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Cerebral Venous Sinus Thrombosis: A rare and Uncommon Medical Condition

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Cerebral Venous Sinus Thrombosis: A rare and Uncommon Medical Condition

Cerebral venus sinus thrombosis (CVST) occurs when a blood clot forms in the brain’s venous sinuses that prevents blood from draining out of the brain. As a result, blood cells may break and leak blood into the brain tissues, forming a hemorrhage. This chain of events is part of a stroke that can occur in adults and children, even in newborns and babies in the womb. A stroke can result in damage to the brain and central nervous system. A stroke is serious and requires immediate medical attention. This condition may also be called cerebral sinovenous thrombosis.

Cerebral venous sinus thrombosis (CVST) is the presence of thrombosis (a blood clot) in the dural venous sinuses, which drain blood from the brain. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures. The diagnosis is usually by computed tomography (CT/CAT scan) or magnetic resonance imaging (MRI) employing radiocontrast to demonstrate obstruction of the venous sinuses by thrombus.
Treatment is with anticoagulants (medication that suppresses blood clotting), and rarely thrombolysis (enzymatic destruction of the blood clot). Given that there is usually an underlying cause for the disease, tests may be performed to look for these. The disease may be complicated by raised intracranial pressure, which may warrant surgical intervention such as the placement of a shunt. There are several other terms for the condition, such as cerebral venous and sinus thrombosis, (superior) sagittal sinus thrombosis, dural sinus thrombosis and intracranial venous thrombosis as well as the older term cerebral thrombophlebitis.
Facts about venous sinus thrombosis

CVST is a rare form of stroke. It affects about five people in 1 million each year. The risk for this kind of stroke in newborns is greatest during the first month. Overall, about three out of 300,000 children and teens up to age 18 will have a stroke.Children and adults have different risk factors for CVST.

Risk factors for children and infants include:
• Pregnancy and peripartum
• Problems with blood clotting; for example, antiphospholipid syndrome, protein C and S deficiency, antithrombin III deficiency, lupus anticoagulant, or factor V Leiden mutation
• Cancer
• Collagen vascular diseases like lupus, Wegener’s granulomatosis, and Behcet syndrome
• Obesity
• Intracranial hypotension
• Inflammatory bowel disease like Crohn’s disease or ulcerative colitis
• Symptoms

Nine in ten people with sinus thrombosis have a headache; this tends to worsen over the period of several days, but may also develop suddenly (thunderclap headache). The headache may be the only symptom of cerebral venous sinus thrombosis. Many patients have symptoms of stroke: inability to move one or more limbs, weakness on one side of the face or difficulty speaking. This does not necessarily affect one side of the body as in the more common "arterial" stroke.
40% of all patients have seizures, although it is more common still in women who develop sinus thrombosis peripartum (in the period before and after giving birth). These are mostly seizures affecting only one part of the body and unilateral (occurring on one side), but occasionally the seizures are generalised and rarely they lead to status epilepticus (persistent or recurrent seizure activity for a long period of time).

In the elderly, many of the aforementioned symptoms may not occur. Common symptoms in the elderly with this condition are otherwise unexplained changes in mental status and a depressed level of consciousness.
The pressure around the brain may rise, causing papilledema (swelling of the optic disc) which may be experienced as visual obscurations. In severely raised intracranial pressure, the level of consciousness is decreased, the blood pressure rises, the heart rate falls and the patient assumes an abnormal posture.

These are the physical symptoms that may occur:
• Headache
• Blurred vision
• Fainting or loss of consciousness
• Loss of control over movement in part of the body
• Seizures
• Coma
Complications of venous sinus thrombosis include:
• Impaired speech
• Difficulty moving parts of the body
• Problems with vision
• Headache
• Increased fluid pressure inside the skull
• Pressure on nerves
• Brain injury
• Developmental delay
• Death

Diagnosis
Doctors typically take a medical history and do a physical exam. Family and friends can describe the symptoms they saw, especially if the person who had the stroke is unconscious. The final diagnosis, however, is usually made based on how the blood is flowing in the brain. Imaging tests show areas of blood flow. These tests may be used to diagnose venous sinus thrombosis:
• MRI scan
• CT scan
• Venography
• Angiography
• Ultrasound
• Blood tests
The diagnosis may be suspected on the basis of the symptoms, for example the combination of headache, signs of raised intercranial pressure and focal neurological abnormalities, or when alternative causes of headache and neurological abnormalities, such as a subarachnoid hemorrhage, have been exclud

CT venogram showing a filling defect in the sagittal sinus
There are various neuroimaging investigations that may detect cerebral sinus thrombosis. Cerebral edema and venous infarction may be apparent on any modality, but for the detection of the thrombus itself, the most commonly used tests are computed tomography (CT) and magnetic resonance imaging (MRI), both using various types of radiocontrast to perform a venogram and visualise the veins around the brain.

Computed tomography, with radiocontrast in the venous phase (CT venography or CTV), has a detection rate that in some regards exceeds that of MRI. The test involves injection into a vein (usually in the arm) of a radioopaque substance, and time is allowed for the bloodstream to carry it to the cerebral veins - at which point the scan is performed. It has a sensitivity of 75-100% (it detects 75-100% of all clots present), and a specificity of 81-100% (it would be incorrectly positive in 0-19%). In the first two weeks, the "empty delta sign" may be observed (in later stages, this sign may disappear).

Magnetic resonance venography employs the same principles, but uses MRI as a scanning modality. MRI has the advantage of being better at detecting damage to the brain itself as a result of the increased pressure on the obstructed veins, but it is not readily available in many hospitals and the interpretation may be difficult.

Cerebral angiography may demonstrate smaller clots than CT or MRI, and obstructed veins may give the "corkscrew appearance". This, however, requires puncture of the femoral artery with a sheath and advancing a thin tube through the blood vessels to the brain where radiocontrast is injected before X-ray images are obtained. It is therefore only performed if all other tests give unclear results or when other treatments may be administered during the same procedure.

D-dimer
A 2004 study suggested that the D-dimer blood test, already in use for the diagnosis of other forms of thrombosis, was abnormal (above 500 μg/l) in 34 out of 35 patients with cerebral sinus thrombosis, giving it a sensitivity of 97.1%, a negative predictive value of 99.6%, a specificity of 91.2%, and a positive predictive value of 55.7%. Furthermore, the level of the D-dimer correlated with the extent of the thrombosis. A subsequent study, however, showed that 10% of patients with confirmed thrombosis had a normal D-dimer, and in those who had presented with only a headache 26% had a normal D-dimer. The study concludes that D-dimer is not useful in the situations where it would make the most difference, namely in lower probability cases.

Further tests
In most patients, the direct cause for the cerebral sinus thrombosis is not readily apparent. Identifying a source of infection is crucial; it is common practice to screen for various forms of thrombophilia (a propensity to form blood clots).

Pathogenesis
The veins of the brain, both the superficial veins and the deep venous system, empty into the dural venous sinuses, which carry blood back to the jugular vein and thence to the heart. In cerebral venous sinus thrombosis, blood clots usually form both in the veins of the brain and the venous sinuses. The thrombosis of the veins themselves causes venous infarction–damage to brain tissue due to a congested and therefore insufficient blood supply. This results in cerebral edema (both vasogenic and cytotoxic edema), and leads to small petechial haemorrhages that may merge into large haematomas. Thrombosis of the sinuses is the main mechanism behind the increase in intracranial pressure due to decreased resorption of cerebrospinal fluid (CSF). The condition does not lead to hydrocephalus, however, because there is no difference in pressure between various parts of the brain.

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.

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

Treatment
Treatment should begin immediately and must be done in a hospital. A treatment plan could include:
• Fluids
• Antibiotics, if infections are present
• Antiseizure medication
• Monitoring and controlling the pressure inside the head
• Medication called a coagulant to stop the blood from clotting
• Surgery
• Continued monitoring of brain activity
• Measuring visual acuity and monitoring change
• Rehabilitation

Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded. Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable. Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagulants are commenced, while no anticoagulants are given if there is no reduction.

The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely.

Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.

Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), medication (acetazolamide), or neurosurgical treatment (optic nerve sheath fenestration or shunting). In certain situations, anticonvulsants may be used to prevent seizures; these are focal neurological problems (e.g. inability to move a limb) and/or focal changes of the brain tissue on CT or MRI scan.

Prognosis
In 2004 the first adequately large scale study on the natural history and long-term prognosis of this condition was reported; this showed that at 16 months follow-up 57.1% of patients had full recovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms or impairments, and 8.3% had died. Severe impairment or death were more likely in those aged over 37 years, male, affected by coma, mental status disorder, intracerebral hemorrhage, thrombosis of the deep cerebral venous system, central nervous system infection and cancer. A subsequent systematic review of nineteen studies in 2006 showed that mortality is about 5.6% during hospitalisation and 9.4% in total, while of the survivors 88% make a total or near-total recovery. After several months, two thirds of the cases has resolution ("recanalisation") of the clot. The rate of recurrence was low (2.8%).
In children with CVST, the mortality averages 50%. Poor outcome is more likely if a child with CVST develops seizures or has evidence of venous infarction on imaging.

Prevention
You can do a lot to prevent stroke by leading a heart healthy lifestyle:
• Eat a low-fat diet including lots of fruits and vegetables.
• Get daily exercise.
• Avoid cigarette smoke.
• Control chronic health conditions, such as diabetes.
• Managing after venous sinus thrombosis
What you need to do to recover and then stay healthy after CVST will depend on how the stroke affected your brain. Everyone can benefit from a healthy diet and exercise.
You may also need to participate in a special rehabilitation program or physical therapy if you have lost some movement or speech.
Other possible effects of the stroke, such as headaches or changes in vision, can be treated by specialists.
If you have had this type of stroke, you may need to avoid certain types of medications such as oral contraceptives that can increase your risk for blood clots.

Recent case: Hillary Clinton has cerebral venous thrombosis.
Hillary Clintons has cerebral venous thrombosis -- is a rare and potentially "life-threatening" condition, according to medical experts, but one from which the globe-trotting secretary of state is likely to recover from. In an update from her doctors, Clinton's brain scans revealed a clot had formed in the right transverse venous sinus, and she was being successfully treated with anticoagulants.
"She is lucky being Hillary Clinton and had a follow-up MRI -- lucky that her team thought to do it," said Dr. Brian D. Greenwald, medical director at JFK Johnson Rehabilitation Center for Head Injuries. "It could have potentially serious complications. "The backup of blood flow could have caused a stroke or hemorrhage, according to Greenwald.

"Imagine this vein, where all the cerebral spinal fluid inside the head and spine no longer flows through this area," he said. "You get a big back up and that itself could cause a stroke. In the long-term … the venous system can't get the blood out of the brain. It's like a Lincoln Tunnel back up."A transverse sinus thrombosis is a clot arising in one of the major veins that drains the brain. It is an uncommon but serious disorder.

According to Greenwald, the clot was most likely caused by dehydration brought on by the flu, perhaps exacerbated by a concussion she recently suffered.

"The only time I have seen it happen is when people are severely dehydrated and it causes the blood to be so thick that it causes a clot in the area," said Greenwald. "It's one of the long-term effects of a viral illness."
Drs. Lisa Bardack of the Mt. Kisco Medical Group and Dr. Gigi El-Bayoumi of George Washington University discovered the clot during a routine follow-up MRI on Sunday.

"This is a clot in the vein that is situated in the space between the brain and the skull behind the right ear," they said in a statement today. "It did not result in a stroke, or neurological damage. To help dissolve this clot, her medical team began treating the secretary with blood thinners. She will be released once the medication dose has been established."
Clinton is "making excellent progress," according to her doctors. "She is in good spirits, engaging with her doctors, her family, and her staff."

Clinton, 65, was hospitalized at New York-Presbyterian Hospital Sunday. She suffered a concussion earlier this month after she hit her head when she fainted because of dehydration from a stomach virus, according to an aide.
Dehydration can also precipitate fainting, according to Dr. Neil Martin, head of neurovascular surgery at University of California, Los Angeles Medical Center.

He agreed that the condition could potentially have caused a brain hemorrhage or stroke and been fatal.
"In patients with no symptoms after many days, full recovery is the norm," said Martin. "However, some cases show extension of the thrombus or clot into other regions of the cerebral venous sinuses, and this can worsen the situation considerably -- thus the use of anticoagulants to prevent extension of the thrombus."

But, he said, anticoagulants can be a "double-edged sword." With even a tiny injury within the brain from the concussion, these medications can cause "symptomatic bleed," such as a subdural or intracerebral hemorrhage.
The clot location is not related to the nasal sinuses, but are rather large venous structures in the dura or protective membrane covering the brain, which drains blood from the brain.

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