracranial hypotension. A, Sagittal noncontrast T1-weighted image showing cerebellar tonsillar descent (arrowhead) and flattening of the anterior pons (arrows). B, Axial postgadolinium T1-weighted image showing diffuse pachymeningeal enhancement (arrows).
Comment. This patient with thunderclap headache has several features that are consistent with a diagnosis of intracranial hypotension: (1) orthostatic headache; (2) auditory muffling; and (3) brain MRI showing pachymeningeal enhancement, cerebellar tonsil descent, and flattening of the anterior pons. However, since LP is part of the routine initial evaluation of patients with thunderclap headache, it will often be unclear if the thunderclap headache was due to spontaneous intracranial hypotension or if the intracranial hypotension is secondary to the LP. In this situation, other causes for the thunderclap headache must be considered prior to attributing the thunderclap headache to spontaneous intracranial hypotension.
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For more information, refer to the article ‘‘Spontaneous Intracranial Hypotension’’ by Bahram Mokri, MD, FAAN, . in this issue of Other Causes of Thunderclap Headache Numerous other causes of thunderclap headache exist (Table 8-1). When evaluating the patient with thunderclap headache, the clinician must initially consider the possible causes associated with the greatest risk to the patient (eg, SAH, intracerebral hemorrhage). The prevalence of each disorder and how often each one presents with thunderclap headache should also be considered. Aneurysmal SAH and RCVS account for the majority of secondary thunderclap headache cases. Other conditions rarely present with thunderclap headache but are relatively common conditions, such as cerebral infections and hypertensive crisis. Others commonly present with thunderclap headache but are quite rare, such as pituitary apoplexy. Finally, the headaches associated with cough, exercise, and sexual activity might initially be indistinguishable from a thunderclap headache and thus necessitate the thunderclap headache evaluation. Although headaches provoked by cough, exercise, and sexual activity might be primary headaches, typically it is not possible to differentiate primary cough headache, primary exercise headache, and primary headache associated with sexual activity from secondary headaches based upon clinical symptoms alone.41,42 Therefore, diagnostic evaluations are needed to rule out underlying causes, including, but not limited to, SAH, RCVS, arterial dissection, intracranial hypotension, Chiari malformation, middle cranial fossa tumors, and posterior fossa tumors.41,42 Once determined to be primary in nature, headaches associated with cough, exercise, and sexual activity are comContinuum (Minneap Minn) 2015;21(4):1058–1071
monly responsive to treatment with indomethacin. An evaluation that includes efficient collection of clinical history, vital signs, physical and neurologic examination, brain CT, and LP will adequately investigate for the potential causes of thunderclap headache that require emergent treatment. However, if a diagnosis is not reached after this initial investigation, additional testing with contrast-enhanced brain MRI and noninvasive vascular imaging is necessary to investigate for other causes of thunderclap headache.
KEY POINT
h Aneurysmal subarachnoid hemorrhage and reversible cerebral vasoconstriction syndrome account for the majority of secondary thunderclap headache cases.
Unruptured Aneurysms and Thunderclap Headache It is not uncommon to encounter a patient with thunderclap headache and an unruptured intracranial aneurysm. This might be by chance alone, since unruptured intracranial aneurysms are found in 3% to 6% of the general population, or might be due to a causal relationship.43 Of patients who have an aneurysmal SAH, 10% to 43% retrospectively report having had a thunderclap headache within days to weeks prior to their SAH, a headache that has been termed a warning or sentinel headache.44 A sentinel headache might be due to a small amount of blood seepage from the aneurysm or due to structural changes (eg, stretching or thinning) in the aneurysm wall or the wall of the artery adjacent to the aneurysm. Since the nature of the relationship between thunderclap headache and an unruptured intracranial aneurysm is difficult to determine, patients with thunderclap headaches with unruptured intracranial aneurysms should be evaluated for other potential causes of the thunderclap headache. The decision of whether to treat the unruptured aneurysm should be based on current guidelines for the management of unruptured intracranial aneurysms. For patients who do not undergo aneurysm treatment, close follow-up is indicated. www.ContinuumJournal.com
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CONCLUSION A thunderclap headache is a very severe headache that reaches maximum intensity in less than 1 minute, often nearly instantaneously. Although numerous causes for thunderclap headache exist, SAH and RCVS seem to be the most common. Patients with thunderclap headache need to be evaluated emergently. Following efficient collection of the medical history, vital signs, and general physical and neurologic examinations, noncontrast brain CT should be performed. If the CT is nondiagnostic, LP is required. If a diagnosis cannot be reached after CT and LP, brain MRI with contrast and imaging of the cerebral and cervical arteries is recommended. REFERENCES 1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33(9):629Y808. doi:10.1177/0333102413485658. 2. Backes D, Rinkel GJ, Kemperman H, et al. Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage. Stroke 2012;43(8):2115Y2119. doi:10.1161/ STROKEAHA.112.658880. 3. Boesiger BM, Shiber JR. Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are fifth generation CT scanners better at identifying subarachnoid hemorrhage? J Emerg Med 2005;29(1):23Y27. 4. Byyny RL, Mower WR, Shum N, et al. Sensitivity of noncontrast cranial computed tomography for the emergency department diagnosis of subarachnoid hemorrhage. Ann Emerg Med 2008;51(6):697Y703. doi:10.1016/j.annemergmed.2007.10.007. 5. Gee C, Dawson M, Bledsoe J, et al. Sensitivity of newer-generation computed tomography scanners for subarachnoid hemorrhage: a Bayesian analysis. J Emerg Med 2012;43(1):13Y18. doi:10.1016/ j.jemermed.2011.09.012. 6. Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid
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