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.
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 . 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 . 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.
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:
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 .
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.
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 . 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 . 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 . 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 :
Antiepileptic treatment in case of seizures
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 .
A multinational study on the outcome of cerebral vein and sinus thrombosis yielded the following results after a median follow-up of 16 months :
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 .
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:
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 . 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 .
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 . 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 .
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 . 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 .
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.
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.
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.