| OCR Text |
Show STATE OF THE ART Cerebral Venous Thrombosis Isabelle Crassard, MD and Marie- Germaine Bousser, MD Abstract: Cerebral venous thrombosis is an infrequent condition characterized by extreme variability in its clinical presentation and mode of onset. The combination of magnetic resonance imaging and magnetic resonance angiography is currently the best method for diagnosis. The proportion of cases of unknown etiology remains high. The prognosis, although better than previously thought, remains unpredictable. Treatment, which should be started as soon as the diagnosis is established, consists of reversing the underlying cause when known, control of seizures and intracranial hypertension, and the use of antithrombotics. Heparin should be the first- line antithrombotic agent. Recent studies have confirmed its safety even in patients with hemorrhagic parenchymal lesions. Local thrombolysis is indicated in the very rare cases that deteriorate despite adequate anticoagulation. Cerebrospinal fluid diversion or optic nerve fenestration is used for vision- threatening papilledema when intracranial pressure control is difficult. ( JNeuro- Ophthalmol 2004; 24: 156- 163) Cerebral venous thrombosis ( CVT), first described by Ribes ( 1) in 1825, was long thought to be a rare and severe disease responsible for alternating or bilateral focal deficits, seizures, and coma often leading to death. Diagnosis occurred only at autopsy. During the last 30 years, the rapid development of neuroimaging has contributed to a better understanding of CVT and to the recognition of its wide clinical spectrum. Heparin is the treatment of choice. The prognosis is usually good, but adverse outcomes occur unpredictably, justifying early diagnosis and rapid management. INCIDENCE The incidence of CVT is unknown but is certainly higher than thought on the basis of old autopsy series ( 2- 5). This supposition is supported by the recent publication of several large clinical series ( 6- 13). All age groups can be affected. There is, however, a small preponderance in Department of Neurology, Hopital Lariboisiere, Paris, France. Address correspondence to Marie- Germaine Bousser, MD, Department of Neurology, Hopital Lariboisiere, 2, rue Ambroise Pare 75475, Paris cedex 10, France; E- mail: mg. bousser@ lrb. ap- hop- paris. fr young women because of pregnancy, the puerperium, and the use of oral contraceptives. PATHOLOGY As in other venous territories, a red thrombus is progressively replaced by fibrous tissue, sometimes showing recanahzation. The effect of the thrombosis on cerebral tissue depends on the availability of collateral venous channels and on the propagation of the thrombus. The outcome can vary from no cerebral lesion, to edema of various degrees, to massive- often bilateral- hemorrhagic lesions called " venous infarcts." Cerebral infarcts are characterized macroscopically by pallor and edema of the cortex and of the adjacent white matter in the territory drained by a thrombosed vein. In addition, there are multiple petechial hemorrhages that may become confluent, especially in the white matter ( 2,14,15). These venous infarcts differ significantly from arterial infarcts in having more edema and less necrosis, explaining a much higher potential for recovery. DIAGNOSIS In contrast with arterial stroke, CVT can present with an extreme variety of symptoms, modes of onset, and clinical courses ( 14). This variability of clinical features depends on several factors, such as the site and extent of the thrombosis, the rate of propagation of the occlusion, the age of the patient, and the nature of the underlying disease. Thrombosis most often affects the superior sagittal sinus ( SSS), the lateral ( transverse) sinus ( LS) ( one or both) and cavernous sinus ( one or both). Thrombosis of the galenic system is less frequent. Thrombosis of petrosal sinuses or isolated cortical or cerebellar veins is rare but may be underdiagnosed because of the difficulty of recognizing its manifestations. Cavernous sinus thrombosis is a complication of infections of the face, nose, or orbits. Mode of Onset CVT is acute ( duration of fewer than two days) in 30%, subacute ( duration of two days to one month) in 50% of cases, and chronic in 20% ( duration of greater than 156 J Neuro- Ophthalmol, Vol. 24, No. 2, 2004 Cerebral Venous Thrombosis JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 one month). Occasionally, symptoms can progress over more than six months ( 6). Acute onset, often associated with focal signs, is typical of obstetrical and infectious CVT. Subacute or chronic onset is frequently observed in inflammatory diseases and in coagulation disorders ( 8,9). The chronic pattern of onset is typical of isolated intracranial hypertension ( ICH). Manifestations CVT is characterized by a wide variety of symptoms ( Table 1). Headache is the most frequent, occurring in over 80% of patients ( 14,16). It is also the most common inaugural symptom, present in 70% to 75% of patients before the onset of other neurologic manifestations. The headache of CVT has no specific features; it can be of any grade of severity, diffuse or localized, mostly persistent but also intermittent, sometimes occurring in attacks mimicking migraine. Its duration is usually a few days, but it may arise suddenly and be severe, mimicking subarachnoid hemorrhage. Headache can occur in the absence of any other neurologic signs, raising great diagnostic difficulties. Papilledema is present in approximately 50% of patients with CVT. It can be associated with bilateral transient visual obscurations. In the absence of treatment, papilledema can lead to optic atrophy. Seizures occur during the course of CVT in about 40% of patients ( 14); they may be partial or generalized. Focal sensory or motor signs occur in 30% to 80% of patients ( 14); alternation from one side of the body to the other is a highly suggestive but late pattern of presentation of SSS thrombosis. Other manifestations include aphasia, hemianopia, various cognitive disturbances, psychiatric disturbances, cranial nerve palsies, and cerebellar signs. Unilateral or bilateral sixth nerve palsy is frequent and secondary to intracranial hypertension. Some cranial nerve palsies are suggestive of a particular location: total ophthalmoplegia for cavernous sinus thrombosis; ninth and tenth nerve palsies for internal jugular vein thrombosis ( 17). Impaired mental status is present during the evolution of CVT in almost 50% of cases. It is, however, rarely an initial symptom ( 4% in Cantu series) ( 11). Usually moderate in degree, it is secondary to raised intracranial pressure, and associated with headache and seizures. Severely altered mental status can be a post- ictal event or a sign of deep venous system thrombosis ( 14). Patterns of Presentation Despite the diverse clinical manifestations and modes of onset, there are four main clinical patterns of CVT ( 8,14): 1. Focal deficits or partial seizures. If found in association with headaches, seizures, or altered consciousness, extremity weakness or sensory loss should immediately arouse suspicion for CVT. However, CVT may also manifest isolated seizures or isolated transient focal deficits, mimicking migrainous auras ( 18) or transient ischemic attacks. Acute persistent focal patterns of presentation mimic arterial strokes, while subacute manifestations mimic abscesses or tumors. 2. Isolated intracranial hypertension with headache, nausea, vomiting, papilledema, transient visual obscurations, and eventually sixth nerve palsy ( 8,9,14, 19- 21). CVT presenting as isolated ICH can be mistaken for idiopathic ICH if appropriate investigations are not performed. 3. Subacute diffuse encephalopathy, characterized by a decreased level of consciousness and sometimes seizures without clearly localizing signs or recognizable features of ICH. Such cases can mimic encephalitis or metabolic disorders ( 8,9,14). 4. Painful ophthalmoplegia caused by lesions of the third, fourth or sixth cranial nerves, chemosis and proptosis ( 2,22- 23) in patients with cavernous sinus thrombosis. In some cases, often because of the masking effect of an TABLE 1. Principal clinical manifestations in reported series of cerebral venous thrombosis Cantu and Barrinagarrementeria ( 11) Manifestations Headache Papilledema Focal deficit Seizures Altered consciousness Einhaupl et al ( n = 71) 91% 27% 66% 48% 56% ( 13) Puerperal CVT ( n = 67) 88% 40% 79% 60% 63% Nonpuerperal CVT ( n = 46) 70% 52% 76% 63% 59% Daifetal( 12) ( n = 40) 82% 80% 27% 10% 10% Authors' series* ( n = 200) 85% 52% 42% 41% 29% : Adapted with permission ( 14). 157 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Crassard and Bousser inadequate antibiotic regimen, cavernous sinus thrombosis can take a more indolent form with an isolated sixth nerve palsy, mild chemosis, andproptosis ( 22). Extension to other sinuses and stenosis of the intracavern-ous portion of the internal carotid arteries are particularly dreaded ( 22). Many other unusual manifestations have been reported, including subarachnoid hemorrhage simulating a ruptured intracranial aneurysm ( 16,24), recurrent transient neurologic deficits ( 8,9,25), migraine- like phenomena ( 18), hearing loss ( 17,26), isolated amnesia ( 27), confusion, and isolated psychiatric disturbances. These symptoms can be inaugural and are particularly misleading in the puerpe-rium, when they are often mistaken for postpartum psychosis ( 14,28). Finally, CVT can also be asymptomatic, particularly in the case of LS thrombosis, which can be found on a routine computed tomography ( CT) scan ( 29). Investigative Studies Computed Tomography CT of the brain, usually the first investigation performed on an emergency basis, is useful to rule out many of the conditions that can be mimicked by CVT. It can also show abnormalities suggestive of CVT ( 8- 12,14,29), such as the dense triangle ( occlusion of SSS by fresh clot on non-contrast CT), the empty delta sign ( filling of collateral veins in the SSS wall after contrast injection, contrasting with the absence of enhancement of the clot inside the thrombosed sinus), the cord sign ( visualization of a thrombosed cortical vein on non contrast CT), and a LS hyperdensity ( visualization of the thrombosed LS). Contrast CT scan can be useful in demonstrating cavernous sinus thrombosis as multiple irregular filling defects with bulging cavernous sinuses and enlarged orbital veins. Noncontrast CT can also detect such nonspecific changes as brain swelling, and localized hypodense or hy-perdense areas corresponding to " venous infarcts." Non-hemorrhagic infarcts are almost as frequent as hemorrhagic infarcts, which are often multifocal or petechial. In SSS thrombosis, they are seen superficially in the cerebral hemispheres. In deep venous system thrombosis, they are seen within the basal ganglia. Contrast CT may also reveal gyral or ring enhancement in areas of venous infarctions and tentorial enhancement. However, in up to 30% of cases, the CT is normal, particularly in patients with isolated intracranial hypertension. Other neuroradiologic investigations, such as magnetic resonance imaging ( MRI) and magnetic resonance angiography ( MRA), helical CT venography or conventional angiography, are frequently necessary to demonstrate abnormalities ( 8,9). They can confirm the diagnosis by showing the thrombosis and by precisely delineating its location. FIG. 1. Unenhanced axial CT shows left cerebral hemispheric hemorrhagic venous infarct caused by lateral ( transverse) venous sinus thrombosis. Magnetic Resonance Imaging and Magnetic Resonance Angiography MRI, in combination with MRA, is currently the modality of choice for the diagnosis and follow- up of CVT ( 8,9,14,30- 32) ( Figs. 2 and 3). The advantage of MRI is direct visualization of the clot in the sinus ( Fig. 2). It can also show the associated cerebral lesions. The clot can have different appearances based on the duration of the thrombosis. At a very early stage (< five days), the occluded vessels appear isointense on Tl MRI and hypointense on T2 MRI. This is the only time when MRI gives a false negative result. It can be corrected with MRA, which shows the missing sinus. A few days later, the flow void is absent and the thrombus becomes hyperintense, first on Tl and later on T2 MRI. This change corresponds to the conversion in the thrombus of oxyhemoglobin to methemoglobin. It occurs on or about day five after the onset of symptoms and lasts until day 30 to 35. After the first month, MRI patterns are variable because the thrombosed sinus can either remain totally or partially occluded or can recanalize and return to normal. In the majority of cases, there is an isointensity on Tl and hyperintensity on T2 MRI. At six months, abnormalities persist in about two- thirds of cases. The signal is then often heterogeneous but predominantly isointense on Tl MRI and isointense or hyperintense on T2 MRI. 158 © 2004 Lippincott Williams & Wilkins Cerebral Venous Thrombosis JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 FIG. 2. T2 coronal MRI shows increased signal in superior sagittal sinus { thin arrow) with left cerebral hemispheric infarct { thick arrow). The interpretation of MRI is usually straightforward, particularly when the thrombosed sinus is hyperintense both on Tl and T2 images and on different slices. However, in some cases, false- negative and false- positive images occur. False- negatives are rare and represent acute thrombosis studied during the very early stage, thrombosis of isolated cortical veins, and partial recanalization of the sinus. In these cases, MRA is indispensable in showing the absence of flow in the affected sinus ( Fig. 3). False positives occur when there is a slow flow of blood without thrombosis. To differentiate flow artifacts from a thrombus, time- of- flight techniques are useful. MRI is also useful in showing the parenchymal lesions secondary to venous occlusion, including brain swelling with normal signal, edema or infarction with hy-pointense, or isointense signal on Tl MRI and hyperintense signal on T2 MRI, or hemorrhagic infarct with hyperintense signal on both sequences ( 33). Diffusion- weighted imaging ( DWI) ( 34- 3 8) shows a pattern highly different from that of arterial infarcts, usually a heterogeneous signal intensity with normal or increased apparent diffusion coefficient ( ADC), signifying vasogenic edema combined with some areas of cytotoxic edema. Another pattern consists of multifocal increased signal with moderately decreased ADC; this signal pattern predicts a low likelihood infarction compared with that which follows arterial occlusion. In a third pattern, there is no abnormality on DWI. Thus, the DWI/ ADC pattern of brain lesions in CVT is highly heterogeneous, mostly suggestive of vasogenic edema and markedly different from that of arterial infarcts. This difference probably corresponds in part to the much better recovery observed in venous occlusion than in arterial occlusion. Helical Computed Tomography Venography Helical CT venography has recently been developed as an excellent tool to detect CVT ( 39). Frequent abnormalities obtained in the case of CVT are filling defects, sinus wall enhancement, abnormal collateral venous drainage, and tentorial enhancement. CT venograms may be easier to interpret and have fewer artifacts than MRA. They may be especially helpful in the very acute or late stages of CVT, when MRI can be misleading. Conventional ( Catheter) Arteriography Conventional arteriography has been the key procedure in diagnosis of CVT for many years and is still necessary in cases of diagnostic difficulty such as cortical vein thrombosis ( 14,25,30,40). It requires four- vessel injection FIG. 3. 2D Time- of- Flight coronal magnetic resonance angiogram ( MRA) shows absence of signal in right lateral ( transverse) and sigmoid venous sinuses suggesting thrombosis. 159 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Crassard and Bousser with visualization of the entire venous phase. The most reliable sign of CVT is the partial or complete lack of filling of veins or sinuses ( Fig. 4). Some indirect signs include dilated collateral veins with a corkscrew appearance, delayed venous emptying, and dilated collateral circulation. Some locations can be difficult to interpret such as the anterior third of the SSS and the left LS, which may be hypoplastic. Lumbar Puncture Lumbar puncture remains useful to measure intracranial pressure and as a means to decrease it if it is elevated and threatening vision. The cerebrospinal fluid ( CSF) formula is often abnormal, with an elevated protein level ( 50%), excessive red blood cells ( 60%), or leukocytosis ( 30%) ( 14). CSF analysis may also be crucial to rule out meningitis. CAUSES OF CVT CVT can occur in a great variety of causes and underlying conditions. ( Table 2) ( 14). Septic Cerebral Venous Thrombosis The incidence of septic CVT has been considerably reduced in developed countries since the introduction of antibiotics with only 10% of CVT currently attributed to infection ( 22,41). Septic CVT is usually caused by a contiguous propagation from infection of the ethmoid, sphenoid, or mastoid sinuses, or to hematogenous spread from the nose, ear, face, or neck. Purulent meningitis can also be a cause FIG. 4. Conventional ( catheter) arteriogram shows no dye in a superior sagittal venous sinus suggesting thrombosis. 160 TABLE 2. Recognized noninfectious settings for cerebral venous thrombosis Focal Head or neck tumors compressing cerebral venous drainage pathway ( cholesteatoma, meningioma, metastasis, jugular tumors) Occlusion of the internal jugular vein After head injury After neurosurgery After lumbar puncture, epidural, or spinal anesthesia Systemic General surgery Pregnancy Puerperium Oral contraceptive use Cardiac insufficiency Nephrotic syndrome Severe dehydration Systemic malignancy ( especially visceral carcinoma, lymphoma, leukemia) Inherited thrombophilia ( especially antithrombin III, protein C, or protein S deficiency, factor V Leiden and prothrombin gene mutations, hyperhomocysteinemia, antiphospholipid antibodies, disorders of fibrinolysis, sickle cell disease, paroxysmal nocturnal hemoglobinuria) Acquired prothrombotic state ( disseminated intravascular coagulation, thrombotic thrombocytopenica, heparin-induced purpura, cryofibrinogenemia, hyperviscosity, myeloproliferative disorders) Polycythemia ( vera and secondary) Thrombocythemia ( primary or secondary) Anemia Hepatic cirrhosis, Crohn disease, ulcerative colitis Vasculitis ( systemic lupus erythematosus, Behcet disease, Wegener granulomatosis, giant cell arteritis) Sarcoidosis Medications ( especially corticosteroids, L asparaginase, epsilon- aminocaproic acid) or consequence of CVT. A more distant focus is exceptional ( 41). Puerperal Cerebral Venous Thrombosis In young women, CVT occurs more frequently during the puerperium than in pregnancy and remains very common in developing countries. Oral Contraceptive- associated Cerebral Venous Thrombosis Oral contraceptive ( OC) use is an important cause among women with CVT in developed countries. OC can © 2004 Lippincott Williams & Wilkins Cerebral Venous Thrombosis JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 also be associated with congenital thrombophilia, reinforcing the need for an extensive coagulation work- up. Hypercoagulability- associated Cerebral Venous Thrombosis Among the numerous noninfective medical conditions related to CVT, congenital thrombophilia is the most frequent, particularly the increased resistance to activated protein C with factor V Leiden mutation and the 20210 G to A mutation of the prothrombin gene. It is preferable to perform the coagulation work- up before starting anticoagulation because heparin and warfarin preclude the diagnosis of antithrombin, protein S and C deficiencies or the lupus anticoagulant. There is frequently an association among several thrombophilic abnormalities, which stresses the importance of a complete coagulation work- up even in the presence of another obvious cause or risk factor. Idiopathic Cerebral Venous Thrombosis Despite the continuing description of new causes, the proportion of cases of unknown etiology remains between 20% and 35%> in recent series. In these cases, a long follow-up is warranted since it can lead to the identification of an underlying cause, most often a systemic disease ( 6). OUTCOME AND PROGNOSIS Before the introduction of angiography, CVT was mainly diagnosed at autopsy and thought to be lethal. In recent series, the rate of mortality appears to be lower- between 6%> and 33%> ( 6,8,9,14,42). The main causes of death are the brain lesion itself ( especially in massive brain hemorrhagic infarct), uncontrolled seizures, sepsis, pulmonary embolism, underlying infection, or malignancy. Factors associated with a bad prognosis include the extreme age of the patient, a rapid onset, the presence of focal symptoms, altered consciousness, and hemorrhagic infarct ( 4). Thrombosis in the deep cerebral and cerebellar venous system carries a much higher morbidity than thrombosis in a dural sinus or cortical vein ( 14). Among the underlying conditions, the prognosis of septic CVT is worse than that of nonseptic CVT. In one series ( 41), the mortality was almost 80%> in patients with septic thrombosis of the SSS. In another series ( 43), mortality was 30% in septic cavernous sinus thrombosis. In yet another series ( 22), mortality was 50%> if the cortical veins were affected. By contrast, postpartum CVT usually has a good prognosis, with a survival of 90%> in most recent series ( 14). It has long been recognized that if survival occurs in CVT, the prognosis for recovery of function is much better that in arterial thrombosis. In recent series ( 8- 12,14), patients with CVT have recovered completely in52% o to 76% o of cases. However, the prognosis remains largely unpredictable. Indeed, some cases have a catastrophic course leading to death in a few days. By contrast, there are benign ( probably under- recognized) forms limited to headache, transient neurologic deficits, or epilepsy. Unlike arterial stroke, few patients are left with disabling consequences. Affecting about 15% of patients ( 8- 12,14), these consequences consist of focal weakness or sensory loss, neuropsychologic disturbances, and visual loss. In patients with papilledema, visual loss may be insidious and should be systematically monitored with regular neuro- ophthalmologic evaluations. The long- term outcome of CVT is not well known. Residual epilepsy has been reported usually during the first year in 10% to 30% o of the patients who had seizures during the acute phase. Some reports have suggested that LS thrombosis can induce arteriovenous malformations ( 14). Recurrence of CVT was estimated at 11.7% in a recent series of 77 patients followed for a mean of 77.8 months ( 44). TREATMENT Treatment of CVT, which remains controversial because the natural history of this condition is so variable, is aimed at the underlying cause, its manifestations ( seizures, elevated intracranial pressure, and headaches), and at containing or dissolving the thrombus. Treatment of the Underlying Cause This is particularly indicated in the case of septic CVT, which requires prompt and specific antibiotic therapy. In some cases, surgical treatment of the primary site of infection must be considered. Treatment of underlying malignancies or connective tissue disease should also be initiated. Treatment of Manifestations Anticonvulsants are required in patients with seizures but need not be prescribed prophylactically ( 8). The appropriate duration of treatment is unsettled. To relieve elevated intracranial pressure, heparin is often sufficient to improve venous outflow. In patients with isolated ICH, if papilledema threatens vision, we favor lumbar puncture to remove CSF before starting heparin. This is often followed by a rapid improvement in headache and improvement of the patient's visual function. In more severe ICH, intracranial pressure- lowering agents such as acet-azolamide, glycerol, or mannitol may be used. The use of corticosteroids is controversial because of the potential inhibition of the fibrinolysis. If vision continues to worsen, lumbar puncture may be repeated. Eventually, lumboperitoneal or ventriculoperi-toneal shunt or optic nerve sheath fenestration may be performed. In the rare cases of worsening of consciousness with raised intracranial pressure resistant to all previous 161 JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 Crassard and Bousser treatments, ventriculostomy, lumbar CSF drainage, lateral venous bypass, and even craniectomy decompression have been used. Treatment of Thrombosis Heparin is the first- line agent. Its goal is to limit the spread of thrombus and thus to diminish the intracapillary pressure. Its use has been disputed because of the fear of an increased risk of intracerebral hemorrhage. However, there is now good evidence that heparin is safe in CVT, even in patients with hemorrhagic infarcts ( 14,45- 47). Two randomized trials ( 46,47) have assessed the benefits and risks of heparin. The first trial ( 46) compared dose- adjusted intravenous heparin with placebo and was stopped after the inclusion of 22 patients because of a significant difference between the two groups. Eight heparin- treated patients fully recovered whereas only one placebo- treated patient did. No deaths occurred in the heparin group, but three occurred in the placebo group. The second trial ( 47) compared low-molecular- weight ( LMW) heparin with placebo in 60 patients. There were no significant differences in adverse outcomes, defined as death or a Barthel index score greater than 15 at 12 weeks ( 13% in the LMW heparin and 21% in the placebo group). New or enlarged cerebral hemorrhages did not occur even in the 15 patients with hemorrhagic infarcts on initial CT. A meta- analysis of these two studies ( 47) has shown that heparin treatment is associated with a 14% absolute risk reduction ( ARR) in mortality and a 15% ARR in death or dependency, with relative risk reductions of 70% and 56% o, respectively. Though not quite statistically significant, these results favor heparin treatment. Heparin treatment is recommended in all forms of CVT, even in cases of isolated ICH to prevent the onset of neurologic deficits because of extension of the thrombus into the cerebral veins ( 21). Because it is impossible to predict which patients will have such an extension, heparin is recommended in all varieties of CVT. The optimal duration of heparin is not established, but with the advent of neurologic improvement, heparin therapy is switched over to oral anticoagulation ( warfarin) adjusted to maintain an international normalized ratio ( INR) between two and three. As in deep vein thrombosis of the legs, the usual duration of treatment is six months in the absence of underlying conditions ( Behget disease, systemic lupus erythematosus with circulating anticoagulant, high- risk congenital thrombophilia) requiring long- term treatment. The evidence in favor of the efficacy of endovascular thrombolysis remains inconclusive. Urokinase was first reported in treatment of CVT in 1971 ( 48), but to date there are no prospective, randomized, controlled trials of endovascular thrombolysis in CVT. There are some uncontrolled cases ( 49) and a retrospective analysis of the effects of urokinase ( 50) administered by the internal jugular or the femoral route to approximately 50 patients. More recently, local recombinant tissue plasminogen activator ( rtPA) has been used in combination with heparin ( 51,52). Although both treatments carry a risk of hemorrhagic complications ( bleeding at the femoral puncture site, pelvic bleeding, worsening of intracranial bleeding), local thrombolysis appears safe in the absence of a hemorrhagic brain lesion. However, there is no good reason to use local thrombolysis as long as heparin seems to be working and the patient is improving, which is the case in the vast majority of patients. Thus, on the basis of the present data, there is no evidence to recommend local thrombolysis as first- line treatment ( 53). Local thrombolysis may be indicated if the condition of the patient worsens despite adequate anticoagulation ( biologically verified) and other causes of worsening have been ruled out. This approach applies to patients with focal neurologic symptoms and signs due to a progressing thrombosis and not to patients with isolated ICH, who should be treated with CSF diversion or optic nerve sheath fenestration. Some patients who are refractory to anticoagulant therapy have undergone mechanical endovascular thrombectomy with or without stenting ( 54) or have had surgical thrombectomy. Still experimental, such techniques are generally performed only in highly specialized centers and only in the very few patients who have an unusually deleterious course. REFERENCES 1. Ribes MF. Des recherches faites sur la phlebite. Revue Medicale Franchise et Etrangere et Journal de Clinique de l'Hotel- Dieu et de la Charite de Paris. 1825; 3: 5- 41. 2. Garcin R, Pestel M. Thrombophlebites Cerebrates. Paris: Masson et Cie; 1949. 3. Bamett HJ, Hyland HH. Non- infective intracranial venous thrombosis. Brain 1953; 76: 36- 49. 4. Kalbag RM, Wolf AL. Cerebral Venous Thrombosis, vol 1. London: Oxford University Press; 1967. 5. Ehlers H, Courville CB. Thrombosis of internal cerebral veins in infancy and childhood. Review of literature and report of five cases. JPediatr 1936; 8: 600- 23. 6. Bousser MG, Chiras J, Bories J, et al. Cerebral venous thrombosis. A review of 38 cases. Stroke 1985; 16: 199- 213. 7. Milandre L, Gueriot C, Girard N, et al. Les thromboses veineuses cerebrales de l'adulte. Ann Medlnt 1988; 139: 544- 54. 8. Ameri A, Bousser MG. Cerebral venous thrombosis. Neurol Clin 1992; 10: 87- 111. 9. Biousse V, Bousser MG. Cerebral venous thrombosis. TheNeurolo-gistf 1999; 5: 236^ 19. 10. DeVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345: 417- 23. 11. Cantu C, Barinagarrementaria F. Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 1993; 24: 1880^ 1. 12. Daif A, Awada A, Al- Rajeh S, et al. Cerebral venous thrombosis in adults: a study of 40 cases from Saudi Arabia. Stroke 1995; 26: 1193- 5. 13. Einhaupl KM, Masuhr F. Cerebral venous and sinus thrombosis: an update. Eur J Neurol 1994; 1: 109- 26. 14. Bousser MG, Russell RR. Cerebral Venous Thrombosis. London: WB Saunders; 1997. 162 © 2004 Lippincott Williams & Wilkins Cerebral Venous Thrombosis JNeuro- Ophthalmol, Vol. 24, No. 2, 2004 15. Hacker H. Normal supratentorial veins and dural sinuses. In Newton TH, Potts DG, editor( s). Radiology of the skull and brain, vol 2. Angiography. St Louis: CV Mosby, 1974: 1851- 77. 16. Ameri A, Bousser MG. Cerebral venous thrombosis. In Olesen J, Tfelt- Hansen P, Welch KM editor( s). The Headaches. New York: Raven Press, 1993: 671- 3. 17. Kuehnen J, Schwartz A, Neff W, et al. Cranial nerve syndrome in thrombosis of the transverse/ sigmoid sinuses. Brain 1998; 121: 381- 8. 18. Newman DS, Levine SR, Curtis VL, et al. Migraine- like visual phenomena associated with cerebral venous thrombosis. Headache 1989; 29: 82- 5. 19. Purvin VA, Trobe JD, Kosmorsky G. Neuro- ophthalmic features of cerebral venous obstruction. Arch Ophthalmol 1995; 52: 880- 5. 20. Tehindrazanarivelo A, Evrard S, Schaison M, et al. Prospective study of cerebral venous thrombosis in patients presenting with benign intracranial hypertension. Cerebrovasc Dis 1992; 2: 22- 7. 21. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology 1999; 53: 1537^ 12. 22. Dinubile MJ. Septic thrombosis of the cavernous sinuses. Arch Neurol 1988; 45: 567- 72. 23. Levine SR, Twyman RE, Gilman S. The role of anticoagulation in cavernous sinus thrombosis. Neurology 1988; 38: 517- 22. 24. De Bruijn SF, Stam J, Kappelle LJ. Thunderclap headache as first symptom of cerebral venous thrombosis. Lancet 1996; 348: 1623- 5. 25. Park DC, Sohn YH. Lee PH. Neurologic deficits with isolated cortical venous congestion. Neurology 1999; 52: 671- 2. 26. Crassard I, Biousse V, Bousser MG, et al. Hearing loss revealing lateral sinus thrombosis in a patient with factor V Leiden mutation. Stroke 1997; 28: 867- 7. 27. Forderreuther S, Straube A, Yousry TA. Amnestic episode caused by thrombosis of internal cerebral veins. Eur J Neurol 1997; 4: 512- 4. 28. Ruel M, Montfort JC, Pinta P. Symptomatologie trompeuse des thrombophlebites cerebrales au cours de la grossesse et du postpartum. PresseMed 1986; 15: 1367- 8. 29. Goldberg AL, Rosenbaum AE, Wang H, et al. Computed tomography of dural sinus thrombosis. J Comput Assist Tomogr 1986; 10: 16- 20. 30. Perkin GD. Cerebral venous thrombosis: Developments in imaging and treatment. J Neurol Neurosurg Psychiatry 1995; 59: 1- 3. 31. Padayachee TS, Bingham JB, Graves MJ, et al. Dural sinus thrombosis: diagnosis and follow- up by magnetic resonance angiography and imaging. Neuroradiology 1991; 33: 165- 7. 32. Mattle HP, Wentz KU, Edelman RR, et al. Cerebral venography with MR. Radiology 1991; 178: 453- 8. 33. Yuh WT, Simonson TM, Wang AM, et al. Venous sinus occlusive disease: MRI findings. Am JNeuroradiol 1994; 15: 309- 16. 34. Corvol JC, Oppenheim C, Manai R, et al. Diffusion- weighted magnetic resonance imaging in a case of a cerebral venous thrombosis. Stroke 1998; 29: 2649- 52. 35. Keller E, Flacke S, Urbach H, et al. Diffusion and perfusion-weighted magnetic resonance imaging in deep cerebral venous thrombosis. Stroke 1999; 30: 1144- 6. 36. Ducreux D, Oppenheim C, Vandamme W, et al. Diffusion-weighted imaging patterns of brain damage associated with cerebral venous thrombosis. Am J Neuroradiol 2001; 22: 261- 8. 37. Chu K, Kang DW, Yoon BW et al. Diffusion- weighted magnetic resonance in cerebral venous thrombosis. Arch Neurol 2001 ; 58: 1569- 76. 38. Forbes KP, Pipe JG, Heiserman JE. Evidence for cytotoxic edema in the pathogenesis of cerebral venous infarction. Am J Neuroradiol 2001; 57: 450- 5. 39. Casey SO, Alberico RA, Patel M. Cerebral CT venography. Radiology 1996; 198: 163- 70. 40. Jacobs K, Moulin T, Bogousslavsky J, et al. The stroke syndrome of cortical vein thrombosis. Neurology 1996; 47: 376- 82. 41. Southwick FS, Richardson EP Jr, Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine 1986; 65: 82- 106. 42. Thron A, Wessel K, Linden D, et al. Superior sagittal sinus thrombosis: neuroradiological evaluation and clinical findings. J Neurol 1986; 233: 283- 8. 43. Bharucha NE, Bharucha EP, Bhabba SK. Bacterial infections. In Bradley, WG, Daroff RB, Fenichel GM, Marsden CD, eds. Neurology in Clinical Practice. Butterworth- Heinemann, Boston. 1996: 1181- 243. 44. Preter M, Tzourio C, Ameri A, et al. Long- term prognosis in cerebral venous thrombosis. Follow- up of 77 patients. Stroke 1996; 27: 243- 6. 45. Easton JD, Bousser MG, Stam J. Treatment of cerebral venous thrombosis. Cerebrovasc Dis 1993; 3: 329- 32. 46. Einhaupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet 1991; 338: 597- 600. 47. De Bruijn SF, Stam J. Randomized placebo controlled trial of anticoagulant treatment with low molecular weight heparin for cerebral sinus thrombosis. Stroke 1999; 30: 484- 8. 48. Vines FS, Davis DO. Clinical radiological correlation in cerebral venous occlusive disease. Radiology 1971; 98: 9- 22. 49. Di Rocco C, Ianelli A, Leone G, et al. Heparin- urokinase treatment in aseptic dural sinus thrombosis. Arch Neurol 1981; 38: 431- 5. 50. Smith TP, Higashida RT, Barnwell SL, et al. Treatment of dural sinus thrombosis by urokinase infusion. Am J Neuroradiol 1994; 15: 801- 7. 51. Kim S Y, Suh JH. Direct endovascular thrombolytic therapy for dural sinus thrombosis: infusion of alteplase. Am J Neuroradiol 1997: 18: 639- 45. 52. Frey JL, Muro GJ, McDougall CG, et al. Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin. Stroke 1999; 30: 489- 94. 53. Bousser MG. Cerebral venous thrombosis: nothing, heparin or local thrombolysis? Stroke 1999; 30: 481- 3. 54. Dowd CF, Malek AM, Phatouros CC, et al. Application of a rheolytic thrombectomy device in the treatment of dural sinus thrombosis: a new technique. Am J Neuroradiol 1999; 20: 568- 70. 163 |
