Headache is a common emergency department chief complaint. Although most are benign, emergency physicians must rapidly identify and manage the uncommon, sometimes subtle, presentation of headache from a life-threatening cause. Cerebral venous thrombosis imparts significant morbidity and mortality, and can be a challenging diagnosis. It most commonly occurs in those under 50 years of age with thrombosis of the cerebral veins/sinuses. Diagnosis is frequently delayed. The disease can present with 1 or more clinical syndromes, including intracranial hypertension with headaches, focal neurologic deficits, seizures, and encephalopathy. Diagnosis requires imaging. Treatment includes stabilization, management of complications, and anticoagulation.
Key points
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Cerebral venous thrombosis (CVT) is a rare and difficult diagnosis owing to a wide variety of signs and symptoms, commonly occurring in patients under 50 years of age.
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Scenarios warranting CVT investigation include atypical headache, stroke without risk factors or with seizure, unexplained intracranial hypertension, multiple hemorrhagic infarcts, hemorrhagic infarcts not in a specific arterial distribution, or objective neurologic examination findings.
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Laboratory examination, such as d -dimer testing and lumbar puncture, is not reliable for diagnosis.
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Imaging is required, including computed tomography with venography or magnetic resonance (MR) imaging/MR venography
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Treatment includes immediate stabilization, anticoagulation (even with hemorrhage present), and managing complications.
Introduction
Many conditions emergency physicians evaluate are simple and straightforward; however, emergency physicians train to recognize conditions that can be life threatening. Most patients with headaches will have benign etiologies, although some may be suffering a condition with high morbidity and mortality. Emergency physicians must expertly evaluate each patient for “red flags” that signify potential risk for morbidity and mortality. Cerebral venous thrombosis (CVT) is one such disorder.
CVT is a rare, accounting for approximately 0.5% to 1.0% of strokes, with an annual incidence of 1.32 cases per 100,000 population in the Netherlands and 0.22 cases per 100,000 population in Portugal. The disease includes thrombosis of the cerebral veins and major dural sinuses. CVT is more common in patients with a history of thrombophilia, women on oral contraceptives, and during pregnancy. It is 3 times more common in women. The diagnosis is often delayed, approximately 4 to 7 days after symptoms onset. The majority of patients present under the age of 50 years (80%), with a mean age of 39 years. Less than 10% of patients present over the age of 60 years.
Introduction
Many conditions emergency physicians evaluate are simple and straightforward; however, emergency physicians train to recognize conditions that can be life threatening. Most patients with headaches will have benign etiologies, although some may be suffering a condition with high morbidity and mortality. Emergency physicians must expertly evaluate each patient for “red flags” that signify potential risk for morbidity and mortality. Cerebral venous thrombosis (CVT) is one such disorder.
CVT is a rare, accounting for approximately 0.5% to 1.0% of strokes, with an annual incidence of 1.32 cases per 100,000 population in the Netherlands and 0.22 cases per 100,000 population in Portugal. The disease includes thrombosis of the cerebral veins and major dural sinuses. CVT is more common in patients with a history of thrombophilia, women on oral contraceptives, and during pregnancy. It is 3 times more common in women. The diagnosis is often delayed, approximately 4 to 7 days after symptoms onset. The majority of patients present under the age of 50 years (80%), with a mean age of 39 years. Less than 10% of patients present over the age of 60 years.
Discussion
Disease Presentation
Owing to the variety of signs and symptoms, CVT can be a challenging diagnosis. CVT should be suspected in several clinical scenarios ( Box 1 ). The signs and symptoms are highly variable, as is the onset, which may be acute, subacute, or chronic. The wide variety of symptoms and signs, combined with the rarity of the disease, make CVT an easy diagnosis to overlook. For example, a young female on oral contraceptive pills with a persistent headache is more likely to be experiencing a tension or migraine headache, and certainly neuroimaging is not appropriate in all such patients. However, the emergency physician must closely evaluate for other features of the presentation that are concerning for CVT, especially objective neurologic findings.
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Headache in a patient with risk factors and focal neurologic findings.
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Stroke without typical risk factors or in the setting of seizure.
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Unexplained intracranial hypertension.
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Multiple hemorrhagic infarcts, or hemorrhagic infarcts not in a specific arterial distribution.
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Objective neurologic deficits in a patient with risk factors for cerebral venous thrombosis.
Symptoms may vary with thrombus location. However, thrombus location does not reliably predict the actual clinical presentation, and patients may experience bilateral symptoms owing to venous sinus anatomy. Cortical vein thrombosis frequently presents with motor and sensory deficits, as well as seizure. Sagittal sinus thrombosis may present with motor deficits, sometimes bilateral, and seizures. Lateral sinus thrombosis may present with intracranial hypertension and headache alone. Thrombosis of the left transverse sinus can present as aphasia, whereas thrombosis of the deep venous sinus can cause behavioral symptoms owing to thalamic involvement. Cavernous sinus thrombosis, a different entity, is associated with eye pain, chemosis, proptosis, and oculomotor palsies. This condition is often associated with sinus infection; thus, treatment usually requires antibiotics in addition to the other standard treatments for CVT.
Four major CVT syndromes have been described in the literature: isolated intracranial hypertension (which is the most common), focal neurologic abnormality, seizure, and encephalopathy. The patient may present with one or more of the following syndromes.
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For intracranial hypertension, the most frequent symptom is a localized, persistent headache, which is seen in up to 90% of patients presenting acutely. This means that 10% of patients will not have a headache during their course, often accounting for a delay in diagnosis. Headache may be sudden in onset and severe, mimicking subarachnoid hemorrhage, or it may be persistent and gradually worsening. Visual symptoms may occur in association with the headache. The intensity of pain often increases with coughing, Valsalva maneuver, or bending over owing to increased intracranial pressure (ICP).
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Focal neurologic deficits are found in 37% to 44% of patients, with motor weakness the most common focal symptom. Motor weakness may include monoparesis, hemiparesis, or bilateral involvement. Fluent aphasia may also be seen, although sensory deficits are not common.
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Seizures, including focal, generalized, and status epilepticus, are seen in 30% to 40% of patients. Because seizures are rare in strokes, CVT should be considered in any patient with a focal neurologic deficit and seizure.
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The final syndrome is encephalitis, which can be found in patients with thrombosis of the straight sinus or with severe cases, including extensive hemorrhage, edema, and large venous infarcts leading to herniation. Elderly patients more commonly present with altered mental status and confusion.
Pathophysiology
Two major pathophysiologic mechanisms are associated with CVT, both leading to increased ICP, vasogenic and cytotoxic edema, and hemorrhage. The first mechanism includes thrombosis of cerebral veins and sinuses with increasing venular and capillary pressures. As local venous pressure increases, cerebral perfusion decreases causing ischemic injury and cytotoxic edema. Vasogenic edema occurs owing to disruption of the blood–brain barrier. This may lead to parenchymal hemorrhage if pressures continue to increase. The second mechanism includes decreased absorption of cerebrospinal fluid owing to obstruction of the cerebral sinuses. This blockage also leads to increased pressures, cytotoxic and vasogenic edema, and parenchymal hemorrhage.
Risk Factors
At least 1 risk factor is present in 85% of patients with CVT, although many of these risk factors are not identified until the diagnosis is made and further testing for thrombophilic conditions is completed. CVT is often multifactorial with several risk factors present, such as infection in a patient with an underlying thrombophilia. In fact, multiple risk factors are found in 50% of cases. A thrombophilia, such as deficiencies of antithrombin, protein C, and protein S, or the factor V Leiden mutation, is present in 34% of patients. Pregnancy, the postpartum state, and hormonal contraceptives are frequent risk factors in women. Local infections, including osteitis, mastoiditis, sinusitis, and meningitis, are associated with CVT. Chronic inflammatory states, such vasculitis, inflammatory bowel disease, malignancy, nephrotic syndrome, and hematologic disorders such as polycythemia and essential thrombocytosis, may also be contributory. Other risk factors include head trauma, local injury to the cerebral sinuses, and neurosurgical procedures ( Box 2 ).
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Thrombophilic state
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Oral contraceptive use
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The puerperium
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Central nervous system infection
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Systemic inflammatory states such as lupus or inflammatory bowel disease
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Cancer
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Hematologic disorders
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Neighboring site infection, such as sinusitis
Diagnosis
Delays in diagnosis are common owing to the wide variety of presentations. This disease must be considered in patients under 50 years of age with acute, subacute, or chronic headaches with atypical features, including focal neurologic deficit(s) (often not fitting a specific anatomic distribution or involving multiple vascular territories), seizures, signs of intracranial hypertension, or hemorrhagic infarction. Papilledema may be present on funduscopic examination, but this is neither sensitive nor specific. Patients may improve with pain medication; however, if focal deficit or seizure is present, further evaluation for CVT should be considered. Emergency physicians are masters of considering and evaluating for the subtle nuances of common complaints. This clinical acumen plays a large role in selecting the subset of patients with headache or neurologic symptoms for whom neuroimaging for possible CVT is appropriate.
Laboratory examination including complete blood cell count, metabolic panel, and a coagulation panel should be obtained. An elevated d -dimer may be found in patients with CVT. However, a d -dimer test cannot rule out the condition, especially in patients with risk factors. One study found a false-negative rate of 24% and false-positive rate of 9% in a cohort of 239 patients. Other studies have found a false-negative rate approaching 40% in patients with CVT presenting with isolated headache. Unfortunately, emergency physicians cannot rely on a normal d -dimer to rule out CVT, and a positive test does little to increase the likelihood of the diagnosis.
A lumbar puncture may be considered to evaluate for other causes of headache, such as meningitis or subarachnoid hemorrhage. Notably, in patients with CVT the lumbar puncture often reveals nonspecific findings such as increased protein, increased red blood cells, and lymphocytosis that may mimic other disease processes, including viral meningitis. These are present in 30% to 50% of cases. Increased ICP may occur in 25% of patients. If concern for CVT remains after obtaining lumbar puncture, neuroimaging should be strongly considered.
Neuroimaging is ultimately required for diagnosis. The American Heart Association and American Stroke Association guidelines recommend imaging of the cerebral venous system for patients with lobar intracerebral hemorrhage of unclear origin or with infarction in multiple arterial territories. Imaging should also be obtained in patients with idiopathic intracranial hypertension and headache with atypical features.
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Head computed tomography (CT) is the most common imaging modality in many neurologic situations, including patients with a new headache, focal neurologic deficit, seizure, or altered mental status. The American College of Emergency Physicians 2008 clinical policy provides a level B recommendation for obtaining head CT in any patient with headache and new abnormal neurologic finding(s). A noncontrast head CT is normal in 30% of CVTs, with the majority of scans demonstrating nonspecific abnormalities. As such, a negative noncontrast head CT cannot be used to rule out the disease. One-third of noncontrast head CTs demonstrate signs of CVT. Head CT noncontrast followed by administration of intravenous contrast may demonstrate direct signs, such as dense triangle sign (hyperdensity with triangular shape in posterior superior sagittal sinus), empty delta sign (triangular pattern of contrast enhancement surrounding a central area with no enhancement), and the cord sign (curvilinear density over the cerebral cortex). Indirect signs of CVT are more common and include contrast enhancement over the falx and tentorium, dilated venous structures, small ventricles, and parenchymal abnormalities (seen in 80%, including hemorrhagic and nonhemorrhagic lesions). As discussed and as shown in Box 1 , multiple infarctions or infarctions in several arterial distributions warrant further testing. Fig. 1 and the following images ( https://radiopaedia.org/cases/cerebral-venous-thrombosis-ct-only and https://radiopaedia.org/cases/cerebral-venous-thrombosis-5 ) demonstrate CT findings of CVT.
