Cerebral venous thrombosis (CVT), also called cerebral venous sinus thrombosis (CVST), is a cerebrovascular disease with diverse clinical manifestations that often affects young adults, women of childbearing age, and children. It's most common clinical manifestations are headache, seizures, altered consciousness, and neurological focal signs on physical examination. CVT can manifest as a single symptom, or it can present as a syndrome consisting of multiple symptoms. This non-specific clinical picture makes diagnosing CVT difficult. Although the mortality rate of CVT has been significantly reduced by improvements in treatment and diagnostic techniques, the mortality rate of severe CVT remains as high as 34.2%. Survivors of this type of CVT have varying degrees of residual symptoms and are not able to return to their previous work. Hence, we performed a comprehensive literature search in the PubMed, EMBASE, and Medline databases to review the diagnosis and treatment of CVT.
CVT is a special type of cerebrovascular disease that present with focal cerebral edema, venous cerebral infarction, seizures, and intracranial hypertension as its most prominent clinical features (Stam, 2005; Scheffer et al., 2017). The disease often affects young adults, women of childbearing age and children. Previously, the incidence was thought to be 0.2–0.5 per 100, 000 person-years (Stam, 2005; Bousser and Ferro, 2007). However, more recent studies have shown that the incidence of CVT is higher than expected and may be as high as 1.32–1.57 per 100, 000 person-years (Coutinho et al., 2012; Devasagayam et al., 2016). This difference may be the result of the use of more advanced diagnostic techniques. More importantly, CVT has received an increased amount of attention by clinicians. Patients with CVT often have headaches, seizures, altered consciousness, and neurological focal signs, all of which are non-specific manifestations, making it difficult to diagnose this disease. One study reported that 50% of CVT patients had a poor prognosis (Khealani et al., 2008). However, if an early correct identification of CVT is achieved, the patient should receive appropriate treatment, such as anticoagulation therapy, the reduction of intracranial pressure or neurological surgery. The majority of patients who are diagnosed and treated early have a generally good prognosis (Nasr et al., 2013; Sidhom et al., 2014; Terni et al., 2015; Kalita et al., 2016; Sassi et al., 2016; Lee et al., 2017).
We performed a literature search in the PubMed, EMBASE, and Medline databases through to September 1, 2017. The following search query was used in PubMed: (“Sinus Thrombosis, Intracranial”[Mesh]) OR (sinus*[Title] AND thrombosis[Title]) OR (cerebral[Title] AND (venous[Title] OR vein*[Title]) AND thrombosis[Title]). An equipollent search query was used to search the EMBASE and Medline databases. The references in eligible papers identified in the initial search were also screened. To collect information related to older cases, the relevant books and monographs were also searched. The author reviewed the titles and abstracts of the papers identified in the search to make a preliminary evaluation of their eligibility. The full text of all potentially eligible papers was then accessed and read. Only when a paper met the eligibility criteria and was found to be relevant to this review was it included (see Figure 1). The following eligibility criteria were applied: (1) Only human studies were considered. (2) Because the clinical manifestations of childhood and neonatal patients are different, pediatric studies were excluded except for some relevant epidemiological studies. (3) Publications written in English or in other languages but with an English abstract that contained sufficient information were eligible. (4) All patients included in the study were diagnosed by surgery or an autopsy or based on an imaging examination, such as intra-arterial angiography (DSA), magnetic resonance imaging (MRI), MR angiography (MRA), MR venography (MRV), computed tomography venography (CTV), or CT angiography (CTA). All studies that contained patients with an unconfirmed diagnosis of CVT were excluded. (5) With regard for case reports, a detailed and reliable medical history, the results of a physical examination, or the results of laboratory and imaging examinations were required. (6) To minimize bias, retrospective and prospective studies were required to contain at least 30 patients diagnosed with CVT to be eligible, whereas case and case-series reports were not required to meet this limit. (7) Papers concerning the epidemiology, clinical manifestations, treatment, or prognosis of CVT were eligible.
Proposed Flow Chart For The Management Of Cerebral Sinus Or Splanchnic...
In 1825, Ribes (1825) described the first case of CVT, which was later confirmed by autopsy, in a 45-year-old male with severe headache, seizures, delirium, and thrombosis involving the superior sagittal and lateral sinuses. In 1828, Abercrombie (1828) reported the first postpartum CVT in a 24-year-old woman who developed headache and seizures 2 weeks after an unremarkable delivery. A subsequent autopsy revealed thrombosis of the superior sagittal sinus and cortical veins. Since these cases were published, many additional sporadic cases have been reported, and all of these were confirmed by autopsy. In rare cases, a diagnosis was achieved by angiography. Because it is difficult to diagnose, CVT is considered a serious and rare disease (Goldman et al., 1964; Rousseaux et al., 1977). In 1968, (Krayenbuhl, 1968) conducted a retrospective study of 92 patients with CVT diagnosed by angiography, surgery, or autopsy. Thirty-seven of these cases (40%) were associated with infection, and 17 of the remaining 55 non-infectious CVT cases were associated with pregnancy, abortion, or the perinatal period. In these patients, headache (60/92), varying degrees of paresis (56/92), and seizures (34/92) were the most common manifestations. Headache was often unilateral, and seizures were usually furious. Among these 92 patients, 35 (38%) died. In 1985, Bousser et al. (1985) found that the incidence of infectious CVT was significantly reduced by the use of antibiotics, whereas the incidence of CVT associated with other factors, including trauma, Behcet's disease, the perinatal period, the use of oral contraceptives, neoplasms, nephrotic syndrome, coagulation factor, and other abnormalities, was higher. With the advent of new diagnostic techniques, such as CTV and MRA, it has become easier to achieve an early diagnosis of CVT (Poon et al., 2007). Currently, the largest studies to explore CVT are an Italian multicenter study of 706 CVT patients and a multicenter, multi-country study of 624 patients (the International study on Cerebral Vein and Dural Sinus Thrombosis, ISCVT; Ferro et al., 2004; Dentali et al., 2012).
In 1995, studies estimated that the incidence of CVT was lower than 10 cases per million per year (Daif et al., 1995). In 2012, Coutinho et al. (2012) conducted a retrospective cross-sectional study and found that the incidence of CVT was higher than previously expected and perhaps as high as 13.2 cases per million per year. A large retrospective census conducted by Devasagayam et al. (2016) in 2016 also supported this conclusion. The incidence of CVT in neonates and children is ~0.67 cases per 100, 000 children per year, and the incidence of perinatal CVT is ~11.6 cases per 100, 000 deliveries in pregnant women (Lanska and Kryscio, 2000; deVeber et al., 2001).
In 1985, it was found that the male to female ratio in CVT was 1:0.8 (Bousser et al., 1985). In two studies published in 2014 and 2016, there were 3.7–5.3 times more female than male patients (Karadas et al., 2014; Gunes et al., 2016). Zuurbier et al. (2016b) conducted a systematic analysis of the proportions of male and female patients in 23, 638 patients across 112 studies published from 1966 to 2014. They found that the proportion of CVT patients who were female gradually increased over time and that the median proportion of female patients was 54.8% in studies published before 1981 and 69.8% in studies published after 2001. This difference was significant (P = 0.002), and the year of publication of the studies was associated with the proportion of patients who were female (P = 0.01). The proportion of female CVT cases that were pregnancy-related remained stable over time, whereas the proportion of affected patients using oral contraceptives increased over time (Pearson's correlation coefficient 0.29, P = 0.01). This may explain the observed increase in the proportion of female patients.
Cerebral Vein Thrombosis
CVT often occurs in young people and women of childbearing age. Affected children are usually newborns. The age of CVT patients ranges from newborn to 82 years old, but this condition mainly occurs in individuals between 30 and 41 years old (Table 1; deVeber et al., 2001; Wasay et al., 2008; Sidhom et al., 2014; Kalita et al., 2016).
In the majority of patients, multiple venous sinuses are involved. The superior sagittal sinus, lateral sinus, and sigmoid sinus are most frequently involved. Sassi et al. (2016) conducted a retrospective study of 160 patients diagnosed with CVT. The most common thrombosis sites were the superior sagittal sinus (65%) and the transverse sinus (60.5%). In most patients, multiple venous sinuses (114 cases, 71.2%) were involved. In a study conducted by Sidhom et al. (2014), the most frequently involved sinuses were the lateral sinus (56%) and the superior sagittal sinus (51%), and in nearly half of all affected patients, multiple venous sinuses were involved. Uzar et al. (2012) conducted a retrospective study of 47 patients. The sigmoid sinus was involved in 35 (74.5%), the transverse sinus was involved in 29
In 1825, Ribes (1825) described the first case of CVT, which was later confirmed by autopsy, in a 45-year-old male with severe headache, seizures, delirium, and thrombosis involving the superior sagittal and lateral sinuses. In 1828, Abercrombie (1828) reported the first postpartum CVT in a 24-year-old woman who developed headache and seizures 2 weeks after an unremarkable delivery. A subsequent autopsy revealed thrombosis of the superior sagittal sinus and cortical veins. Since these cases were published, many additional sporadic cases have been reported, and all of these were confirmed by autopsy. In rare cases, a diagnosis was achieved by angiography. Because it is difficult to diagnose, CVT is considered a serious and rare disease (Goldman et al., 1964; Rousseaux et al., 1977). In 1968, (Krayenbuhl, 1968) conducted a retrospective study of 92 patients with CVT diagnosed by angiography, surgery, or autopsy. Thirty-seven of these cases (40%) were associated with infection, and 17 of the remaining 55 non-infectious CVT cases were associated with pregnancy, abortion, or the perinatal period. In these patients, headache (60/92), varying degrees of paresis (56/92), and seizures (34/92) were the most common manifestations. Headache was often unilateral, and seizures were usually furious. Among these 92 patients, 35 (38%) died. In 1985, Bousser et al. (1985) found that the incidence of infectious CVT was significantly reduced by the use of antibiotics, whereas the incidence of CVT associated with other factors, including trauma, Behcet's disease, the perinatal period, the use of oral contraceptives, neoplasms, nephrotic syndrome, coagulation factor, and other abnormalities, was higher. With the advent of new diagnostic techniques, such as CTV and MRA, it has become easier to achieve an early diagnosis of CVT (Poon et al., 2007). Currently, the largest studies to explore CVT are an Italian multicenter study of 706 CVT patients and a multicenter, multi-country study of 624 patients (the International study on Cerebral Vein and Dural Sinus Thrombosis, ISCVT; Ferro et al., 2004; Dentali et al., 2012).
In 1995, studies estimated that the incidence of CVT was lower than 10 cases per million per year (Daif et al., 1995). In 2012, Coutinho et al. (2012) conducted a retrospective cross-sectional study and found that the incidence of CVT was higher than previously expected and perhaps as high as 13.2 cases per million per year. A large retrospective census conducted by Devasagayam et al. (2016) in 2016 also supported this conclusion. The incidence of CVT in neonates and children is ~0.67 cases per 100, 000 children per year, and the incidence of perinatal CVT is ~11.6 cases per 100, 000 deliveries in pregnant women (Lanska and Kryscio, 2000; deVeber et al., 2001).
In 1985, it was found that the male to female ratio in CVT was 1:0.8 (Bousser et al., 1985). In two studies published in 2014 and 2016, there were 3.7–5.3 times more female than male patients (Karadas et al., 2014; Gunes et al., 2016). Zuurbier et al. (2016b) conducted a systematic analysis of the proportions of male and female patients in 23, 638 patients across 112 studies published from 1966 to 2014. They found that the proportion of CVT patients who were female gradually increased over time and that the median proportion of female patients was 54.8% in studies published before 1981 and 69.8% in studies published after 2001. This difference was significant (P = 0.002), and the year of publication of the studies was associated with the proportion of patients who were female (P = 0.01). The proportion of female CVT cases that were pregnancy-related remained stable over time, whereas the proportion of affected patients using oral contraceptives increased over time (Pearson's correlation coefficient 0.29, P = 0.01). This may explain the observed increase in the proportion of female patients.
Cerebral Vein Thrombosis
CVT often occurs in young people and women of childbearing age. Affected children are usually newborns. The age of CVT patients ranges from newborn to 82 years old, but this condition mainly occurs in individuals between 30 and 41 years old (Table 1; deVeber et al., 2001; Wasay et al., 2008; Sidhom et al., 2014; Kalita et al., 2016).
In the majority of patients, multiple venous sinuses are involved. The superior sagittal sinus, lateral sinus, and sigmoid sinus are most frequently involved. Sassi et al. (2016) conducted a retrospective study of 160 patients diagnosed with CVT. The most common thrombosis sites were the superior sagittal sinus (65%) and the transverse sinus (60.5%). In most patients, multiple venous sinuses (114 cases, 71.2%) were involved. In a study conducted by Sidhom et al. (2014), the most frequently involved sinuses were the lateral sinus (56%) and the superior sagittal sinus (51%), and in nearly half of all affected patients, multiple venous sinuses were involved. Uzar et al. (2012) conducted a retrospective study of 47 patients. The sigmoid sinus was involved in 35 (74.5%), the transverse sinus was involved in 29
In 1825, Ribes (1825) described the first case of CVT, which was later confirmed by autopsy, in a 45-year-old male with severe headache, seizures, delirium, and thrombosis involving the superior sagittal and lateral sinuses. In 1828, Abercrombie (1828) reported the first postpartum CVT in a 24-year-old woman who developed headache and seizures 2 weeks after an unremarkable delivery. A subsequent autopsy revealed thrombosis of the superior sagittal sinus and cortical veins. Since these cases were published, many additional sporadic cases have been reported, and all of these were confirmed by autopsy. In rare cases, a diagnosis was achieved by angiography. Because it is difficult to diagnose, CVT is considered a serious and rare disease (Goldman et al., 1964; Rousseaux et al., 1977). In 1968, (Krayenbuhl, 1968) conducted a retrospective study of 92 patients with CVT diagnosed by angiography, surgery, or autopsy. Thirty-seven of these cases (40%) were associated with infection, and 17 of the remaining 55 non-infectious CVT cases were associated with pregnancy, abortion, or the perinatal period. In these patients, headache (60/92), varying degrees of paresis (56/92), and seizures (34/92) were the most common manifestations. Headache was often unilateral, and seizures were usually furious. Among these 92 patients, 35 (38%) died. In 1985, Bousser et al. (1985) found that the incidence of infectious CVT was significantly reduced by the use of antibiotics, whereas the incidence of CVT associated with other factors, including trauma, Behcet's disease, the perinatal period, the use of oral contraceptives, neoplasms, nephrotic syndrome, coagulation factor, and other abnormalities, was higher. With the advent of new diagnostic techniques, such as CTV and MRA, it has become easier to achieve an early diagnosis of CVT (Poon et al., 2007). Currently, the largest studies to explore CVT are an Italian multicenter study of 706 CVT patients and a multicenter, multi-country study of 624 patients (the International study on Cerebral Vein and Dural Sinus Thrombosis, ISCVT; Ferro et al., 2004; Dentali et al., 2012).
In 1995, studies estimated that the incidence of CVT was lower than 10 cases per million per year (Daif et al., 1995). In 2012, Coutinho et al. (2012) conducted a retrospective cross-sectional study and found that the incidence of CVT was higher than previously expected and perhaps as high as 13.2 cases per million per year. A large retrospective census conducted by Devasagayam et al. (2016) in 2016 also supported this conclusion. The incidence of CVT in neonates and children is ~0.67 cases per 100, 000 children per year, and the incidence of perinatal CVT is ~11.6 cases per 100, 000 deliveries in pregnant women (Lanska and Kryscio, 2000; deVeber et al., 2001).
In 1985, it was found that the male to female ratio in CVT was 1:0.8 (Bousser et al., 1985). In two studies published in 2014 and 2016, there were 3.7–5.3 times more female than male patients (Karadas et al., 2014; Gunes et al., 2016). Zuurbier et al. (2016b) conducted a systematic analysis of the proportions of male and female patients in 23, 638 patients across 112 studies published from 1966 to 2014. They found that the proportion of CVT patients who were female gradually increased over time and that the median proportion of female patients was 54.8% in studies published before 1981 and 69.8% in studies published after 2001. This difference was significant (P = 0.002), and the year of publication of the studies was associated with the proportion of patients who were female (P = 0.01). The proportion of female CVT cases that were pregnancy-related remained stable over time, whereas the proportion of affected patients using oral contraceptives increased over time (Pearson's correlation coefficient 0.29, P = 0.01). This may explain the observed increase in the proportion of female patients.
Cerebral Vein Thrombosis
CVT often occurs in young people and women of childbearing age. Affected children are usually newborns. The age of CVT patients ranges from newborn to 82 years old, but this condition mainly occurs in individuals between 30 and 41 years old (Table 1; deVeber et al., 2001; Wasay et al., 2008; Sidhom et al., 2014; Kalita et al., 2016).
In the majority of patients, multiple venous sinuses are involved. The superior sagittal sinus, lateral sinus, and sigmoid sinus are most frequently involved. Sassi et al. (2016) conducted a retrospective study of 160 patients diagnosed with CVT. The most common thrombosis sites were the superior sagittal sinus (65%) and the transverse sinus (60.5%). In most patients, multiple venous sinuses (114 cases, 71.2%) were involved. In a study conducted by Sidhom et al. (2014), the most frequently involved sinuses were the lateral sinus (56%) and the superior sagittal sinus (51%), and in nearly half of all affected patients, multiple venous sinuses were involved. Uzar et al. (2012) conducted a retrospective study of 47 patients. The sigmoid sinus was involved in 35 (74.5%), the transverse sinus was involved in 29
