18 Veno-Occlusive Disorders
Armin Thron and Michael Mull
A. Thron, MD; M. Mull, MD
Department of Neuroradiology, Clinic for Diagnostic Radiology, University Hospital of the Technical University, Pauwelsstr. 30, 52074 Aachen, Germany
CONTENTS
18.1 Introduction 269
18.2 Etiology and Risk Factors 269 18.3 Clinical Features and Typical Symptom Combinations 269
18.3.5 Treatment 270 18.4 Imaging 270
18.4.1 Magnetic Resonance Imaging and Magnetic Resonance Angiography 273 18.4.2 Diagnostic Problems, Potential Artefacts and Pitfalls 282
References 283
18.1
Introduction
Veno-occlusive disorders of the brain may affect the dural sinuses, the superficial cortical veins and the deep venous system. Occlusion may be due to aseptic or septic thrombosis, to stenoses of the large sinuses at the base of the skull of different origin and to tumors compressing or infiltrating the sinus wall, especially meningiomas. Impaired venous drainage results in venous congestion or congestive infarction which can be accompanied by hemorrhage. Arteriov- enous shunting in case of dural arteriovenous fistulas or arteriovenous malformations may have a similar clinical effect. In general practice, cerebral venous and sinus thrombosis (CVST) play the most impor- tant role in the group of veno-occlusive diseases.
18.2
Etiology and Risk Factors
Several etiological factors are known to cause CVST, although no specific cause for CVST can be found in about 25% of all cases (Deschiens et al. 1996).
One has to differentiate between aseptic CVST as the most common form, septic venous and sinus throm- bosis, tumor-induced and trauma-induced CVST.
Disease processes that may cause aseptic CVST include hypercoagulopathic states such as those present in polycythemia vera, sickle cell disease, deficiencies of fibrinolytic factors (antithrombin III, protein C, protein S) or disseminated intravascular coagulopathy (Deschiens et al. 1996). Oral con- traceptives, pregnancy, and puerperium are also known risk factors for developing an aseptic CVST (Cantu and Barinagarrementeria 1993). In addition, systemic malignancies with paraneoplas- tic syndromes, lupus erythematodes, drug abuse or low flow situations as present during dehydration or shock may cause CVST. Septic causes are most often encountered in childhood with a chronic or acute mastoiditis involving the neighbouring trans- verse or sigmoid sinus (Isensee et al. 1992a; Reul et al. 1997). Meningitis, brain abscesses or septicemia are, however, more seldom causes of septic CVST.
Concerning tumor induced CVST, meningiomas are prone to obliterate the lumen of the dural sinuses;
however, this process evolves slowly over time, therefore, venous collaterals are often present and an acute venous congestion is the exception rather than the rule. Apart from meningiomas other tumor entities only rarely infiltrate the dural sinus walls.
CVST caused by trauma is also rather rare; however, fractures that lead to a laceration of the dural wall might cause a venous occlusion.
18.3
Clinical Features and Typical Symptom Combinations
CVST generally shows a subacute onset and course
of symptoms. Clinical symptomatology is depend-
ant on the cause, localization, extension and time
of development of the venous occlusion. The lead-
ing symptom is headache in 70%-90% of all cases
(Strupp et al. 2003), often associated with nausea and vomiting (Thron et al. 1986). But the spectrum of symptoms and signs varies between an asympto- matic course and rapidly progressive neurological deficits and impaired consciousness.
In asymptomatic cases, the occlusion of an iso- lated sinus is typically compensated by collaterals or in case of the transverse sinus by a contralateral sinus of adequate size (Thron 2001).
Idiopathic intracranial hypertension (synonyms:
benign intracranial hypertension, pseudotumor cerebri syndrome) is characterized by increased CSF pressure (> 250 mm H
2O) in the absence of an intracranial space occupying lesion or inflammation. About 30%-50% of CVST-patients present with this syndrome (Thron et al. 1986). They complain of headache and have papille- dema or other symptoms and signs of increased intrac- ranial pressure. In most of these cases a main venous channel is occluded and drainage of the brain depends on smaller sinuses or veins. An example of this situa- tion is the unilateral occlusion of the dominant trans- verse sinus. The collateral drainage is poor, but suffi- cient to prevent focal lesions. Recently, advanced MRA techniques have provided evidence that focal sten- otic lesions in the transverse sinuses (or comparable venous outflow obstructions of non-thrombotic origin) may be another frequent cause of this syndrome (see Fig. 17.2c-e; Higgins et al. 2002, 2004; Farb et al. 2003) Using more invasive techniques, pressure gradients could be measured in a part of these patients. The rela- tionship between these focal stenoses and the increased intracranial pressure remains to be clarified.
Neurological deficits and seizures occur in the group of patients in whom focal congestive and hemorrhagic lesions occur. The stroke-like symp- toms depend on the localization of the brain damage and may be accompanied by seizures (Thron et al.
1986; Strupp et al. 2003). In these cases extension of the thrombus in cortical veins has occurred or the collateral drainage for a distinct area of the brain parenchyma is not sufficient. A typical example of this is the occlusion of a transverse sinus together with the vein of Labbé (see Fig. 18.8; Isensee et al.
1992b). Focal sensorimotor deficits and/or seizures are also the clinical feature of the solitary thrombo- sis of a superficial cerebral vein which in our expe- rience is rare. This entity may be accompanied by a cortical subarachnoid hemorrhage.
Impaired consciousness and coma may develop with increasing intracranial pressure.
A decrease in mental status, drowsiness, progres- sive confusion and impaired consciousness may also be the major symptoms of deep cerebral venous
thrombosis (Ameri and Bousser 1992; Crawford et al. 1995). Drainage impairment affects mainly the thalamus uni- or bilaterally with venous congestion and/or bleeding (Lafitte et al. 1999) (see Fig. 18.6).
Thrombosis of the cavernous sinus is character- ized by proptosis, chemosis, impaired vision and ophthalmoplegia. If it is not septic, prognosis is good because of collateral drainage and spontane- ous recanalization. The same symptoms, with the exception of a possible bruit, may result from arte- riovenous shunting in carotid-cavernous fistulae.
The treatment of choice in this case is endovascular occlusion (thrombosis!) of the cavernous sinus.
The prognosis of extensive CVST is unpredictable and variable. The 5%-30% mortality of CVST still reported in studies between 1991 and 1999 (Strupp et al. 2003) has significantly dropped. In our experience early diagnosis with noninvasive techniques of MRI and MRA has an important influence on prognosis.
Early diagnosis, however, can only be achieved if radiologists contribute to the identification of the subset of patients complaining of headache and who have this potentially life-threatening disease which requires immediate therapy. They need to know the clinical background, be aware of suspect findings in routine MRI and should know the advantages and potential pitfalls and limitations of different MRA techniques and flow-sensitive sequences.
18.3.5 Treatment
Typically, patients with confirmed CVST are treated with intravenous heparin even in the presence of intracerebral hemorrhage. Although there is only one placebo-controlled, double-blind study show- ing a significant advantage of intravenous dose- adjusted unfractionated heparin therapy in patients with CVST (Einhäupl et al. 1991), heparin as the first-line treatment is recommended because of its efficacy, safety and feasibility (Ameri and Bousser 1992; Bousser 1999). Only in rare cases may fibri- nolytic therapy or thrombectomy be considered as alternative treatment options.
18.4 Imaging
To interpret imaging, it is necessary to know the
normal anatomy of the cerebral venous system and
to transfer this knowledge to the transversal cuts of the axial cranial CT (CCT) and MRI or to 3D recon- structions of the blood vessels. Moreover, the most important anatomical variants of the dural sinuses must be readily perceived. The normal venous angi- ogram as detected by digital subtraction angiogra- phy (DSA) and MRI is illustrated in Figs. 18.1 and 18.2a,b.
Frequently encountered anatomical variants include (Thron 2001):
• The unilateral hypoplastic transverse and sig- moid sinus with compensation via the contralat- eral transverse sinus.
• The aplasia of the frontal superior sagittal sinus anterior to the coronary suture with compensa- tion via large bridging veins.
• The high division of the superior sagittal sinus (cranial to the internal occipital protuberance, where the confl uens sinuum is normally encoun- tered).
• Pacchioni granulations may be seen as circum- script intraluminal fi lling defects or gaps.
Fig. 18.1. Venous anatomy in digital subtraction angiography (DSA) in lateral projection. FV, frontal veins; PV, parietal veins;
OV, occipital veins; SSS, superior sagittal sinus; ISS, inferior sag-
ittal sinus; TS, transverse sinus; SIS, sigmoid sinus; IJV, internal jugular vein; SS, straight sinus; CS, confl uens sinuum; VL, vein of Labbé; SV, sylvian vein; CS, cavernous sinus; VG, vein of Galen;
ICV, internal cerebral vein; IJV, internal jugular vein
Fig. 18.2. a,b Normal venous anomaly in a 3D phase contrast venous angiogram performed at 1.5 T. c,d 3D phase contrast venous angiogram in a patient with idiopathic intracranial hypertension displayed in different projections. The bilateral short sten- oses (arrows) are well shown by MR venography. e digital subtraction angiogram in an oblique projection. Confi rmation of the obstructed vessel lumen on both sides (arrows), but the fi nding at this location can only be demonstrated on special projections
a b
c d e
Although this book is primarily devoted to mag- netic resonance imaging, a brief description of cra- nial computed tomographic findings in CVST seems to be reasonable since we have learned from CCT that in imaging of brain parenchyma and cerebral veins we have to differentiate between direct and indirect signs of CVST. The direct signs prove the diagnosis by demonstrating thrombus or missing flow within a dural sinus or pial vein, the indirect signs simply raise the suspicion of CVST by demonstrating dif- ferent forms of venous congestion (Chiras et al.
1985).
In CCT direct signs include the hyperdense sinus in the non-contrast-enhanced scan, the “cord sign”
(hyperdense bridging vein) and the “empty triangle sign” in the contrast-enhanced CCT (Virapongse et al. 1987) (see Fig. 18.10). Within the first 2 weeks, thrombosed blood is typically hyperdense on CCT compared to brain parenchyma. Therefore, it is important to start with a non-enhanced CCT scan in patients with suspected CVST (Thron 2001). The density of the thrombus might otherwise be mis- taken for a contrast-enhanced vessel lumen. After 2 weeks the thrombus will have become isodense or
hypodense to the brain parenchyma. Now the diag- nosis can be made following the injection of contrast media which will show the thrombus as a filling defect of the lumen surrounded by either residual contrast-enhanced blood, the contrast enhancing meningeal wall or collateral venous channels out- side the dura. This constitutes the empty triangle or empty delta sign on contrast enhanced CCT in a later stage of thrombus evolution.
Indirect signs include global and focal brain edema (see Figs. 18.6, 18.8, 18.9), intraparenchy- mal hemorrhages that might be solitary or multiple (Fig. 18.3) involving both grey and (preferentially) white matter and intense tentorial enhancement.
Concerning the edema that is demonstrated as a hypodense area, the form and localization will typi- cally not correspond to the classical arterial terri- tories (see Fig. 18.8). Hemorrhages will also not suit the typical localization of parenchymal hyper- tensive bleeds but instead typically also expand to the cortical surface. The tentorium and the falx will appear thickened, engorged and will demon- strate pronounced enhancement that is due to dural venous collaterals.
Fig. 18.3a–e. Signal intensity of the thrombus and hemorrhage at dif- ferent stages of disease evolution. a T1-weighted image in the acute stage of CVST (< 3 days). Both hemorrhage (small arrows) and thrombus in the superior sagittal sinus appear iso- /hypointense. b Proton density image in the acute stage of CVST with hypointensity of hemorrhage (small
arrows) and fresh thrombus (arrow).c–e In the subacute stages of CVST (> 3 days) the thrombus develops a hyperintense appearance on T1- weighted and T2-weighted images.
(Compare with Table 18.1)
a b
c d e
18.4.1
Magnetic Resonance Imaging and Magnetic Resonance Angiography
The combination of these two MR techniques has become the imaging modality of first choice for the diagnosis and follow-up of CVST (Villringer et al. 1989; Vogel et al. 1994). MRI alone faces the problem that the MR signal of blood and blood products varies with clot age as is shown in Table 18.1 (Gomori et al. 1985). Therefore, a dif- ferent appearance of a thrombosed vein in T1 and T2 sequences during different stages of thrombus evolution has to be taken into account (Isensee et al. 1994). The very fresh blood clot may be hyper- intense in T1- and hypointense in T2-weighted images during the first 12 h. In this very early phase it is very unlikely that patients with CVST are symptomatic and undergo diagnostic proce- dures. Afterwards the oxyhemoglobin of the acute thrombus has changed to deoxyhemoglobin which is iso- to slightly hypointense to cortex on T1- weighted sequences with a hypointense signal in T2-weighted images (12 h-3 days). Late acute clots (3-7 days) contain intracellular methemoglobin and are hyperintense on T1-weighted sequences and hypointense on T2-weighted images. Suba- cute thrombi (1-4 weeks after initial thrombosis) are hyperintense on both T1 and T2 scans due to extracellular methemoglobin. Chronically throm- bosed sinuses undergo fibrosis with hemosiderin deposition and may develop extensive collaterals.
It is clear that the main problem of MRI standard sequences for CVST diagnosis is the iso-hypoin- tense appearance of the acute clot (12-36 h) sim- ulating flow. Problems may also be encountered in chronically thrombosed sinuses (Isensee et al.
1994). During the other phases of clot evolution an abnormal signal within the vessel lumen is evident
in at least one of the standard sequences. Bearing this consideration in mind, the sinuses are best vis- ualized using axial and coronal sequences in which the superior and inferior sagittal sinus, as well as the transverse sinuses and the internal veins, are well imaged. Using these standard sequences, it is possible to evaluate normal anatomy or to detect anatomic variations like hypoplasia of one of the transverse sinuses.
Direct signs of CVST in MRI:
• Demonstration of an intraluminal thrombus within a dural sinus or a cerebral vein. This is easy during the time interval between 4 days and 4 weeks of thrombus age due to the high signal of methemoglobin on T1-weighted images (Table 18.1;
Fig. 18.3) It may be diffi cult in cases of a very fresh (< 3 days) or old (> 4 weeks) thrombus which can be organized or partially recanalized (Figs. 18.3, 18.7). Absence of the normal “fl ow-void” in large veins should raise suspicion of CVST, but this sign is unreliable, as it also appears with slow fl ow.
• Demonstration of an “empty triangle” or “delta sign” within a sinus, comparable to the fi nding in CT (see Figs. 18.9, 18.10) following contrast- enhancement.
Indirect signs of CVST in MRI:
• Uni- or bilateral areas of edema that do not corre- spond to arterial territories (see Figs. 18.6-18.9)
• Uni- or bilateral hemorrhages (see Figs. 18.3, 18.8).
• Pronounced regional enhancement of the lep- tomeninges (falx, tentorium, convexity) due to the involvement of these structures in collateral drainage (see Fig. 18.9).
• Regional subarachnoid hemorrhage, especially if it is situated on the convexity of the brain. It may be a sign of the rare isolated cerebral vein throm- bosis.
Table 18.2 summarizes the sequences and MR techniques which in our experience can be pro- posed (as mandatory or optional) in the diagnos- tic management of veno-occlusive disorders of the brain. Venous MRA can either be performed with the time-of-flight (TOF) or with the phase- contrast (PC) technique. In addition to the tomo- graphic images, a flow sensitive gradient-echo sequence should be obtained if CVST is in ques- tion. As a fast screening examination we prefer a TOF 2D FLASH sequence (Table 18.2; Fig. 18.4, see 18.6c), oriented 90 degree to the flow direc-
Table 18.1. Time dependant MR signal pattern in intraparen- chymal hemorrhage and thrombosed dural sinuses. [Modifi ed from Gomori et al. 1985; Isensee et al. 1994)
Time Molecule T1 T2
0-12 h Oxy Hb Iso-hypointense Hyperintense 12-72 h Deoxy Hb Iso-hypointense Hypointense 3-7 Days MetHb
intracellular
Hyperintense Hypointense
1-4 Weeks MetHb extracellular
Hyperintense Hyperintense
> 4 Weeks Hemosiderin Iso-hypointense Hypointense
tion (coronal). It provides sufficient anatomical details and gives reliable information whether there is flow (high signal) or no flow (no signal).
The only information which is required for cor- rect interpretation is the presence of methemo- globin with a high signal on T1-weighted images.
This substance also appears hyperintense on the FLASH image, thus simulating f low. This is one of several reasons why a combination of MR tomo- graphic and angiographic sequences has to be postulated in CVST. 2D or 3D PC MR angiograms, coded for slow flow, are established techniques for the selective demonstration of cerebral veins and should be used as additional standard sequences when evaluating CVST (Fig. 18.2, 18.8--18.11).
These sequences create angiographic images and may facilitate image interpretation. However, loss of information on the maximum intensity projec- tion (MIP) images or pitfalls due to artefacts must be taken into account (Fig. 18.10). Therefore, the source images always need to be included in the evaluation. In the case of 3D sequences the exami- nation time is considerably prolonged to about 10 min. Contrast-enhanced venous MRA is an advanced and costly technique (Farb et al. 2003) which, on the other hand, avoids problems created by turbulent f low and improves image quality.
Another promising new technique is 2D dynamic (time resolved) contrast-enhanced MR subtrac- tion angiography (Table 18.2; Figs. 18.5, 18.6). It is based on a single-slice T1-weighted gradient-echo sequence and has a temporal resolution of about 0.34 s/image (Krings and Hans 2004). It covers
the arterial and venous phase in coronal and sag- ittal direction and is useful not only in the detec- tion of venous drainage obstruction, but also in the diagnosis of arteriovenous (AV) shunts. This is important because AV fistulae or AV malforma- tions are other important causes for venous drain- age impairment. Contrast-enhanced T1-weighted studies can be helpful but are not mandatory. As already mentioned they can demonstrate – simil- iar to the contrast enhanced CT – an “empty trian- gle” or delta-sign (Figs. 18.9, 18.10).
An axial fluid-attenuated inversion recovery sequence (FLAIR) is usually acquired additionally to demonstrate parenchymal involvement of CVST.
Diffusion-weighted MRI in CVST has gained spe- cial attention in recent years because the patho- physiology of diffusion abnormalities is less well understood compared to arterial stroke (Sarma et al. 2004). The more complex pathophysiological process of venous congestion and infarction obvi- ously leads to both vasogenic and cytotoxic edema (Corvol et al. 1998; Keller et al. 1999; Lövblad et al. 2001). Three types of lesions were identified by Mullins et al. (2004). Resolving lesions with elevated diffusion coefficient (vasogenic edema), persisting lesions with low diffusion (cytotoxic edema, patients without seizure activity) and resolving lesions with low diffusion (cytotoxic edema, patients with seizure activity). The obser- vation of the reversibility of restricted diffusion in extensive venous thrombosis was interpreted by Sarma et al. (2004) as the existence of an “intracel- lular edema” which is reversible for an undefined, variable time.
Our typical MR protocol for suspected CVST includes an axial FLAIR, axial diffusion-weighted MRI, coronal T1 SE and T2 TSE sequences, a coro- nal gradient echo and a 3D phase contrast venous angiogram with a total imaging time of approxi- mately 20 min.
7.4.1.1
MRA Findings in (Benign and Idiopathic) Intracranial Hypertension
Chronic thrombosis or only partially recanal- ized dural sinus thrombosis may be diagnosed in these patients (Thron et al. 1986; Wessel et al.
1987). This type is less obvious on the static MRI (Isensee et al. 1994) and requires MR venogra- phy, if possible in a contrast-enhanced technique.
In children, purulent mastoiditis is an important cause of septic thrombosis (Reul et al. 1997) or
Table 18.2. Diagnostic management of suspected CVST by MRI and MRA
MRI + MRA Specific Parameters T1 axial
T2 coronal
TOF angiogram (FLASH) TR/TE/FA: 23/7 ms/40°, 5 slices, 5 mm, coronal, 1:36 min
(2D FLASH)
2D-PCA (optional) TR/TE/FA: 20/5.2/15°,1 slice, 30 mm, sagittal+axial, 1:14 min 3D-PCA (optional) TR/TE/FA : 16/6.8/10°, 200 slices,
0.8 mm, axial, 9:32 min DWI (optional) TR/TE 5100/137 ms, 19 slices,
5 mm, axial
FLAIR (optional)
3D contrast-enhanced MRA (optional)
2D dynamic contrast-enhanced subtraction MRA (optional)
TR/TE/FA 3.5/1.0/40 coronal+sagittal
Fig. 18.4. Coronal 2D fast low angle shot (FLASH) (section). This fl ow-sensitive sequence offers a quick (1:30 min) screening for
all major sinuses with additional anatomical information. Important: Comparison with the T1-weighted images is necessary
because not only fl ow, but also methemoglobin appear bright
inf lammatory stenosis (Isensee et al. 1992) of the ipsilateral transverse sinus (Reul et al. 1997), fol- lowed by raised intracranial pressure. A cystic developmental lesion within a sinus (Küker et al. 1997), or other space-occupying or infiltrating processes, obstructing the lumen of a dural sinus are rare causes.
In patients with idiopathic intracranial hyper- tension bilaterally narrowed segments in the lateral venous sinuses have been demonstrated compared to normal findings in asymptomatic volunteers using advanced techniques of MR
venography (Higgins et al. 2002, 2004; Farb et al. 2003). We have observed similar cases in recent years with unilateral sinus stenosis and contralateral hypoplasia or bilateral stenoses (see Fig. 18.2c-e).
Fig. 18.5a–d. 2D dynamic contrast- enhanced MR sub- traction angiography.
Normal fi nding. Selected images from the arterial (a,b) and venous phase (c,d) are shown
a b
c d
Fig. 18.6a–d. Deep cerebral venous thrombosis in an 8-year-old girl presenting with headache, state of confusion and somno- lence. a Axial FLAIR image with bilateral swelling and hyperintensity of the thalami and right-sided basal ganglia. b Coronal T2-weighted image with high signal in both thalami due to edema and/or infarction, suspicious of thrombosis of the deep venous system (internal cerebral veins, straight sinus). c On the coronal fl ow-sensitive Sequence (FLASH) no fl ow is shown in the internal cerebral veins (arrows). d 2D dynamic contrast-enhanced MR subtraction angiography. The images from the arte- rial phase (upper row) are normal, in the late venous phase (lower row) an area of reduced parenchymal contrast and absence of the internal cerebral veins and straight sinus are shown. (Compare with normal fi ndings in Fig. 18.5)
a b
c d
Fig. 18.7a,b. Isolated cortical vein thrombosis in a 16 y old female presenting with focal epileptic seizures. a Axial GE (T2*) images show a hypointense signal along the course of a cortical vein (arrows) which was also seen as a hyperdense structure on CT (not shown). b Axial DWI shows small areas of restricted diffusion in the corresponding brain parenchyma
a
b
Fig. 18.8a–d. Thrombosis of the transverse sinuses with temporolateral congestive and hemorrhagic infarction on the right side. The lesion corresponds to the drain- age territory of the vein of Labbé. a CT aspect of the partially hemorrhagic lesion.
b FLAIR images showing areas of different hyperin- tensity. c DWI with a very inhomogeneous pattern of diffusion abnormalities. d 3D PC venography. Extensive thrombosis with incomplete occlusion mainly of the transverse sinuses (arrows).
On the right side, corre- sponding to the lesion loca- tion, temporal cortical veins (vein of Labbé) are missing (short arrow)
a b
c d
Fig. 18.9a–e. Extensive thrombosis of all main dural sinuses. a Coronal T2-weighted images. Only small cortical lesions are present. The signal of the big sinuses is iso-/hypointense and does not indicate thrombotic occlusion. b Axial T1-weighted contrast-enhanced images. Intraluminal thrombus is evident in the superior sagittal sinus (arrowheads) and increased leptome- ningeal enhancement can be demonstrated (arrows) indicating collateral drainage through small veins. c Axial FLAIR images.
Small cortical/subcortical areas of infarction are present (arrows). d 3D PC MR venogram. Extensive thrombosis of all major dural sinuses. The drainage is restricted to superfi cial collateral veins. e 3D PC MR venogram after 3 months of anticoagulation.
Improvement with partial restoration of fl ow in the superior sagittal and transverse sinuses (arrows)
d e
a b c
