Cerebral vein thrombosis refers to the formation of a blood clot in intracranial veins. This condition comprises cortical vein thrombosis, dural vein thrombosis and venous sinus thrombosis.
Presentation
Clinical presentation of CVT patients largely depends on location and extent of thrombosis and possibly hemorrhagic infarction. Furthermore, symptom onset may be acute (< 48 hours; 37%), subacute (> 48 hours but < 30 days; 56%) or chronic (> 30 days; 7%) [1].
Most symptoms observed in CVT patients either correspond to intracranial hypertension, focal neurological deficits, seizures or encephalopathy [7].
- CVT interferes with blood drainage and causes an increase in venular, capillary and finally arterial blood pressure. Therefore, CVT patients may experience intense headaches that may aggravate or ease with posture changes. In fact, headaches are the most frequent cause of initial presentation. Elevated intracranial blood pressure may also provoke papilledema, visual impairment and disturb awareness.
- Focal neurological anomalies may comprise motor deficits and aphasia. Sensory malfunctions have been reported but are less common.
- Seizures are as common as neurological deficits and may be observed in about one out of three patients. Both focal and generalized seizures have been reported in CVT and patients may enter status epilepticus.
- Mental status changes are the main manifestation of encephalopathy.
Entire Body System
- Weakness
While the first patient presented with severe unremitting headache with papilledema due to raised intracranial pressure, the second patient presented with seizures and focal weakness due to parenchymal hemorrhage. [neurology.org]
Possible neurological signs include hemiparesis, weakness of the lower limbs, sometimes bilaterally, aphasia, ataxia, chorea and hemianopia. [patient.info]
Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures. [en.wikipedia.org]
In addition, one patient developed unilateral weakness and parasthesias, whereas a second patient developed a partial seizure. [ajnr.org]
Seventy-three patients had limb weakness with 68 having hemiplegia (right side 40; left side 28) and five had quadriplegia without difference between the groups. Two patients had isolated aphasia and three had ataxia. [jscisociety.com]
- Anemia
Deep cerebral vein thrombosis due to iron deficiency anemia: A case report Abstract We report on a 28-year-old woman who developed deep cerebral vein thrombosis (CVT) associated with iron deficiency anemia (IDA). [sciedupress.com]
Severe anemia defined as hemoglobin n = 34; 41.97%) than the pregnancy-related CVT group ( n = 10; 14.49%). Fifteen nonpregnant CVT women had used oral contraceptives and five of them also had anemia. [jscisociety.com]
Causes of on-going or recurrent thrombosis should be identified and treated aggressively, such as iron deficiency anemia, parameningeal infection (mastoiditis), inflammatory bowel disease, nephrotic syndrome, and antiphospholipid antibody syndrome. [clinicaladvisor.com]
[…] infection, injury, or abnormality Head and neck infections (ex, otitis media, mastoiditis, sinusitis ) Local trauma Systemic Illness Dehydration Sepsis Cardiac Disease Connective Tissue Disorders Live Disease Nephrotic Syndrome Behcet’s Disease Cancer Anemia [pedemmorsels.com]
Risk factors for children and infants include: Problems with the way their blood forms clots Sickle cell anemia Chronic hemolytic anemia Beta-thalassemia major Heart disease — either congenital (you're born with it) or acquired (you develop it) Iron deficiency [hopkinsmedicine.org]
Eyes
- Chemosis
thrombosis location time since onset presence of parenchymal brain involvement (e.g. haemorrhage) or intracranial hypertension Thrombus location is associated with certain signs and symptoms: Cavernous sinus thrombosis: ocular signs (orbital pain, chemosis [lifeinthefastlane.com]
Rare but classical clinical pictures are that of superior sagittal sinus thrombosis (4%) with bilateral or alternating deficits and/or seizures and cavernous sinus thrombosis (3%) with chemosis, proptosis and painful ophthalmoplegia. [ijri.org]
– Cavernous sinus thrombosis is associated with ocular pain, chemosis, proptosis, and oculomotor palsies. 3,4 Figure 1 – Cerebral venous system components 2, image from Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. [emdocs.net]
Cavernous sinus thrombosis, a different entity, is associated with ocular pain, chemosis, proptosis, and oculomotor palsies [3,4]. [epmonthly.com]
[…] severe clinical presentation with coma, delirium and bilateral motor deficits, but symptoms may be of milder intensity when the thrombosis is limited. [13] In occlusions of the cavernous sinus, the most prominent clinical manifestations are orbital pain, chemosis [annalsofian.org]
Neurologic
- Seizure
Mortality and residual disability are relevant in patients presenting with intracranial hemorrhage or with epileptic seizures. [ncbi.nlm.nih.gov]
If a seizure does not occur, seizure prophylaxis is not necessary. 1,2,11,39 Further testing for underlying etiology is recommended, including thrombophilia. 1,2,3,6 Follow up imaging at 3-6 months is required to assess for recanalization of the affected [emdocs.net]
Seizures, including focal, generalized, and status epilepticus, are seen in 30–40% of patients [7,11]. As seizures are rare in strokes, CVT should be considered in any patient with a focal neurologic deficit and seizure [1,2]. [epmonthly.com]
Sagittal sinus thrombosis: motor deficits, bilateral deficits, seizures Lateral sinus thrombosis: isolated intracranial hypertension Left transverse sinus thrombosis: Aphasia Deep venous sinus (straight) thrombosis: behavioural symptoms (thalamic lesions [lifeinthefastlane.com]
- Papilledema
Check for papilledema in cases presenting with headache. Look for potential risk factors of CVT. [pedemmorsels.com]
and hypertensive encephalopathy (altered mental status with papilledema and end‐organ damage in the setting of severe hypertension) 10 serious causes of headache to consider for every ED patient with headache Lesion on CT scan (blood, pus or tumor): [emergencymedicinecases.com]
While the first patient presented with severe unremitting headache with papilledema due to raised intracranial pressure, the second patient presented with seizures and focal weakness due to parenchymal hemorrhage. [neurology.org]
[…] sigmoid sinuses) or mastoiditis Rhinogenic (e.g., after sinusitis ) Through facial infections Meningitis References: [3] [4] [5] Pathophysiology Clinical features Headache (acute, subacute, or chronic) Nausea, vomiting, vision impairment ; ), bilateral papilledema [amboss.com]
The cranial nerves examination revealed no abnormality except papilledema. There was no other focal deficit. [pubs.sciepub.com]
- Meningism
Other rare cause of CVT with lymphocytic meningitis is neurobrucellosis [ 3 ]. [casereports.in]
[…] infections (e.g.sinusitis, otitis media, meningitis, head and neck infections) mechanical injury to the sinuses or jugular veins (e.g. trauma, venous catheterisation, neurosurgical procedures) drugs (e.g. androgens, IV immunoglobulin) haematological [lifeinthefastlane.com]
The specific causes include meningitis and otitis media, head injury, instrumentation (such as jugular central venous catheter), surgery and drugs. Cerebral vein thrombosis can be asymptomatic or symptomatic. [angiologist.com]
[…] cell disease ) Nephrotic syndrome Dehydration Infectious Otogenic (e.g., after acute otitis media ) → generally infection of the lateral sinuses (transverse/sigmoid sinuses) or mastoiditis Rhinogenic (e.g., after sinusitis ) Through facial infections Meningitis [amboss.com]
There are numerous connections between the cortical veins and dural sinuses, and also with the venous system of the meninges, scalp and nasal sinuses. [jpma.org.pk]
- Confusion
Bizarre behaviour, confusion and adversive seizures occurred later. MRI showed haemorrhagic infarct in the bilateral basal ganglia and thalamus and abnormal signal density in the internal cerebral veins. [ncbi.nlm.nih.gov]
On neurological examination, he was drowsy, but arousable and confused. Fundus examination showed signs of early papilledema. There was no limb weakness but the bilateral plantars were extensor response. [nnjournal.net]
Patient was successfully managed with anticoagulation. » Case Report A 45-year-old female, weighing around 60 kg, presented with severe headache, multiple episodes of vomiting, and confusion for 5 days. [ijccm.org]
Confusion or diminished alertness. Fainting, loss of consciousness or coma. Diagnostic tests for CVT may include blood tests as well as MRI venogram (MRV) or CT venogram (CTV), which provide detailed images of the veins in your head. [elcaminohospital.org]
- Altered Mental Status
Head computed tomography (CT) is a common first line test in patients with new headache, focal neurologic symptom, seizure, or altered mental status. [epmonthly.com]
[…] examination including papilledema 29 (15%) patients, altered mental status 38 (19%), and focal neurological deficit 45 (22%) patients. [link.springer.com]
and hypertensive encephalopathy (altered mental status with papilledema and end‐organ damage in the setting of severe hypertension) 10 serious causes of headache to consider for every ED patient with headache Lesion on CT scan (blood, pus or tumor): [emergencymedicinecases.com]
mental status or GCS Male Age >37 years CVT affects the deep venous system References and Links LITFL CCC — Thrombophilia screen Journal articles Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Rafael Moscote-Salazar L. [lifeinthefastlane.com]
Workup
Diagnostic imaging is applied to confirm a tentative diagnosis of CVT, to locate the thrombus (or thrombi) and to assess brain damage. Magnetic resonance flow imaging and contrast-enhanced computed tomography scans are most commonly carried out to this end, with the former being more sensitive than the latter. As time elapses after thrombus formation, findings vary [1]:
- Initially, thrombi may be depicted as isointense areas in T1-weighted images and hypointense spots in T2-weighted images. Several days later, thrombi appear hyperintense in both weightings.
- In images obtained by contrast-enhanced computed tomography, filling defects indicate thrombi in veins or sinuses. Central, hypodense areas may be surrounded by hyperdense borders. Such findings are not to be expected during the first days after symptom onset, which is why magnetic resonance imaging has a higher sensitivity in cases of acute CVT.
- Brain edema and hemorrhages can be visualized by both techniques.
It is of utmost importance to determine whether a CVT patient is suffering from any systemic prothrombotic condition since such disorders also favor thrombus formation within other vessels. Consequently, affected individuals present increased risks of ischemic stroke, myocardial or renal infarction, and other thrombosis-related diseases. A screen for systemic hypercoagulability may comprise laboratory analysis of blood samples (hemogram, blood biochemistry and coagulation tests), diagnostic imaging (applying those techniques described for diagnosis of CVT itself) and genetic testing [8].
If no risk factor can be identified, repeated analysis after a few weeks is recommended. Certain malignancies, for instance, may cause hypercoagulability. If they are not detected during initial exams but during follow-ups, treatment may still be initialized in a timely manner.
Of note, recovery (principally recanalization and development of collaterals) and possible recurrence should also be monitored in follow-ups, ideally by means of magnetic resonance imaging.
Treatment
Thrombolysis is the mainstay of CVT treatment. For a long time, it has been a matter of debate whether patients who are presenting with intracranial hemorrhage due to CVT should receive heparin and/or fibrinolytics. This therapeutic approach continues to rise significant concern, but available data emphasize the importance of an early thrombolytic therapy in all patients [9]. As has been mentioned above, mortality is significantly higher in those patients who do not receive thrombolytic therapy [1].
Chemical and/or mechanical thrombectomy should be considered in patients who deteriorate under standard therapy or who are moribund on presentation [9]. These patients should nevertheless receive anticoagulants.
Additionally, supportive measures may be provided to relieve symptoms associated with CVT. For instance, patients who suffer from seizures may benefit from anti-epileptic drugs like sodium valproate or phenytoin. Benzodiazepines are generally administered to terminate status epilepticus [10].
Prognosis
Availability, sensitivity and specificity of modern imaging techniques have significantly decreased CVT-associated mortality. A large retrospective study based on data obtained in more than 600 cases diagnosed in nearly two dozen countries yielded the following results: about 80% of all CVT patients recovered completely, 10% remained mild to moderately disabled, 2% remained severely disabled and 8% died [4].
Early initiation of thrombolytic therapy considerably improves the outcome and if thrombolysis is not carried out, mortality rises to more than 60% [1]. Unfavorable prognostic parameters are decreased awareness, cerebral hemorrhages, status epilepticus and paralysis. These symptoms are often associated with hemorrhagic infarctions visible in images obtained by magnetic resonance imaging or computed tomography scans..
Etiology
A plethora of congenital and acquired conditions may incline the balance between coagulation and fibrinolysis towards the former.
With regards to congenital diseases, a variety of genetic disorders may cause a systemic prothrombotic condition. Prothrombin G20210A and factor V Leiden mutation as well as deficiencies in protein C, protein S or antithrombin III shall be mentioned as examples for hereditary diseases associated with an increased risk of CVT [2] [3]. Mutations of the gene encoding for methylenetetrahydrofolate reductase have also been proposed as possible triggers of CVT [2]. Such mutations are commonly associated with thrombosis.
More commonly, CVT is caused by acquired disturbances of hemostasis. Such disorders may provoke thrombi formation in distinct vessels of the whole body or be restricted to determined intracranial areas. Dehydration, use of oral contraceptives, pregnancy and puerperium as well as antiphospholipid syndrome and hypercoagulability due to malignancies are related to an overall increased risk of vein thrombosis. This also applies for pathologies causing polycythemia or thrombocytosis. Head trauma, intracranial neoplasms or inflammatory processes affecting either the brain itself or adjacent tissues are possible local causes of CVT. Malignant otitis media, mastoiditis and sinusitis may compromise cerebral veins; although inflammation is less identified as the cause of CVT.
In the majority of cases, at least one of the aforementioned risk factors is identified in patients presenting with CVT. This particularly applies to pediatric patients and young adults. In the elderly, the proportion of cases that cannot be ascribed to any underlying disease is more prominent.
Epidemiology
In general, CVT is an uncommon disease. It is also a rare cause of cerebral infarction. The annual incidence of CVT has been repeatedly estimated to be less than 1 per 100,000 inhabitants. Incidence rates don't seem to vary among different age groups, but the likelihood of suffering CVT is significantly increased in patients pertaining to the above mentioned risk groups. Pregnancy, for instance, causes a 10-fold increase in the risk of CVT.
In general, most patients are diagnosed with CVT during their fourth and fifth decade of life, but young children account for considerable shares of CVT patients too.
Women are affected three times more often than men [4]. Pregnancy, puerperium and the use of oral contraceptives have been identified as gender-specific risk factors and may partially explain the observed female predilection, which is less marked in children and elder women than in young adults. Women tend to suffer from CVT at younger ages and have a better prognosis than men.
Pathophysiology
Endothelial lesions, blood stasis and alterations of blood composition - commonly known as Virchow's triad - are the main triggers of thrombosis and CVT is no exception to this rule [5]. As indicated in the Etiology section of this article, many conditions may evoke one of those states and since they are mutually dependent, this may lead into a self-perpetuating cycle. Endothelial lesions, for instance, may result from local inflammatory processes. They cause formation of white thrombi, i.e., of blood clots that mainly consist of thrombocytes. However, local disturbances of blood flow cause blood stasis and formation of secondary red thrombi. Consequently, the thrombus grows and blood drainage decreases further.
Reduction of venous drainage due to CVT causes cerebral blood flow to decrease. Those brain regions that are drained by the affected vessel are not supplied with oxygen and nutrients; the patient sustains cerebral infarction. Because vessels passing through the infarct core are filled with blood, CVT triggers hemorrhagic infarction not ischemic stroke. Pathophysiological events following infarction and blood-brain barrier breakdown are neuronal death, cytotoxic and vasogenic edema, hemorrhages, hematoma, microgliosis and astrogliosis. Persistent neuroinflammation may significantly contribute to CVT-associated morbidity and mortality.
Additionally, thrombi may exert a local mass effect and compress adjacent tissues. Cavernous sinus syndrome, for instance, is associated with neurological symptoms due to compression of the oculomotor, trochlear, trigeminal and/or abducens nerves (cranial nerves III, IV, V and VI, respectively). It is caused by space-occupying processes taking place in the cavernous sinus - by CVT, for instance [6].
Prevention
Appropriate hydration is an important preventive measure against CVT. This applies particularly to patients pertaining to any of the above described risk groups, e.g., pregnant women, women who take oral contraceptives, anyone suffering from a systemic illness or a disease affecting the head and neck region.
Patients diagnosed with inherited thrombophilia should receive prophylactic treatment against CVT.
Summary
Cerebral vein thrombosis (CVT) refers to the formation of a blood clot in intracranial veins and most commonly, this condition affects more than one vessel.
Of note, physicians often use the term cerebral thrombosis in a broader sense and may not only refer to thrombus formation within a cerebral vessel, but also to vessel occlusion due to thromboembolism. The former more frequently occurs in veins and vein sinus and is the topic of this article. Emboli, in contrast, tend to lodge in arteries. They block arterial blood supply to dependent tissues and cause ischemic infarction. Thromboembolism is the most common cause of stroke and incidence rates are much higher than those of CVT.
Thrombus formation may be triggered by a variety of local and systemic diseases that provoke endothelial damage or that interfere with the equilibrium between pro- and anticoagulatory factors. And although small thrombi may not significantly diminish blood drainage, they do constitute obstacles that alter fluid mechanics locally. This contributes to the formation of secondary red thrombi and further reduction of venous outflow. In severe cases, the affected vein or vein sinus may become occluded.
The above described events may lead to hemorrhagic infarction of the area drained by the affected vessel and trigger symptoms of stroke. Contrary to thromboembolic stroke, symptom onset is not necessarily acute. Indeed, subacute or chronic onset of symptoms is observed in two out of three patients presenting with CVT [1]. Clinical presentation varies largely and complaints range from headaches, visual impairment and dysarthria to hemiparesis and coma.
CVT is diagnosed by means of neuroimaging and treatment generally consists of thrombolysis.
Patient Information
Cerebral vein thrombosis (CVT) is the medical term for the formation of a blood clot within an intracranial vein. Thrombi may interfere with blood drainage, cause an increase in venular, capillary and finally arterial blood pressure and thus reduce cerebral blood flow. This may lead to hemorrhagic infarction and stroke.
Of note, CVT is an uncommon trigger of stroke. Most cases of cerebral infarction are provoked by thromboembolism, i.e., blood clots form within any vessel and are carried away into cerebral arteries.
Causes
Any condition provoking endothelial damage or blood stasis in cerebral vessels as well as pathologies that incline the balance between coagulation and fibrinolysis towards the former may cause CVT. The following shall be mentioned as examples:
- Genetic disorders like prothrombin G20210A and factor V Leiden mutation, deficiencies in protein C, protein S or antithrombin III
- Head trauma or surgery
- Inflammation of brain, meninges or adjacent tissues
- Pregnancy, puerperium
- Use of oral contraceptives
Symptoms
The most common symptom of CVT are headaches. Symptom onset may be acute, subacute or chronic and patients may claim headaches to intensify within hours, days or weeks. Possibly, headaches aggravate when adopting certain postures.
Further symptoms of CVT are:
- Visual impairment
- Diminished awareness, loss of consciousness
- Motor deficits like hemiplegia
- Aphasia
- Seizures
- Altered mental status
Diagnosis
In order to confirm a tentative diagnosis of CVT, magnetic resonance imaging or computed tomography scans will be applied. By means of these techniques, the affected vein and the thrombus lodged within it can be visualized. They also allow for an evaluation of concomitant brain damage.
As has been indicated above, CVT may be triggered by a variety of conditions. Laboratory analyses of blood samples and genetic tests may be carried out to identify the cause of CVT in an individual case.
Treatment
In most cases, drug-mediated thrombolysis is indicated. Patients receive heparin and/or fibrinolytics that dissolve the thrombus and facilitate recanalization. In severe cases, surgery may be necessary to mechanically remove the blood clot.
References
- Saposnik G, Barinagarrementeria F, Brown RD, Jr., 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):1158-1192.
- Marjot T, Yadav S, Hasan N, et al. Genes associated with adult cerebral venous thrombosis. Stroke. 2011; 42(4):913-918.
- Leach JL, Fortuna RB, Jones BV, et al. Imaging of cerebral venous thrombosis: current techniques, spectrum of findings, and diagnostic pitfalls. Radiographics. 2006; 26 Suppl 1:S19-41; discussion S42-13.
- Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004; 35(3):664-670.
- Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev. 2009; 23(5):225-229.
- Sweis R, Biller J. Cavernous Sinus Thrombosis in Children. Pediatr Neurol Briefs. 2016; 30(1):4.
- Piazza G. Cerebral venous thrombosis. Circulation. 2012; 125(13):1704-1709.
- Reitsma PH. Genetics in thrombophilia. An update. Hamostaseologie. 2015; 35(1):47-51.
- Medel R, Monteith SJ, Crowley RW, et al. A review of therapeutic strategies for the management of cerebral venous sinus thrombosis. Neurosurg Focus. 2009; 27(5):E6.
- Falco-Walter JJ, Bleck T. Treatment of Established Status Epilepticus. J Clin Med. 2016; 5(5).