History of presenting illness
The patient is a male in his 20s who presents to the emergency department (ED) with a chief complaint of headache. He has experienced an intermittent headache for the past month, located on the left side of his head. He describes the pain as aching and throbbing. He is unsure what has been causing the headaches and has not recognized any patterns. The headache worsened today and he had one episode of emesis prior to arrival. He also notes occasional photophobia and blurry vision in his left eye that resolves after closing the eye. He has been taking acetaminophen without re-lief. He denies fevers, neck pain or stiffness, and recent trauma. He denies a history of headaches and has no family history of migraines.
Past Medical History: None
Past Surgical History: None
Medications: Acetaminophen, ibuprofen
Allergies: No known
Vitals T 98.7° HR 76 BP 134/77 RR 16 SaO2 98%
Physical Exam: The patient appears his stated age and is in no apparent distress. He has no signs of external trauma to his head. His pupils are equal, round, and reactive to light, and his extraocular muscles are intact without any notable deficits. He has mild ptosis of his left eye. His cranial nerve exam reveals numbness in the left face along the entire distribution of the trigeminal nerve. His strength and sensation testing is normal in bilateral upper and lower extremities. He performs the finger-to-nose test without difficulty. He exhibits no meningismus. He is observed ambulating in the emergency department without abnormal gait. Pulmonary and cardiac auscultation is normal. The patient’s skin, vascular, and abdominal exams are normal.
Noncontrast CT Head: Mild increased density involving the left transverse sinus. CT venography is recommended to exclude venous sinus thrombosis.
CT Angio Head: Thombosis of the left transverse sinus, left sigmoid sinus, and proximal left internal jugular vein.
The patient was treated symptomatically for his headache with 1 L of lactated ring-ers, 10 mg of prochlorperazine, and 15 mg of ketorolac. The emergency department providers were concerned this was a new onset headache with neurologic findings including blurry vision, ptosis, and facial numbness. A non-contrast CT head showed a mild increased density involving the left transverse sinus, and radiology recommended CT angiography of the head to evaluate for venous sinus thrombosis. The patient’s CT venogram showed a thrombosis of the left transverse sinus, left sigmoid sinus, and proximal left internal jugular vein. A heparin drip was started and both neurosurgery and neurology were consulted. Neurosurgery felt that no surgical intervention was necessary, and the patient was admitted to the neurology service. The patient was bridged with enoxaparin and was transitioned to warfarin on hospital day one. An MRI of the brain confirmed the findings seen on CT, showing an acute thrombosis of the left transverse sinus extending into the sigmoid and jugular bulb with no parenchymal abnormalities. The patient had a hypercoagulability workup that was unremarkable. He also had autoimmune testing that showed a positive ANA, dsDNA and SCL-70. These findings were felt to be non-specific and did not lead to a definitive diagnosis. He was discharged in good condition on hospital day five with outpatient rheumatology follow up.
Cerebral venous thrombosis (CVT) is a rare dis-ease that is challenging to diagnose. CVT is a spectrum of disease that includes thrombosis of the major dural sinuses (most common), the deep cerebral veins, and the cortical veins. Although the term “dural sinus thrombosis” is often used interchangeably with CVT, it actually represents a specific sub-type of CVT based on the location of the thrombosis. Anatomically, the cerebral venous drainage consists of the superficial and deep venous systems. The cortical veins drain into the major dural sinuses with a complex system of anastomosis and high variability in anatomy from person-to-person. The major dural sinuses include the superior sagittal sinus, inferior sagittal sinus, straight sinus, lateral sinus (consisting of the transverse and sigmoid sinus), cavernous sinus, and occipital sinus. All of the sinuses ultimately drain into the internal jugular vein (Figure 4).
CVT accounts for approximately 1% of all neurovascular disease and is three times more likely in women.[2,3] This female predominance is likely due to hypercoagulability secondary to pregnancy/puerperium and oral contraceptives. CVT is more common in young patients, with 80% of patients under the age of 50 and a median age of 39 years. The International Study on Cerebral Vein and Dural Sinus Thrombosis identified that greater than 85% of patients with CVT have at least one risk factor. Prothrombotic states such as Factor V Leiden and deficiencies of antithrombin III or protein C/S can increase the risk of CVT. Acquired conditions such as pregnancy, oral contraceptives use, or malignancy were noted in 34% of patients. Infections, chronic inflammatory diseases, head trauma, and recent neurosurgical procedures were also identified as risk factors for CVT.
The pathophysiology of CVT is due to venous and CSF obstruction. Thrombosis of cerebral veins or dural sinuses obstructs blood drainage from brain tissue, resulting in increased capillary and intracranial pressure (ICP). This leads to decreased cerebral perfusion and ischemic injury to brain parenchyma. Cytotoxic edema develops and causes disruption of the blood-brain barrier. Vasogenic edema occurs from disruption of the blood-brain barrier, ultimately resulting in venous rupture and intraparenchymal hemorrhage (IPH).[5,6]
The clinical presentation of CVT is highly variable and predominantly depends on the location of the thrombosis, the time between onset of symptoms and hospital presentation, and the presence of parenchymal brain involvement. Clinical syndromes at presentation can be divided into four groups.[4,6] The first is isolated intracranial hypertension syndrome, which includes headache, vomiting, papilledema, and visual symptoms. The second syndrome consists of focal motor or sensory deficits. The third syndrome presents with new onset seizures. The final syndrome presents with global encephalopathy and is more common in elderly patients.
Overall, headache is the most common symptom of CVT and is found in ~90% of patients. The headache may be sudden in on-set and severe, mimicking subarachnoid hemorrhage, or it may be persistent and gradually worsening. The location of the headache has no spatial relationship with the occluded sinus or parenchymal lesions.
Isolated thrombosis of a specific dural sinus produces classic symptomatology. Cortical vein thrombosis causes motor and sensory deficits with concomitant seizures. Cavernous sinus thrombosis results in ocular pain, chemosis, proptosis, and oculomotor palsy. Sagittal sinus thrombosis lead to bilateral motor deficits and seizures. Lateral sinus thrombosis presents with isolated intracranial hypertension and auditory symptoms such as tinnitus. Left trans-verse sinus thrombosis leads to language deficits and aphasia. Deep venous sinus thrombosis (i.e. straight sinus) causes altered level of consciousness with severe cases resulting in coma. Deep venous sinus thrombosis usually results in severe motor deficits as well.
The diagnosis of CVT should be suspected in patients under 50 years of age with headaches and atypical features, including focal neurologic deficits, seizures, encephalopathy, or signs of intracrani-al hypertension. Non-contrast head CT is the first test that should be obtained in the ED to rule out other acute or subacute cerebral disorders. 30% of CVT cases have a normal non-contrast head CT and most findings are nonspecific. The gold standard for diagnosis of CVT is with MRI, as it has the highest sensitivity among imaging modalities. However, MRI availability can be limited and must be interpreted by an experienced neuroradiologist. For this reason, CT venography (CTV) may be the preferred imaging modality due to its availability, shorter duration, and easier interpretation. Studies are conflicting on how CTV performs against MRI, but there is emerging evidence that it is as sensitive as MRI.
Aside from neuroimaging, there are no lab tests that can diagnose CVT, but routine blood studies including a CBC, chemistry panel, PT, and aPTT should be obtained anticipating the patient’s anticoagulation need. An elevated D-Dimer supports the diagnosis, but a normal D-dimer level is not sufficient to exclude the diagnosis if the physician has a high index of suspicion for CVT. In one meta-analysis, D-dimer yielded a sensitivity of 94% and specificity of 90%, but was unreliable in patients with isolated headache, subacute or chronic clinical presentations, and in those with a single affected venous sinus. Another study found the false negative rate of the d-dimer to be 24%. Because of the high frequency of thrombophilia among patients who develop cerebral venous thrombosis, screening for hypercoagulable conditions should be performed. Testing can include antithrombin, protein C, protein S, factor V leiden, pro-thrombin G20210A mutation, lupus anticoagulant, anticardiolipin, and anti-beta2 glycoprotein-I antibodies. These studies should be ordered prior to anticoagulation and after discussion with both neurology and hematology.
Acute management of CVT focuses on anticoagulation, management of sequelae (such as seizures and venous infarction), and aggressive ICP management to prevent herniation. Management should be performed in consultation with neurosurgery and neurology. For patients with signs of increased intracranial pressure, immediate action should be taken to reduce ICP. Head of bed elevation, hyperosmolar therapy, intensive care unit admission, and ICP monitoring may be required.
After initial stabilization, early anticoagulation is the mainstay of treatment. The rationale for anticoagulation is to prevent thrombus propagation, recanalize occluded sinuses and cerebral veins. There is also a role in preventing extracranial complications such deep vein thrombosis and pulmonary embolism given the relation to hypercoagulable states. Anticoagulants are safe to use in patients with CVT even with associated IPH, and the presence of IPH is not a contraindication to anticoagulation when the hemorrhage is caused by the CVT. Use of either heparin or low molecular weight heparin is efficacious for initial therapy, and patients can be transitioned to warfarin once stable. While unfractionated heparin has the benefit of a shorter half-life and can be quickly discontinued, it takes longer to reach therapeutic levels compared to low molecular weight heparin. For this reason, emergency physicians should discuss the initial anticoagulation plan with the admitting team to coordinate care and avoid switching from one agent to another as in the case described above. For provoked episodes where an underly-ing risk factor can be identified and treated, patients should remain on anticoagulation for 3-6 months. For unprovoked episodes, oral anticoagulation should be continued for 6-12 months. Currently, there is insufficient evidence for the use of direct oral anticoagulants in CVT. A systematic review of 169 patients with cerebral venous thrombosis suggested a possible clinical benefit with fibrinolysis in severe cases. However, IPH occurred in 17% of patients after fibrinolysis and was associated with clinical deterioration in 5%. Endovascular thrombolysis or mechanical thrombectomy may be considered for cases of anticoagulation failure. There is limited evidence to suggest significant benefit, and this should be reserved for refractory cases.
Most patients have complete or partial recovery after CVT. In one meta-analysis including 1180 patients, only 10% had permanent neurological deficits by 12 months and the 30-day mortality rate was 5.6%. The most common cause of death was brain herniation.
In summary, cerebral venous thrombosis is a rare disease that involves thrombosis in either the dural sinuses or the cortical veins. Most patients have risk factors for hypercoagulability and present most commonly with headache. Additional neurologic findings can be seen and are often related to the location of the thrombosis. Laboratory studies are not beneficial and neuroimaging must be obtained either with MRI or CTV. Anticoagulation is the mainstay of treatment even in the presence of IPH caused by the CVT, and the majority of patients have full to partial neurologic recovery. Although this is a rare diagnosis with favorable outcomes when caught early, emergency physicians must remain vigilant as morbidity and mortality rates increase substantially with delayed diagnosis.
authored by daniel gawron, m.d.
posted by matthew scanlon, m.d.
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