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Cerebral Vein Thrombosis

Cerebral Venous Thrombosis

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.
Hemophilia A
  • Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialities, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. martin@policlinico.mi.it Abstract The estimated annual incidence of cerebral[ncbi.nlm.nih.gov]
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]
  • 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]
  • 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]
  • Lateral Sinus Headache Hemoanopia, contralateral weakness and aphasia Deep Cerebral Venous( internal cerebral vein, vein of Galen and straight sinus) Result in rapid deterioration, secondary to thalamic or basal ganglion infarction.[resus.com.au]
  • It was associated with weakness of right side of the body. On examination, her Glasgow Coma Scale was 14 and motor power was 4/5 in the right upper and lower extremities. Fundoscopy revealed papilledema.[ijccm.org]
Plethora
  • 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.[symptoma.com]
Malaise
  • A 40-year-old man developed general malaise, dizziness and progressive headache 1 week after acute haemorrhagic conjunctivitis. Bizarre behaviour, confusion and adversive seizures occurred later.[ncbi.nlm.nih.gov]
Hyperpnea
  • Postoperatively he failed the weaning trials because of brain dysfunction characterized by confusion, agitation and hyperpnea.[ncbi.nlm.nih.gov]
Seizure
  • Mortality and residual disability are relevant in patients presenting with intracranial hemorrhage or with epileptic seizures.[ncbi.nlm.nih.gov]
  • 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.[symptoma.com]
  • 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]
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]
  • ., after sinusitis ) Through facial infections Meningitis References: [3] [4] [5] Pathophysiology Clinical features Headache (acute, subacute, or chronic) Nausea, vomiting, vision impairment ; ), bilateral papilledema on ophthalmoscopy Cranial nerve symptoms[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]
  • ., after sinusitis ) Through facial infections Meningitis References: [3] [4] [5] Pathophysiology Clinical features Headache (acute, subacute, or chronic) Nausea, vomiting, vision impairment ; ), bilateral papilledema on ophthalmoscopy Cranial nerve symptoms[amboss.com]
  • We have previously covered some important conditions to consider when evaluating headache (ex, AVM, RMSF, Meningitis, Post-LP, Moyamoya, Migraine, Pseudotumor, and Pheochromocytoma ).[pedemmorsels.com]
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]
  • 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]
  • 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]
  • Filling defects should not be confused with Pacchionian bodies (arachnoid granulations) which can be seen in essentially all dural sinuses and are especially common in the superior sagittal sinus and transverse sinus.[radiopaedia.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]
  • 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]
  • 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[symptoma.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.

Brain Edema
  • Brain edema and hemorrhages can be visualized by both techniques.[symptoma.com]
  • Two different mechanisms have to be identified; however, they are interrelated in many cases. [4] The occlusion of a cerebral vein leads to localized brain edema and a so-called venous infarction.[annalsofian.org]
  • The main cause of acute death with CVT is transtentorial herniation secondary to a large hemorrhagic lesion, 5 followed by herniation due to multiple lesions or to diffuse brain edema.[stroke.ahajournals.org]

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.

Sex distribution
Age distribution

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:

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:

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

Article

  1. 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.
  2. Marjot T, Yadav S, Hasan N, et al. Genes associated with adult cerebral venous thrombosis. Stroke. 2011; 42(4):913-918.
  3. 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.
  4. 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.
  5. Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev. 2009; 23(5):225-229.
  6. Sweis R, Biller J. Cavernous Sinus Thrombosis in Children. Pediatr Neurol Briefs. 2016; 30(1):4.
  7. Piazza G. Cerebral venous thrombosis. Circulation. 2012; 125(13):1704-1709.
  8. Reitsma PH. Genetics in thrombophilia. An update. Hamostaseologie. 2015; 35(1):47-51.
  9. 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.
  10. Falco-Walter JJ, Bleck T. Treatment of Established Status Epilepticus. J Clin Med. 2016; 5(5).

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Last updated: 2019-07-11 20:38