POVZETEK

Možganski venski sistem ima ključno vlogo pri ohranjanju primernega možganskega krvnega pretoka, saj zagotavlja odtekanje venske krvi. To dejstvo podpirajo podatki, da možganski venski sistem vsebuje 70 odstotkov celotnega možganskega volumna krvi in da motnje v tem delu možganskega krvnega obtoka lahko dramatično povečajo znotrajlobanjski tlak z resnimi nevrološkimi posledicami. Tipični klinični znaki možganske venske in sinusne tromboze, (MVT), so epileptični napadi, glavobol, žariščni nevrološki znaki in znaki znotrajlobanjske hipertenzije. Klinična slika je običajno huda. Po uvedbi antikoagulantnega zdravljenja se je v klinični praksi zmanjšala visoka stopnja smrtnosti. Klinična slika je tudi zelo raznolika in zaradi tega v strokovni literaturi MVT pogosto imenujemo ’nevrološka posnemovalka’. V 20 do 35 odstotkih ostane neprepoznana. Cilj tega literaturnega pregleda je poudariti glavne klinične značilnosti MVT kot tudi diagnostičnih in terapevtskih protokolov. Opisujemo tudi naše izkušnje pri 32 bolnikih z MVT, ki so bili zdravljeni na Nevrološkem inštitutu med letoma 2001 in 2007, 20 žensk in 12 moških s povprečno starostjo 39,8 ± 3,4 leta. Več kot 90 odstotkov naših bolnikov je kot začetni simptom navajalo glavobol, skoraj polovica od njih je imela tipično klinično sliko z glavobolom, epileptičnimi napadi in žariščnimi nevrološkimi znaki. Etiološki dejavnik je bil pri 50 % okužba ali vnetje ali oboje, koagulopatija pri 31 % in nosečnost pri 22 %, 75 % pa je imelo hkrati dva ali več vzročnih dejavnikov. Pri večini bolnikov smo ugotovili trombozo sagitalnega in transverzalnega venskega sinusa, pri manjšini pa sigmoidnega in kavernoznega sinusa. Tretjina bolnikov je imela sočasno trombozo dveh ali več sinusov. Vsi bolniki so prejemali antikoagulantno zdravljenje, po katerem so se sinusi pri 18 bolnikih popolno rekanalizirani, kar je bilo potrjeno z kontrolno možgansko angiografijo, pri 6 bolnikih pa je nevrološko izboljšanje potekalo z delno rekanalizacijo. Umrljivost v naši skupini je bila sorazmerno velika (19 %).

Ključne besede: Klinična slika; možganska venska in sinusna tromboza; naše izkušnje; pregled literature.

SUMMARY

Cerebral venous system has the key role in keeping adequate cerebral circulation because it provides draining of venous blood. This fact supports the data that cerebral venous system contains 70 % of the total cerebral blood volume and disturbances in this part of the cerebral circulation can raise intracranial pressure dramatically with serious neurological consequences. Typical clinical signs of the cerebral venous and sinus thrombosis (CVT) are epileptic seizures, headache, focal neurological signs and signs of intracranial hypertension. Clinical presentation is usually serious and after introduction of anticoagulant therapy in clinical practice previously high mortality rate is decreased. Clinical presentation is very variable and, because of that in the scientific literature CVT is often called “a neurological forger” and in 20-35 % they are undiagnosed. The aim of this review of the literature is to underline main clinical features of CVT as well as diagnostical and therapeutical protocols. We are also presenting our experiences with 32 patients with CVT treated at the Institute of Neurology between 2001 and 2007, 20 women and 12 men, with average age 39,8 ± 3.4 years. Over 90 % of our patients as initial symptom had headache, and almost half of them had typical presentation: headache, epileptic seizures, and focal neurological signs. Etiological factor in 50 % was infection and/or inflammation, coagulopathy in 31 % and gestation in 22 %. 75 % of our patients had two or more etiological factors at the same time. Majority of patients had superior sagital and transversal sinus thrombosis, and than sygmoid and cavernous sinus. One third of patients had thrombosis of two or more sinuses at the same time. All patients were treated with anticoagulant therapy, 18 patients had complete sinuses recanalisation, confirmed on control cerebral angiography and 6 had neurological improvement, with partial recanalisation. Mortality rate in our group was relatively high (19 %).

Key words: Cerebral venous and sinus thombosis; clinical presentation; review of literature; our experiences.

ANATOMY OF THE CEREBRAL VENOUS CIRCULATION

The drainage venous system of the brain is divided in two main parts, superficial and deep. The superficial system drains blood from the cortex and subcortical white matter, while deep cerebral veins drain blood from deeper parts of the brain hemispheres, white matter, basal ganglia and midbrain. Negative intracranial pressure allows the veins of the brain and venous sinuses to stay open even when the intraluminar pressure is zero. The veins of the brain don’t have valves, so the blood flow is possible in both directions.

The venous sinuses are spaces between endosteal and meningeal layers of the dura. The superior sagittal sinus (SSS) begins at the front third of the falx cerebri and ends in the confluence of sinuses. Most of the venous blood flow to the transverse sinus (TS), which together with the sigmoid sinus (SS) makes the lateral sinus (LS). The sigmoid sinus leaves the skull through the jugular foramen, at which point the sinus becomes continuous with the internal jugular vein (IJV). The cavernous sinus (CS) drains blood from the facial structures and the orbits by the angular and the ophthalmic veins, and then empties into the TS by the superior petrosal sinus (SPS), and into the IJV by the inferior petrosal sinus (IPS).

ETIOLOGY OF THE CEREBRAL VENOUS THROMBOSIS

The cerebral venous thrombosis can be caused by infectious or non-infectious causes (1-3) (Table 1).

Intracranial infection as a cause of cerebral venous thrombosis (CVT) is a rarity nowadays in the era of antibiotics. In majority of recent studies infection as a cause of CVT is present in approximately 10 % of all cases (1, 3-5). CVT may be result of inflammation in non-infectious, inflammatory and systemic diseases including Behcet’s disease, sarcoidosis, Wegener granulomatosis, Crohn’s disease and ulcerative colitis (1, 2, 6-9).

Non-infectious CVT can be result of various states characterized with hypercoagulability of blood (1-3, 6, 7).

The best known physiological hypercoagulability states are pregnancy and puerperium. About 20 % of all CVT is related to these periods of life. According to the literature data for the period from 1979 to 1991, the largest registered incidence of CVT in developed countries was 11,4 per 100.000 deliveries (2, 3, 7-11). This risk is higher in developing countries (10). Imbalance between pro-and anti-coagulant proteins is present in the third trimester of pregnancy and puerperium period, and refers to the increased tendency to platelet aggregation, decreased fibrinolysis, and reduced levels of protein C and S. Pregnant women with inherited coagulation disorders are especially prone to thrombosis (4-6, 10). CVT are twice as likely to occur during puerperium compared to pregnancy, most often during the first 20 days after delivery (10).

Apart from pregnancy, another relatively common predisposing factor for CVT in women is use of oral contraceptives and hormone therapy. One of the latest large prospective randomized studies confirmed the increased risk of cerebrovascular diseases, myocardial infarction and venous thrombosis in postmenopausal women treated with this therapy (10, 11).

Dehydration also represents one of the hypercoagulability conditions, which increases the tendency to CVT, especially in children and poorly nourished individuals, as well as in elderly patients treated with diuretics (12, 13).

When the diagnosis of CVT is determined in the absence of pregnancy and other predisposing factors, examination should be directed to the probable existence of inherited or acquired hypercoagulability states. Factor V Leiden (FVL) mutation is the most common genetic risk factor, followed by the prothrombin gene mutation G20210A. Other less common hereditary risk factors include deficiencies of protein C, protein S and antithrombin III (11, 14). Not so rare cause of CVT is hyperhomocysteinemia, caused by mutations in the gene for methylenetetrahidrofolat-reductase (MTHFR), which participates in the chain of homocysteine metabolism (14). Acquired hyperhomocysteinemia is usually a result of deficiency of vitamins that are cofactors in homocysteine metabolism (vitamins B6, B12 and folic acid).

Acquired hypercoagulability states are common in liver diseases, disseminated intravascular coagulation after surgery and nephrotic syndrome (1, 3-5, 8, 9, 11). Hypercoagulability state is also expressed in patients with myeloproliferative diseases, polycythemia, anemia and various types of malignancies (5-7).

In the development of CVT etiologically important role also have mechanical factors (head trauma, lumbar puncture, and neurosurgical interventions) and a large number of medications (cytostatics, hormones, oral contraceptives, corticosteroids, dihydroergotamine, diuretics) (3, 6, 8, 9).

Despite adequate use of all available diagnostic methods, the cause of CVT remains undiagnosed in up to 20-35 % of all cases (1, 2, 4, 6, 7, 15).

CLINICAL PRESENTATION OF CEREBRAL VENOUS AND SINUS THROMBOSIS

The description of CVT clinical presentation in the medical literature, almost as a rule, begins with the phrase “a neurological forger” or “clinical stubborn” and these terms are used to indicate the variability of the clinical manifestations of this disorder (15, 16). Variability refers to the neurological symptoms and also to the course of the disease. The clinical presentation depends on the site of thrombosis, i.e. which veins sinuses are thrombosed, and also on development of collateral venous circulation and the etiology of CVT (17).

In about 30 % of patients the first symptoms occur within 48 hours of thrombosis, in half of patients between 48 hours and one month, and in 20 % of patients symptoms appear one month after the onset of thrombosis (15, 17-20).

Bousser proposed three clinical forms of CVT: 1) isolated intracranial hypertension (in 30-40 % of patients), 2) form with the focal disturbances and epileptic seizures (50-60 %) and 3) diffuse encephalopathy (10-20 %) that clinically resembles encephalitis or metabolic encephalopathy (1-3, 5, 15).

The most common symptoms include headache, edema of optic nerve, intracranial hypertension, seizures, disturbance of consciousness and focal neurological deficit (1, 2, 15, 17, 21-23).

Headache is present in about 75 % of all patients and it is probably caused by increase intracranial pressure. It may be initial and the only symptom in 15 % of patients with CVT. It is usually diffuse, potentiated by standing, sneezing and coughing. In some cases, headache may start suddenly and with features resembling subarachnoid hemorrhage headache (17, 21-23).

Papilloedema is present in more than half of patients with CVT, particularly young people. It is always present in CVT associated with Behcet’s disease and may be associated with bilateral blurred vision (4, 5, 15-18).

Focal or generalized seizures were the initial symptom in about 15 % of all patients, and they appear in some stage of disease in about 40 % of patients with CVT (18, 24).

Disturbance of consciousness is found in more than a half of patients with CVT and it is usually of moderate intensity, but when is more pronounced it indicates a poor prognosis in over a third of patients (1, 4, 5, 9, 16, 17, 24).

Focal neurological deficit may be the initial manifestation of CVT in 15 % of all cases, and it is present in 60 % of patients in some stage of disease (6, 13, 19, 20).

In the case of infectious etiology of CVT, accompanying symptoms are fever, vomiting and other symptoms of general infectious syndrome, which further hinders the establishing of CVT diagnosis (1, 2, 9, and 15).

In addition to these general symptoms of CVT, there are also symptoms which depend on the site of thrombosis but it should be pointed out that usually more than one sinus are simultaneously affected (18).

The most common thrombosis in clinical practice is thrombosis of the SSS, and it is usually associated with trauma, meningeal inflammation and with pregnancy. When thrombosis is limited only to the SSS, clinical presentation usually resembles the idiopathic intracranial hypertension, and it is rarely associated with epileptic seizures. Isolated LS thrombosis is rare and it is often associated with infections of the ear and mastoid. It is clinically presented as intracranial hypertension, which is associated with pain that extends up to the front edge of the sternocleidomastoid muscle. This clinical presentation should be a warning sign, because there are no other symptoms until thrombosis affects cortical veins also, when the prognosis is unfortunately very poor (3, 15, 17, 18).

Thrombosis of the CS is usually associated with infection of the nose, eye, paranasal sinuses or the middle ear. The classical triad includes chemosis, proptosis, and painful ophthalmoplegia. It usually starts with headache and facial pain, redness of the eye, proptosis and ophthalmoplegia, which are accompanied with signs of development of edema of the retina, orbit and papilla of optic nerve. The loss of vision occurs as a result of central retinal artery occlusion or because of ischemic optic neuropathy. The process can be extended to the internal carotid artery with subsequent symptomatology. Unlike the other disturbances with similar symptoms, that are usually unilateral, cavernous sinus thrombosis in advanced stages is usually bilateral (9, 15-18).

Thrombosis of the superior and inferior petrosal sinus is usually a complication of thrombosis of CS, and can be recognized by occurrence of symptoms resembling the jugular foramen syndrome (9, 18).

Cortical vein thrombosis rarely occur isolated without concomitant deep sinus thrombosis, and thay are clinically manifested as focal neurological deficit of sudden onset. Thrombosis of the Rolandic vein is often associated with thrombosis of SSS, and it is characterized by the crural type of hemiparesis without cranial nerves deficits (18).

Isolated deep vein thrombosis is rare with the exception of the Galen vein thrombosis, which is common in children. Typical symptoms are coma with decerebration or decortication, intracranial hypertension and papilloedema of optic nerve (19).

DIAGNOSE OF CEREBRAL VENOUS AND SINUS THROMBOSIS

Triad of headache, seizures and focal neurological deficits, associated with hypercoagulability states, should always arouse suspicion of CVT. In the case of this triad and the negative findings of computed tomography (CT), lumbar puncture is a useful method for detection of increased intracranial pressure (15, 17, 18). The high level of serum D-dimer may be also helpful, because it is elevated in 75 % of patients with CVT in the acute and subacute phase of illness (25). Venous infarcts on CT appear mainly as mixed density changes of ischemia and hemorrhage or as hemorrhagic transformation of ischemic infarction (Figure 1) (15, 17, and 26). CT can also show some typical signs such as “ribbon sign” (Figure 2) (27) in superficial vein thrombosis of the brain, “a sign of dense triangle” (Figure 3A) (38, 39) in thrombosis of the posterior part of the SSS, which is manifested as “empty delta sign” (Figure 3B) after application of contrast, when “delta” represents hyperdensity of the SSS wall, while the thrombus is represented as hypodensity in the middle of the “delta sign” (26, 27).

More sensitive method for detecting CVT is magnetic resonance imaging (MRI) of endocranium, especially MR venography (MRV) (17, 28,). By this diagnostic method, MR-T2 sequence shows ischemic changes in the form of hyperintense signals with frequent mixture of the blood density, where the localization and distribution of lesions do not correlate with normal arterial distribution of infarcts, and the lesions are frequently bilateral and accompanied with edema (17, 26, 28-33, ). The most important finding on the MRV, which shows venous sinus thrombosis, is the absence of direct visualization of the sinus (Figure 4), and the direct detection of thrombus (Figure 5). In a small percentage of cases, MRV does not show lesions, and if CVT is highly suspected, digital subtraction angiography / venography remains as the ultimate and most sensitive method (26, 27, 30-33).

PROGNOSIS

CVT has better prognosis compared with ischemic stroke of arterial origin. Mortality is estimated to be 5-30 % (16, 34, and 35). The most common sequels of the CVT are blindness, persistent convulsions (14%), focal deficits and neuropsychological disorders (11 %) (36-38). The outcome of thrombosis depends very much on the causes of CVT, and it is poor in cases of malignancies and hematological disorders (39, 40). The risk of recurrent thrombosis within the first year is estimated to be up to 12 %, and it is higher in patients with Behcet’s disease and persistent hypercoagulability conditions (37, 38, 40, and 16).

TREATMENT

Hydration is one of the most important aspects of CVT treatment, and it is the only therapeutical method of CVT in infants. Theoretically, the adequate hydration reduces blood viscosity and prevents further development of thrombosis (15-17).

Prophylactic therapy of seizures is a controversial issue both in all cerebrovascular diseases and in the CVT separately. If antiepileptic therapy is applied, its withdrawal should be taken into consideration after 6-12 months, because the risk of epileptic seizures after this period is small (15, 16, and 41).

Usage of hyperosmolar solution as antiedematous therapy is a reasonable therapeutic strategy, while corticosteroid therapy did not show a significant positive effect.

Repeated lumbar puncture used to reduce intracranial pressure is not recommended particularly because of the risk of development of spinal epidural hematoma with a higher risk after additional heparin use (15-18).

The use of broad-spectrum antibiotics is the therapy of choice in CVT cases with infectious etiology (1, 15-18).

Anticoagulant therapy with conventional form of heparin and low molecular weight heparin is a recommended therapeutic procedure. However, the studies with high numbers of patients did not fully confirm its efficacy. Thus, two large randomized studies showed a reducing trend of mortality and later disability, but without high statistical significance which would have demonstrated the undoubted benefit of this therapy (42, 43). Both studies confirmed that the anticoagulant therapy is a safe and low-risk procedure in patients with CVT, and it is recommended even in cases with hemorrhagic transformation of infarction. The first of these two studies was conducted in 1991, and was originally envisaged 60 patients, but it was stopped after first 20 randomized patients due to undoubtedly better outcome achieved by giving the active substance in comparison to placebo (15). Another larger study of de Bruijn et al. compared the effects of the low molecular heprin (nadroparin) and placebo in 60 patients (43). Nadroparin was administered for 3 weeks and then was continued with oral anticoagulant therapy during 10 weeks. This study showed a reducing trend of mortality and disability, but the established difference did not show statistical significance.

Despite the lack of strong evidence, anticoagulant therapy is considered to be a therapy of choice for CVT, and in clinical practice a low-molecular heparin in dose of 100 IJ /kg/ 12 hours is advised, usually lasting for 2 weeks, then continuing with oral anticoagulants for 3-6 months, except in patients with known prothrombotic condition where anticoagulant therapy is lifelong (15, 42-44).

Antiplatelet therapy has not been tested in the previous studies, but it is recommended in cases when anticoagulant therapy is contraindicated (15-17, 44).

Until now, thrombolytic therapy in CVT has been evaluated only on the basis of its beneficial effects in single cases, but without major randomized studies. In these cases, several therapeutic protocols with local administration of urokinase and t-PA were applied to patients with severe clinical manifestations when there was no improvement after use of anticoagulant therapy (44-46).

Long-term CVT therapy has not been investigated in prospective studies, but it has been suggested that the risk of thrombosis after three months is small, so the 3-6 months lasting therapy is sufficient for adequate recanalization and prevention of further thrombosis (43).

CONCLUSION

CVT represents a diagnostic challenge and potentially disabling or lethal disease, but in recent years, improvement in diagnosis and treatment provides a good outcome in the majority of patients. Acute or subacute neurological symptoms, especially the typical triad of signs and loss of consciousness, particularly in patients with some of predisposing conditions or illnesses, should arouse suspicion of CVT. Diagnostic confirmation of CVT includes angiographic or MRI examination, but in the cases with clinical suspicion of CVT, the appropriate therapeutic measures should be applied immediately, because their early implementation significantly improves final outcome.

OUR RESULTS

In a 6-year period (2001-2007) in the Neurology Clinic of the Clinical Center of Serbia, 32 patients were investigated and treated for CVT, 20 women and 12 men, mean age 39,8 ± 3,4 years, and the largest number of cases (56, 2 %) were aged between 19 and 39 years. In the tables 2, 3, 4 and 5 the clinical characteristics, causes, findings established by diagnostic procedures, treatment and outcome of 32 patients are shown.

Majority of our patients had inflammation and/or coagulopathy as etiological factors, infection was on the third place, while 18,8 % of patients remained without determined etiological factor.

Disease onset was sudden more frequently, almost all patients had headache as initial symptom and almost half of them had typical triad. SSS and TS were the most frequently thrombosed sinuses and a quarter of patients had two or more sinuses involved at the same time.

Two thirds of our patients had optic nerve edema. Serum D-dimer was elevated in 63,6 % of patients. Thrombosis was confirmed by MR venography in 62,5 % of patients.

Anticoagulant therapy was applied in almost all of our patients (93,75 %). Recanalisation was achieved in 56,3 % and neurological improvement despite only partial recanalisation in 12,5 % of patients. Mortality rate was 18,8 % in our cohort.

LITERATURE

• 1.Biousse V, Tong F, Newman NJ. Cerebral Venous Thrombosis Curr Treat Options Neurol. 2003 Sep; 5(5):409-420.
• 2.Biousse V, Tong F, Newman NJ. Cerebral Venous Thrombosis. Curr Treat Options Cardiovasc Med. 2003 Jul; 5(3):181-192.
• 3.Niclot P, Bousser MG. Cerebral Venous Thrombosis. Curr Treat Options Neurol. 2000 Jul;2(4):343-352
• 4.Ferro JM. Cerebral venous thrombosis. J Neuroradiol. 2002 Dec; 29(4):231-9.
• 5.Bousser MG. Cerebral venous thrombosis. Report of 76 cases. J Mal Vasc. 1991; 16(3):249-54.
• 6.Masson C, Colombani JM. Cerebral venous thromboses. Presse Med. 1999 Sep 25; 28(28):1547-52.
• 7.Masuhr F, Hehraein S, Einhaupl K. Cerebral venous sinus thrombosis. J Neurol 2004; 251:11–23.
• 8.Bousser MG, Russell R. Cerebral Venous Thrombosis: Major Problem in Neurology. Philadelphia, Pa: WB Saunders, 1997.
• 9.J. Stam. Thrombosis of the Cerebral Veins and Sinuses. N. Engl. J. Med., April 28, 2005; 352(17): 1791 - 1798
• 10.Cantu C, Barinagarrementeria F. Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases.Stroke.1993; 24: 1880–1884.
• 11.F. Dentali, M. Crowther, and W. Ageno. Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis. Blood, April 1, 2006; 107(7): 2766 - 2773.
• 12.DeVeber G, Andrew M, Adams C, Bjorson B, Booth F, Buckley DJ, Camfield CS, Davis M, Humphreys P, Langevin P, MacDonald A, Gillett J, for the Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med. 2001; 345: 417–423.
• 13.J. M. Ferro, P. Canhao, M.-G. Bousser, J. Stam, F. Barinagarrementeria, and for the ISCVT Investigators. Cerebral Vein and Dural Sinus Thrombosis in Elderly Patients. Stroke, September 1, 2005; 36(9): 1927 - 1932.
• 14.Ahmed A. Genetics of cerebral venous thrombosis. J Pak Med Assoc. 2006 Nov; 56(11):488-90.
• 15.Bousser MG. Cerebral venous thrombosis: diagnosis and management. J Neurol. 2000 Apr; 247(4):252-8.
• 16.F. Dentali, M. Gianni, M. A. Crowther, and W. Ageno. Natural history of cerebral vein thrombosis: a systematic review. Blood, August 15, 2006; 108(4): 1129-34.
• 17.Fink JN, McAuley DL. Cerebral venous sinus thrombosis: a diagnostic challenge. Intern Med J 2001; 31:384–90.
• 18.Einhäupl KM, Villringer A, Haberl RL, Pfister W, Deckert M, Steinhoff H, Schmeidek P. Clinical spectrum of sinus venous thrombosis. In: Einhauple KM, Kempski O, Baethmann A, eds. Cerebral Sinus Thrombosis/Experimental and Clinical Aspects. New York, 1990.
• 19.P. W. Huh, K. S. Cho, D. S. Yoo, J. K. Kim, D. S. Kim, J. K. Kang . Deep Cerebral Venous Thrombosis. Acta Neurochirurgica, 2002 Jan; 144(1):103-4.
• 20.Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999 Oct 22; 53(7):1537-42.
• 21.Gladstein J. Secondary headaches. Current Pain and Headache Reports 2006; 10(5).
• 22.H-C Diener. Cerebral venous thrombosis - headache is enough. J. Neurol. Neurosurg. Psychiatry, August 1, 2005; 76(8): 1043 - 1043.
• 23.R Cumurciuc, I Crassard, M Sarov, D Valade, and M G Bousser.Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J. Neurol. Neurosurg. Psychiatry, August 1, 2005; 76(8): 1084 - 1087.
• 24.Pearce JM. The craniospinal venous system.Eur Neurol. 2006; 56(2):136-8. Epub 2006.
• 25.C. M. Kosinski, M. Mull, M. Schwarz, B. Koch, R. Biniek, J. Schlafer, E. Milkereit, K. Willmes, and J. Schiefer. Do Normal D-dimer Levels Reliably Exclude Cerebral Sinus Thrombosis? Stroke, December 1, 2004; 35(12): 2820 - 2825.
• 26.Duncan IC, Fourie PA. Imaging of cerebral isolated cortical vein thrombosis. AJR Am J Roentgenol. 2005; 184: 1317–1319.
• 27.Ahn TB, Roh JK. A case of cortical vein thrombosis with the cord sign. Arch Neurol. 2003 Sep; 60(9):1314-6.
• 28.Millan M, Garcia S, Capellades J, Ferrer X, Escudero D, Vila N. Diffusion-weighted magnetic resonance in deep cerebral venous thrombosis. Neurologia. 2002 Oct; 17(8):443-6.
• 29.Ahmed Idbaih, Monique Boukobza, Isabelle Crassard et al. MRI of clot in cerebral venous thrombosis: high diagnostic value of susceptibility-weighted images. Stroke.2006 Apr; 37(4):991-5. Epub 2006 Feb 16.
• 30.Connor SE, Jarosz JM. Magnetic resonance imaging of cerebral venous sinus thrombosis. Clin Radiol. 2002; 57: 449–461.
• 31.Hypointense thrombus on T2-weighted MR imaging: a potential pitfall in the diagnosis of dural sinus thrombosis. Eur J Radiol. 2002; 41: 147–152.
• 32.Surendrababu Narayanam, Subathira, Livingstone RS. Variations in the cerebral venous anatomy and pitfalls in the diagnosis of cerebral venous sinus thrombosis: Low field MR experience. Indian J Med Sci. 2006 Apr; 60(4):135-42.
• 33.Cakmak S, Hermier M, Montavont A, Derex L, Mauguiere F, Trouillas P, Nighoghossian N. T2*SW-weighted MRI in cortical venous thrombosis. Neurology. 2004; 63: 1698.
• 34.Peter M, Tzourio C, Ameri A et al: Long term prognosis in cerebral venous thrombosis. A follow-up of 77 patients. Stroke1996; 27: 243-246.
• 35.J.M. Ferro, M.G. Lopes, M.J. Rosas, M.A. Ferro, J. Fontes, for the Cerebral Venous Thrombosis Portuguese Collaborative Study Group (VENOPORT). Long-Term Prognosis of Cerebral Vein and Dural Sinus Thrombosis. Results of the VENOPO- RT Study. Cerebrovasc Dis 2002; 13:272–8.
• 36.Strupp M et al. Cerebral venous thrombosis: correlation between recanalization and clinical outcome--a long-term follow-up of 40 patients. J Neurol. 2002 Aug; 249(8):1123-4.
• 37.Petzold A, Smith M. High intracranial pressure, brain herniation and death in cerebral venous thrombosis. Stroke. 2006 Feb; 37(2):331-2; author reply 332. Epub 2006 Jan 5.
• 38.Canhao P. Ferro JM et al. Causes and predictors of death in cerebral venous thrombosis. Stroke. 2005 Aug; 36(8):1720-5. Epub 2005 Jul 7.
• 39.Girot M, Ferro JM et al. Predictors of outcome in patients with cerebral venous thrombosis and intracerebral hemorrhage.Stroke. 2007 Feb; 38(2):337-42. Epub 2007 Jan 4.
• 40.José M. Ferro, MD, PhD; Patrícia Canhão, MD; Jan Stam, MD; Marie-Germaine Bousser, MD Fernando Barinagarrementeria, MD for the 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 Mar; 35(3):664-70. Epub 2004 Feb 19.
• 41.J.M. Ferro, M. Correia, M.J. Rosas, A.N. Pinto, G. Neves, for the Cerebral Venous Thrombosis Portuguese Collaborative Study Group (Venoport). Seizures in Cerebral Vein and Dural Sinus Thrombosis. Cerebrovac Dis. 2003; 15(1-2):78-83.
• 42.Nagaraja D, Sarma GR. Treatment of cerebral sinus/venous thrombosis. Neurol India 2002; 50:114-6.
• 43.De Bruijn SFTM, Stam J: For the cerebral venous sinus thrombosis study group: Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999; 30: 484-488.
• 44.C. Rottger, K. Madlener, M. Heil, T. Gerriets, M. Walberer, T. Wessels, G. Bachmann, M. Kaps, and E. Stolz. Is Heparin Treatment the Optimal Management for Cerebral Venous Thrombosis? Effect of Abciximab, Recombinant Tissue Plasminogen Activator, and Enoxaparin in Experimentally Induced Superior Sagittal Sinus Thrombosis. Stroke, April 1, 2005; 36(4): 841 - 846.
• 45.Canhão P, Falcão F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis. 2003; 15: 159–166.
• 46.Yang YH et al. Streptokinase in the treatment of venous sinus thrombosis: a case report. Kaohsiung J Med Sci. 2003 Aug; 19(8):421-7.