Definition
Cerebral venous thrombosis (CVT) are due to the formation of clots (thrombus) in the veins of the brain. They are a rare cause of stroke. They may lead to difficulties in the circulation of cerebro-spinal fluid (CSF) and be responsible for intracranial hypertension, cerebral lesions (intracranial hemorrhages or infarction), sometimes in multiple locations. They can be difficult to diagnose. The prognosis is better than it is for arterial stroke.
Epidemiology
The actual incidence of CVT remains unclear (number of new cases per year). However it is estimated to represent approximately 0.5% of all strokes. CVTs can occur at any age, with a slight predominance in young women because of predisposing factors such as oral contraceptives, pregnancy and childbirth.
Clinical Description
There are no specific clinical signs of CVT.
The most frequent symptoms are headache (85%) of all types, focal deficits (40%; motor and/or sensory deficit, speech difficulties etc.) and epilepsy (40%, partial or generalised). Unconsciousness affects approximately one-third of patients. Another feature of CVTs is the wide variation in the onset of symptoms, unlike arterial stroke. 50% of symptoms occur over several days (or up to one month), 20% as acute symptoms and 30% over a period of one month or more. The absence of any pathognomonic clinical presentation implies rapid recourse to the relevant additional examinations.
Etiology/Pathophysiology
Thrombosis can reach any sinus or vein in the cerebral venous system but, in decreasing order of frequency, tends to affect the lateral and superior sagittal sinus, the right sinus and the cavernous sinus. In most cases, several sinuses and/or veins are affected at the same time. Added to the fact that the number and location of territories of cortical veins are variable, this explains why there is no well-defined anatomical or clinical syndrome as there is in the case of arterial infarctions.
The cerebral lesions vary in CVT. Their type and number depend on the location of the thrombosis, and to the possibility of anastomotic network. Cerebral edema may be the only consequence of the occlusion of a sinus whereas the occlusion of a cerebral vein usually leads to a venous infarction, which includes a much larger edema and hemorrhage in more cases that in an arterial infarction. In the case of venous occlusion, a hematoma will form. This hemorrhagic component explains the possible onset of subarachnoid hemorrhage and even subdural hematoma.
Many etiologies and triggering factors have been implicated in CVTs. In short, these factors correspond to all the causes of peripheral venous thromboses in addition to the local causes (cranial trauma, proximity infection, brain tumor etc.). Some causes constitute a medical emergency e.g. infections (mastoiditis, meningitis etc.) and require rapid diagnosis and appropriate treatment as much as the CVT does. The association of several causes or predisposing factors is common, which implies the need for a complete etiological report in all cases, even where the etiology seems to be evident.
Diagnosis
When CVT is given as the likely diagnosis, a brain scan allows for the elimination of the main differential diagnoses. Among the signs that can suggest CVT are, on the scanner with no injection of dye, spontaneous hyperdensity of the thrombus in the sinus or, much more rarely, in a cortical vein ("cord" sign). On the scan with injection of dye, the “delta” sign or “empty triangle” can sometimes be seen, corresponding to the uptake of contrast between the richly vascularised sides of the superior sagittal sinus, contrasting with the non-injection of the thrombosed lumen.
The diagnosis is usually confirmed by an MRI of the brain. In the parenchymal regions, the thrombosis causes a change in the intravascular signal, which varies depending on the age of the thrombosis and the type of sequence undertaken. During the phase of organisation of the thrombosis (2nd and 3rd weeks), a hypersignal within the vascular lumen replaces the normal hyposignal of the blood flow on T1 and T2 -weighted sequences, confirming the diagnosis. Before the 5th day, an MRI may give a false negative result because of an isosignal on T1 and a hyposignal on T2. From the 3rd week onwards, the hypersignal may disappear on T1 but persists on T2, unless there has been recanalisation, shown by the reappearance of an isosignal. The T2*-weighted gradient echo sequence (very sensitive to the presence of blood products) also indicates the thrombus within the veins or sinus as a very easily identified hyposignal. It is more clearly visible than the signal variations observed on the other sequences.
Modifications of the signal from the occluded sinus may sometimes be absent, especially in the first few days, or be difficult to interpret. It is then essential to perform angiography to see the cerebral veins. This may take the form of a magnetic resonance veinography, an angioscan or even a conventional angiography (injection of a contrast dye into an artery). These examinations show that the thrombosed sinus is no longer visible.
Measurement of D-dimers may be useful for diagnostic purposes because of the negative predictive value of a level less than 500 ng/mL.
If not contraindicated, a lumbar puncture often remains an essential part of the work-up in CVT. It is used to measure the opening pressure of the spinal fluid and to rapidly decrease any intracranial hypertension that can threat the optic nerves. A study of the cerebro-spinal fluid (CSF) is also useful, as an emergency measure, in CVT with fever to eliminate meningitis and, more generally, in CVT with no apparent cause where it can be used to test for chronic meningitis.
Treatment
Although the development of CVT is much less severe than the former series suggested, it nevertheless varies greatly. Certain cases can evolve in a few days and lead rapidly to death, total cure or persistence of sequellae.
There are three approaches for the treatment:
- Etiological treatment (treatment of the cause) when possible, is particularly important in infectious forms of CVT. Likewise, specific treatment may be necessary during certain general diseases (cancers, hemopathies, systemic diseases etc.).
- Treatment must always be provided to relieve symptoms.
- Antiepileptic treatment is reserved for forms of the disease leading to epileptic seizures. There is no preference for any particular drug. The treatment is usually continued for a year then gradually decreased if no new attack occur and if the EEG is normal.
- The treatment of intracranial hypertension is usually medical. Acetazolamide or restrictions of water intake are currently preferred. In forms with isolated ICHs, a lumbar puncture before the introduction of heparin, combined with acetazolamide, usually results in rapid improvement of headache and adequate control of visual function.
- Finally, analgesics are usually essential during the acute phase because of the sometimes intense headache. The headaches are usually rapidly improved by anticoagulant medication, and the use of major analgesics is not usually necessary.
- Anticoagulant medication (to reduce the thrombus and its extension) is based on curative doses of heparin. In fact, this drug is prescribed as soon as the diagnosis has been confirmed. There is no consensus on the conditions, type (unfractionated heparin or low-molecular-weight heparin) or duration of the treatment. After a few days, and in the absence of any clinical deterioration, treatment is usually provided by means of anticoagulants administered orally. The duration of the treatment depends on the underlying cause (but generally lasts for several months). Thrombolysis, whether or not associated with mechanical efforts to remove the obstruction (intravascular introduction of a probe to remove the clot) remains exceptional at the present time, and reserved for types which worsen despite the correct medical treatment.
Development Prognosis
Once considered as almost always fatal, CVTs now have mortality of less than 5% during the acute phase and they usually result in recovery without any relapse.
Some factors have been identified that indicate the likely gravity of the case :
- age with high mortality at each end of the normal lifespan (in children and the elderly)
- the presence of focal signs or coma
- the joint existence of an ICH and a delta sign on CT-scan
- damage to the deep vein system or veins in the posterior fossa
- and, in particular, the underlying etiology especially septic thromboses
The ability to recover full function is very high and fewer than 15% of patients suffer any relapse. In most cases, the sequellae consist of focal deficits or, in rare cases, visual impairment with optical atrophy after an intracranial hypertension that was diagnosed too late.
