Cerebral venous sinus thrombosis (CVST) is a rare type of ischemic cerebrovascular disease. Due to its low incidence, complex etiology, highly variable and non-specific symptoms and clinical manifestations, it has been misdiagnosed and missed due to the lack of effective examination and treatment tools, and has a high mortality rate. Early diagnosis and timely and effective treatment are the keys to improve patient prognosis and reduce mortality. In this paper, we summarized 46 cases of CVST diagnosed in recent years in the Department of Neurosurgery of Xuanwu Hospital of Capital Medical University, analyzed their clinical manifestations, imaging features and treatment and prognosis, and discussed the pathogenesis of CVST and the relationship between early diagnosis and treatment and prognosis.
Materials and Methods
General data
The patients were hospitalized in the Department of Neurosurgery of Xuanwu Hospital of Capital Medical University from January 2000 to October 2006, including 21 males and 25 females, aged 20-61 years, with an average age of 34.7 years.
Course and Causes of Disease
There were 9 cases of CVST caused by head and facial infections, 18 cases of CVST during pregnancy and delivery, 7 cases of CVST caused by craniocerebral trauma, 3 cases of CVST caused by malignant tumors, 3 cases of hereditary tendency to thrombosis (protein C deficiency), and 6 cases of unknown cause. The time interval between the onset of first symptoms and hospital admission was used as the criterion for determining the form of onset, with 9 cases of acute onset (within 1 week), 17 cases of subacute onset (1 week-1 month), and 20 cases of chronic onset (more than 1 month).
Clinical manifestations
38 cases of headache, 30 cases of nausea and vomiting, 25 cases of optic papilloedema, 23 cases of seizure, 9 cases of speech disorder, 6 cases of urinary incontinence, 18 cases of hemiparesis, 10 cases of bilateral lower limb paralysis, 22 cases of consciousness disorder, 3 cases of fever, 13 cases of blurred vision and diplopia, 6 cases of fundus hemorrhage, 8 cases of oculomotor nerve palsy, 7 cases of abducens nerve palsy, 6 cases of tinnitus and hearing loss, 3 cases of limb movement disorder and sensory abnormalities The meningeal irritation sign (+) was found in 9 cases.
Imaging examination
CT: 1 case of high-density cortical shadow, 5 cases of skull fracture, including 2 cases of occipital fracture, 3 cases of parietal fracture, 4 cases of fracture line crossing the midline, 3 cases of epidural hematoma, 2 cases of subdural hematoma, 6 cases of subarachnoid hemorrhage, 9 cases of cerebral parenchymal hemorrhage, and 18 cases of cerebral infarction
MRI: speckled short T1 and long T2 signals in the venous sinus region, parietal midline cerebral edema and diffuse intracranial cerebral edema in 35 cases, MRV intracranial venous sinus was poorly displayed or not shown. The superior sagittal sinus was involved in 31 cases, the transverse sinus in 22 cases, the sigmoid sinus in 7 cases, and the cavernous sinus in 3 cases.
DSA: cerebral arteriovenous circulation time was significantly prolonged and venous sinus filling defects were observed in all cases, including 28 cases with non-display of superior sagittal sinus; 22 cases with filling defects of transverse sinus and 24 patients with occlusion of more than two venous sinuses.
Laboratory tests
Routine blood tests: 28 cases with elevated white blood cells, red blood cells (2.70-5.31) × 1012/L, hemoglobin 90-154 g/L, platelets (53-213) × 109/L.
Cerebrospinal fluid examination: (120-420 mmH2O), all patients underwent lumbar puncture examination in which the pressure was increased in 42 cases, and cerebrospinal fluid routine were: leukocytes increased in 9 cases, red blood cells increased in 6 cases.
Coagulation tests: plasma prothrombin time (PT) 12-20s, PT activity 75%-170%, activated partial thromboplastin time (APTT) 32-48s. 1 routine renal function test creatinine 294umol/L, urea nitrogen 15.3mmol/L. 5 routine electroencephalography 4 cases suggest abnormalities.
Treatment
The treatment of 46 patients included general dehydration and cranial pressure lowering treatment, 30 cases of sexual anti-infection treatment, 3 cases of craniectomy and decompression, 2 cases of epidural hematoma removal, 2 cases of subdural hematoma removal, 9 cases of emergency cesarean section due to fetal distress, 28 patients treated with subcutaneous heparin injection, and 18 patients treated with local intravenous thrombolysis.
Results
Among 46 patients, 26 patients were cured (56.5%), patients’ clinical symptoms basically disappeared, MRI, MRV, MRV showed complete recanalization of venous sinus; 11 patients were discharged with improvement (23.9%), patients’ clinical symptoms and signs were significantly reduced, MRV showed partial recanalization of venous sinus or no new thrombosis, total efficiency 80.4%; 9 patients died, accounting for 19.6%. The efficacy was stable in 30 patients from six months to five years after follow-up, and there was no recurrence in one case, but two cases still had different degrees of high cranial pressure symptoms.
Discussion
CVST is a rare cerebrovascular disease first reported by Ribes in 1825. CVST used to be considered a lethal disease and was found more frequently at autopsy. In recent years, due to the development of neuroimaging, the emergence of new thrombolytic drugs, and the rapid development of neurointerventional radiology techniques, the early diagnosis and cure rates of CVST have increased significantly, and the prognosis has improved significantly.
The causes of CVST are complex and can be caused by abnormal venous blood flow, inflammatory reaction or exudation in the venous wall, or pre-thrombotic state. Non-infectious causes include pregnancy, puerperium, oral contraceptives and other medications, surgery, trauma and local compression, various causes of blood hypercoagulability such as systemic lupus erythematosus, acute lymphoblastic leukemia, nephrotic syndrome, leukoaraiosis, etc. In addition, there are congenital or genetic causes of blood hypercoagulability such as protein C and protein S deficiency, anticoagulant factor III deficiency, antiphospholipid antibody syndrome, etc. [1]. Nevertheless, in about 30% of patients, the exact cause or risk factors cannot be identified.
In our group, all of the patients were young and middle-aged, and 18 cases (39%) of CVST occurred during pregnancy and childbirth, which accounted for a large proportion of CVST in young and middle-aged patients. After analyzing the possible causes of CVST in patients during pregnancy and childbirth, there are several possible causes: (1) prenatal history of gestational hypertension syndrome, massive sweating and blood loss during delivery, increased blood viscosity, and slow blood flow due to decreased blood pressure after delivery, which can easily lead to thrombosis. ②Some patients have a history of infection after delivery, which can cause elevated body temperature and increased white blood cell count, and eventually lead to blood stasis in the venous sinuses and the formation of thrombosis. ③Thrombosis of the pelvic venous plexus during childbirth, and embolism occurs when the embolus is dislodged through the venous system into the intracranial veins. Infectious intracranial venous thrombosis is mostly secondary to infectious lesions, such as those in the orbit, nasal cavity, face, mastoid process, middle ear, pharynx, and meningitis, brain abscess, sepsis, intracranial infection after craniocerebral trauma, mastoid surgery, etc. Due to anatomical features, the cavernous sinus and sigmoid sinus are the frequent sites [2]. In our group of cases, CVST was caused by cephalofacial infection in 7 cases, which caused cavernous sinus thrombosis in 3 cases, sigmoid sinus, and transverse sinus involvement in 4 cases. It is reported that 4% of CVST is caused by trauma, and it is more common to have a skull fracture with the fracture line crossing the midline, and the exact mechanism is unclear, but it may be that the endothelial damage to the venous sinus during the skull fracture activates the coagulation system, thus causing thrombosis [3]. In our group, four of the seven patients (15%) with CVST caused by craniocerebral trauma had a fracture line crossing the midline and two had an associated epidural hematoma, which is higher than that reported in the literature. Malignant tumors leading to venous sinus thrombosis are more common in elderly patients, and it is believed that the causes of malignant tumors leading to the formation of CVST are multiple, such as direct compression of venous sinuses by tumors, which changes the altered blood flow status; patients with malignant tumors are in poor physical condition and often suffer from severe water loss, and blood concentration makes thrombosis easy to form; tumor cells release various cytokines to increase blood coagulation [4]. Protein C inhibits thrombosis through three effects: (i) activation of coagulation factors Va and VIIIa inhibits the production of thrombin. (ii) Inactivating factor Va, the receptor of factor Xa, and inhibiting Xa binding to platelets. (iii) Promoting the release of fibrinogen and increasing fibrinolysis [5]. Therefore, protein C deficiency causes a hypercoagulable state of the blood with a tendency to thrombosis.
The disease has no specific signs and symptoms, but manifests itself with signs of increased intracranial pressure such as headache, vomiting, optic papilloedema, cervical resistance, seizures and focal neurological deficits, but mostly atypical, sometimes with a single symptom [6]. In our group, there were 40 cases of increased intracranial pressure manifestations, 22 cases of cortical damage signs and symptoms, and 23 cases of seizures in 46 cases. Imaging is the main tool to confirm the diagnosis of CVST. direct signs of venous sinus thrombosis diagnosed by CT include the striated sign, high-density triangle sign and “empty triangle sign” after enhancement scan, and indirect signs of extensive cerebral edema, small ventricles, cerebral softening or cortical hemorrhage [7]. DSA was once the gold standard for the diagnosis of intracranial venous sinus thrombosis, which clearly shows the degree of intracranial venous sinus occlusion and determines the venous sinus visualization time, which is generally considered to be more than 6 seconds for delayed venous sinus visualization, but because of the invasive nature of the test, it is currently only available on CT, MRI, and MRI. MRI/MRV cannot confirm the diagnosis.
The treatment of this disease is still controversial, and the main principles of comprehensive treatment include reduction of intracranial pressure, etiological treatment, symptomatic supportive therapy, anticoagulation and thrombolytic therapy [8]. Anticoagulation is the more recognized treatment, which can improve clinical symptoms, prevent thrombus expansion, enhance blood return compensation without new bleeding and reduce mortality, and can also be applied in patients with concomitant intracranial hemorrhage [9]. Interventional thrombolytic therapy can rapidly improve cerebral blood flow status and allow rapid recanalization of occluded veins, and is considered an effective method for CVST treatment in the acute phase; in addition, interventional thrombolytic therapy can be used in cases where anticoagulation therapy is ineffective and neurological symptoms are progressively worsening [10]. We treated 46 patients with CVST with anticoagulation and thrombolysis along with symptomatic supportive therapy, 26 cases were cured and 11 cases improved, with a total effective rate of 80.4% and satisfactory results. The prognosis of CVST is reported in the literature to be good, with a severe disability and mortality rate of about 10% [12]. The mortality rate in our group was 19.6%, which is higher than that reported in the literature, and may be related to severe infection and craniocerebral injury, and systemic failure of malignant tumors.
Therefore, neuroimaging and laboratory tests should be performed as early as possible to clarify the diagnosis in patients with increased intracranial pressure of unknown origin. Early diagnosis and treatment can reduce the death and disability rates of CVST and significantly improve the prognosis. With the increasing understanding of CVST, the development of interventional neuroradiology and neuroimaging, and standardized anticoagulation treatment, the early diagnosis and treatment rate of CVST will be further improved.