Chapter 13 – Management of Cerebral Venous Thrombosis in the Neurocritical Care Unit




Abstract




Cerebral venous thrombosis (CVT) refers to clot formation within the dural venous sinuses or the cerebral venous drainage system. The most commonly affected sinuses are the superior sagittal sinus, transverse sinuses, straight sinus, cortical veins, internal jagular veins, and deep veins.





Chapter 13 Management of Cerebral Venous Thrombosis in the Neurocritical Care Unit


Xiaomeng Xu , Xiaoying Yao , and Magdy Selim



Definition and Epidemiology



Definition


Cerebral venous thrombosis (CVT) refers to clot formation within the dural venous sinuses or the cerebral venous drainage system. The most commonly affected sinuses are the superior sagittal sinus, transverse sinuses, straight sinus, cortical veins, internal jagular veins, and deep veins.



Incidence


Cerebral venous thrombosis is a rare but important cause of stroke, especially among young individuals. The reported incidence of CVT in different studies varies greatly. It was traditionally estimated to be 2 to 4 cases per million per year, but recent studies reported a much higher incidence of 13 cases [Reference Coutinho, Zuurbier, Aramideh and Stam1] to 15 cases [Reference Devasagayam, Wyatt, Leyden and Kleinig2] per million each year, as a result of improved diagnosis by advanced imaging techniques [Reference Devasagayam, Wyatt, Leyden and Kleinig2,Reference Silvis, de Sousa, Ferro and Coutinho3].



Age and Sex


CVT occurs predominantly in young and middle-aged patients, of whom >90% are less than 65 years old [Reference Ferro, Canhao and Bousser4]. The male to female ratio is 1:3, and the prevalence in women is likely due to sex-specific risk factors such as the use of oral contraceptives, pregnancy, and postpartum [Reference Ferro and Canhao5,Reference Kovacs6]. However, despite previous CVT, pregnancy caused a low absolute risk for recurrent CVT. Therefore, prior CVT should not be a contraindication for pregnancy [Reference Aguiar de Sousa, Canhao and Crassard7].



Risk Factors


There are several risk factors that predispose to CVT. In women, oral contraceptives, pregnancy, and postpartum are predominant risk factors. In addition, hereditary and acquired prothrombotic conditions can increase the risk for CVT. Table 13.1 lists many of these risk factors. A thorough history and exam will often identify acquired factors.




Table 13.1 Risk factors for CVT










































































































































RISK CATEGORY RISK FACTOR Prevalence
INFECTIOUS
Infection of head and neck 8%
Central nervous system 2%
Other 4%
NONINFECTIOUS
GENETIC Antithrombin deficiency 22%
Protein C deficiency
Protein S deficiency
Factor V Leiden thrombophilia
Prothrombin G20210A mutation
ACQUIRED:
SEX-SPECIFIC a Pregnancy and postpartum 21%
Oral contraceptives 54%
Hormone replacement therapy 4%
DISEASE-RELATED:
MALIGNANCY Cancer 5%
Myeloproliferative neoplasms 3%
AUTOIMMUNE DISEASE Systemic lupus erythematosus 1%
Antiphospholipid syndrome 6%
Behçet’s disease 1%
Inflammatory bowel disease 2%
Sarcoidosis 0%
OTHER DISEASE Thyroid disease 2%
Nephrotic syndrome 1%
Anemia 9%
Hyperhomocysteinemia 5%
Dehydration 2%
Central nervous system malformation 2%
MECHANICAL INJURY Head trauma 1%
Lumbar puncture 2%
Neurosurgical operation 1%
Jugular vein catheterization 1%
NONE IDENTIFIED 13%


Prevalence per ISCVT cohort study [Reference Coutinho, Zuurbier, Aramideh and Stam1].




a Prevalences of sex-specific risk factors were calculated.



Diagnosis


The diagnosis of CVT requires: (1) Clinical suspicion based on the presenting symptoms and signs, (2) using brain imaging to confirm CVT, and (3) additional laboratory tests and imaging to determine the underlying cause of CVT.



Clinical Manifestations of CVT


The clinical features of CVT are usually diverse and unspecific, which adds to the difficulty in making a timely diagnosis. Clinical manifestations of CVT are attributed to two mechanisms: (1) elevation of overall intracranial pressure (ICP) and brain edema resulting from the obstruction of the cerebral venous sinus and cerebral blood outflow, and (2) focal brain injury due to the local effects of the clot and venous infarction. Compared with other forms of stroke, the symptoms of CVT are usually slow in the onset, progressive, and may be bilateral. Abrupt onset is rare, and is mostly seen in obstetrical and infectious cases.


Headache is the most common and earliest symptom of CVT affecting about 90% of cases, and may be the only symptom in up to 25% of patients [Reference Saposnik, Barinagarrementeria and Brown8]. The headache is usually progressive over days to weeks, but thunderclap headache has been reported in some cases. Other symptoms and signs of increased ICP, such as papilledema and transient visual obscurations, may manifest themselves later on. Seizures, focal or generalized, occur in ~40% patients, and are usually secondary to a venous infarct. Altered level of consciousness may be seen in ~5% of cases, and may be postictal or attributed to increased ICP. In addition, venous infarct(s) may result in focal neurological deficit in affected regions. These are variable, but hemiparesis is most common. Rare presentations of CVT include tinnitus, vertigo, cranial nerve palsies, and cerebellar symptoms/signs. Coma, stupor, extensor spasms, or abulia may be seen with deep CVT leading to involvement of the basal ganglia and thalami.



Imaging of the Brain and Venous Sinuses


Imaging studies are key to establish the diagnosis of CVT in suspected cases.



Computed Tomography

Noncontrast computed tomography (CT) is usually the first imaging examination in these clinical scenarios, due to its readiness in emergent settings and value in excluding other neurological conditions with similar signs and symptoms. However, radiological changes on noncontrast CT scans are too subtle to be diagnostic in most cases of CVT. Therefore, a negative CT result cannot entirely rule out the possibility of CVT. Indeed, an initial CT scan is interpreted as “normal” in 25% to 40% of patients with CVT.


CT findings may include: changes in the mastoid or middle ear structures in patients with septic lateral sinus thrombosis, venous infarctions, which tend to be hemorrhagic and located in nonarterial or subcortical locations, and effacement of the sulci or slit-like ventricles due to brain edema or high ICP. The most straightforward and direct evidence of CVT is to directly visualize the thrombus in the vein or sinus. On plain CT scans, an acute clot can appear as homogeneous hyperdensity of a cortical vein or a cerebral sinus, mimicking a subarachnoid hemorrhage. In the cases of superior sagittal sinus CVT, the clot may emerge as a dense triangle due to the anatomic structure of the superior sagittal sinus, which is referred to as the filled delta sign (Figure 13.1). One of the drawbacks of plain CT scans is that an acute clot can only be seen in the first 7–14 days. After that, the clot becomes isodense or hypodense, and difficult to visualize.





Figure 13.1 Filled delta sign on plain CT (arrow). The clot in superior sagittal sinus causes increased density than normal.


Therefore, in subacute and chronic cases, contrast-enhanced CT scan and CT venography are recommended. On contrast-enhanced CT scans, the filling defect sign and empty delta sign are equivalent to the above findings on plain CT scans.



Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is the imaging modality of choice in CVT. Compared with CT, MRI is more sensitive in detecting parenchymal abnormalities, such as focal edema and infarctions, and the thrombus during the acute, subacute, and chronic stages. The clot appears isointense on T1- and hypointense on T2-weighted images during the acute phase, and gradually becomes hyperintense on both T1- and T2-weighted images by the second week.


The main direct sign of thrombus on MRI is the absence of flow void within the affected venous sinus (Figure 13.1), which is equivalent to a hyperdensity sign on plain CT and filling defect sign on contrast-enhanced CT. However, T1- and T2-weighted images have limitations, and false positives due to slow blood flow are not uncommon. While susceptibility-weighted MRI may allow direct visualization of deoxyhemoglobin in the thrombus as an area of signal loss/darkening within the affected sinus (Figure 13.2), contrast-enhanced MRI and MR venography are always recommended.





Figure 13.2 MRI T1-weighted images. The clot in the superior sagittal sinus (arrows) appears isointense during the acute phase (A), and hyperintense during the chronic phase (B).



Venography

Plain CT or MRI can be entirely normal in about 30% of cases. Therefore, CT or MR venography is recommended when CVT is suspected, even when plain CT or MRI are negative [Reference Saposnik, Barinagarrementeria and Brown8,Reference Long, Koyfman and Runyon9]. Although the diagnostic value of CTV and MRV is equivalent, due to concerns about radiation and iodine contrast, MRV is the most widely used modality (Figure 13.3). The 2D time-of-flight (TOF) is the most commonly used MRV technique (Figure 13.5A). However, TOF MRV has limitations because flow gaps are not uncommon. The use of gadolinium-enhanced MRV is less likely to be affected by flow artifacts, and when combined with a 3D magnetization-prepared rapid gradient-echo (MP-RAGE) sequence (Figure 13.5B) is superior to TOF MRV, particularly in complicated cases with anatomic variants [Reference Saposnik, Barinagarrementeria and Brown8].





Figure 13.3. Gradient echo T2* MRI showing susceptibility artifact within the left transverse sinus (arrow) consistent with sinus thrombosis.





Figure 13.4 A left transverse and sigmoid sinuses thrombosis (arrow) confirmed by MRV.





Figure 13.5 (A) TOF-MRV shows lack of flow in right transverse sinus (arrow). (B) MP-RAGE with gadolinium shows patency of the sinus (arrow).


The use of invasive digital subtraction angiography (DSA), the historical gold standard for diagnosing CVT, is declining due to improvement in the sensitivity and specificity of noninvasive CT/MR venography. Nowadays, DSA use is often limited to patients in whom MRV/CTV is inconclusive, or equivocal cases where it is difficult to ascertain if CVT detected on CTV/MRV is attributable to sinus hypoplasia or filling defects due to arachnoid granulations.



Blood Tests and Other Imaging Studies


The use of D-dimer as an alternative to imaging to exclude CVT diagnosis in low-risk patients has been debatable. Serum levels >500 μg/L have 91% specificity, 97% sensitivity, and 55% positive predictive value. However, there are many causes for elevated D-dimer, and false-negative results may be seen in subacute or chronic cases, small clot burden, and cases presenting with isolated headache.


Laboratory tests are mostly helpful in determining the etiology of CVT (Table 13.1), including underlying infection, malignancy, hematological and inflammatory disorders, or prothrombotic conditions. Recommended initial tests include: complete blood count, chemistry, sedimentation rate, and coagulation studies. In cases where the cause of CVT remains undetermined after careful history and initial tests, testing for an inherited thrombophilia, including factor V Leiden, prothrombin gene mutation, antithrombin III deficiency, and protein C and S deficiencies, should be considered. Ideally, testing should be done before initiation of anticoagulation and repeated four to six weeks later, particularly in patients whose initial work-up is negative. Work-up for an occult malignancy should be undertaken in those whose evaluation and thrombophilia testing are unrevealing.

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Aug 17, 2020 | Posted by in ANESTHESIA | Comments Off on Chapter 13 – Management of Cerebral Venous Thrombosis in the Neurocritical Care Unit
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