Dr. Kranz and Dr. Provenzale are in the Department
of Radiology, Duke University Medical Center, Durham, NC, and Dr.
Provenzale is also at Emory University School of Medicine, Atlanta, GA.
is a common indication for brain imaging studies performed in the
emergency department (ED). When patients present with the“worst headache
of my life,” imaging often plays a major role in differentiating benign
causes of headache from life-threatening causes, and noncontrast
computed tomography (NCT) is the most commonly performed imaging test.1
NCT can detect many emergent causes of the“worst headache of my life,”
such as hemorrhage, hydrocephalus, ischemia, tumors, and posterior
reversible encephalopathy syndrome.However, not all emergent causes of
headache are excluded by a negative head CT. Identifying which patients
should undergo further imaging work-up, as well as the precise nature of
that evaluation, can be a challenge for emergency room physicians and
In the first part of this 2-part series, the
authors reviewed potentially life-threatening causes of headache that
commonly result in visible abnormalities on NCT. In the second part of
this series, we consider causes of headache in which the initial NCT
usually or often fails to detect the disease, but other imaging may
ultimately allow one to make the correct diagnosis.
these particular conditions can be difficult, as physicians in the ED
may not pursue further diagnostic imaging if the initialNCT is negative.
Nonetheless, some of these conditions may in fact be life-threatening,
requiring urgent treatment. Correctly establishing the diagnosis, then,
requires appropriate levels of clinical suspicion, and also requires
that the radiologist be aware of the potential limitations of the
initial NCT and be prepared to suggest alternative imaging strategies
for appropriate patients.
Dural sinus thrombosis
sinus thrombosis (DST) causes headache by virtue of impairment of
venous outflow from the brain with resultant increase in intracranial
pressure. Occasionally the headache is accompanied by altered mentation,
decreased level of consciousness, and papilledema. The diagnosis can be
difficult to establish on NCT. As a result, patients are often not
diagnosed until subsequent imaging studies are performed.
specific feature on NCT is that of a hyperdense dural sinus. However,
thrombosed dural sinuses commonly do not show this characteristic
hyperdensity, which can lead to a false-negative diagnosis (Figure 1).2
The sensitivity of the hyperdense sinus sign has been reported as low
as 20%, and therefore the diagnosis may be missed in a large proportion
of NCT examinations.3 To compound the problem,clinicians may
not consider the diagnosis because DST is a relatively uncommon entity.
As a result, neither clinician nor radiologist may pursue further
On contrast-enhanced CT, DST is seen as lack of
opacification of the thrombosed dural sinus. More sensitive noninvasive
imaging techniques for diagnosis of DST include magnetic resonance (MR)
imaging (showing loss of a flow void within the affected dural sinus),
MR venography (showing loss of flow-related enhancement), and CT
venography (in which the thrombus will be seen as a filling defect).
of the brain parenchyma may be present in some cases of DST. Venous
infarction results from thrombosis of dural venous sinuses and/or
cortical veins. Although venous infarction can be associated with
evidence of thrombosis on NCT (ie, a hyperdense sinus),this is not
always the case. In some cases of DST, the parenchymal findings may be
the only abnormality seen on NCT. It is therefore useful to consider the
appearance of venous infarction on NCT, as its appearance may mimic
other disease processes.
On initial inspection, venous infarction
may mimic the appearance of arterial infarction. Importantly, however,
venous infarctions will not be confined to the usual arterial vascular
territories, which may provide a clue to the correct diagnosis.
Furthermore, in contrast to arterial infarction, venous infarction
characteristically involves the subcortical white matter first and may
initially spare the overlying cortex,although cortical infarction may
follow if venous occlusion is severe or prolonged.4 As a
result of this cortical sparing, in some cases, the initial NCT
appearance may also mimic vasogenic edema associated with a neoplasm,
such as a metastasis (Figure 2). There may be associated hemorrhage in
the brain parenchyma in some patients with DST, although this is not
present in all cases. Patients presenting with headache who demonstrate
subcortical edema or hemorrhage on initial CT imaging should therefore
undergo further investigation of the venous sinuses.
is present in approximately 70% of patients with dissection of the
carotid or vertebral artery (co-called cervicocephalic arterial
dissection).5 Similar to DST, cervicocephalic arterial
dissection is a cause of worst headache of my life that is often
clinically unsuspected,which causes delay in performance of the
appropriate imaging study. The most common locations of cervicocephalic
arterial dissections are in the cervical portion of the internal carotid
artery (within a few centimeters of the carotid bifurcation) and the
segment of the vertebral artery that extends around the C1-C2 vertebral
body complex. Although arterial dissection can result in stroke,
ischemia may be present in fewer than half of patients with acute
dissection at initial presentation.6 Thus, it is not uncommon that brain imaging does not detect any abnormality (Figure 3).
CT imaging of the neck is of limited help in establishing the diagnosis
of arterial dissection; the dissection is inconspicuous against the
background of soft tissue. Instead, CT angiography or MR angiography are
sensitive imaging techniques for the diagnosis.Findings potentially
seen using either technique can include luminal narrowing due to the
intramural hematoma or pseudoaneurysm. When findings on these studies
are equivocal, catheter angiography may be indicated. Particular
clinical features that should prompt imaging investigation for the
possibility of dissection include the presence of neck or facial pain,
orbital pain, or Horner syndrome.6
Although it can be a cause of severe
headache, the diagnosis of meningitis is established by cerebrospinal
fluid (CSF) analysis and clinical symptoms. In uncomplicated cases of
meningitis, imaging is not necessary.7 In such cases, CT is usually normal and does not influence management.8 When an abnormality is present, it usually takes the form of mild, transient hydrocephalus.8
Occasionally, leptomeningeal enhancement can be seen on postcontrast
imaging (Figure 4); the absence of such enhancement does not exclude
Uncommonly, other complications can arise in the
setting of more severe infections, and imaging can play an important
role in these cases. Complications of severe meningitis can include
ventriculitis, extra-axial fluid collections (empyemas and subdural
effusions), parenchymal infection (cerebritis or abscess), and secondary
infectious vasculitis.7 Imaging with CT or MR may help to
identify these complications. Additionally, imaging may help to identify
the cause of meningitis in cases where there is a direct pathway for
spread of infection, such as in the case of complicated sinusitis, skull
base fractures, or prior surgery.
apoplexy is an uncommon cause of worst headache of life, and denotes
symptomatic hemorrhage within the pituitary gland,usually into a
pituitary adenoma. In many patients who present with pituitary apoplexy,
the adenoma has not been previously diagnosed, and therefore the
diagnosis is not often suspected initially.9 Clinical symptoms most commonly consist of headache, vomiting, and visual disturbance.9, 10
what may be pronounced clinical symptoms, initial imaging may fail to
reveal an abnormality. In a previous series of patients presenting with
pituitary apoplexy, intrasellar hemorrhage was not recognized on initial
NCT in the majority of cases, although intrasellar tumors were visible
in almost all cases on NCT.10,11 Failure to detect
intrasellar hemorrhage on the initial CT potentially could result from
partial volume averaging, and in some cases multiplanar reformation may
prove helpful in evaluating the sella when clinical suspicion is high.
abnormalities of the pituitary gland are visible, CT may reveal
expansion and hyperdensity of the gland, which may be accompanied by
mass effect on the suprasellar structures, including the optic chiasm
(Figure 5). MRI, by contrast, has demonstrated very high sensitivity for
the detection of pituitary apoplexy, and can be used to confirm the
diagnosis.10 Careful scrutiny of the sella and suprasellar
region should be a routine part of the search pattern when reviewing the
initial imaging of patients presenting with the “worst headache of my
life,” then, especially in patients presenting with headaches
accompanied by visual disturbances.
Disorders of CSF pressure
caused by disorders of CSF pressure are not uncommon. In some patients
with headache, CSF pressure may be too high, as in the case of
idiopathic intracranial hypertension (IIH, aka, pseudotumor cerebri), or
too low, as in the case of intracranial hypotension.
with IIH may present to the ED acutely with severe headache, but often
have a preexisting history of chronic headaches. They most commonly are
young, obese women.12 On physical exam, these patients may
have papilledema as a result of the increased intracranial pressure. The
discovery of papilledema may result in a head CT being performed to
exclude an intracranial mass, but in most cases of IIH the initial CT is
Patients with papilledema often undergo additional
imaging of the venous sinuses in order to exclude venous sinus
thrombosis as a cause for elevated intracranial pressure. Once
thrombosis is excluded, one sign suggesting the presence of IIH that may
be visible on venous sinus imaging is narrowing at the junction of the
transverse and sigmoid sinuses (Figure 6). This finding is hypothesized
to be due either to intrinsic stenosis of the vessel or collapse of the
sinus due to increased CSF pressure.13 On MRI, other
potentially subtle findings associated with IIH include flattening of
the posterior globe, dilation, and tortuosity of the optic nerve sheath,
and an empty sella.12 It should be emphasized that these
signs might suggest the diagnosis of IIH, but that ultimately the
diagnosis is established by lumbar puncture with measurement of opening
Patients with intracranial hypotension usually present
with headache that is worse when standing and improves when lying down.
Intracranial hypotension may be iatrogenic (due to lumbar puncture or
surgical penetration of the thecal sac), but in many cases is due to
spontaneous leakage of CSF from around the spine.14 In cases
of spontaneous intracranial hypotension, the onset of symptoms may be
abrupt,resulting in presentation to the emergency room with severe
Initial clinical misdiagnosis of intracranial
hypotension is common, which is compounded by the fact that initial CT
imaging in these patients is often normal (Figure 7).15 When
present, subtle features of cranial sagging and cerebellar tonsillar
ectopia may be appreciated on CT. Bilateral subdural hygromas or
hematomas may also accompany intracranial hypotension, and can be
identified on the initial scan, although the cause of the collections
may not be immediately recognized.16 In patients without a
history of trauma, bilateral subdural collections should prompt
consideration of the diagnosis of intracranial hypotension, and MRI
should be pursued as the next appropriate imaging step.
smooth dural enhancement is the most suggestive MR imaging feature.
Other variably present findings include crowding of the basilar cisterns
due to brain sagging, pituitary enlargement, cerebellar tonsillar
ectopia, and distension of the venous sinuses.17 Diagnosis is
ultimately determined through the combination of clinical symptoms, imaging findings, and CSF pressure measurement.18
NCT is the most common modality for evaluating the “worst headache of
my life,” several potentially life-threatening diseases will commonly
fail to show abnormalities on the initial NCT. These conditions may be
easily missed if they are not actively considered by treatingED
physicians and radiologists. While certain details of patients’
presentations may provide clues to suggest the presence of these
conditions,appropriate selection of additional imaging is also critical
to successful diagnosis. By understanding the strengths and limitations
of various imaging modalities, the radiologist may be uniquely
positioned to anticipate conditions at risk of being missed on initial
imaging, and to makesuggestions to help avoid this potential hazard.
Goldstein JN, Camargo CA, Jr., Pelletier AJ, et al. Headache in United
States emergency departments: Demographics, work-up and frequency of
pathological diagnoses. Cephalalgia. 2006;26:684-690.
C, Cazenave C, Quisling R, et al. The empty delta sign: Frequency and
significance in 76 cases of dural sinus thrombosis. Radiology. 1987;162:779-785.
- Provenzale JM, Joseph GJ, Barboriak DP. Dural sinus thrombosis: Findings on CT and MR imaging and diagnostic pitfalls. AJR Am J Roentgenol. 1998;170:777-783.
- Provenzale JM. Imaging evaluation of the patient with worst headache of life—it’s not all subarachnoid hemorrhage. Emerg Radiol. 2010;17:403-412.
- Mokri B. Headaches in cervical artery dissections. Curr Pain Headache Rep. 2002;6:209-216.
- Silbert PL, Mokri B, Schievink WI. Headache and neck pain in spontaneous internal carotid and vertebral artery dissections. Neurology 1995;45:1517-1522.
DC, Raghavan A, Mordekar SR, et al. Role of imaging in the diagnosis of
acute bacterial meningitis and its complications. Postgrad Med J. 2010;86:478-485.
- Cabral DA, Flodmark O, Farrell K, et al. Prospective study of computed tomography in acute bacterial meningitis. J Pediatr. 1987;111:201-205.
- Nawar RN, AbdelMannan D, Selman WR, et al. Pituitary tumor apoplexy: a review. J Intensive Care Med 2008;23:75-90.
- Bills DC, Meyer FB, Laws ER, Jr., et al. A retrospective analysis of pituitary apoplexy. Neurosurgery. 1993;33:602-608; discussion 608-609.
- Randeva HS, Schoebel J, Byrne J, et al. Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf). 1999;51:181-188.
- Degnan AJ, Levy LM. Pseudotumor cerebri: brief review of clinical syndrome and imaging findings. AJNR Am J Neuroradiol. 2011;32:1986-1993.
- Farb RI, Vanek I, Scott JN, et al. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology. 2003;60:1418-1424.
- Inamasu J, Guiot BH. Intracranial hypotension with spinal pathology. Spine J. 2006;6:591-599.
- Schievink WI. Misdiagnosis of spontaneous intracranial hypotension. Arch Neurol. 2003;60:1713-1718.
- Schievink WI, Maya MM, Moser FG, et al. Spectrum of subdural fluid collections in spontaneous intracranial hypotension. J Neurosurg. 2005;103:608-613.
PG, Gray L, Taylor JN. CT-guided epidural blood patching of directly
observed or potential leak sites for the targeted treatment of
spontaneous intracranial hypotension. AJNR Am J Neuroradiol. 2011;32:832-838.
- Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006;295:2286-2296.