Cerebral venous sinus thrombosis
Encyclopedia
Cerebral venous sinus thrombosis (CVST) is a rare form of stroke
that results from thrombosis
(a blood clot) of 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 anticoagulant
s (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.
). 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 seizure
s, 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 intracranial pressure
(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.
, have been excluded.
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.
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.
(a propensity to form blood clots).
s 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 petechia
l 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 lung
s, 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.
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, anticoagants 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, anticonvulsant
s 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.
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.
found a doubled incidence at 7 cases per 100,000; this was attributed to the fact that Behçet's disease
, which increases risk of CVST, is more common in the Middle East.
A 1973 report found that CVST could be found on autopsy
(examination of the body after death) in nine percent of all people. Many of these were elderly and had neurological symptoms in the period leading up to their death, and many suffered from concomitant heart failure.
In children, a Canadian study reported in 2001 that CVST occurs in 6.7 per million annually. 43% occur in the newborn (less than one month old), and a further 10% in the first year of life. Of the newborn, 84% were already ill, mostly from complications after childbirth and dehydration.
and others allowed for the clinical diagnosis of cerebral venous thrombosis, using characteristic signs and symptoms and results of lumbar puncture
.
Improvements on the diagnosis of cerebral venous sinus thrombosis in life were made with the introduction of venography
in 1951, which also aided in the distinction from idiopathic intracranial hypertension
, which has similar presenting signs and symptoms in many cases.
The British gynecologist Stansfield is credited with the introduction, in 1942, of the just recently introduced anticoagulant heparin in the treatment of CVST in 1942. Clinical trials in the 1990s finally resolved the concern about using anticoagulants in most cases of CVST.
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
that results from thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
(a blood clot) of the dural venous sinuses
Dural venous sinuses
The dural venous sinuses are venous channels found between layers of dura mater in the brain...
, which drain blood from the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. Symptoms may include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, abnormal vision, any of the symptoms of stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
such as weakness of the face and limbs on one side of the body, and seizures. The diagnosis is usually by computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT/CAT scan) or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) employing radiocontrast
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
to demonstrate obstruction of the venous sinuses by thrombus.
Treatment is with anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s (medication that suppresses blood clotting), and rarely thrombolysis
Thrombolysis
Thrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
(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
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, which may warrant surgical intervention such as the placement of a shunt
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...
. 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.
Signs and 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 headacheThunderclap headache
A thunderclap headache is a headache that is severe and sudden-onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. It can be indicative of a number of medical problems, most importantly subarachnoid hemorrhage, which can be potentially life-threatening...
). 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
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
. This does not necessarily affect one side of the body as in the more common "arterial" stroke.
40% of all patients have seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, 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
Focal seizures
Partial seizures are seizures which affect only a part of the brain at onset. The brain is divided into two hemispheres, each consisting of four lobes - the frontal, temporal, parietal and occipital lobes...
and unilateral (occurring on one side), but occasionally the seizures are generalised
Tonic-clonic seizure
Tonic–clonic seizures are a type of generalized seizure that affects the entire brain...
and rarely they lead to status epilepticus
Status epilepticus
Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 5 minutes, or recurrent seizures without regaining consciousness between seizures...
(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 intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
(pressure around the brain) may rise, causing papilledema
Papilledema
Papilledema is optic disc swelling that is caused by increased intracranial pressure. The swelling is usually bilateral and can occur over a period of hours to weeks. Unilateral presentation is extremely rare....
(swelling of the optic disc
Optic disc
The optic disc or optic nerve head is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point. This causes a break in the visual field called "the blind spot" or the "physiological blind spot"...
) which may be experienced as visual obscurations. In severely raised intracranial pressure, the level of consciousness is decreased, the blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
rises, the heart rate falls
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
and the patient assumes an abnormal posture.
Causes
Cerebral venous sinus thrombosis is more common in particular situations. 85% of patients have at least one of these risk factors:- ThrombophiliaThrombophiliaThrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
, a tendency to develop blood clots due to abnormalities in coagulation, e.g. factor V LeidenFactor V LeidenFactor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...
, deficiency of protein CProtein CProtein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
, protein SProtein SProtein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...
or antithrombinAntithrombinAntithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...
, or related problems - Nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
, a kidney problem causing protein loss in the urine - Chronic inflammatory diseases, such as inflammatory bowel diseaseInflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, lupusLupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
and Behçet's diseaseBehçet's diseaseBehçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements... - PregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and puerperium (the period after giving birth) - Particular blood disorders, especially polycythemia veraPolycythemia veraPolycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
and paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis... - Use of estrogen-containing forms of hormonal contraceptionHormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
- MeningitisMeningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
and infections of the ear, nose and throat area such as mastoiditisMastoiditisMastoiditis is an infection of mastoid process, the portion of the temporal bone of the skull that is behind the ear which contains open, air-containing spaces. It is usually caused by untreated acute otitis media and used to be a leading cause of child mortality. With the development of...
and sinusitisSinusitisSinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days... - Direct injury to the venous sinuses
- Medical procedures in the head and neck area
Diagnosis
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 hemorrhageSubarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
, have been excluded.
Imaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
investigations that may detect cerebral sinus thrombosis. Cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
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
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) and magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI), both using various types of radiocontrast to perform a venogram and visualise the veins around the brain.
Computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
, with radiocontrast
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
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
Magnetic Resonance Angiography
Magnetic resonance angiography is a group of techniques based on Magnetic Resonance Imaging to image blood vessels. Magnetic resonance angiography is used to generate images of the arteries in order to evaluate them for stenosis , occlusion or aneurysms...
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
Cerebral angiography
Cerebral angiography is a form of angiography which provides images of blood vessels in and around the brain, thereby allowing detection of abnormalities such as arteriovenous malformations and aneurysms....
may demonstrate smaller clots than CT or MRI, and obstructed veins may give the "corkscrew appearance". This, however, requires puncture of the femoral artery
Femoral artery
The femoral artery is a general term comprising a few large arteries in the thigh. They begin at the inguinal ligament and end just above the knee at adductor canal or Hunter's canal traversing the extent of the femur bone....
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-dimerD-dimer
D-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
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
Negative predictive value
In statistics and diagnostic testing, the negative predictive value is a summary statistic used to describe the performance of a diagnostic testing procedure. It is defined as the proportion of subjects with a negative test result who are correctly diagnosed. A high NPV means that when the test...
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 thrombophiliaThrombophilia
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
(a propensity to form blood clots).
Pathogenesis
The veinVein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s 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
Jugular vein
The jugular veins are veins that bring deoxygenated blood from the head back to the heart via the superior vena cava.-Internal and external:There are two sets of jugular veins: external and internal....
and thence to the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. 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
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
–damage to brain tissue due to a congested
Back pressure
Back pressure refers to the resistance to a moving fluid by obstructions or tight bends in the confinement vessel along which it is moving, such as piping or air vents, against its direction of flow....
and therefore insufficient blood supply. This results in cerebral edema
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
(both vasogenic and cytotoxic edema), and leads to small petechia
Petechia
A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
l 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
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
, however, because there is no difference in pressure between various parts of the brain.
Any blood clot forms due to an imbalance between coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
(the formation of the insoluble blood protein fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
) and fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
. The three major mechanisms for such an imbalance are enumerated in Virchow's triad
Virchow's triad
Virchow's triad describes the three broad categories of factors that are thought to contribute to thrombosis.*Hypercoagulability*Hemodynamic changes *Endothelial injury/dysfunction...
: 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
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
) to the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s, causing a pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
. An analysis of earlier case reports concludes that this occurs in about 10% of cases, but has a very poor prognosis.
Treatment
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 heparinHeparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
or low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
in the initial treatment, followed by warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, 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, anticoagants 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
Thrombolysis
Thrombolysis is the breakdown of blood clots by pharmacological means. It is colloquially referred to as clot busting for this reason...
(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
European Federation of Neurological Societies
The European Federation of Neurological Societies is a body formed by 42 societies of neurology of European countries. As a result, it indirectly represents 12,000 neurologists. It was founded in 1991 in Vienna, Austria.-External links:* *...
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
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
(removal of excessive cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
), medication (acetazolamide
Acetazolamide
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...
), or neurosurgical
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
treatment (optic nerve sheath fenestration or shunting
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...
). In certain situations, anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s 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 reviewSystematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
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.
Epidemiology
Cerebral venous sinus thrombosis is rare, with an estimated 3-4 cases per million annual incidence in adults. While it may occur in all age groups, it is most common in the third decade. 75% are female. Given that older studies show no difference in incidence between men and women, it has been suggested that the use of oral contraceptives in women is behind the disparity between the sexes. A 1995 report from Saudi ArabiaSaudi Arabia
The Kingdom of Saudi Arabia , commonly known in British English as Saudi Arabia and in Arabic as as-Sa‘ūdiyyah , is the largest state in Western Asia by land area, constituting the bulk of the Arabian Peninsula, and the second-largest in the Arab World...
found a doubled incidence at 7 cases per 100,000; this was attributed to the fact that Behçet's disease
Behçet's disease
Behçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements...
, which increases risk of CVST, is more common in the Middle East.
A 1973 report found that CVST could be found on autopsy
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
(examination of the body after death) in nine percent of all people. Many of these were elderly and had neurological symptoms in the period leading up to their death, and many suffered from concomitant heart failure.
In children, a Canadian study reported in 2001 that CVST occurs in 6.7 per million annually. 43% occur in the newborn (less than one month old), and a further 10% in the first year of life. Of the newborn, 84% were already ill, mostly from complications after childbirth and dehydration.
History
The first description of thrombosis of the cerebral veins and sinuses is attributed to the French physician Ribes, who in 1825 observed thrombosis of the saggital sinus and cerebral veins in a man who had suffered from seizures and delirium. Until the second half of the 20th century it remained a diagnosis generally made after death. In the 1940s, reports by Dr Charles SymondsCharles Symonds
Sir Charles Putnam Symonds KBE CB was an English neurologist.His initial medical training was at Guy's Hospital, followed by specialised training at the National Hospital for Neurology and Neurosurgery...
and others allowed for the clinical diagnosis of cerebral venous thrombosis, using characteristic signs and symptoms and results of lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
.
Improvements on the diagnosis of cerebral venous sinus thrombosis in life were made with the introduction of venography
Venography
Venography is a procedure in which an x-ray of the veins, a venogram, is taken after a special dye is injected into the bone marrow or veins. The dye has to be injected constantly via a catheter, making it an invasive procedure...
in 1951, which also aided in the distinction from idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension , sometimes called by the older names benign intracranial hypertension or pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases...
, which has similar presenting signs and symptoms in many cases.
The British gynecologist Stansfield is credited with the introduction, in 1942, of the just recently introduced anticoagulant heparin in the treatment of CVST in 1942. Clinical trials in the 1990s finally resolved the concern about using anticoagulants in most cases of CVST.