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Cerebral Thrombosis

Cerebral Thromboses

Cerebral thrombosis refers to partial or complete occlusion of an artery supplying brain brain tissue or a vein draining such regions by a blood clot. Additionally, thrombi may form within or be carried to a cerebral vein sinus.


Presentation

CTE and ischemic stroke may manifest within minutes or hours, and affected individuals frequently suffer from sensory deficits, limb weakness, ataxia, hemiparesis, speech disturbances, unilateral visual impairment, and reduced consciousness [14]. Headaches, nausea, vomiting and seizures are only observed in some patients.

In contrast, headaches are by far the most common symptom of cerebral vein and sinus thrombosis. They are experienced by almost 90% of affected individuals [8]. More than a third of them sustains seizures, with generalized seizures occurring more frequently than focal seizures. Many patients present with hemiparesis. Other symptoms are observed in a minor share of cases and comprise diplopia and vision loss, aphasia, an altered mental status and reduced consciousness.

Of note, it is rarely possible to deduce the site of lesion from the clinical picture, although the nature of neurological deficits presented by an individual patient reflects the function of the affected brain region. The complexity of the neuronal network doesn't allow for reliable conclusions besides the fact that right-sided paresis indicates an infarction of the left hemisphere and vice versa.

Dutch
  • Case series from Dutch hospitals from 2003 to 2008. Five out of six patients were male, age ranged from 30 to 73 years (mean age, 47 years).[ncbi.nlm.nih.gov]
  • Look up "cerebral thrombosis" at Merriam-Webster Look up "cerebral thrombosis" at dictionary.com In other languages: Spanish French Italian Portuguese Romanian German Dutch Swedish Russian Polish Czech Greek Turkish Chinese Japanese Korean Arabic Advertisements[wordreference.com]
  • A Dutch study found an age-adjusted odds ratio of 13 for oral contraceptive use and risk of CVST. 10 Hereditary prothrombotic conditions such as Factor V Leiden (leading to increased resistance to activated protein C), deficiency of proteins C and S and[pmj.bmj.com]
  • The Dutch trial [62] compared fixed high-dose of subcutaneous nadroparin with placebo in 60 patients. It failed to show any statistically significant difference between groups.[annalsofian.org]
Turkish
  • The results of this study suggested that factor V G1691A and MTHFR C677T genotypes may be associated with an increased risk of developing CT in Turkish children.[ncbi.nlm.nih.gov]
  • Look up "cerebral thrombosis" at Merriam-Webster Look up "cerebral thrombosis" at dictionary.com In other languages: Spanish French Italian Portuguese Romanian German Dutch Swedish Russian Polish Czech Greek Turkish Chinese Japanese Korean Arabic Advertisements[wordreference.com]
Coronary Artery Disease
  • Causes of atrial fibrillation include dysfunction of the sinus node (the heart's pacemaking area in the right atrium), coronary artery disease, rheumatic heart disease, hypertension and hyperthyroidism. atrial flutter An atrial flutter is a very rapid[heart.org]
Stroke
  • Plasma tHcy concentrations of stroke patients with normal serum creatinine concentrations were not significantly different to those of controls. Hyperhomocysteinemia in Black patients with stroke may be partially caused by renal insufficiency.[ncbi.nlm.nih.gov]
  • In the group with unspecified type of stroke the blood-group distribution was practically the same as the distribution in the controls.[ncbi.nlm.nih.gov]
  • According to the National Stroke Association, stroke is the third leading cause of death in the United States but is the principal cause of disability in adults.[livestrong.com]
  • Blood tests The Stroke team will request that blood tests be done to test to see if your child has any underlying blood problems that could cause a stroke.[chop.edu]
Focal Neurologic Deficit
  • Headaches are a typical presenting manifestation of CVT, while focal neurological deficits, seizures , and increased intracranial pressure may develop as the disease progresses.[amboss.com]
  • Symptoms headaches decreased/altered conscious state decreased/altered vision nausea/vomiting Signs papilloedema cranial nerve palsies focal neurological deficits seizures coma CVT pathogenesis remains poorly understood 5 .[radiopaedia.org]
  • It often worsens with valsalva or coughing due to increased ICP. 9,10 Focal neurologic deficits are found in 37%-44% of patients , with motor weakness the most common focal symptom. 7,9 Sensory deficits are not common. 1,2 Seizures (focal, generalized[emdocs.net]
  • neurologic deficits (25-71%) – hemianopsia, contralateral weakness, aphasia etc Differential Diagnosis Ischemic stroke Intracranial Hemorrhage (ICH) Encephalitis Subarachnoid Hemorrhage Mass Effect (tumor, abscess etc) Hyperdensity of Dural Sinus on[coreem.net]
Lethargy
  • Patients with lethargy, coma, and status epilepticus should prompt consideration for treatment of brain herniation. NCHCT is a reasonable first-line test but cannot rule out the disease.[coreem.net]
  • In the most severe cases, lethargy progresses to coma, herniation, and death.[clinicaladvisor.com]
  • CVT in the Pediatric Population The incidence of pediatric CVT is 0.67 per 100 000 children per year. 91 When neonates are excluded, the reported incidence is 0.34 per 100 000 children per year. 249 Neonates present with seizures or lethargy, whereas[stroke.ahajournals.org]
Stupor
  • 69 ] According to the SCVT, the course of clinical manifestations can be summarized as follows: intensive and progressive cephalea, the main symptom; seizures (39.3%); paresis (37.2%); papilledema (28.3%); altered mental state (22%), aphasia (19.1%), stupor[ncbi.nlm.nih.gov]
Hyperactivity
  • Our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive.[ncbi.nlm.nih.gov]

Workup

The sudden onset of neurological deficits is highly suggestive of CT and subsequent infarction. However, the disease may also follow a subacute or chronic course, particularly in case of a partial occlusion of vessels or cerebral vein thrombosis. Furthermore, there is a considerable overlap of symptoms triggered by CT and intracranial hemorrhages, both of which may even occur concomitantly. Because "time is brain" in any type of stroke, it is of utmost importance to confirm the diagnosis, to localize the site of thrombosis and to assess the extent of brain damage as soon as possible. Conventional magnetic resonance imaging/angiography as well as computed tomography scans/angiography are most commonly employed to this end. The following may be observed:

  • With respect to magnetic resonance imaging, thrombi initially depict as isointense and hypointense foci in T1- and T2 weighted images, respectively. Over the course of time, the aspect of thrombi changes: After several days, they appear as hyperintense areas in both weightings. Ischemic brain tissue is best visualized in diffusion-weighted images.
  • In images obtained by means of contrast-enhanced computed tomography, acute CT may merely display as a filling defect in vascular structures. Remodelling processes eventually lead to thrombi appearing as hypodense areas surrounded by a hyperdense border. An intracranial hemorrhage depicts as a region of hyperdense signal intensity. Of note, non-contrast-enhanced computed tomography is preferred in patients presenting with acute stroke within three hours of symptom onset.

Moreover, transcranial Doppler sonography may be used to visualize an occlusion of vessels forming the circle of Willis or to diagnose CT in patients presenting with vertebrobasilar insufficiency [15].

In any case, blood specimens should be obtained to assess the overall condition of the patient (e.g., glucose, electrolytes, metabolic profile) and to carry out coagulation tests. Depending on the patient's medical history and the presence of additional symptoms, further measures may be necessary to diagnose an underlying condition predisposing for CT.

Listeria Monocytogenes
  • CSF culture yielded Streptococcus pneumoniae in ten patients and Listeria monocytogenes in one.[ncbi.nlm.nih.gov]

Treatment

Treatment primarily aims at reestablishing the blood flow through the occluded vessel. Although dependent brain tissue may already be irreversibly damaged, the ongoing disturbance of blood flow in downstream vasculature does predispose for additional thrombus formation and an exacerbation of the disease. Thrombolysis may be achieved by intravenous administration of recombinant tissue-type plasminogen activator (tPA), which is the only drug approved for ischemic stroke to date. The recommended dosage is 0.9 mg/kg, with a maximum dose of 90 mg. 10% of the total dose are given as a bolus within one minute, and the remaining dose is infused over an hour [16]. tPA application has to be initiated within a few hours after the onset of stroke, and the respective time window has been defined as 3 and 4.5 hours in North America and Europe, respectively. For country-specific recommendations, the reader is referred to a recent publication on this topic [17]. Mechanical thrombolysis may constitute an alternative to tPA therapy, particularly in patients who present past the abovedefined time window or in those individuals who fail to respond to intravenous tPA [18]. Angioplasty and stenting may be performed. Patients suffering from malignant middle cerebral artery occlusion may require an emergency decompression by means of craniotomy. This procedure has been shown to improve survival rates.

Additional therapeutic measures may comprise the following [16]:

  • Assessment of airways, breathing and circulation; possibly supplementation of oxygen, mechanical ventilation
  • Maintenance of physiological body temperature, e.g., by administering antipyretics
  • Fluid therapy
  • Oral administration of aspirin as an antiplatelet agent
  • Administration of antihypertensive medication like labetalol and nicardipine: While indicated in case of severely increased blood pressure, moderate hypertension may favor cerebral perfusion and recanalization. Patients presenting with hypotension may thus be given vasopressors.
  • Antiepileptic treatment in case of seizures

Prognosis

In cases of an association of CT with ischemic or hemorrhagic stroke, morbidity and mortality rates are high. In fact, ischemic infarction has been reported to account for 5 deaths per 100,000 inhabitants and year, while hemorrhagic stroke causes twice as many deaths within the same period of time. Considering that incidence rates of ischemic stroke are much higher, these values indicate a worse prognosis for those patients sustaining hemorrhagic infarction. Case fatality rates for ischemic and hemorrhagic stroke were 6 and 20% at ten days, and 21 and 32% at one year, respectively [12].

A multinational study on the outcome of cerebral vein and sinus thrombosis yielded the following results after a median follow-up of 16 months [8]:

  • No sequelae in 57% of patients
  • Minor, mild, moderate, and severe disability in 22, 8, 3 and 2% of patients, respectively
  • Overall mortality of 8%

Unfavorable prognostic factors include increased age, male sex, seizures, hemiparesis, severe neurological deficits, coma, thrombosis of the deep venous system, and intracranial hemorrhage, among others [13].

Etiology

A plethora of pathologies may lead to CT, either by inducing ICT or by increasing the overall likelihood to develop thrombi and to suffer the consequences of CTE. They may be classified as follows:

  • Any inflammatory process affecting the brain - be it encephalitis, meningitis or an inflammation of adjacent tissues - may cause endothelial lesions of brain vessels and trigger the coagulation cascade, leading to ICT. Sinusitis, for instance, is a very common disease that may spread to the brain [1]. Similarly, endothelial damage may be inflicted by trauma sustained during an accident or surgery. Intracranial neoplasms may also interfere with brain vessel function and predispose for local thrombus formation. This applies particularly to hematogenous metastases.
  • Some diseases are known to induce cerebral vasculitis and as has been explained above, inflammatory processes facilitate thrombus formation [2]. In detail, cerebral vasculitis and ICT may be observed in patients suffering from these disorders:
  • Additionally, any condition leading to generalized hypercoagulability may provoke CT. Since these are systemic disorders, they may be associated with ICT and CTE. The following shall serve as examples:
  • By far the most common cause of ICT and CTE is atherosclerosis. Risk factors for atherosclerosis and thus for the thrombotic occlusion of brain vessels are hypertension, hypercholesterolemia, diabetes mellitus, overweight/obesity and tobacco consumption [3]. Atherosclerotic plaques that develop in cerebral vessels may narrow their lumen and thus render the respective vascular structure more susceptible to thrombotic occlusion, independent of the origin of the thrombus.
  • Patients suffering from endocarditis are prone to CTE.
  • Further enumeration of pathologies that may lead to peripheral thrombosis and subsequent CTE is beyond the scope of this article, but several extensive works regarding this topic have been published [4] [5].

Epidemiology

Cerebral infarction is one of the leading causes of death and long-term disability, especially in developed countries. About 87% of strokes are ischemic, only 10% are hemorrhagic, and 3% result from conditions not discussed in this article [6]. While atherosclerosis with superimposed thrombosis is the most common cause of ischemic infarction, CT only accounts for a minor share of hemorrhagic strokes: Cerebral vein and sinus thrombosis have been estimated to cause less than 1% of strokes [7].

Racial predilection has been reported for ischemic stroke, e.g., first-ever incidence rates in the United States have been calculated to 88, 149, and 191 per 100,000 Caucasians, Hispanics, and Blacks, respectively. The annual incidence of cerebral vein and sinus thrombosis is about 1 per 100,000 inhabitants, with two-thirds of affected individuals being children. The risk of developing atherosclerosis, CTE and ischemic stroke does increase with age, though, and the patients' median age at first-ever stroke is about 70 years.

Gender predilection has been described for cerebral vein and sinus thrombosis, which affects women about three times more often than men [8]. In this context, it has been hypothesized that the wide-spread use of oral contraceptives contributes to women's propensity for CT. Meta-analyses of studies on ischemic stroke did not reveal marked differences between incidence rates in men and women, though [9].

Sex distribution
Age distribution

Pathophysiology

As has been indicated above, CT may affect arteries, veins and vein sinuses: Thrombi rarely form within arteries, but are generally carried here. If thrombi lodge in a cerebral artery, dependent tissues are suddenly deprived of oxygen, glucose and further nutrients, and the affected individual sustains an ischemic stroke. In contrast, thrombi located in veins and vein sinuses hinder the drainage of blood, which may accumulate before the mechanical obstacle and increase the intravascular pressure. This rapidly causes a passage of blood beyond the boundaries of the vascular system, which is the eponym for hemorrhagic infarction or intracranial hemorrhage. Local mass effects largely contribute to the extent of brain damage in these cases.

In any case, a cerebrovascular accident interferes with the function of dependent brain regions. Neurons are highly dependent on aerobic metabolism and upon cessation of blood supply, energy-sparing mechanisms leading to membrane hyperpolarization are initiated. Nevertheless, ATP-dependent processes like the maintenance of membrane potentials by sodium-potassium pumps ceases within minutes [10]. Neurons depolarize and cytotoxic edema develops. A dysregulation of neurotransmitter release ensues and excess glutamate mediates excitotoxicity and an exacerbation of brain damage. Within several hours, vasogenic edema develops. Contrary to cytotoxic edema, vasogenic edema is associated with an overall increased content of water and electrolytes, and this condition leads to an enhanced intracranial pressure.

The primary thrombus (or thromboembolus) does not necessarily occlude the entire lumen of the affect vessel. However, even a small thrombus may induce rheological anomalies that favor the local formation of secondary thrombi. Consequently, the perfusion disorder augments in severity. At the same time, the partial or complete occlusion of a cerebral vessel ensues disturbances of blood flow in downstream vasculature, i.e., CT of a major artery may lead to the formation of secondary thrombi in arterioles, CT of arterioles may be followed by thrombus formation in venules [11].

Prevention

Atherosclerosis is the single most important risk factor for ICT and CTE and thus, any measure to reduce the formation of atherosclerotic plaques contributes to lower a patient's risk of CT. In detail, such measures may include an adequate control of body weight, blood pressure, glucose and lipid levels. Patients are to be advised to refrain from smoking and to take care of proper hydration, a healthy diet and regular exercise. Furthermore, women at risk of thrombosis should avoid the use of oral contraceptives. Diseases related to hypercoagulability may indicate prophylactic treatment with anticoagulants.

Summary

Cerebral thrombosis (CT) refers to the presence of a blood clot in blood vessels of the brain. Thrombi may form within or be carried to cerebral arteries, veins and vein sinuses, and consequently interfere either with oxygen and nutrient supply to brain tissue or with venous drainage. Depending on the type of vessel, the extent of vessel occlusion and vascular wall damage, CT may lead to ischemic infarction or hemorrhagic infarction.

In the narrow sense of the term, CT occurs if a thrombus develops within a cerebral vessel (intrinsic cerebral thrombosis, ICT). On the one hand, this may happen at sites of endothelial lesions that induce activation of the coagulation cascade via the extrinsic pathway. Such lesions, in turn, may be provoked by a local inflammatory process, trauma or neoplasm. Furthermore, systemic coagulopathies may evoke thrombus formation in the whole cardiovascular system, including but not limited to cerebral vessels. Thrombi form more frequently within cerebral veins and vein sinuses than within cerebral arteries.

In contrast, cerebral thromboembolism (CTE) mainly affects cerebral arteries. Here, thrombi develop in any other part of the cardiovascular system and are subsequently dragged away by the bloodstream. Patients sustaining CTE often suffer from atherosclerosis or endocarditis, because both conditions are associated with endothelial lesions. Inside the brain, thrombi may eventually reach an artery whose lumen does not allow the blood clot to pass through. This results in artery occlusion, ischemia and stroke.

Patient Information

Thrombosis refers to the formation of a blood clot within a vessel, and if this process occurs within a cerebral artery, vein or sinus, it is denominated cerebral thrombosis (CT). Additionally, blood clots may form within any other vascular structure, may be dragged away by the bloodstream and lodge in intracranial arteries. Because predisposing factors, clinical symptoms and treatment regimens are largely similar, the latter may also be considered a subtype of CT.

Brain tissue is highly dependent on aerobic metabolism and an occlusion of cerebral vessels is associated with their sudden deprivation of oxygen, glucose and further nutrients, which may result in cerebral infarction or stroke. Common symptoms include visual impairment, ataxia, hemiparesis, and aphasia. On the other hand, CT may be related to subacute or chronic symptoms like recurrent headaches. These may be experienced in case of an incomplete occlusion of cerebral vessels, venous or sinus thrombosis and a reduction of blood drainage. An exacerbation of such apparently mild forms of CT may occur at any time.

Because brain damage is mostly irreversible, CT and stroke should be treated as soon as possible. In this context, the administration of recombinant tissue-type plasminogen activator aims at thrombolysis and recanalization, i.e., at dissolving the blood clot and reestablishing blood flow. Thrombi may also be destroyed mechanically. Additional measures are undertaken to control underlying pathologies that predispose for CT, e.g., hypertension, hypercholesterolemia, diabetes mellitus, and overweight/obesity.

Patients may contribute to lowering their individual risk of CT by preventing the aforementioned conditions, and by undergoing regular check-ups to assure blood pressure, glucose and lipid levels are well controlled. Furthermore, they are advised to refrain from tobacco consumption, to adhere to a healthy diet and to realize physical activity to maintain normal weight.

References

Article

  1. Yeh CH, Chen WC, Lin MS, Huang HT, Chao SC, Lo YC. Intracranial brain abscess preceded by orbital cellulitis and sinusitis. J Craniofac Surg. 2010; 21(3):934-936.
  2. Kempster PA, McLean CA, Phan TG. Ten year clinical experience with stroke and cerebral vasculitis. J Clin Neurosci. 2016; 27:119-125.
  3. Feigin VL, Roth GA, Naghavi M, et al. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol. 2016; 15(9):913-924.
  4. Levi M, van der Poll T, Schultz M. Infection and inflammation as risk factors for thrombosis and atherosclerosis. Semin Thromb Hemost. 2012; 38(5):506-514.
  5. Ashrani AA, Heit JA. Risk factors for thrombosis in cancer patients. Cancer Treat Res. 2009; 148:95-114.
  6. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015; 131(4):e29-322.
  7. Amoozegar F, Ronksley PE, Sauve R, Menon BK. Hormonal contraceptives and cerebral venous thrombosis risk: a systematic review and meta-analysis. Front Neurol. 2015; 6:7.
  8. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F. 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.
  9. Zhang Y, Chapman AM, Plested M, Jackson D, Purroy F. The Incidence, Prevalence, and Mortality of Stroke in France, Germany, Italy, Spain, the UK, and the US: A Literature Review. Stroke Res Treat. 2012; 2012:436125.
  10. Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest. 2000; 106(6):723-731.
  11. Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood. 2008; 112(9):3555-3562.
  12. Goulart AC, Bensenor IM, Fernandes TG, Alencar AP, Fedeli LM, Lotufo PA. Early and one-year stroke case fatality in Sao Paulo, Brazil: applying the World Health Organization's stroke STEPS. J Stroke Cerebrovasc Dis. 2012; 21(8):832-838.
  13. 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.
  14. Arboix A, Roig H, Rossich R, Martinez EM, Garcia-Eroles L. Differences between hypertensive and non-hypertensive ischemic stroke. Eur J Neurol. 2004; 11(10):687-692.
  15. Tsivgoulis G, Alexandrov AV, Sloan MA. Advances in transcranial Doppler ultrasonography. Curr Neurol Neurosci Rep. 2009; 9(1):46-54.
  16. Jauch EC, Saver JL, Adams HP, Jr., et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 44(3):870-947.
  17. Cheng NT, Kim AS. Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between 3 and 4.5 Hours of Symptom Onset. Neurohospitalist. 2015; 5(3):101-109.
  18. Lambrinos A, Schaink AK, Dhalla I, et al. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review. Can J Neurol Sci. 2016; 43(4):455-460.

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Last updated: 2018-06-22 04:45