Cerebral venous sinus thrombosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Sharmi Biswas, M.B.B.S

Cerebral venous thrombosis(CVT)is thrombosis of cerebral veins, a rare form of stroke which is different from arterial strokes. CVT incidence is 1.3 in per 1,00,000/year in developed countries. Young children and women especially pregnant/puerperium have a higher frequency of CVT. Due to the wide spectrum of clinical features, CVT frequently gets misdiagnosed as other strokes. Commonly known risk factors and causes of cerebral venous thrombosis are venous thromboembolism, thrombophilia (especially antithrombin deficiency, protein C and S deficiency and factor V Leiden mutation), pregnancy, oestrogen therapy/oral contraceptives, hypercoagulability as part of inflammatory disease, head trauma, local infections and underlying cancer. Pathophysiology of CVT includes two mechanisms including thrombosis of cerebral veins creating local edema and venous infarction; intracranial hypertension created by increased venous pressure and decreased absorption of CSF. Clinical presentations of CVT can be categorized into 4 categories as isolated intracranial hypertension, neurological deficits, encephalopathy and seizure. Symptoms related to increased intracranial hypertension are headache, diplopia, papilledema, sixth nerve palsy and decreased consciousness; focal neurological deficits present as motor and sensory impairments, aphasia. Though in 90% of patients with CVT , headache is the most common symptom, followed by seizures in 40% patients and 20 % patients with seizure.

Superior sagittal sinus is the most commonly involved sinus approximately 62% of patients and transverse sinus is the next common site (40-45%). Internal cerebral vein and straight sinus are less commonly involved in CVT but associated with worse outcomes. Diagnosis of CVT is based on clinical findings and neuroimaging. D-dimer level is more than 500 μg/L in most of the patients with CVT. Per recommendation of American Heart Association (AMA) and the European Federation of Neurological Societies (EFNS), MRI/MRV is preferred for brain imaging. But CT can be considered if MRI is unavailable. Treatment of CVT includes early initiation of anticoagulant therapy and treatment of other underlying causes as sepsis, dehydration, discontinuation of prothrombotic medications; seizure and intracranial hypertension management.

CVT has good prognosis in 75% of patients with full functional recovery while in 15% of patients die or become dependent. Male sex, older age, confusion or coma, intracranial hemorrhage, deep vein involvement, infection and malignancy are the risk factors for poor outcomes.

Cerebral venous sinus thrombosis (CVT) as first described by a French physician Ribes in 1825. But till the second half of 20th century, CVT was a diagnosis after death as it was frequently misdiagnosed due to overlapping of clinical symptoms and physical findings overlapping with other strokes. In 1951, introduction of venography made a drastic change in diagnosis of CVT.

There is no classification of cerebral venous thrombosis (CVT).

Imbalance in prothrombotic and fibrinolysis processes are the main pathophysiologic mechanisms leading to cerebral venous sinus thrombosis. Hypercoagulability is the main cause of cerebral venous thrombosis.

Genetic or acquired conditions causing thrombosis are considered as risk factors for developing cerebral venous sinus thrombosis. Some of the common causes are thrombophilia due to factor V Leiden mutation, protein C and S deficiency, pregnancy, puerperium, oral contraceptive use, Nephrotic syndrome and other related factors.

Cerebral venous sinus thrombosis is often get misdiagnosed due to the overlapping of symptoms with other neurological conditions

Cerebral venous sinus thrombosis is a rare disease that mostly occurs in children and women. Mostly common in Asia, Middle East.

Any prothrombotic event acquired or genetic is considered a risk factor for cerebral venous sinus thrombosis.

There is no screening test for cerebral venous thrombosis.

Common complications of cerebral venous thrombosis are death, coma, neurological impairments, visual impairment, seizure and encephalopathy. The prognosis of CVT is favorable than other strokes. Complete functional recovery has been reported in 75% of patients but 15% of patients die or become dependent. Study showed women has better prognosis than men. 81% of women recovered completely while only 71 % of men had so.[4] Recurrent thrombosis is a common complication in CVT, around 6.5% per year but mostly in patients who are not on anticoagulants.

MRI venography is the confirmatory test for cerebral venous thrombosis (CVT). CT scan can be an alternative choice where MRI is not available. To detect smaller blood clots cerebral angiography is more helpful.

Symptoms of cerebral venous sinus thrombosis often overlap with the clinical presentations of other strokes. Headache is the most common presenting symptom followed by seizure, unconsciousness, cognitive impairments.

Physical examination in cerebral venous thrombosis is mostly related to intracranial hypertension as papilledema, hypertension. Weakness of muscles in single side of the body might be found.

No specific lab finding is related to diagnose cerebral venous sinus thrombosis. MRI venography is the confirmatory brain imaging to diagnose cerebral venous sinus thrombosis.

CT scan is helpful to rule out space occupying brain lesions and CT venogram rules out any thrombosis in cerebral veins.

MRI venography of the brain is considered the most confirmatory test in cerebral venous sinus thrombosis. MRV in association with MRI shows non visualization of vessels, flow defect and collateral vessels near the occluded vessels.

There are no other imaging findings associated with cerebral venous thrombosis.

There are no other diagnostic studies associated with cerebral venous thrombosis.

Pharmacologic therapy is indicated in cerebral venous sinus thrombosis. Medical therapy includes anticoagulants, acetazolamide, and anticonvulsants. Empiric antimicrobial therapy is required and generally includes the combination of Metronidazole, a penicillinase-resistant penicillin, and a third generation cephalosporin.

Surgical decompression or surgical thrombectomy is required in the treatment of cerebral venous thrombosis with life-threatening intracranial hypertension.

Primary prevention of cerebral venous thrombosis is focussed on preventing or reducing the risk of systemic thrombosis.

For patients with cerebral venous thrombosis, a long-term anticoagulant is highly recommended to prevent future events.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2] Sharmi Biswas, M.B.B.S

Cerebral venous sinus thrombosis (CVT) as first described by a French physician Ribes in 1825. But till the second half of 20th century, CVT was a diagnosis after death as it was frequently misdiagnosed due to overlapping of clinical symptoms and physical findings overlapping with other strokes. In 1951, introduction of venography made a drastic change in diagnosis of CVT.

A French physician named Ribes is the first one to report a case of cerebral vein thrombosis(CVT) in a 45 years old woman who presented with headaches and seizures. Autopsy findings revealed that there were superior sagittal sinus and lateral sinus thrombosis causing the symptoms. This is the first case report defining the features of cerebral vein thrombosis. The relationship between cerebral vein thrombosis and pregnancy was revealed a few years later when John Abercrombie, physician to King George IV, reported a case of a 24years old female who died 2 weeks after delivery due to status epilepticus and her autopsy showed thrombosis in superior sagittal sinus and cortical veins. In the second half of the 20th century, the introduction of catheter cerebral angiography helped to conduct larger clinical studies and more information about clinical characteristics, risk factors of CVT has been available.^[1].Dr.Charles Symonds in 1940 explained the clinical diagnosis of CVT using clinical signs, symptoms, and lumbar puncture results.^[2][3] In 1951, the introduction of venography brought a drastic improvement in diagnosing CVT^[4]which also aided in the distinction from idiopathic intracranial hypertension,^[5] which has similar presenting signs and symptoms in many cases.

In 1942, a British gynecologist Stansfield started using anticoagulant heparin to treat CVT. Clinical trials in the 1990s finally resolved the concern about using anticoagulants in most cases of cerebral venous sinus thrombosis. Early non-invasive diagnosis of CVT became easier with the widespread availability of CT with venography and MRI with venography in late 1980.^[1]

There is no established system for the classification of the cerebral venous sinus thrombosis

There is no established system for the classification of the cerebral venous sinus thrombosis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Imbalance in prothrombotic and fibrinolysis processes are the main pathophysiologic mechanisms leading to cerebral venous sinus thrombosis.

There are two mechanisms for cerebral venous thrombosis. The first is thrombosis of cerebral veins causing local effects due to venous obstruction and the second cause is thrombosis of the cerebral sinuses leading to intracranial hypertension. Both of these processes occur in the majority of patients with CVT. Increased venous pressure due to the occlusion of the cerebral vein causes cytotoxic edema and venous infarction,blood brain barrier disruption associated vasogenic edema and parenchymal hemorrhage due to venous and capillary rupture.

Increased intracranial hypertension develops due to the occlusion of major cerebral venous sinuses.In normal condition, cerebrospinal fluid (CSF) is transported from the cerebral ventricles to subarachnoid spaces and arachnoid villi is responsible for the absorption of CSF and eventually drain to the superior sagittal sinus.Thrombosis of cerebral venous sinuses leads to increased venous pressure, decreased absorption of CSF and as a consequence intracranial pressure get increased along with parenchymal hemorrhage and cytotoxic and vasogenic edema.^[1][2]

Any blood clot forms due to an imbalance between coagulation (the formation of the insoluble blood protein fibrin) and fibrinolysis. The three major mechanisms for such an imbalance are enumerated in Virchow’s triad: alterations in normal blood flow, injury to the blood vessel wall, and alterations in the constitution of blood (hypercoagulability). Most cases of cerebral venous sinus thrombosis are due to hypercoagulability.^[2]

It is possible for the clot to break off and migrate (embolism) to the lungs, causing a pulmonary embolism.^[2][3] An analysis of previous case reports concludes that this occurs in about 10% of cases, but has a very poor prognosis.^[4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Genetic or acquired conditions causing thrombosis are considered as risk factors for developing cerebral venous sinus thrombosis.

There are more than 100 different causes of cerebral venous sinus thrombosis (CVT). Virchow’s principles (blood stasis, modification of vascular wall, and blood rheology) should be used to identify all the predisposing conditions for CVT. There are also some genetic and acquired causes leading to CVT. In the cohort of an International study of cerebral vein and dural sinus thrombosis(ISCVT), 34% of patients had thrombophilia while 22% of them had acquired thrombophilia.^[1][2]

Genetic prothrombotic causes ^[1][2]

– Antithrombin deficiency

– Protein C and S deficiency

– Factor v Leiden mutation

– Resistance to activated protein C

– prothrombin mutation (A–G at position 20210)

– mutations leading to homocysteinemia

– methylenetetrahydrofolate reductase (MTHFR)

Acquired Prothrombotic States^[1][2]

– pregnancy

– puerperium

– homocysteinemia

– antiphospholipid antibody

– nephrotic syndrome

Infection ^[1][2]

– meningitis

– otitis

– mastoiditis

– sinusitis

– neck, face, mouth infection

– systemic infectious diseases

– AIDS

Inflammatory Autoimmune Diseases^[1][2]

– systemic lupus erythematosus

– Adamantiades-Behçet disease

– Wegener granulomatosis

– sarcoidosis

– inflammatory bowel disease

– thromboangiitis obliterans

Hematology^[1][2]

– polycythemia

– thrombotic thrombocytopenic purpura

– thrombocythemia

– severe anemia and autoimmune hemolytic anemia

– paroxysmal nocturnal hemoglobinuria

– heparin-induced thrombocytopenia

Drugs^[1][2]

– oral contraceptives

– lithium, androgens

– sumatriptan

– intravenous immunoglobulin

– hormone replacement therapy

– asparaginase

– steroids

– illicit drugs (such as ecstasy)

Mechanical Causes^[1][2]

– head trauma

– neurosurgical procedures

– jugular vein catheterization

– lumbar puncture

– injury to cerebral sinuses

– intravenous drug abuse

Malignancy^[2]

– CNS tumors

– systemic malignancies

– ”’solid”’ tumors outside [[CNS]]

Other Causes^[1][2]

– dehydration, especially in children

– toxicosis

– arteriovenous malformations

– dural fistulae

– congenital heart disease

– post radiation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Cerebral venous sinus thrombosis is often get misdiagnosed due to the overlapping of symptoms with other neurological conditions

Cerebral venous sinus thrombosis should be differentiated from other diseases causing severe headache for example: ^{[1][2][3][4][5][6][7][8][9][10]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: : Kalsang Dolma, M.B.B.S.[2] Sharmi Biswas, M.B.B.S

Cerebral venous sinus thrombosis is a rare disease that mostly occurs in children and women.

• Cerebral venous sinus thrombosis is rare, with 0.3 to 0.4 per 100,000 annual incidence in adults and 0.7 per 100,000 incidence in children (predominantly in the newborn^[1]).

• In adults, the disease occurs most often in the third decade.^[1]

• 75% of cases are in women; some historical evidence suggests that the use of oral contraceptives in women is behind the disparity between the sexes.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2] Sharmi Biswas, M.B.B.S

Any prothrombotic event acquired or genetic is considered a risk factor for cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is more common in particular situations. 85% of patients have at least one of these risk factors:^[1]

• Thrombophilia (a tendency to develop blood clots due to abnormalities in coagulation, e.g. deficiency of protein C, protein S, antithrombin or related problems)
• Nephrotic syndrome (a kidney problem causing protein loss in the urine)
• Chronic inflammatory diseases (inflammatory bowel disease, lupus, Behçet’s disease)
• Pregnancy and puerperium (the period after giving birth)
• Particular blood disorders, especially polycythemia vera and paroxysmal nocturnal hemoglobinuria
• Use of the contraceptive pill
• Meningitis and infections of the ear, nose and throat area (mastoiditis, sinusitis)
• Direct injury to the venous sinuses, and medical procedures in the area

Other less well understood situations that increase the risk for cerebral sinus thrombosis are hyperthyroidism^[2] and myelodysplastic syndrome.^[3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Common complications of cerebral venous thrombosis include neurological deficits, coma, and death.

• The symptoms of cerebral venous thrombosis(CVT) usually develop in the first decade of life, and start with symptoms such as headache, seizures, neurological deficits, visual impairment, decreased level of consciousness. ^[1][2]

• 15% of patients with CVT may progress to develop residual epilepsy, cognitive impairment, recurrent CVT or systemic thromboembolism.

• Common complications of cerebral venous thrombosis (CVT) include:
  • Hydrocephalus^[2][1]
  • Cognitive impairment
  • Neurological deficit
  • Residual epilepsy
  • Coma
  • Death

The prognosis of CVT is favorable than other strokes. Complete functional recovery has been reported in 75% of patients but 15% of patients die or become dependent.^[3] Study showed women has better prognosis than men. 81% of women recovered completely while only 71 % of men had so.^[4] Recurrent thrombosis is a common complication in CVT, around 6.5% per year but mostly in patients who are not on anticoagualnts.^[3]