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Overview of thunderclap headache

Author Section Editors Deputy Editor

Todd J Schwedt, MD, MSCI Jerry W Swanson, MD, MHPE Richard P Goddeau, Jr, DO, FAHA
Jonathan A Edlow, MD, FACEP

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2021. | This topic last updated: Jul 14, 2020.
INTRODUCTION — Thunderclap headache (TCH) refers to a severe headache of sudden onset. Its
explosive and unexpected nature is likened to a "clap of thunder." Although TCH initially referred to
pain associated with an unruptured intracranial aneurysm [1], multiple etiologies are now recognized
[2] (table 1). This topic will review the clinical presentation, etiologies, and diagnostic evaluation of
TCH.

DEFINITION — A TCH is a very severe headache of abrupt onset that reaches its maximum intensity
within one minute or less of onset [3]. The key feature that differentiates TCH from other headaches
is the rapidity with which it develops; extreme severity alone is insufficient [4].

However, "sudden" may be to some extent subjective; patients or physicians are not always so precise.
In a series of 2131 patients with acute onset headache peaking within one hour, including 132 with
subarachnoid hemorrhage, the interobserver agreement about sudden onset was only fair, and 6 of 132
patients with subarachnoid hemorrhage had a time to peak headache intensity of up to one hour [5].
Therefore, care must be taken in defining sudden onset. Other severe headaches may be worrisome
and compel a diagnostic evaluation, but would not qualify as TCH unless reaching maximum intensity
quickly.

CLINICAL PRESENTATION — By definition, TCH is a very severe headache that begins abruptly and
reaches maximum intensity within one minute or less of onset. Patients may present with TCH either in
isolation or accompanied by additional symptoms and signs (eg, meningismus, fever, tinnitus,
orthostatic worsening of headache, altered mental state, seizure, motor or sensory deficits, or cranial
nerve palsies) that reflect the underlying cause.

Given the serious and potentially life-threatening nature of underlying intracranial etiologies (table 1),
TCH is a medical emergency requiring immediate evaluation. (See 'Diagnostic evaluation' below.)

Although the cause of TCH cannot be determined with certainty based upon the presentation alone,
some clues to the possible etiology can be gleaned from the history and from accompanying clinical
features [2,4]:

TCH associated with altered consciousness, seizures, or focal neurologic symptoms and signs can be due
to multiple possible causes, including subarachnoid hemorrhage, other intracranial hemorrhage,
reversible cerebral vasoconstriction syndrome (RCVS), posterior reversible encephalopathy syndrome
(PRES), hypertensive crisis, cerebral sinus thrombosis, cervical artery dissection, or ischemic stroke.

Other clinical presentations may suggest specific causes of TCH:

●Recurrent TCH over days to weeks suggest RCVS

●TCH associated with orthostatic headaches suggests spontaneous intracranial hypotension

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●Postpartum setting suggests RCVS or cerebral venous thrombosis

●Recent minor trauma suggests cervical artery dissection or spontaneous intracranial hypotension

●Horner syndrome or pulsatile tinnitus suggests dissection of the ipsilateral internal carotid artery

●Papilledema and visual symptoms suggest intracranial hypertension related to cerebral venous
thrombosis

●Fever or meningismus suggests meningitis

●Facial pain, ear, nose, and throat symptoms suggest complicated sinusitis

COMMON CAUSES — TCH has multiple causes (table 1). The most frequent are subarachnoid
hemorrhage and reversible cerebral vasoconstriction syndromes (RCVS).

Subarachnoid hemorrhage — The primary symptom of aneurysmal subarachnoid hemorrhage is a

sudden, severe headache. Approximately one-half of patients with subarachnoid hemorrhage present
with TCH [2]. While there are no symptoms or signs that can reliably differentiate primary from
secondary TCH, the following features are associated with increased odds of subarachnoid hemorrhage
in a patient with TCH [6-8]:

●Impaired consciousness

●Neck stiffness

●Nausea, vomiting

●Exertion or Valsalva immediately preceding onset of TCH

●Elevated blood pressure

●Occipital headache

●History of smoking

Whether or not these features are present, all patients with TCH need to be evaluated for subarachnoid
hemorrhage and other underlying causes (see 'Diagnostic evaluation' below). Misdiagnosis or delay in
diagnosis of subarachnoid hemorrhage is not uncommon. Misdiagnosis occurs because of failure to
recognize the spectrum of possible presentations of subarachnoid hemorrhage, lack of knowledge
regarding the limitations of head CT, and failure to perform lumbar puncture and interpret cerebrospinal
fluid tests correctly. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and
diagnosis", section on 'Evaluation and diagnosis'.)

Initial evaluation for subarachnoid hemorrhage must include noncontrast CT of the brain (algorithm 1).
Lumbar puncture is indicated when there is clinical suspicion of subarachnoid hemorrhage and the head
CT is normal.

The diagnosis of subarachnoid hemorrhage as well as the utility of head CT and lumbar puncture are
discussed in greater detail separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical
manifestations and diagnosis", section on 'Evaluation and diagnosis' and 'Diagnostic evaluation' below.)

Reversible cerebral vasoconstriction syndromes — RCVS are a group of conditions characterized

by reversible segmental narrowing of the cerebral arteries. These are reviewed here briefly and
discussed in detail elsewhere. (See "Reversible cerebral vasoconstriction syndrome".)

The clinical presentation of RCVS is usually dramatic with sudden, severe recurrent thunderclap
headaches over the span of a few days that simulate aneurysmal subarachnoid hemorrhage; however,
in patients with RCVS, thunderclap headaches often recur over a span of one to four weeks and the
duration of headache in RCVS is generally shorter (ie, several hours with resolution between attacks).

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Headaches of RCVS are frequently triggered by diverse conditions such as sexual activity, heat or cold
exposure, various therapeutic and recreational drugs, and the postpartum state [9]. (See "Reversible
cerebral vasoconstriction syndrome", section on 'Clinical presentation and course'.)

Clinical suspicion for RCVS is warranted for patients who present with the following manifestations (see
"Reversible cerebral vasoconstriction syndrome", section on 'Evaluation'):

●Recurrent TCH; or

●Single TCH, particularly if combined with border zone infarcts or vasogenic edema on neuroimaging;
or

●No TCH but abnormal angiography and no brain lesions on neuroimaging; the absence of brain lesions
virtually rules out primary angiitis of the central nervous system

Despite the presence of widespread cerebral vasoconstriction, the admission brain scan is normal in 30
to 70 percent of patients with RCVS. (See "Reversible cerebral vasoconstriction syndrome", section on
'Brain imaging'.)

Cerebral angiographic abnormalities may be absent during the first days after symptom onset; the
changes are dynamic and progress proximally, resulting in a "sausage on a string" appearance of the
circle of Willis arteries and their branches. These abnormalities begin to resolve spontaneously (without
specific therapy) over a few weeks [2]. (See "Reversible cerebral vasoconstriction syndrome", section
on 'Neurovascular imaging'.)

There is no proven therapy for RCVS. Supportive care is directed towards managing blood pressure,
severe headaches, and other complications such as seizures. (See "Reversible cerebral vasoconstriction
syndrome", section on 'Management'.)

The clinical outcome is benign in 95 percent of patients. Rare patients develop severe irreversible
deficits or death from progressive strokes or cerebral edema. Recurrence of an episode of RCVS is rare.
(See "Reversible cerebral vasoconstriction syndrome", section on 'Clinical course and prognosis'.)

LESS COMMON CAUSES — Conditions that are less common causes of TCH include the following:

●Cerebral infection (eg, meningitis, acute complicated sinusitis)

●Cerebral venous thrombosis

●Cervical artery dissection

●Spontaneous intracranial hypotension

●Posterior reversible leukoencephalopathy syndrome (PRES)

●Ischemic stroke

These are discussed in the sections that follow.

Cerebral venous thrombosis — Patients with cerebral venous thrombosis may present with TCH.
Headache is the most common presenting symptom in cerebral venous thrombosis, occurring in
approximately 90 percent of patients. In addition to headaches, patients with cerebral venous
thrombosis usually present with some combination of papilledema, seizures, bilateral focal deficits,
and/or altered level of consciousness. However, about 15 percent of patients may present with isolated
headache. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis", section on
'Headache'.)

TCH accompanies cerebral venous thrombosis in 2 to 15 percent of patients [10-12]. Most commonly,
however, the headaches of cerebral venous thrombosis have a gradual subacute onset; they may be
localized or diffuse, persistent, exacerbated by Valsalva, and positional with worsening on recumbency.

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In cases of cerebral venous thrombosis associated with TCH, the initial presentation of cerebral venous
thrombosis may be clinically indistinguishable from that of subarachnoid hemorrhage. MRI with
venography should be considered when cerebral venous thrombosis is suspected, as initial testing for a
suspected diagnosis of subarachnoid hemorrhage with head CT and lumbar puncture will not always
detect cerebral venous thrombosis. The cerebrospinal fluid abnormalities in cerebral venous thrombosis
are nonspecific but the opening pressure is often elevated, especially when the sagittal sinus is
involved. In patients with cerebral venous thrombosis who have normal neurologic exams, the head CT
is normal in approximately 25 percent, whereas in patients with cerebral venous thrombosis who have
focal neurologic signs, the head CT is normal in less than 10 percent [13,14]. (See "Cerebral venous
thrombosis: Etiology, clinical features, and diagnosis", section on 'Diagnosis'.)

Cervical artery dissection — Headache and/or neck pain is the most frequent initial symptom of
cervicocephalic dissection, found in 60 to 90 percent of cases. (See "Cerebral and cervical artery
dissection: Clinical features and diagnosis", section on 'Local symptoms'.)

Although the onset of headache in cervical artery dissection is usually gradual, a minority present with
TCH [15-17]. In a series of 970 consecutive patients with dissection, approximately 5 percent had a
presentation consistent with a TCH (approximately 4 percent in carotid dissections and 9 percent in
vertebral dissections) [17]. Diagnostic criteria from the International Classification of Headache
Disorders 3rd edition (ICHD-3) for headache secondary to cervical artery dissection stipulate that the
headache must be ipsilateral to the dissected artery [3].

Cervical artery dissection can cause ischemic stroke, transient ischemic attack, or rarely, subarachnoid
hemorrhage. In addition to neck pain and headache, other local manifestations of dissection can include
a Horner syndrome, pulsatile tinnitus, an audible bruit, or cranial neuropathies. Ischemia from vertebral
dissections may present with vestibular symptoms and signs that may be subtle. (See "Cerebral and
cervical artery dissection: Clinical features and diagnosis", section on 'Ischemic stroke or TIA' and
"Cerebral and cervical artery dissection: Clinical features and diagnosis", section on 'Subarachnoid
hemorrhage'.)

Common causes of dissection include various degrees of trauma or spontaneous events, with underlying
predispositions in some cases. Dissection can also result from major head and neck trauma, but most
dissections occur spontaneously or after minor or trivial injury. (See "Cerebral and cervical artery
dissection: Clinical features and diagnosis", section on 'Etiology'.)

In the absence of ischemic stroke, routine CT scanning of the brain and lumbar puncture are typically
unrevealing in patients with dissection. Additional diagnostic tests are necessary if there is clinical
suspicion for cervical artery dissection; these could include ultrasound, CT angiography, magnetic
resonance angiography, conventional angiography, or MRI of the neck with a fat saturation protocol.
The diagnosis is confirmed by neuroimaging findings, particularly the demonstration of a long tapered
arterial stenosis, a tapered occlusion, a dissecting aneurysm (pseudoaneurysm), an intimal flap, a
double lumen, or an intramural hematoma. (See "Cerebral and cervical artery dissection: Clinical
features and diagnosis", section on 'Choice of neuroimaging study'.)

The management of cervicocephalic dissection is reviewed elsewhere. (See "Cerebral and cervical artery
dissection: Treatment and prognosis".)

Infections — Bacterial and viral meningitis are most commonly associated with headaches of a gradual
onset, but may rarely present with TCH. A prospective analysis of 148 patients presenting to their
primary care physician with TCH found four (3 percent) with infectious etiologies [18]. Lumbar puncture
for cerebrospinal fluid examination is required for diagnosis.

Headaches related to acute sinusitis may also rarely be of the thunderclap variety. Although headaches
and facial pain are frequent in patients with acute rhinosinusitis, most commonly these are acute to
subacute in presentation and not consistent with TCH. However, TCH may occasionally be the presenting

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manifestation of sinusitis when related intracranial complications have occurred, such as with extension
through the sphenoid sinus [19].

Spontaneous intracranial hypotension — Patients with spontaneous intracranial hypotension (SIH)

usually present with orthostatic headaches and some combination of nausea/vomiting, dizziness,
auditory changes, diplopia, visual blurring, interscapular pain, and/or upper extremity radicular pain.
This syndrome is also known as spontaneous low cerebrospinal fluid pressure headache.

Cerebrospinal fluid (CSF) leakage from spinal meningeal defects or dural tears may be the most
common causes of this syndrome [20]. The headache is caused by displacement of pain-sensitive
structures due to the low CSF pressure. (See "Spontaneous intracranial hypotension: Pathophysiology,
clinical features, and diagnosis".)

A minority of patients with headache attributed to spontaneous intracranial hypotension present with
TCH [21,22]. As an example, in a series of 28 patients with low CSF pressure headache due to CSF
leaks from dural tears, TCH was the presenting sign in 14 percent [21].

The classic features of spontaneous intracranial hypotension are orthostatic headache, low CSF
pressure, and diffuse meningeal enhancement on brain MRI. (See "Spontaneous intracranial
hypotension: Pathophysiology, clinical features, and diagnosis", section on 'Introduction' and
"Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis", section on
'Clinical features'.)

Confirmation of the diagnosis requires evidence of low CSF pressure by MRI or lumbar puncture and/or
evidence of a CSF leak on myelography or radioisotope cisternography. (See "Spontaneous intracranial
hypotension: Pathophysiology, clinical features, and diagnosis", section on 'Evaluation and diagnosis'
and "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis".)

Typical features on brain MRI include diffuse meningeal enhancement, subdural hematomas or
hygromas, sagging of the brain, engorgement of cerebral venous sinuses, and pituitary enlargement.
Brain MRI remains normal in up to 20 percent of patients with spontaneous intracranial hypotension.
(See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis", section
on 'Brain MRI' and "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and
diagnosis", section on 'Spine MRI'.)

Ischemic stroke — TCH may rarely be the presenting feature of ischemic stroke. In most cases,
headaches associated with stroke are not consistent with TCH. However, several cases of ischemic
stroke associated with TCH have been reported, including cases in which TCH was the primary clinical
feature [6,23-25]. Neurologic exam will show a stroke-related deficit but requires careful examination
for cerebellar signs. CT and lumbar puncture may be nondiagnostic in patients with TCH and recent
stroke, suggesting the necessity of MRI in such cases.

Posterior reversible encephalopathy syndrome — The posterior reversible encephalopathy

syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), usually
presents with the insidious onset over hours to days with symptoms that may include headache, visual
changes, altered mental status, seizures, or focal neurologic signs. PRES most often occurs in the
setting of hypertensive crisis, preeclampsia, or cytotoxic immunosuppressive therapy; however, it can
also occur in many other clinical settings. Hypertension is frequent but not invariable. Hypertensive
crisis may precede the neurologic syndrome by 24 hours or longer. (See "Reversible posterior
leukoencephalopathy syndrome".)

TCH may be a rare presenting feature of acute hypertensive crisis/PRES [26]. Evaluation with head CT
and lumbar puncture may miss the diagnosis of PRES. MRI is more sensitive than head CT for revealing
the white matter and cortical edema associated with PRES. These changes typically involve the parietal
and occipital lobes and may also involve the basal ganglia, brainstem, and cerebellum. Since the
imaging changes are secondary to vasogenic edema and not ischemia or infarction, prompt treatment of

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the hypertension is essential and should result in correction of the associated clinical syndrome.

UNCOMMON OR RARE CAUSES — A number of conditions are uncommon or rare causes of TCH,
including:

●Pituitary apoplexy

●Colloid cyst of the third ventricle

●Acute myocardial infarction [27]

●Anaplastic oligodendroglioma [28]

●Aortic arch dissection [29]

●Aqueductal stenosis [30]

●Giant cell arteritis [31]

●Pheochromocytoma [32,33]

●Pneumocephalus [29]

●Retroclival hematoma [34]

●Spinal epidural hematoma [35]

●Varicella zoster virus vasculopathy [36]

●Vogt-Koyanagi-Harada syndrome [37]

Pituitary apoplexy and colloid cyst of the third ventricle are discussed in the sections that follow.

Pituitary apoplexy — Pituitary apoplexy is caused by hemorrhage or infarction of the pituitary gland
in the setting of a pituitary adenoma [38]. The clinical presentation of pituitary apoplexy ranges from
relatively mild symptoms to more severe symptoms including acute headache, ophthalmoplegia,
decreased visual acuity, visual loss, change in mental status, adrenal crisis, coma, or even sudden
death. TCH may be a predominant feature. (See "Causes of hypopituitarism", section on 'Pituitary
apoplexy'.)

Pituitary apoplexy can present with TCH in patients who have normal physical examinations, head CT
scans, and cerebrospinal fluid analyses [39,40]. Pituitary tumors that are isodense to normal brain
tissue may be easily overlooked on CT studies, even if hemorrhage is present. Brain MRI has a much
higher sensitivity than CT for detecting the tumor and associated blood.

Colloid cyst of the third ventricle — Patients with colloid cysts of the third ventricle may also present
with TCH when the cyst, which can act like a ball valve, suddenly impedes the flow of cerebrospinal
fluid, causing acute obstructive hydrocephalus. Headache is reported by 68 to 100 percent of patients
with third ventricular colloid cysts, making it the most commonly associated symptom.

Typically, the headache has an acute onset and resolution, with a duration of seconds to one day [41].
The pain is often severe and may be relieved by taking the supine position. Headaches may be located
in the bilateral frontal, fronto-parietal, or fronto-occipital head regions [42]. Approximately one-half of
patients have associated nausea and vomiting. Loss of consciousness, mental status changes, seizures,
coma, and death can occur [43].

Third ventricular colloid cysts are diagnosed via CT or MRI of the brain.

UNCERTAIN ASSOCIATION — Sentinel headache (due to an unruptured intracranial aneurysm) and

primary TCH are possible causes of TCH, but supporting data are weak.

Sentinel headache — Sentinel headache due to an unruptured intracranial aneurysm is a possible

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cause of TCH, but supporting data are weak. A sentinel headache is an episode of headache similar to
that accompanying subarachnoid hemorrhage but occurring days to weeks prior to aneurysm rupture.
Sentinel headaches develop over seconds and reach maximal intensity within minutes; features of
subarachnoid hemorrhage, such as stiff neck, altered consciousness, and focal neurologic symptoms and
signs, are absent. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis",
section on 'Clinical presentation'.)

Sentinel headaches may be caused by small aneurysmal leaks (ie, "warning leaks") of blood into the
subarachnoid space or physical changes within the aneurysm wall (eg, acute dissection, thrombosis, or
expansion) [44]. In mainly retrospective studies, 10 to 43 percent of patients with aneurysmal
subarachnoid hemorrhage report a history of a sentinel or warning headache [45]. However,
retrospective data may be confounded by recall bias, and a number of reports question the existence of
"warning leaks" as the cause of sentinel headaches [3,18,46,47].

As an example, a meta-analysis of seven different longitudinal studies followed 813 patients who
presented with TCH and had a normal neurological exam, normal cranial CT, and normal cerebrospinal
fluid analysis [47]. No patient developed a subarachnoid hemorrhage or died unexpectedly in the next
year, suggesting that acutely symptomatic unruptured aneurysms are rarely the cause of acute
headache and that routine cerebrovascular angiography looking for unruptured aneurysms may be
unnecessary.

In another meta-analysis of 729 patients with acute severe headache (defined as a "headache that
developed within five minutes"), normal neurologic examination, and normal noncontrast head CT, a
vascular abnormality on CT angiography was found in approximately 7 percent, including aneurysm in
approximately 5 percent [48]. However, a clear relation between the headache and the CT angiography
findings was evident for only 1.6 percent; most of the aneurysms were likely incidental findings.

If, in the evaluation of a patient with TCH, an aneurysm is found, a neurosurgeon or other
cerebrovascular specialist should be consulted. However, some experts believe that routine cerebral
angiography is not necessary in patients with a single TCH who have a normal neurologic examination,
normal cranial CT, and normal cerebrospinal fluid findings [9]. The unruptured aneurysm should be
managed according to an individualized analysis that incorporates factors including the risk of
aneurysm rupture according to size and location, comorbid medical illness, patient age, and risks of
treatment. These issues are discussed in detail separately. (See "Unruptured intracranial aneurysms".)

Following the standard evaluation for TCH will avoid most misdiagnosis (algorithm 1).

Primary TCH — There is controversy as to whether TCH can occur as a benign and potentially
recurrent headache disorder in the absence of underlying organic intracranial pathology [4]. Reported
cases of primary TCH may represent missed diagnosis of the underlying causes. Thus, it cannot be
overstated that primary TCH must be a diagnosis made only after exclusion of all possible underlying
causes [3,49].

For the diagnosis of primary TCH, the International Classification of Headache Disorders, 3rd edition
(ICHD-3) requires fulfilling the following criteria [3]:

●Severe head pain

●Abrupt onset, reaching maximum intensity in <1 minute

●Lasting for ≥5 minutes

●Not better accounted for by another ICHD-3 beta diagnosis

In addition, the diagnosis requires normal brain imaging, including the brain vessels, and normal
cerebrospinal fluid findings [3].

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Primary TCH may occur spontaneously, while a patient is at rest, or may be precipitated by exertion or
Valsalva. Exercise, weight lifting, or sexual activity is a precipitating event in up to one-third of cases.

DIAGNOSTIC EVALUATION — Given the potentially serious nature of possible underlying intracranial
etiologies, TCH must be evaluated and treated as a medical emergency, beginning with an evaluation
for subarachnoid hemorrhage (algorithm 1). The clinical features, imaging characteristics, cerebrospinal
fluid findings of the more common causes of TCH (table 2) should be kept in mind.

The clinician must initially presume that the patient presenting with TCH has a secondary TCH and a
comprehensive search for the etiology should occur immediately.

Evaluation for subarachnoid hemorrhage — A sudden-onset headache, though not necessarily a

TCH, is characteristic of subarachnoid hemorrhage. The evaluation for subarachnoid hemorrhage is
reviewed here briefly and discussed in detail elsewhere. (See "Aneurysmal subarachnoid hemorrhage:
Clinical manifestations and diagnosis", section on 'Evaluation and diagnosis' and "Aneurysmal
subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Identifying the source of
bleeding'.)

All patients with TCH should have a head computed tomography (CT) without contrast as soon as
possible after the onset of TCH (algorithm 1). If the head CT does not reveal the cause, a lumbar
puncture should be performed urgently to evaluate the cerebrospinal fluid for evidence of subarachnoid
hemorrhage or other causes of TCH. A negative head CT and lumbar puncture effectively eliminate the
diagnosis of subarachnoid hemorrhage as long as both tests are performed within a few days of the
event. In such cases, further evaluation for other possible causes of TCH is required. (See 'Evaluation
for other causes' below.)

Brain CT without contrast is highly sensitive and specific for the diagnosis of subarachnoid hemorrhage
when performed very early after headache onset. During the first 12 hours following onset of headache,
third-generation CT scanners have a sensitivity nearing 100 percent and a specificity of 98 percent
[50]. Therefore, some experts believe routine lumbar puncture is not necessary if a technically
adequate CT is done within six hours from headache onset is read as negative by an attending level
radiologist [9,51].

After six hours, in general practice, however, clinicians may easily overlook subtle imaging
abnormalities on CT that are suggestive of subarachnoid hemorrhage. The sensitivity of head CT in
subarachnoid hemorrhage declines rapidly over time, decreasing to 86 percent on day two, 76 percent
after two days, and 58 percent after five days [52]. Furthermore, head CT alone does not adequately
evaluate for other causes of TCH.

Lumbar puncture should include measurement of opening pressure (which may be elevated in patients
with subarachnoid hemorrhage or cerebral venous thrombosis or low in patients with spontaneous
intracranial hypotension), routine cerebrospinal fluid (CSF) analyses including cell counts, and visual
inspection for xanthochromia.

Some experts recommend the use of CSF spectrophotometry, if available, to measure xanthochromia,
especially when a traumatic tap makes CSF interpretation difficult or when the specimen has been
improperly processed. The sensitivity of spectrophotometry approaches 100 percent when lumbar
puncture is performed 12 hours to two weeks after subarachnoid hemorrhage onset [53]. Despite its
high sensitivity, spectrophotometry has only low to moderate specificity for the diagnosis of
subarachnoid hemorrhage and is not universally recommended. As a practical matter,
spectrophotometry is rarely available in North American hospitals. (See "Aneurysmal subarachnoid
hemorrhage: Clinical manifestations and diagnosis", section on 'Lumbar puncture'.)

Evaluation for other causes — For patients with TCH who have a negative initial work-up (ie, a
nondiagnostic head CT and lumbar puncture) for subarachnoid hemorrhage or other definite cause of
TCH, we suggest obtaining brain magnetic resonance imaging (MRI) with contrast and imaging of the

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cerebral vasculature with magnetic resonance (MR) angiography and MR venography (algorithm 1). If
MR imaging is not an option, we suggest imaging the cerebral vasculature with CT angiography and CT
venography.

However, some experts believe that patients who present with a single TCH but are otherwise
asymptomatic and have a normal neurologic examination, normal cranial CT, and normal CSF findings
on lumbar puncture do not require noninvasive angiography or additional work-up unless there is
recurrent TCH [9].

Cerebral venous and sinus imaging should be obtained with MR venography or CT venography in
patients presenting with TCH to exclude the presence of cerebral venous sinus thrombosis.

MRI is more sensitive than head CT for many of the possible underlying causes of TCH, such as cerebral
venous thrombosis, cervical artery dissection, spontaneous intracranial hypotension, and reversible
posterior leukoencephalopathy syndrome.

Likelihood of identifying an underlying cause — An underlying cause for TCH is identified in 27 to

71 percent of patients [6,8,18,29,54]. The wide range of these findings is attributable to the use of
different criteria for defining and diagnosing TCH among the various studies, and to the inclusion of
patients from variable settings (eg, emergency room versus outpatient). While all of the cited studies
used brain CT and lumbar puncture for diagnosis, angiography was either not used or was used
sparingly. This may have led to missed diagnoses of certain conditions, such as the reversible cerebral
vasoconstriction syndromes, and to underestimation of secondary TCH frequency.

Subarachnoid hemorrhage is consistently the most frequent cause for TCH in these series [6,8,18,54].
Other vascular conditions (ie, cervical artery dissection, cerebral venous thrombosis, and reversible
cerebral vasoconstriction syndromes) are the next most frequent secondary causes of TCH; these
disorders can present with TCH in isolation [2,55].

Supporting evidence comes from a series of 56 consecutive patients with recurrent TCH of unknown
etiology, including no evidence of subarachnoid hemorrhage on both CT head and cerebrospinal fluid
examination, who were referred to a headache clinic in Taiwan [56]. MR angiography performed at a
mean interval of 11 days after the first headache attack showed segmental vasoconstriction involving
Circle of Willis vessels in 39 percent (see 'Reversible cerebral vasoconstriction syndromes' above). This
finding must be interpreted cautiously, since the utility of MR angiography for determination of
segmental vasoconstriction is not established. Nevertheless, this report illustrates the potential for
serious causes of TCH other than subarachnoid hemorrhage and the importance of a thorough
investigation, including vascular imaging of the extracranial and intracranial circulation, in patients
presenting with TCH who have no evidence of subarachnoid hemorrhage.

MANAGEMENT — The management of TCH depends on the underlying etiology. This is discussed
separately for the following conditions:

●Cerebral aneurysm (see "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and
"Unruptured intracranial aneurysms")

●Reversible cerebral vasoconstriction syndromes (see "Reversible cerebral vasoconstriction syndrome",

section on 'Management')

●Cerebral venous thrombosis (see "Cerebral venous thrombosis: Treatment and prognosis")

●Spontaneous intracranial hypotension (see "Spontaneous intracranial hypotension: Treatment and

prognosis")

●Cervical artery dissection (see "Cerebral and cervical artery dissection: Treatment and prognosis")

●Ischemic stroke (see "Initial assessment and management of acute stroke" and "Initial evaluation and

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management of transient ischemic attack and minor ischemic stroke")

●Posterior reversible encephalopathy syndrome and acute hypertensive crisis (see "Drugs used for the
treatment of hypertensive emergencies" and "Moderate to severe hypertensive retinopathy and
hypertensive encephalopathy in adults" and "Reversible posterior leukoencephalopathy syndrome",
section on 'Prevention and treatment')

●Pituitary apoplexy (see "Causes of hypopituitarism", section on 'Pituitary apoplexy')

SUMMARY AND RECOMMENDATIONS

●Thunderclap headache (TCH) refers to a severe headache of sudden onset that reaches its maximum
intensity within one minute or less of onset. (See 'Definition' above.)

●Patients may present with TCH either in isolation or accompanied by additional symptoms and signs
(eg, meningismus, fever, tinnitus, orthostatic worsening of headache, altered mental state, seizure,
motor or sensory deficits) that reflect the underlying cause. (See 'Clinical presentation' above.)

●TCH may be a symptom of subarachnoid hemorrhage due to aneurysmal rupture. However, a wide
range of different etiologies must be considered when evaluating a patient with TCH (table 1 and table
2). These include other types of intracranial hemorrhage, reversible cerebral vasoconstriction
syndromes (RCVS), cerebral venous thrombosis, cervical artery dissection, viral and bacterial
meningitis, acute complicated sinusitis, spontaneous intracranial hypotension, ischemic stroke, acute
hypertensive crisis, third ventricular colloid cysts, pituitary apoplexy, and unruptured intracranial
aneurysms. (See 'Common causes' above and 'Less common causes' above and 'Uncommon or rare
causes' above and 'Uncertain association' above.)

●For all patients with TCH, we recommend noncontrast head computed tomography (CT) and, if head CT
is normal, lumbar puncture with measurement of opening pressure and cerebrospinal fluid analysis
(algorithm 1). For patients with TCH who have nondiagnostic head CT and lumbar puncture, imaging of
the cerebral circulation is suggested; we typically obtain contrast-enhanced brain magnetic resonance
imaging (MRI) and noninvasive neurovascular imaging with magnetic resonance or computed
tomographic angiography/venography. However, for patients with a single isolated TCH and normal
neurologic examination, some experts defer further investigations unless there are additional episodes
of TCH. (See 'Diagnostic evaluation' above.)

●The management of TCH depends on the underlying etiology. (See 'Management' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David W Dodick, MD, who
contributed to an earlier version of this topic review.

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Topic 3346 Version 15.0

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