What Is Cerebral Venous Thrombosis?

The characteristics of this group of diseases are complex etiology, various forms of onset, clinical manifestations are not specific, diagnosis is difficult, and misdiagnosis is easy to miss. Let s first understand a misdiagnosed case: a middle-aged male patient who has experienced a decrease in intelligence and paired vision in the past two months, and his brain tissue has been slightly swollen on MRI. At that time, he did not carefully observe the imaging performance, only considered For a glioma or lymphoma, a biopsy was performed to determine that the patient had intracranial venous thrombosis. With the development of imaging technology, such as the widespread use of magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance venous imaging (MRV) in the diagnosis of CVT, the detection rate of the disease has increased significantly compared to the past.

Martial arts sword	(Chief physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University
Li Xiaoying	(Resident)	Department of Neurology, Xuanwu Hospital, Capital Medical University

Intracranial venous thrombosis (CVT) is a group of vascular diseases in which cerebral venous return is blocked for a variety of reasons, including intracranial venous sinus and venous thrombosis. Intracranial venous sinus (dural sinus) includes superior sagittal sinus, inferior sagittal sinus, superior petrosal sinus, inferior petrosal sinus, cavernous sinus, straight sinus, lateral sinus (transverse sinus, sigmoid sinus), sinus sink; cerebral vein is divided They are the deep vein group (deep cerebral vein, basal vein, inner cerebral vein and great cerebral vein) and the superficial vein group (superior cerebral vein, superficial cerebral vein and inferior cerebral vein).

Western Medicine Name: Intracranial venous thrombosis
English name: cerebral venous thrombosis, CVT

Affiliated Department: Internal Medicine-Neurology
Disease site: brain
Contagious: Non-contagious

Introduction to Intracranial Venous Thrombosis

Intracranial venous thrombosis epidemiology

About 5 per million people develop an illness each year, accounting for about 0.5-1% of all stroke events. It occurs in young people and children. Three quarters of adult patients are women, and most patients have a good prognosis. Sinus thrombosis occurs in 70-85% of women during the reproductive age.

Causes and pathogenesis of intracranial venous thrombosis

All causes of deep vein thrombosis in other sites can cause CVT. There is no clear line between the etiology and risk factors of CVT. There are many causes of CVT, and more than 100 causes have been identified. Vascular wall disease, hypercoagulable function, and slowed blood flow caused by various causes can lead to clinical occurrence of CVT. Table 1: Causes and Risk Factors of Sinus Thrombosis

Risk factor	Prevalence
Prethrombotic state	34.1
Antiprotease III deficiency
Protein C deficiency
Protein S deficiency
Antiphospholipid antibodies and anticardiolipin antibodies	5.9
Activated protein C resistance and factor V Leiden mutation
Factor II G20210A mutation
Hyperhomocysteinemia	4.5
Pregnancy and puerperium	twenty one
Oral contraceptive	54.3
Drugs: Androgens, Vitamin A, etc.	7.5
Tumor-related	7.4
Local oppression
Hypercoagulable state
Antitumor drugs
infection
Parameningeal infections (ear, sinus, oral cavity, etc.)
Mechanical factor	4.5
Complications of epidural blood spots
Spontaneous hypocranial pressure
Waist wear	1.9
Other blood disorders	12
Nocturnal paroxysmal hemoglobinuria
Iron deficiency anemia
Nephrotic syndrome	0.6
Erythrocytosis, thrombocytosis	2.8
Systemic disease	7.2
Systemic lupus erythematosus	1
Behcet's disease	1
Inflammatory bowel disease	1.6
Thyroid disease	1.7
Sarcoidosis	0.2
other	1.7
Unknown factor	12.5

The etiology is mainly divided into infectious and non-infectious. The cause is unknown in about 20-35% of patients.

(1) Infectivity can be divided into localized and systemic.

1) Limitations: purulent infections of the head and face, such as skin infections in the dangerous triangle of the face, otitis media, mastoiditis, parasinusitis, alveolar infections, cranial osteomyelitis, meningitis, etc. Infection often causes cavernous sinus, transverse sinus, and sigmoid sinus thrombosis. The pathogenesis is that the infection of the head and face directly involves the corresponding cavernous sinus through the facial vein, or because the infection site (such as the mastoid atrium) is adjacent to the corresponding sinus (such as the transverse sinus and sigmoid sinus), the infection can pass through the skull to the corresponding Sinus causes infectious thrombosis.

2) Systemic: caused by various bloodstream infections.

(2) Non-infectious can also be divided into systemic and limited.

1) Systemic

a) Obstetrics and Gynecology: pregnancy, puerperium, oral contraceptives, etc .;

b) surgery: after any type of surgery;

c) Internal medicine: severe dehydration, shock, cachexia, cardiac insufficiency, some blood diseases (such as erythrocytosis, sickle cell anemia, malignant anemia, leukemia, and coagulopathy).

These factors often lead to a hypercoagulable state of the blood, blood stagnation, and easily induce venous thrombosis. Such causes often cause superior sagittal sinus thrombosis, and are often accompanied by superior cerebral venous thrombosis.

2) Limitations: found in head trauma (open or closed, with or without fractures), brain tumors, after brain surgery, etc. ^[1]

Intracranial venous thrombosis pathology

A clotted blood clot or pus was seen in the sinuses, and vasodilation, congestion, and brain tissue edema appeared in the drained sinus drainage area. There were spotting hemorrhages, infarcts or softening of the brain. Pathologically, venous thromboembolism increases venous and capillary blood neck pressure, leading to exudation of red blood cells, which is why CVT often has hemorrhagic infarction. When recanalization occurs, venous pressure drops, preventing further bleeding. In infectious thrombosis, the infection can spread to the surrounding area and cause localized or diffuse meningitis, brain abscess, or cerebral infarction.

Clinical manifestations of intracranial venous thrombosis

The clinical manifestations of CVT are complex and atypical, depending on the affected area, location, and thrombotic activity. A larger primary thrombus often causes a range of symptoms such as headache, cranial hypertension, dizziness, eye discomfort (including visual impairment and eye swelling, or conjunctival congestion), epilepsy, neurological dysfunction, tinnitus, brain ringing, and neck Department discomfort. In patients with cerebral cortex venous thrombosis alone, symptoms are more limited, such as motor and paresthesia, focal epilepsy, and so on. Deep venous thrombosis is rare and often causes mesencephalic edema, similar to a tumor or a thalamic hemorrhage. It should be emphasized that headache is the most common symptom, and about 80% of patients have headache. Other common symptoms and signs include papillary oedema, focal nerve signs, epilepsy, and altered consciousness. The clinical manifestations of CVT in different parts have different characteristics. The details are as follows:

Intracranial venous thrombosis cavernous sinus thrombosis

Cavernous sinus thrombosis is mostly caused by purulent infections or systemic infections around the orbit, nose and face. Non-infectious thrombosis is rare. Common in tumors, trauma, arteriovenous malformation and obstruction. There may be a history of squeezing in the dangerous triangle of the face. Lesions affect one or both cavernous sinuses. Often acute, with symptoms such as fever, headache, nausea and vomiting, and disturbance of consciousness. Orbital venous reflux disorders can cause bulbar conjunctival edema, protruding eyes, inability to close the eyelids, and redness and swelling of the soft tissues around the eyes. Multiple brain nerves such as the oculomotor nerve, the pulley nerve, the abductor nerve, and the trigeminal nerve can be damaged. They appear as dilated pupils, disappeared light reflections, drooping eyelids, diplopia, restricted eye movements, Fixation, hypoalgesia in the first and second branches of the trigeminal nerve, and disappearance of the corneal reflex. Further aggravation can cause visual nipple edema and visual impairment. Infections and thrombosis of the cavernous sinus segment of the internal carotid artery can present with clinical manifestations of carotid tenderness and internal carotid infarction, such as contralateral hemiplegia and hemiplegia. Severe cases are complicated by meningitis and brain abscess. Cerebrospinal fluid tests for increased white blood cells. If thrombosis progresses rapidly, deep cerebral or cerebellar vein involvement, septic emboli, coma of the patient, and being too young or too old all indicate a poor prognosis.

Intracranial venous thrombosis superior sagittal sinus thrombosis

Superior sagittal thrombosis (superior sagittal thrombosis) occurs mostly in the puerperium, and it is common in 1-3 weeks postpartum. It can also occur in pregnancy, oral contraceptives, severe dehydration, infection or cachexia in infants or the elderly, mostly non-infectious thrombosis. Acute or subacute onset, the main clinical manifestations are symptoms of increased intracranial pressure, such as headache, nausea, vomiting, and papillary edema. 33% of patients present with unexplained intracranial hypertension, and papilledema can be the only sign. Patients with superior sagittal sinus thrombosis may experience seizures or mental disorders. In most patients, thrombus affects one or both sides of the sinus and the important manifestation is intracranial hypertension. Thrombosis that extends to the cortex, especially the motor area and parietal veins, is common. It is characterized by acute or progressive motor or sensory disturbances, and the lower extremities are more likely to be affected with focal or generalized seizures. Involvement of the paracentral lobules can cause urinary incontinence and paralysis of the lower limbs. Some patients develop systemic or focal seizures early. In some patients, there are focal signs of the nervous system. Cortical and subcortical white matter hemorrhage occurs in the involvement of large veins, resulting in corresponding loss of neurological function. Babies can present with jet vomiting, anteroposterior iliac vein rupture, cranial suture separation, venous irritation and tortuosity around the cardia and on the forehead, face, and neck pillow. Elderly patients generally have symptoms such as mild dizziness, vertigo, headache, and dizziness, making diagnosis difficult. Lumbar puncture shows increased cerebrospinal fluid pressure, protein and white blood cells can also increase. At this time, the visible signs on the CT are the thin rope signs and triangular signs formed by the increased density of intracranial venous thrombosis. Non-specific signs include hemorrhage, cerebral edema, smaller ventricles and enlarged cerebellar veins. MRV can be diagnosed with sinus filling defects.

Intracranial venous thrombosis lateral sinus thrombosis

Lateral sinus thrombosis The lateral sinus includes the transverse sinus and sigmoid sinus. Due to its proximity to the mastoid, pyogenic sinus thrombosis is often caused by purulent mastoiditis or otitis media.

The clinical manifestations of lateral sinus thrombosis are:

The main symptoms of intracranial hypertension. Headache, vomiting, and papillary edema.

Focal nerve symptoms: Thrombus extends to the superior and inferior petrosal sinuses, ipsilateral trigeminal nerve and abductor nerve damage can occur; thrombus extends to the jugular vein, and jugular vein foramen including pharyngeal, vagus, and accessory nerve damage Symptoms include symptoms such as difficulty swallowing, drinking water, coughing, hoarseness, bradycardia, and weak shoulders and turning heads.

Symptomatic mastoiditis or inflammation of the middle ear, fever, chills, increased white blood cells in the peripheral blood, reddening and swelling of the mastoid area behind the affected ear, tenderness, and venous bulging. The spread of infection can be complicated by purulent meningitis, epidural (lower) abscesses, and cerebellar and temporal lobe abscesses.

Intracranial venous thrombosis

Vein of Galen Thrombosis The great cerebral vein is the main vein that receives the deep veins of the brain. Major cerebral venous thrombosis is mostly non-infectious venous thrombosis, which mainly involves deep structures such as the mesencephalon, basal ganglia, and internal capsule, often showing bilateral lesions. Most manifested as symptoms of intracranial hypertension: headache, vomiting, and papillary edema. There may be extrapyramidal manifestations such as drowsiness, mental symptoms, slow response, loss of memory and computing power, and orientation, hand and foot movements, or dance-like movements. The condition is critical, with severe coma, high fever, seizures, rigidity and even death.

Intracranial venous thrombosis

CVT lacks specific clinical manifestations, and it is difficult to diagnose only by clinical symptoms and signs. Auxiliary examination, especially imaging examination, is very important to help diagnosis, and has important differential diagnosis value.

Intracranial venous thrombosis cerebrospinal fluid examination

Mainly due to increased pressure, early routine and biochemical are generally normal, mild to moderate cerebrospinal fluid protein may appear in the middle and late stages, and red blood cells are found to indicate bleeding. Patients with infectious CVT can develop leukocytes at an early stage, which is more common in cavernous sinus and lateral sinus thrombosis.

Intracranial venous thrombosis imaging

1) Brain CT and CT venous angiography (CTV): In the early stages of superior sagittal sinus thrombosis, CT contrast scans of some patients show empty triangle signs, that is, the sinus wall shows high-density triangle edges, of which the density is equal Blood clot. The straight sinuses and Galen veins show strip signs but are not characteristic. Indirect signs of CT are cerebral infarction or hemorrhagic infarction. CTV showed missing or unclear images of veins and sinuses at the infarct site, while collateral veins were clearly visualized.

2) Magnetic Resonance (MRI) and Magnetic Resonance Venous Angiography (MRV): In the early stage of brain MRI, the normal blood flow phenomenon of T1 weighted images disappeared, showing the vascular filling images of equal T1 and short T2. After 1-2 weeks, methemoglobin increased, and T1 and T2 images showed high signals. Late flow phenomenon reappeared. MRI can also show cerebral infarction. MRV is recognized as the best noninvasive cerebral vein imaging diagnostic method at present, and it shows better for larger cerebral vein and sinus lesions. In the acute phase (0-3 days), the thrombus vein showed equal T1 and short T2 signals; in the subacute phase (3-15 days), short T1 and long T2 signals appeared; in the chronic phase (after 15 days), infarcted vessels appeared Re-opening to varying degrees, we can see the phenomenon of flow. Combined with MRI, the diagnosis is more reliable.

3) Cerebral angiography: Including digital subtraction cerebral angiography (DSA), DSA can directly display the location and contour of the thrombus, which is the gold standard for CVT diagnosis. But because it is invasive and expensive, its clinical application is limited.

Diagnosis and differential diagnosis of intracranial venous thrombosis

Although the clinical manifestations are complex and changeable, those who have encountered cerebral lobe hemorrhage for unknown reasons, or those whose infarcts do not match the distribution of cerebral arterial blood supply areas, should undergo imaging examination of the cerebral venous system. For patients with purely increased intracranial pressure, with or without signs of neurological focal points, or patients with subacute encephalopathy, mainly with disturbance of consciousness, the possibility of cerebral venous system thrombosis should be considered. Combining CTV, MRV, and especially DSA can help confirm the diagnosis. For patients with atypical headache, imaging examination of the cerebral venous system is also recommended to rule out CVT. The time from onset of symptoms to diagnosis is approximately 7 days. The most sensitive are MRI and MRV. Differential diagnosis should consider the identification of brain abscess, benign intracranial hypertension, encephalitis, infective endocarditis, central nervous system vasculitis, arterial cerebral infarction and diseases causing eye symptoms. ^[2]

The diagnosis of cavernous sinus thrombosis can be diagnosed based on eye protrusion, edema, and restricted movement in all directions of the eyeball, especially from one side of the eyeball to the other side. But sometimes it needs to be distinguished from other diseases such as exophthalmos and restricted eye movements, such as post-orbital cellulitis, post-autumn mass lesions, glioblastoma at the optic foramen, and subperiosteal abscess. Eyeballs on both sides should also be distinguished from hyperthyroidism.

Thrombosis of the superior sagittal sinus and lateral sinuses can only show signs of intracranial hypertension, and must be distinguished from intracranial occupying lesions such as hematomas, tumors, and abscesses. Patients with mastoiditis, otitis media, and sepsis mainly consider the possibility of lateral sinus thrombosis. Such as lumbar spine puncture, cervical pressure test, cerebrospinal fluid pressure does not rise, cerebrospinal fluid is bloody or yellow, we must highly suspect the formation of sigmoid sinus thrombosis. Consider sagittal sinus thrombosis when the baby is suffering from severe anemia, diarrhea, malnutrition, failure, or intracranial hypertension or coma, localized convulsions, or paralysis of the mother within 1-3 months of delivery.

The following is the recommended management process for CVT in the latest guidelines:

CVT Management Process

Treatment of intracranial venous thrombosis

Currently the best clinically recommended treatment for CVT is anti-platelet agglutination, which can reduce mortality and severe disability without increasing the risk of bleeding. The results of large-scale international clinical trials show that compared with placebo, all patients in the heparin-treated group recovered, including patients with bleeding, no new blood was emitted, and novices in the placebo group died. Patients with coma may require local thrombolytic therapy, which may be better than heparin, and there is no standard for thrombolysis. Patients have mild symptoms and a single symptom, which can be cured without treatment, but lacking reliable prognostic criteria, it is difficult to choose whether to use effective and safe regimens for the crisis of life status. ^[3]

Etiology of intracranial venous thrombosis

For infectious CVT, the main purpose is to use sensitive, sufficient, and sufficient antibiotics for the pathogenic bacteria and to treat the primary lesion as early as possible; for non-infectious CVT, corresponding treatment should be based on known or possible causes and correct dehydration, increase blood volume, reduce Treatments such as blood viscosity and improving cerebral blood circulation.

Symptomatic treatment of intracranial venous thrombosis

Patients with cerebral edema and intracranial hypertension should be actively treated for dehydration and intracranial pressure reduction. Frequent intravenous drip of mannitol can be added, and diuretics can be added to assist dehydration. Blood viscosity, electrolytes and renal function should be noted. Acetazole is also available. Amines inhibit cerebrospinal fluid secretion, subtemporal decompression is feasible when cranial pressure is high and life-threatening; authors of epilepsy should be given anti-epileptic therapy, patients with high fever should be physically cooled, and basic care and supportive treatment should be strengthened for patients with disturbance of consciousness, and prevention complication.

Intracranial venous thrombosis specific treatment

According to the anticoagulation and thrombolytic therapy of thrombus itself, in theory, venous occlusion can be released and blood flow can be restored. However, this method is still controversial in clinical practice, and the specific methods are not uniform.

1) Anticoagulation: Heparin-type anticoagulants are used to treat cerebral venous system thrombosis in order to prevent the thrombus from expanding and partially or completely recanalize the occluded blood vessels. At present, domestic and foreign tendencies are that heparin anticoagulation therapy may be safe and effective. In the acute phase, heparin can be given intravenously or subcutaneously injected with low molecular weight heparin.

2) Thrombolysis: The thrombolytic method for systemic intravenous administration of cerebral venous thrombosis, due to the low local drug concentration and easy to cause intracranial hemorrhage, has been rarely used. For severe cases, intravascular intervention with local administration of thrombolysis or removal of thrombus can be considered, but the effect is to be evaluated and the technique is difficult, and it is only applicable to conditional hospitals.

Long-term treatment of intracranial venous thrombosis

Withdraw contraceptives, treat primary disease and risk factors, and continue oral anticoagulants for 3-6 months.

Intracranial venous thrombosis

1) Pregnancy: Low-molecular-weight heparin treatment of sufficient foot course in CVT during pregnancy is essential. Sufficient low-molecular-weight heparin should be continuously applied throughout pregnancy, and low-molecular-weight heparin or vitamin K antagonists should be used for at least 6 weeks after delivery. Female patients with a previous history of CVT are not contraindicated. Low-molecular-weight heparin may be recommended for pre-pregnancy and postpartum use. Further, due to the underlying cause, further examinations should be performed during pregnancy. Consult a hematologist and a fetal medical expert.

2) Childhood: Children's CVT is another special group. While supplementing fluids, controlling epilepsy and intracranial hypertension, it should use a sufficient amount of low molecular weight heparin to screen for possible infections and other causes, and treat severely ill children. EEG detection. Severe or long-term intracranial hypertension may cause vision loss. Vision and visual field should be evaluated regularly and effective control of intracranial hypertension. Infants with acute CVT can consider low-molecular-weight heparin for 6 weeks to 3 months. Children diagnosed with CVT 28 days after birth should be treated with sufficient low-molecular-weight heparin, even if there is intracranial hemorrhage. Continue to use low-molecular-weight heparin or oral vitamin K antagonists for 3 to 6 months. The effectiveness and safety of vascular intervention in pediatric patients is uncertain. Only patients with worsening nervous system under adequate anticoagulation therapy and strict screening should consider intravascular intervention.

In all children with CVT, it is recommended to repeat neuroimaging examinations, including venous imaging, 1 week after the diagnosis to detect the spread of initial thrombus and cardiac infarction or bleeding. In all children with acute CVT, CT or MRI scans should be performed in the first week after treatment to detect new intracranial hemorrhage. At the same time, a prone to thrombosis test should be performed to identify potential coagulation abnormalities that may cause embolism recurrence. . Children with CVT should undergo blood culture and X-rays of the sinuses to determine if there is a potential infection. Because children with CVT are more likely to have seizures, patients with unconsciousness or mechanical ventilation may consider continuous EEG monitoring.

Prognosis of intracranial venous thrombosis

The prognosis of CVT is good, and the mortality rate is about 6-10%. In 23% of patients, symptoms may worsen within a few days after diagnosis, manifested as disturbances of consciousness, mental disorders, new onset of epilepsy, increased focal symptoms, increased number of headaches, or loss of vision. New lesions are seen in about a third of patients who have become worse. 3-15% of patients can die in the acute stage (within one month), which is more common in young people. The main cause of death is cerebellar notch hernia caused by massive cerebral hemorrhage. Late deaths are often associated with underlying conditions, especially malignancies, and are more common in the elderly. The main reasons for the poor long-term prognosis are infection of the central nervous system, any malignant tumor, deep vein thrombosis, and images suggesting cerebral hemorrhage. The location of the thrombus also affects the prognosis. Generally, the prognosis of the thrombus in the brain and cerebellum is poor. There was no significant difference in the incidence of persistent nervous system dysfunction in patients with complete or partial recanalization, and the sequelae of those with no recanalization were obvious. Although the survival rate of patients is high, there are many residual neurological sequelae, such as recurrent epilepsy, decreased vision, focal neurological deficits, and impaired cognitive function. The risk of CVT recurrence is low. People with a previous history of CVT should consider whether CVT relapses and the presence of intracranial hypertension if a new and persistent severe headache occurs. Generally, the risk of recurrence is relatively large within one year, but patients with relapse generally do not have residual sequelae of the nervous system.