Introduction
Cerebral venous sinus thrombosis (CVST) is a rare condition accounting for around 1% of brain strokes. It can happen at any age, but is more frequent in children and young adults (1). It can occur within several medical or surgical contexts, for which reason it is important to know how it presents itself clinically and how to diagnose, treat, and improve the prognosis.
Over the last years there has been significant advancement in this field, particularly thanks to the undertaking of a prospective and multicentric study, the International Study on Cerebral Vein and Dural Sinus Thrombosis - ISCVT. The Department of Neurology of Santa Maria Hospital was the coordinator centre of this study.
Eighty nine centres from 21 countries participated in the ISCVT, and being able to include such high number of cases allowed us to know this disease and its prognosis better(5).
Clinical presentation
CVST can be acute, subacute, or chronic (1,5). Most common symptoms are headache, seizures, abnormal vision, mental status disturbance, focal signs and changes in conscience.
Symptoms can be grouped into three syndromes:
1) Isolated intracranial hypertension syndrome (headache with or without vomiting, papilledema, and visual problems)
2) Focal syndrome (focal deficits, seizures, or both);
3) Encephalopathy (multifocal signs, alteration of mental status, stupor or coma).
It can present itself in less usual forms: cavernous sinus syndrome, thunderclap headache, multiple cranial nerve paralysis, migraine aura, pulsatile tinnitus.
Diagnosis
Diagnosis requires confirmation of occlusion of a vein/dural sinus by brain imaging examination.
The computed tomography (CT) scan is normally the first exam to be carried out, mostly to rule out other conditions (tumour, subdural hematoma, subarachnoid haemorrhage, encephalitis). In a large number of cases, the CT will prove normal or unspecific, and in 60-80% of cases it will show brain lesions, such as oedema/infarction or haemorrhage.
An angio-CT could display the filling defects due to occluded veins or dural sinuses.
Brain Magnetic Resonance (MR) with venous-MR is the best technique to diagnose CVST.
The T1 or T2-weighted images show signal change in the occluded dural sinus or vein, while with venous-MR blood flow cannot be seen inside the occluded vessels.
Figure: Left lateral sinus venous thrombosys diagnosed by MRI (the arrow reveals the thrombus as hypertense signal in the left lateral sinus (A) and by veno-MRI (arrows indicate that the aforementioned sinus is not in view) (B)
The T2* weighting is useful to diagnose isolated cortical vein thrombosis. Brain angiography is used in situations that are difficult to diagnose or for purposes of endovascular therapeutics.
Search of the causes
An important aspect in the evaluation of patients suffering from CVST is to look for its cause (Table). The most important risk factors are prothrombotic conditions, whether genetic or acquired. There is more than one risk factor in over half of patients. In about 15% of cases, it is not possible to identify any CVST predisposing factor. Those patients should be followed in the long term, since a cause may be identified (neoplasia, vasculitis).
Clinical Course and Prognosis
Prognosis is generally good. Monitoring should be done during the acute stage, since one quarter of patients may get worse and 5% can die. Patients who died during the ISCVT showed, upon admission, higher rates of change of consciousness, alteration of mental status, deep venous system thrombosis, right hemisphere haemorrhage and lesion in the posterior fossa. Death was caused mostly by herniation due to unilateral brain lesion or multiple lesions (3).
The large majority of patients recover in the long term (80% in ISCVT). Factors associated with a poor prognosis are: SNC infection, malignancy, deep venous system thrombosis, brain haemorrhage, coma, alteration of mental status, male gender, and age >37. Following discharge from hospital, patients may have complications, such as headaches, seizures or recurrent thrombotic episodes (5).
Treatment
Treatment is based on various types of interventions:
1) Treatment of the causes (infections, vasculitis, inflammatory disease)
2) Antithrombotic therapeutics
The main therapy for CVST is anticoagulants (fractionated or non-fractionated heparin). Four trials and a meta-analysis of two of those trials were carried out, which indicated a nonsignificant reduction in the risk of death 0.33 (95% CI 0.08-1.21) and of poor prognosis 0.46 (95% CI 0.16 to 1.31). Anticoagulants are safe in the presence of hemorrhagic cerebral lesions.
In some patients, their condition worsens when taking anticoagulants. Endovascular therapeutics by injection of thrombolytics into the occluded sinuses may be considered (2).
The use of warfarin anticoagulants should be continued after an acute phase: for 3 months in the presence of a precipitating risk factor, for 6-12 months if there is mild thrombophilia, and on a permanent basis in case of serious thrombophilia(4).
3) Treatment of symptoms and complications
Intracranial hypertension can be reduced with the use of acetazolamide, lumbar punctures (in the absence of cerebral lesions) or by placing a lumbo-peritoneal shunt (if there is worsening of visual acuity). In the presence of serious intracranial hypertension, cerebral lesions and risk of transtentorial herniation, surgery/decompressing craniotomy should be considered.
Should seizures occur at the initial stage of CVST, the use of antiepileptic drugs is recommended
Conclusions
CVST clinical research, an uncommon disease, requires the involvement of several centres so that a high number of patients can be included. ISCVT was the first step towards the establishment of an organised network of centres for the study of CVST. New studies are currently underway to improve therapeutics, namely a random trial to study endovascular thrombolysis (To-ACT) and prospective registry of decompressing craniotomy.
Patrícia Canhão
Neurology University Clinic
pcanhao@fm.ul.pt
__________________
Bibliography
1. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007;6:162-170.
2. Canhão P, Falcão F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis 2003;15:159-166.
3. Canhão P, Ferro JM, Lindgren AG, et al; ISCVT Investigators. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005;36:1720-1725.
4. Einhäupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol. 2010;17(10):1229-1235.
5. Ferro JM, Canhão P, Stam J, et al; ISCVT Investigators: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670.
Cerebral venous sinus thrombosis (CVST) is a rare condition accounting for around 1% of brain strokes. It can happen at any age, but is more frequent in children and young adults (1). It can occur within several medical or surgical contexts, for which reason it is important to know how it presents itself clinically and how to diagnose, treat, and improve the prognosis.
Over the last years there has been significant advancement in this field, particularly thanks to the undertaking of a prospective and multicentric study, the International Study on Cerebral Vein and Dural Sinus Thrombosis - ISCVT. The Department of Neurology of Santa Maria Hospital was the coordinator centre of this study.
Eighty nine centres from 21 countries participated in the ISCVT, and being able to include such high number of cases allowed us to know this disease and its prognosis better(5).
Clinical presentation
CVST can be acute, subacute, or chronic (1,5). Most common symptoms are headache, seizures, abnormal vision, mental status disturbance, focal signs and changes in conscience.
Symptoms can be grouped into three syndromes:
1) Isolated intracranial hypertension syndrome (headache with or without vomiting, papilledema, and visual problems)
2) Focal syndrome (focal deficits, seizures, or both);
3) Encephalopathy (multifocal signs, alteration of mental status, stupor or coma).
It can present itself in less usual forms: cavernous sinus syndrome, thunderclap headache, multiple cranial nerve paralysis, migraine aura, pulsatile tinnitus.
Diagnosis
Diagnosis requires confirmation of occlusion of a vein/dural sinus by brain imaging examination.
The computed tomography (CT) scan is normally the first exam to be carried out, mostly to rule out other conditions (tumour, subdural hematoma, subarachnoid haemorrhage, encephalitis). In a large number of cases, the CT will prove normal or unspecific, and in 60-80% of cases it will show brain lesions, such as oedema/infarction or haemorrhage.
An angio-CT could display the filling defects due to occluded veins or dural sinuses.
Brain Magnetic Resonance (MR) with venous-MR is the best technique to diagnose CVST.
The T1 or T2-weighted images show signal change in the occluded dural sinus or vein, while with venous-MR blood flow cannot be seen inside the occluded vessels.
Figure: Left lateral sinus venous thrombosys diagnosed by MRI (the arrow reveals the thrombus as hypertense signal in the left lateral sinus (A) and by veno-MRI (arrows indicate that the aforementioned sinus is not in view) (B)
The T2* weighting is useful to diagnose isolated cortical vein thrombosis. Brain angiography is used in situations that are difficult to diagnose or for purposes of endovascular therapeutics.
Search of the causes
An important aspect in the evaluation of patients suffering from CVST is to look for its cause (Table). The most important risk factors are prothrombotic conditions, whether genetic or acquired. There is more than one risk factor in over half of patients. In about 15% of cases, it is not possible to identify any CVST predisposing factor. Those patients should be followed in the long term, since a cause may be identified (neoplasia, vasculitis).
Clinical Course and Prognosis
Prognosis is generally good. Monitoring should be done during the acute stage, since one quarter of patients may get worse and 5% can die. Patients who died during the ISCVT showed, upon admission, higher rates of change of consciousness, alteration of mental status, deep venous system thrombosis, right hemisphere haemorrhage and lesion in the posterior fossa. Death was caused mostly by herniation due to unilateral brain lesion or multiple lesions (3).
The large majority of patients recover in the long term (80% in ISCVT). Factors associated with a poor prognosis are: SNC infection, malignancy, deep venous system thrombosis, brain haemorrhage, coma, alteration of mental status, male gender, and age >37. Following discharge from hospital, patients may have complications, such as headaches, seizures or recurrent thrombotic episodes (5).
Treatment
Treatment is based on various types of interventions:
1) Treatment of the causes (infections, vasculitis, inflammatory disease)
2) Antithrombotic therapeutics
The main therapy for CVST is anticoagulants (fractionated or non-fractionated heparin). Four trials and a meta-analysis of two of those trials were carried out, which indicated a nonsignificant reduction in the risk of death 0.33 (95% CI 0.08-1.21) and of poor prognosis 0.46 (95% CI 0.16 to 1.31). Anticoagulants are safe in the presence of hemorrhagic cerebral lesions.
In some patients, their condition worsens when taking anticoagulants. Endovascular therapeutics by injection of thrombolytics into the occluded sinuses may be considered (2).
The use of warfarin anticoagulants should be continued after an acute phase: for 3 months in the presence of a precipitating risk factor, for 6-12 months if there is mild thrombophilia, and on a permanent basis in case of serious thrombophilia(4).
3) Treatment of symptoms and complications
Intracranial hypertension can be reduced with the use of acetazolamide, lumbar punctures (in the absence of cerebral lesions) or by placing a lumbo-peritoneal shunt (if there is worsening of visual acuity). In the presence of serious intracranial hypertension, cerebral lesions and risk of transtentorial herniation, surgery/decompressing craniotomy should be considered.
Should seizures occur at the initial stage of CVST, the use of antiepileptic drugs is recommended
Conclusions
CVST clinical research, an uncommon disease, requires the involvement of several centres so that a high number of patients can be included. ISCVT was the first step towards the establishment of an organised network of centres for the study of CVST. New studies are currently underway to improve therapeutics, namely a random trial to study endovascular thrombolysis (To-ACT) and prospective registry of decompressing craniotomy.
Patrícia Canhão
Neurology University Clinic
pcanhao@fm.ul.pt
__________________
Bibliography
1. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007;6:162-170.
2. Canhão P, Falcão F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis 2003;15:159-166.
3. Canhão P, Ferro JM, Lindgren AG, et al; ISCVT Investigators. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005;36:1720-1725.
4. Einhäupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol. 2010;17(10):1229-1235.
5. Ferro JM, Canhão P, Stam J, et al; ISCVT Investigators: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670.
