OVERVIEW
Cerebral venous system thrombosis, including intracranial venous and venous sinus thrombosis (CVST), is a relatively rare but life-threatening cerebrovascular event with an incidence of approximately 5/100,000 and accounts for 0.5% of all strokes at any age. It can occur at any age 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 is 7/100,000 in newborns and children and 2/100,000 to 5/100,000 in adults. Of these patients, 54% are taking oral contraceptives, 34% have a hereditary or acquired pre-thrombotic state, 2% are pregnant or puerperal women, and other contributing factors include infections (12%), cancer (7%), and hematologic disorders (12%).
Etiology
The etiology and pathogenesis is complex and has long been recognized as an infectious disease, but more recently non-infectious lesions have been reported in the literature.
1. Hereditary hypercoagulable states
Antithrombin deficiency, complement proteins C and S deficiency, activated protein V resistance, factor V mutation, prothrombin mutation, methylenetetrahydrofolate reductase mutation resulting in homocysteinemia.
2. Acquired hypercoagulability
Pregnancy, puerperium, homocysteinemia, antiphospholipid antibodies, nephrotic syndrome, etc.
3. Infection
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, tuberculosis, inflammatory bowel disease, thromboembolic vasculitis, Adamantiades-Bechet disease, etc.
5.Tumors
Neurological tumors, systemic malignant tumors, solid tumors outside the nervous system, etc.
6.Blood Diseases
Erythrocytosis, thrombotic thrombocytopenic purpura, thrombocytosis, severe anemia and autoimmune hemolytic disease, paroxysmal nocturnal hemoglobinuria, heparin-induced thrombocytopenia, etc.
7. Drugs
Oral contraceptives, lithium, androgens, sumatriptan, intravenous immunoglobulin, hormone replacement therapy, asparaginase, steroids, prohibited drugs, etc.
8. Physical factors
Head trauma, neurosurgery, jugular vein cannulation, lumbar puncture, cerebral venous sinus injury, intravenous drug abuse.
9. Other factors
Dehydration (especially in children), thyrotoxicosis, arteriovenous malformation, dural arteriovenous fistula, congenital heart disease, after radiation therapy, etc.
Symptoms
Because of its variable clinical manifestations, the main ones are headache, nausea and vomiting, optic papillae edema, spreading nerve palsy, loss of vision, signs of localized brain damage, seizures, altered mental status and coma. Headache is the most common clinical symptom and occurs in 90% of patients. 40% of patients experience focal or generalized epileptic seizures; optic disk edema caused by elevated intracranial pressure, which can result in progressive vision loss; and focal neurological deficits, including motor and sensory dysfunction, cerebral palsy, aphasia, and cerebellar signs.The lack of specificity in the clinical manifestations of CVST makes it difficult to diagnose and treat CVST promptly and accurately, and the misdiagnosis rate is as high as 62.5%. The misdiagnosis rate is as high as 62.5%.
Clinical manifestations are complex and nonspecific, and cranial CT often has no direct signs of thrombus, or even is completely normal, so it is easy to lead to misdiagnosis and omission of diagnosis. Literature reports that the misdiagnosis rate can be as high as 62.5%. When headache, nausea, vomiting, meningeal irritation, EEG abnormalities and cerebrospinal fluid changes occur after a “cold” or fever, it is similar to post-infectious encephalitis or meningitis. When cranial CT and MRI show multifocal distribution, it is easy to be misdiagnosed as heavy inflammatory demyelinating encephalopathy; when the patient has chronic otitis media and presents with headache, vomiting, and increased cranial pressure, it can be misdiagnosed as brain abscess again; when the patient manifests headache, nausea, vomiting, fundus optic papilla edema, increased pressure on cerebrospinal fluid examination, and the other examinations are not obvious, it is easy to misdiagnose intracranial space-occupying lesions; when the patient presents with limb hemiparesis, particularly When the patient has hemiplegia, especially when the cranial CT shows low density foci, it is easy to be misdiagnosed as cerebral infarction; headache, limb paralysis, hemorrhagic foci seen on cranial CT, it is easy to be misdiagnosed as cerebral hemorrhage; when the patient suddenly has headache, vomiting, positive meningeal irritation sign, and even the cerebrospinal fluid is pale bloody, it is easy to be misdiagnosed as subarachnoid hemorrhage; when the patient has quadriplegia or bilaterality, accompanied with fever and cerebrospinal fluid changes, it is easy to be misdiagnosed as acute spondylitis and other spinal cord disorders.
Examination
According to the possible causes of the disease, appropriate tests should be selected.
1. Laboratory tests
(1) Blood glucose, immune program, cerebrospinal fluid examination: blood routine, coagulation index, D-dimer and antibody, inflammatory reaction index examination.
(2) Lumbar puncture examination: pressure is often increased, >300cmH20 (1cmH20=0.098kPa) patients often have more severe clinical symptoms.
2.Imaging examination
(1) Head CT and CTA examination: the characteristic changes of CT are abnormal high-density foci in venous sinuses or high-density foci in cerebral veins, i.e., stripe sign, and an empty triangular shadow can be seen behind the superior sagittal sinus after enhanced scanning, i.e., α sign. the changes of CT also include the images of cerebral edema, hemorrhage and infarction, and changes of the ventricular system, but 20%-30% of the patients’ CT scans are shown to be normal. Indirect signs of deep venous thrombosis are images of bilateral thalamic and basal nuclei infarcts or hemorrhagic infarcts.CT angiography (CTA) shows poor visualization of venous sinuses and veins with thrombus, but good visualization of collateral veins.
(2) Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the head: in the acute phase (<1 week after onset), the normal vascular flow and emptying phenomenon in the venous sinuses or veins disappears in the T1- and T2-weighted phases, with equal signal in the T1 and low signal in the T2; in the subacute phase (1-2 weeks after onset), the high signal in the T1 and T2; and in the chronic phase (2 weeks-3 months after onset), the vascular flow and emptying phenomenon reappears, with weakened signals in the T1 and T2. In the chronic phase (2 weeks to 3 months after the onset of disease), the phenomenon of vascular hollowing reappears and the T1 and T2 signals are weakened. In some patients, 4 months after the onset of the disease, MRI showed isointense signals in the lumen without normal flow phenomenon, indicating persistent occlusion.The indirect signs of MRI and CT are the same as those of cerebral edema, hemorrhage, infarction, and alterations of the ventricular system.MRV (Magnetic resonance venography): the direct signs show a complete occlusion of the affected cerebral venous sinus, irregular stenosis, and the presence of low signals with non-smooth edges, or the development of a The direct sign is the complete occlusion, irregular narrowing and low signal with irregular edges of the affected cerebral venous sinus, or the disappearance of the high flow signal of the normal cerebral venous sinus, or the formation of low signal with blurred edges and irregularities after recanalization; the indirect sign is the formation of venous collateral circulation at the place of obstruction, and the abnormal dilatation of draining veins.
(3) Digital subtraction angiography (DAS): it can show partial or complete obstruction of venous sinuses and veins, spiral dilatation of cortical veins in the drainage area, and venous reflux phenomenon, but the disadvantages are traumatic and expensive, and it is suitable for those who can not be diagnosed by MPI and MRA.
Diagnosis
Although, MRI and MRV examination can basically confirm the diagnosis in some patients, the manifestations of DAS such as partial or complete opacification of veins and venous sinuses, spiral dilatation of cortical collateral veins, prolonged passage time of cerebral circulation and reflux from obstructed dural sinuses or veins are still the gold standard for confirmation of the diagnosis.
Treatment
According to the treatment guidelines issued by the European Union Neuroscience Society in 2006, a combination of treatment including targeting the cause, anticoagulation, and symptomatic treatment is proposed.
(I) Acute phase treatment
1. Treatment of etiologic factors
According to the known or possible causes of the disease, appropriate treatment should be carried out to correct dehydration, blood viscosity, and improve cerebral blood circulation. For infectious CVST, anti-infection should be carried out as early as possible against the pathogenic bacteria and the primary foci should be dealt with.
2. Anticoagulation
In the absence of contraindications to anticoagulation, the dosage of low molecular heparin adjusted according to body weight should be injected subcutaneously or heparin should be administered intravenously, so as to make the activated partial thromboplastin time (APTT) reach two times of the control value. Oral warfarin was administered during the same period to control the International Normalized Ratio (INR) to 2.0 to 3.0 (plasma prothrombin time prolonged to twice the normal value). For patients with clear etiology and improved clinical symptoms, warfarin can be used for 3 months; for hypercoagulable state with unclear etiology, warfarin can be taken for 6 to 12 months: lifelong anticoagulation can be considered for recurrent patients.
3.Thrombolytic therapy
If the condition is serious, and the condition continues to deteriorate despite adequate anticoagulation and other causes of deterioration are ruled out, some hospitals with the conditions can carry out endovascular intervention to locally dissolve or remove the thrombus, but the effect is yet to be evaluated.
(1) Systemic intravenous thrombolysis: through intravenous drip of thrombolytic agent, through the blood circulation to the intracranial venous sinus to dissolve the sinus thrombus, so that the venous sinus recanalization, the operation of this treatment is fast, simple, relatively low treatment costs, and urokinase or recombinant tissue-type plasminogen activator (r-tPA) thrombolysis effect is accurate. 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 thrombus in the venous sinus has completely occluded the venous sinus, the blood flow in the sinus is slow or even no blood flow, after intravenous infusion, the thrombolytic drugs are mostly refluxed through the collateral pathway, resulting in a very low concentration of local thrombolytic drugs in the sinus thrombus, and the thrombolytic effect is reduced or even ineffective.
(2) Venous sinus contact thrombolysis: the microcatheter is placed in the thrombus through the femoral vein access, on the one hand, the concentration of thrombolytic drugs in the thrombus has been significantly increased; on the other hand, for patients with longer time of thrombosis and slower thrombolysis rate, the microcatheter is placed at the distal end of the thrombus, and slow and continuous pumping of urokinase is carried out for thrombolytic therapy, so that the urokinase is repeatedly circulated to dissolve the thrombus, which can increase the recanalization rate of venous sinus and shorten the time of venous sinus recanalization. It can increase the recanalization rate of venous sinus and shorten the recanalization time.
(3) Arterial thrombolysis: Arterial thrombolysis is used for deep vein or small vein thrombosis and thrombus that cannot be reached by venous sinus thrombolysis. Thrombolysis via arterial route can deliver thrombolytic drugs to the venous end, which can effectively dissolve the thrombus of cortical and deep veins, and promote the establishment of collateral circulation and open the collateral venous reflux pathway if the main draining vein is not smooth.
(4) Mechanical thrombus fragmentation: At present, there are methods of mechanical thrombus fragmentation at home and abroad, such as cutting thrombus, balloon, umbrella and Solitaire thrombus extraction. They can be carefully selected according to the patient’s condition, personal experience and unit conditions.
(5) Stenting: Stenting can be considered for patients who have been under regular treatment for more than 6 months, with chronic thrombus, localized stenosis, no improvement in symptoms, and a pressure difference between the distal and proximal ends of the patient of more than 10mmHg.
(ii) Long-term treatment
Patients with stabilized or improved condition after the acute phase should take oral warfarin for 6 to 12 months to maintain the international normalized ratio (INR) at 2.0 to 3.0. prevent recurrence of CVST and prevent thrombosis in other veins. Long-term oral anticoagulation with warfarin should be used in patients with hereditary or acquired hypercoagulable states including antiphospholipid antibody syndrome. Treatment of the primary disease and removal of risk factors such as discontinuation of birth control pills is required. Antiepileptic therapy is required for patients with CVST secondary to epilepsy, and the exact course has not been standardized.