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Table of Contents
REVIEW ARTICLE
Year : 2019  |  Volume : 16  |  Issue : 4  |  Page : 232-235

Cortical venous thrombosis – A case series and review of recent updates


1 Department of Neurology, Institute of Neurosciences, Indraprastha Apollo Hospitals, New Delhi, India
2 Department of Critical Care, Max Super Speciality Hospital, New Delhi, India

Date of Submission10-Oct-2019
Date of Acceptance19-Oct-2019
Date of Web Publication12-Dec-2019

Correspondence Address:
Pushpendra Nath Renjen
C-85, Anand Niketan, New Delhi - 110 021
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_60_19

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  Abstract 


Thrombosis of the dural sinus and/or cerebral veins (cerebral venous thrombosis [CVT]) is an uncommon form of stroke, usually affecting young individuals. Early diagnosis and timely institution of appropriate treatment is usually associated with a good outcome. However, its non-specific and extremely varied clinical presentation makes it difficult to diagnose. In this article, we review the etiology, clinical features, diagnostic tools, and mainstay therapy of CVT with recent advancements to help clinicians keep a high degree of suspicion for this disease in appropriate clinical scenarios. We also provide two clinical case scenarios from our hospital as an example of its diverse presentation.

Keywords: Cord sign, cortical venous thrombosis, delta sign, dense triangle sign, venous recanalization


How to cite this article:
Garg S, Chaudhari D, Renjen PN, Ahmad K, Kumar A, Pradhan R, Mishra A. Cortical venous thrombosis – A case series and review of recent updates. Apollo Med 2019;16:232-5

How to cite this URL:
Garg S, Chaudhari D, Renjen PN, Ahmad K, Kumar A, Pradhan R, Mishra A. Cortical venous thrombosis – A case series and review of recent updates. Apollo Med [serial online] 2019 [cited 2020 Jan 18];16:232-5. Available from: http://www.apollomedicine.org/text.asp?2019/16/4/232/272826




  Introduction Top


Cortical venous thrombosis, i.e., thrombosis of intracranial veins and sinuses is a rare form of cerebral vascular disorder accounting for 0.5% of all strokes. Earlier thought to be infective and usually affecting the superior sagittal sinus, it is now recognized as a noninfective disorder. Despite being associated with a relatively fair outcome with treatment, the remarkable diversity in clinical symptoms, etiology, mode of onset, and neuroimaging signs makes it a diagnostic and therapeutic challenge. Magnetic resonance (MR) imaging with venography is the best diagnostic methods, and Heparin is the first-line treatment.[1],[2],[3],[4],[5] However in a few cases, more aggressive treatments, such as local intravenous thrombolysis, mechanical thrombectomy, and decompressive hemicraniectomy, may be required.


  Case Reports Top


Case 1

A 39-year-old lady presented to the emergency department of our hospital with an episode of generalized tonic-clonic seizure. On history taking, the husband said that she had been complaining of throbbing intermittent headache with photophobia and severe vomiting for the past few days. On examination, she was in -postictal phase and severely dehydrated. Her D-dimer was elevated with a value of 987, and test for pregnancy was negative. Plain computed tomography (CT) of the head showed hemorrhagic focus in the left frontal lobe with the surrounding enema and mild mass effect. On magnetic resonance (MR) venography with time-of-flight (TOF) and contrast, extensive filling defect was seen in the superior sagittal sinus with thrombus extending into the bilateral transverse and sigmoid sinuses [Figure 1]. She was screened for prothrombotic states and detected to have Protein S deficiency – level of 10.8 (normal >65). It was postulated that this episode of cerebral venous thrombosis (CVT) was precipitated by severe dehydration. She was treated with low-molecular-weight heparin (LMWH) adjusted according to the body weight and recovered well. Warfarin therapy was instituted for chronic management, and she has been doing well with no further thromboembolic episodes on follow-up.
Figure 1: Magnetic resonance imaging of the brain and magnetic resonance venography showing superior sagittal sinus thrombus extending into the bilateral transverse and sigmoid sinuses

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Case 2

A 34-year-old nonpregnant lady presented to us with complaint of severe headache, vomiting, and blurred vision for the past 2 days. She had no focal neurological deficit on examination. However, fundus examination revealed bilateral papilledema with left macular edema indicating raised intracranial pressure. Noncontrast CT of the head showed hyperdense signal from the right transverse and sigmoid sinus and small hemorrhagic foci in the right temporal region [Figure 2]. MR venogram of the brain with TOF and contrast was performed for a detailed study which showed thrombus in the superior sagittal sinus, right transverse, sigmoid sinus, and jugular vein. She was started on LMWH but did not show much improvement in her clinical symptoms. Hence, LMWH was substituted with intravenous (IV) heparin infusion at a dose adjusted to keep activated partial thromboplastin time 1.5–2.5 times the normal range. She showed improvement with this course of treatment and was switched to oral warfarin later. She has been doing well on follow-up.
Figure 2: Magnetic resonance imaging and magnetic resonance venography showing thrombus in the superior sagittal sinus, right transverse, sigmoid sinus, and jugular vein

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  Etiology of Cerebral Venous Thrombosis Top


Several disorders can cause or predispose patients to CVT. These disorders include all medical, surgical, and gyneco-obstetric causes of deep-vein thrombosis in the legs, genetic and acquired prothrombotic disorders, cancer, hematological diseases, vasculitis and other inflammatory systemic disorders, pregnancy and puerperium, infections, as well as several local causes, such as brain tumors, arteriovenous malformations, head trauma, CNS infections, and infections of the ear, sinus, mouth, face, or neck.[5],[6],[7],[8] Diagnostic and therapeutic procedures such as surgery, lumbar puncture, jugular catheter, and some drugs – in particular oral contraceptives, hormonal replacement therapy, steroids, and oncology treatments – can also cause or predispose people to CVT. However, the relative weight of these cases varies in different countries.[9]


  Clinical Features Top


CVT is difficult to diagnose on clinical grounds alone, as it has no single pattern of presentation. According to the grouping of symptoms and signs, four main patterns have been identified: isolated intracranial hypertension, focal syndrome, cavernous sinus syndrome, and subacute encephalopathy; however, there are many other presentations. The most common symptoms and signs are headache, seizures, focal neurological deficits, altered consciousness, and papilledema.[2],[4],[5] The headache of CVT is typically described as diffuse and often progresses in severity over days to weeks. A minority of patients may present with a thunderclap headache, suggestive of subarachnoid hemorrhage, and a migraine type of headache has also been described.[10] Isolated headache without focal neurological findings or papilledema occurs in up to 25% of patients with CVT and presents a significant diagnostic challenge.[11] Focal or generalized seizures, including status epilepticus, are more common in CVT than in other stroke types. Seizures are more typical in patients with parenchymal lesions, sagittal sinus, and cortical vein thrombosis.[12] Focal neurological deficit may occur depending on the area involved. Thus, hemiparesis may be encountered, and in some cases of sagittal sinus thrombosis, there is involvement of bilateral lower extremities. Many other unusual presentations have been described: isolated headache, transient ischemic attacks, attacks of migraine with aura, isolated psychiatric disturbances, tinnitus, isolated or multiple cranial nerve involvement, and subarachnoid hemorrhage.[2],[3],[4],[5],[13]


  Diagnosis Top


Routine laboratory tests including complete blood count, urinalysis, prothrombin time, and activated partial thromboplastin time are recommended for all patients with CVT.[14],[15] The results from these tests may suggest the presence of conditions that contribute to the development of CVT such as an underlying hypercoagulable state, an infection, or an inflammatory process. Screening for potential prothrombotic conditions that predispose to CVT may be required. Measurement of D-dimer before neuroimaging is recommended in patients with suspected CVT, except in those with an isolated headache or prolonged duration of symptoms where there is a high probability of false-negative results.[16] Cranial CT is usually the first investigation performed in the emergency department. In about one-third of the cases, the CT demonstrates direct signs of CVT, which are as follows: the cord sign, usually seen on head CT with contrast, is the visualization of the hyperdense thrombosed cortical vein [Figure 1]; the dense triangle sign, seen on noncontrast head CT, is the visualization of a fresh thrombus in the posterior part of the sagittal sinus; and the most frequent direct sign is the “empty triangle” or delta sign, seen as nonfilling of the confluence of sinuses after contrast injection. MR venography and CT venography are both adequate for the diagnosis of CVT, but the former is clearly superior for the visualization of brain parenchymal lesions.[15],[17] Theoretically, catheter angiography remains the most accurate method for the diagnosis of CVT but is almost never required anymore. As catheter angiography is an invasive technique with a non-negligible risk of stroke, a patient should only undergo this procedure when CT venography or MR venography is inconclusive, a dural arteriovenous fistula is suspected, or when an endovascular therapeutic intervention is planned.


  Treatment Top


Theoretically, the recanalization of the sinuses or veins should improve regional perfusion and, therefore, allow salvage of threatened tissues. However, several factors may weaken this relationship, particularly if this occurs too late to benefit affected tissues or if collateral circulation, common in the venous territories, protects perfusion. Besides, the recanalization of the sinuses may not restore drainage effectively if veins or microcirculation remain occluded.[18] The studies assessing the relationship between venous recanalization and prognosis in patients with CVT have shown conflicting results.[19],[20],[21] As described for low-extremity deep-vein thrombosis, recanalization may also influence the risk of CVT recurrence. This association has already been suggested in a large cohort of pediatric patients with CVT [22] but remains to be shown in adult patients. A systemic review and meta-analysis study [23] reviewed 19 studies which reported 818 cases of CVT, in which venous recanalization was assessed. It concluded that the lack of venous recanalization was associated with worse clinical outcome.

Anticoagulant therapy is the most common treatment for CVT. Both body-weight-adjusted LMWH and activated partial thromboplastin time-adjusted IV unfractionated heparin (UFH) can be used to treat CVT. The presence of concomitant intracranial hemorrhage related to CVT is not a contraindication for heparin therapy. Most scholars have proposed that LMWH is more appropriate for treatment, except when the patient may need a surgical intervention, in which case anticoagulation should be immediately reversed.[18],[24],[25] Misra et al.[25] conducted a randomized controlled trial (RCT) in which they compared the efficacy and safety of LMWH and UFH in CVT. They concluded that hospital mortality was significantly lower in patients treated with LMWH than in patients treated with UFH. After the acute phase, the patient is switched onto oral anticoagulation for the prevention of venous thromboembolic event recurrence. Although results regarding the association between recurrence and duration of anticoagulation are conflicting, it is usually administered for 3–12 months.[26]

Warfarin (Vitamin K antagonist [VKA]) is still the mainstay of treatment and is usually adjusted to obtain an international normalized ratio between 2 and 3. To overcome the limitations of VKA therapy such as risk of major bleeding, need for constant monitoring, and drug and dietary interactions, non-vitamin K antagonist oral antagonists (NOACs), which are target specific for factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran), are being considered. Few case series have been published supporting the safety and efficacy of these drugs in CVT.[27],[28],[29],[30] Recently at World Stroke Congress in 2018, the results of one RCT – RCT of the safety and efficacy of dabigatran etexilate vs. dose-adjusted warfarin in patients with CVT (RESPECT CVT) – were presented.[31] The trial randomized 120 patients to either dabigatran or warfarin and showed no recurrence of venous thrombotic events and a small number of major bleedings in both the arms. An open-label, comparative study from 2019[32] reporting on the largest cohort of CVT patients treated with new oral anticoagulants shows that the use of NOACs (mainly rivaroxaban and dabigatran) appears to be safe and may be as effective as warfarin in patients with CVT. The findings of this study provide external validity for the RESPECT CVT results in a real-world setting and support the growing trend of NOAC use for this potentially devastating condition.

Direct endovascular thrombolysis is another option and includes chemical thrombolysis, mechanical thrombectomy, or both methods at the same time. Although no randomized control trial has evaluated systemic or local thrombolysis for the treatment of CVT, it is supported by small case series and case reports. In a recent editorial by Murthy,[33] it was concluded that endovascular therapy should be a treatment option in patients who have neurological deterioration in spite of adequate supportive treatment and optimal anticoagulation, with no evidence of intracerebral hemorrhage (ICH), elevated intracranial pressure, or brain herniation. Mechanical thrombectomy may be the preferred option in patients with ICH. The leading cause of death in patients with CVT is the hemorrhagic conversion of large venous infarcts resulting in brain herniation. In these situations, emergency decompressive hemicraniectomy can prevent death. In a study conducted by Ferro et al., the authors concluded that in patients with CVT with a large parenchymal lesion causing herniation, decompressive surgery was life-saving and often resulted in a good functional outcome, even in patients with severe clinical manifestations.[34]


  Discussion Top


Although an infrequent disease, it is important to have a high clinical suspicion for CVT because treatment is associated with a good prognosis. Not much is known about the relationship between recanalization and clinical outcome in patients with CVT. The above mentioned two patients treated at our center were diagnosed early and showed a very good response to anticoagulation treatment. Anticoagulation is the mainstay of medical therapy and is associated with improved clinical outcome.[16] This could be due to any number of reasons such as prevention of progression of thrombosis, restoration of anterograde drainage and salvage of brain tissue from permanent damage, or reduction of the risk of other venous thrombotic events. It is important to confirm and characterize the strength and timing of the association of recanalization with clinical outcomes to better understand the pathophysiology of the disease. This will further help us design and assess the feasibility of treatment trials in CVT, particularly with endovascular interventions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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34.
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