Intracranial venous and venous sinus thrombosis (CVST) was first described by Ribes in 1825, and at that time and for quite some time thereafter it was mostly reported in the literature as an autopsy finding. In 1942, Lyons described systemic anticoagulation for intracranial venous and venous sinus thrombosis (CVST), and anticoagulation prevented deterioration or improved the condition, but did not dissolve the formed thrombus.
In 1971, VmeS et al. performed systemic thrombolysis in patients with intracranial venous and venous sinus thrombosis (CVST), in which thrombolytic agents dissolved the formed thrombus and opened the obstructed venous sinus, and the patient’s prognosis was greatly improved. Subsequently, thrombolytic modalities were further developed, and in 1988, Scott performed contact thrombolysis using transcranial boreholes, and in 1991, Bamwell performed contact thrombolysis of venous sinuses through the jugular and femoral veins using vascular interventional techniques, thus enriching the treatment of intracranial venous and venous sinus thrombosis (CVST).
Currently, anticoagulation is the treatment of choice for intracranial venous and venous sinus thrombosis (CVST), and randomized controlled studies have demonstrated that anticoagulation is safe for CVST, not only reducing patient mortality and disability, but also not increasing the risk of recurrent intracranial hemorrhage, even in patients with combined intracranial hemorrhage.
A large body of literature reports a higher rate of revascularization in patients treated with thrombolysis, especially if the patient continues to deteriorate despite anticoagulation or has high intracranial pressure despite other management measures. However, the current evidence comes only from series of case study reports, and there is a lack of evidence-based medical studies demonstrating the advantages and disadvantages of thrombolytic versus anticoagulant therapy and the efficacy of different thrombolytic treatment methods.
In China, although intracranial venous and venous sinus thrombosis (CVST) is rare clinically, it is often misdiagnosed or missed due to its diverse forms and clinical manifestations, and has a high disability and mortality rate, and because the causes of its pathogenesis are not clearly understood, the existing clinical treatment and evaluation methods lack uniform standards. Based on this situation, this group of experts jointly developed a consensus on the treatment of intracranial venous and venous sinus thrombosis (CVST), aiming to improve clinicians’ understanding of CVST and to determine the uniform treatment and evaluation methods.
I. Epidemiological features and etiology
Intracranial venous and venous sinus thrombosis (CVST) accounts for 0.5%-1% of all strokes and is most common in pregnant women, women taking oral contraceptives, and young adults <45 years of age. In the normal population, the annual incidence of intracranial venous and sinus thrombosis (CVST) is 7/100,000 in neonates and children and about 2-5/100,000 in adults. 54% of these patients are taking oral contraceptives, 34% are in a hereditary or acquired prethrombotic state, 2% are pregnant or puerperal women, and other contributing factors include infection (12%), cancer (7%), and hematologic risk. (7%) and hematologic disorders (12%).
Common etiologies.
(1) Inherited hypercoagulable states: antithrombin deficiency, complement protein CBS deficiency, activator protein V resistance, factor v mutations, prothrombinogen mutations, methylenetetrahydrofolate reductase mutations causing homocysteinemia, etc.
(2) Acquired hypercoagulable states: pregnancy, puerperium, homocysteinemia, antiphospholipid antibodies, nephrotic syndrome, etc.
(3) Infections: meningitis, otitis, mastoiditis, sinusitis, neck, face and mouth infections, systemic infections, acquired immunodeficiency syndrome, etc.
(4) Inflammatory reactions and autoimmune diseases: systemic lupus erythematosus, Wegener’s granulomatosis, nodular disease, inflammatory bowel disease, thrombo-occlusive vasculitis, Adamantiade-Bechet disease, etc.
(5) Tumors: neurological tumors, systemic malignancies, extra-neurological solid tumors, etc.
(6) Hematologic diseases: erythrocytosis, thrombotic thrombocytopenic purpura, thrombocytosis, severe anemia and autoimmune hemolytic diseases, paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, etc.
(7) Drugs: oral contraceptives, lithium, androgens, sumatriptan, intravenous immunoglobulin infusion, hormone replacement therapy, asparaginase, steroids, banned drugs, etc.
(8) Physical factors: head trauma, neurosurgery, jugular venous cannulation, lumbar puncture, cerebral venous sinus injury, intravenous drug abuse, etc.
(9) Other factors: dehydration (especially in children), thyrotoxicosis, arteriovenous malformation, dural arteriovenous impotence, congenital heart disease, after radiation therapy, etc.
Second, pathology and pathophysiological changes
First, cerebral vein occlusion causes venous infarction and local cerebral edema. Pathology can be seen as thickened veins, local edema, ischemic neuronal injury and petechial hemorrhage, the latter of which can form intracranial hemorrhage.
Secondly, venous sinus occlusion causes venous drainage obstruction, resulting in venous hypertension: on the one hand, it causes blood-brain barrier disruption, reduced effective circulating blood volume and energy-dependent cell membrane pump dysfunction resulting in cerebral edema; on the other hand, it affects cerebrospinal fluid absorption obstruction resulting in increased intracranial pressure.
III. Clinical manifestations
Headache is the most common clinical symptom of intracranial venous and venous sinus thrombosis (CVST), which occurs in 90% of patients. 40% of patients have focal or generalized epileptic seizures; optic disc edema caused by elevated intracranial pressure, which can cause progressive loss of vision; focal neurological dysfunction, including motor and sensory dysfunction, cerebral nerve palsy, aphasia and cerebellar signs.
IV. Auxiliary examinations
(A) Laboratory and lumbar puncture examination
1, laboratory tests: blood routine, coagulation indicators, D-dimer and antibody, inflammatory response indicators.
2, lumbar puncture examination: pressure is often increased, >300cmH2O (1cmH2O = 0.098kPa) patients often have more severe clinical symptoms.
(II) Imaging examination
1.CT examination: the direct signs are rope sign, triangle sign, high-density image of venous sinus; the indirect signs may show venous infarction, hemorrhagic infarction, dense cerebral sickle and cerebellar curtain enhancement.
2.Magnetic resonance imaging.
①Acute phase: the normal blood flow signal in the cerebral venous sinus disappears, and there is isosignal on T1-weighted imaging (WI) and low signal on T2WI;
(ii) Subacute stage: high signal on T1WI and T2WI;
(3) Chronic stage: due to partial recanalization of the vessel, the flow-void effect reappears, typically showing isosignal on T1w and high signal or isosignal on T2w.
3.Magnetic resonance venography (MRV): the direct signs are complete occlusion of the affected cerebral venous sinuses, irregular stenosis and the presence of low signal with unsmooth edges, or the disappearance of high blood flow signal in the normally developed cerebral venous sinuses, or the formation of low signal with blurred and irregular edges after recanalization; the indirect signs are the formation of venous collateral circulation and abnormal dilatation of the draining veins where the obstruction occurs.
4.CT venography (CTV): CTV can provide a rapid and reliable method to detect intracranial venous and venous sinus thrombosis (CVST). CTV is particularly helpful in the diagnosis of subacute or chronic intracranial venous and venous sinus thrombosis (CVST) because of the diversity in density of the thrombosed venous sinuses. cTV provides a rapid and reliable evaluation of cerebral venous system thrombosis, which is mainly characterized by filling defects of the venous system, enhancement of the venous sinus walls, opening of collateral veins and increased drainage.
5.Digital subtraction angiography (DSA): The main signs are complete obstruction of the venous sinuses by the thrombus and the “empty sinus phenomenon”. Other signs may include poor visualization of cortical veins or deep veins, marked dilatation of scalp veins and conduit veins, prolonged arteriovenous circulation time (mainly prolonged venous phase time >10 seconds, showing the formation of dilated and tortuous collateral circulation and venous reflux phenomenon. It is important to note that DSA is recommended for patients with intracranial venous and venous sinus thrombosis (CVST) who have prolonged or recurrent disease, who are treated with anticoagulation, etc., or who need to exclude other bleeding disorders.
V. Diagnosis
The diagnosis can generally be confirmed based on clinical manifestations, laboratory tests and imaging manifestations.
This consensus suggests
Although plain CT or MRI is useful for the initial evaluation of patients with suspected intracranial venous and venous sinus thrombosis (CVST), a negative result does not exclude intracranial venous and venous sinus thrombosis (CVST).
Venography (CTV or MRV) is recommended for patients with suspected intracranial vein and venous sinus thrombosis (CVST) who have negative plain CT or MRI results or who have been identified with plain CT or MRI suggestive of intracranial vein and venous sinus thrombosis (CVST) to the extent that intracranial vein and venous sinus thrombosis (CVST) is present. (Class I, Level C evidence)
Early follow-up CTV or MRV is recommended for patients with intracranial venous and venous sinus thrombosis (CVST) with persistent or progressive symptoms despite medical therapy or for patients with intracranial venous and venous sinus thrombosis (CVST) with signs of thrombotic expansion. (Class I, Level C evidence)
Review of CTV or MRV is recommended for patients with clinical signs of recurrent intracranial vein and venous sinus thrombosis (CVST) and a clear previous history of intracranial vein and venous sinus thrombosis (CVST).(Class I, Level C evidence)
Combined with the gradient-echo T of MR, susceptibility-weighted images can help improve the accuracy of the diagnosis of intracranial venous and venous sinus thrombosis (CVST). (Class IIa, Level B evidence)
Cerebral angiography is helpful in patients with a high clinical suspicion of intracranial venous and venous sinus thrombosis (CVST) and inconclusive CTV or MRI findings. (Class IIa, Level C evidence)
In patients with stable disease, it is reasonable to perform CTV or MRV 3-6 months after diagnosis in order to assess recanalization of occluded cortical veins or venous sinuses. (Class IIa, Level C evidence)
VI. Treatment
(i) Anticoagulation therapy
1.Role and deficiency: it can prevent the occurrence of venous thrombosis, stop the development of thrombus continuation, promote the opening of collateral circulation pathways, and prevent deep vein thrombosis and pulmonary embolism. Disadvantage: can not dissolve the formed thrombus.
2, drugs and usage: anticoagulation therapy early can use common heparin (adjusted by dose) or low molecular heparin (adjusted dose by kilogram weight: weight <50kg, 4000u, 0.4ml; weight 50-70kg, 6250u, 0.6ml; weight >70kg, 10000U, 0.8ml). All were injected subcutaneously, 2 times/d. Routine use for 2 weeks prolonged the activated partial thromboplastin time and activated whole blood clotting time to 2 times the normal value; oral warfarin was administered at the same time to control the international normalized ratio (INR) to 2.0-3.0 (plasma prothrombin time prolonged to 2 times the normal value).
Warfarin may be used for 3 months in patients with a clear etiology and clinical improvement; warfarin may be given for 6-12 months in hypercoagulable states of unclear etiology; and lifelong anticoagulation may be considered in patients with recurrent intracranial vein and venous sinus thrombosis (CVST).
This consensus recommends
Patients with intracranial venous and venous sinus thrombosis (CVST) without contraindications to anticoagulation should be given subcutaneous low-molecular heparin therapy or intravenous heparin therapy (adjusted according to dose), depending on patient weight, with the goal of doubling the APTT, followed by a switch to oral warfarin.
Monitor INR values and adjust warfarin dose with a target value of 2.0-3.0. Monitoring of platelet count and coagulation is required, and antagonists such as vitamin K and fisetin sulfate are available.
Intracranial hemorrhage is not a contraindication to anticoagulant therapy; the size of the bleeding volume can be evaluated, the dose of anticoagulants can be adjusted, and anticoagulants can be discontinued in severe cases.
Duration of anticoagulation: warfarin can be used for 3 months for patients with clear etiology and improved clinical symptoms; warfarin can be taken for 6-12 months for hypercoagulable states of unclear etiology; lifelong anticoagulation can be considered for patients with recurrent intracranial venous and venous sinus thrombosis (CVST).
(II) Thrombolytic therapy
1, systemic intravenous thrombolysis: through intravenous injection of thrombolytic agent, through the blood circulation to the intracranial venous sinus to dissolve the sinus thrombus, so that the venous sinus recanalization, this treatment method is fast, simple, relatively low cost of treatment, and urokinase or recombinant tissue-type fibrinogen activator (DPA) thrombolysis effect is exact. However, the premise is that a sufficient (equivalent) dose of thrombolytic agent must enter the sinus and come into contact with the thrombus in order to exert a thrombolytic effect. If the intravenous sinus thrombus has completely occluded the venous sinus, the blood flow in the sinus is slow or even no blood flow, and after intravenous injection, the thrombolytic drug mostly flows back through the lateral branch pathway, resulting in a very low concentration of local thrombolytic drug in the sinus thrombus, and the thrombolytic effect is reduced or even ineffective.
Dosage: urokinase 50-1.5 million U/d for 5-7 d (while detecting fibrinogen >1.0 g); r-tPA, 0.6-0.9 mg/kg, total <50 mg< p="">
2, venous contact thrombolysis: the microcatheter is placed inside the thrombus through the femoral vein, which on the one hand significantly increases the concentration of thrombolytic drugs within the thrombus; on the other hand, for patients with long thrombus formation time and slow thrombolysis rate, the microcatheter is placed at the distal end of the thrombus for slow and continuous pumping of urokinase thrombolytic therapy, so that repeated circulation of urokinase thrombolysis can increase the venous sinus recanalization rate and shorten the time of venous sinus recanalization.
Dosage: Urokinase 500 ~ 1.5 million U/d, intravenous drip, 2 ~ 4 times/d, 3 ~ 7 d. The specific duration of dosing is determined according to whether the patient’s clinical symptoms improve and whether imaging confirms basic venous sinus patency.
This consensus recommends
There is insufficient evidence to support systemic intravenous thrombolysis in patients with intracranial venous and venous sinus thrombosis (CVST), and small case series support contact thrombolysis of the venous sinuses.
In some patients with CVST who progress despite adequate anticoagulation, venous sinus contact thrombolysis may be considered to exclude other conditions causing deterioration, and systemic intravenous thrombolysis requires more rigorous case selection (especially for those without intracranial hemorrhage or large hemorrhagic infarcts at risk of brain herniation).
3.Arterial thrombolysis: deep vein or small vein thrombosis, and thrombosis that cannot be reached by venous sinus thrombolysis are treated by arterial thrombolysis. Thrombolysis via arterial route can deliver thrombolytic drugs to the venous end in a smooth way, which can effectively dissolve the thrombus in the cortex and deep vein, and promote the establishment of collateral circulation and open the collateral venous return pathway in the case of incompetent main draining veins.
Urokinase dosage: transcarotid puncture: 100,000 U/d, 1 time/d, 5-7 d, 10-25 mi slow injection, alternating punctures of the carotid artery. Through the femoral artery access, the total amount of thrombolysis is 500,000 U is appropriate.
4.Mechanical thrombus fragmentation: At present, there are methods of mechanical thrombus fragmentation such as cutting thrombus, balloon, umbrella and solitaire pulling thrombus at home and abroad. Each medical unit can choose carefully according to the patient’s condition, personal experience and unit conditions.
5.Stentoplasty: For patients with formal treatment >6 months, chronic thrombosis, local stenosis, no improvement in symptoms, and distal and proximal pressure difference >10mmHg (1mmHg=0.133kPa), stentoplasty can be considered.