A proposed framework for cerebral venous congestion

Abstract

Background

While venous congestion in the peripheral vasculature has been described and accepted, intracranial venous congestion remains poorly understood. The characteristics, pathophysiology, and management of cerebral venous stasis, venous hypertension and venous congestion remain controversial, and a unifying conceptual schema is absent. The cerebral venous and lymphatic systems are part of a complex and dynamic interaction between the intracranial compartments, with interplay between the parenchyma, veins, arteries, cerebrospinal fluid, and recently characterized lymphatic-like systems in the brain. Each component contributes towards intracranial pressure, occupying space within the fixed calvarial volume. This article proposes a framework to consider conditions resulting in brain and neck venous congestion, and seeks to expedite further study of cerebral venous diagnoses, mechanisms, symptomatology, and treatments.

Methods

A multi-institution retrospective review was performed to identify unique patient cases, complemented with a published case series to assess a spectrum of disease states with components of venous congestion affecting the brain. These diseases were organized according to anatomical location and purported mechanisms. Outcomes of treatments were also analyzed. Illustrative cases were identified in the venous treatment databases of the authors.

Conclusion

This framework is the first clinically structured description of venous pathologies resulting in intracranial venous and cerebrospinal fluid hypertension. Our proposed system highlights unique clinical symptoms and features critical for appropriate diagnostic work-up and potential treatment. This novel schema allows clinicians effectively to approach cases of intracranial hypertension secondary to venous etiologies, and furthermore provides a framework by which researchers can better understand this developing area of cerebrovascular disease.

Background

Venous stasis and congestion are well described in many parts of the body. Phlegmasia cerulea dolens describes venous congestion related to inferior vena cava occlusion. ¹ Pelvic congestion syndrome is associated with infertility and pain, ² and venous thoracic outlet syndrome describes osseous compression of the subclavian vein as it enters the thoracic cavity. ³ Varicose veins develop due to deep venous restriction or occlusion. ⁴ Superior vena cava (SVC) syndrome describes occlusion of the SVC by tumor or thrombosis, ⁵ although more often used synonymously with neoplastic involvement of the SVC. Together, these conditions represent a broad swathe of clinical syndromes that arise when there is obstruction of venous outflow.

Intracranial venous congestion remains controversial, particularly as much of the literature pertaining to cerebral hydrodynamics pertains to either cerebral spinal fluid (CSF) flow or arterial flow. The Monro–Kellie hypothesis and its revisions describe an equilibrium between blood, cerebrospinal fluid, and brain parenchyma, and has been used to explain one of the features of idiopathic intracranial hypertension in the relationship between venous hypertension, venous stenoses, and increased intracranial cerebral spinal fluid pressure.^6,7

Intracranial hypertension: from CSF to venous

Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri, was principally used to describe patients with features of intracranial hypertension who manifested visual complaints, pulsatile tinnitus, headaches, and difficulty with cognition. ⁸ Much of the focus of IIH diagnosis and management centered around CSF pressure/volume management, as that was the initial defining feature. Consequently, the initial treatments of IIH focused on inhibiting CSF production with medications such as acetazolamide, ⁹ or surgically augmenting CSF outflow via shunt ¹⁰ or optic nerve sheath fenestration (ONSF). ¹¹

Elevated CSF pressure is one of the essential grounds of the diagnosis of IIH, and recent advances in venous sinus stenting show a strong interrelationship between cerebral venous hypertension and CSF hypertension. Transverse sinus narrowing has been seen in up to 93% of IIH patients.^12,13 However, the direction of causality is unclear as lowering the CSF pressure with CSF diversion may, in some cases, result in resolution of venous stenoses, while bracing stenotic segments open with a stent lowers CSF pressure.^14–16 One study showed that of 46 patients with IIH, 15 demonstrated isolated non-thrombotic internal jugular vein (IJV) stenosis, with stenting performed with trans-stenotic mean pressure gradient equal to or higher than 4 mmHg, resulting in resolution of IIH symptoms. ¹⁷ While there seems to be a reciprocal relationship between venous hypertension and CSF hypertension, the inciting event often remains unknown.

Direct manometric assessment of venous sinus pressure gradients can be obtained in patients with refractory IIH, and CSF opening pressure has also been shown to be predictive of superior sagittal sinus pressure. ¹⁸ The degree of venous sinus stenoses can also predict the degree of pressure gradient,^19,20 which could eventually obviate direct pressure measurements should models become sufficiently refined. Furthermore, general anesthesia influences pressure gradients, perhaps by end tidal carbon dioxide (CO₂) levels.^21–24

The central venous hypertension hypothesis was articulated by Karahalios et al., ²⁵ citing the body habitus of the archetypal patient. Observations of increased intrathoracic, intra-abdominal, and intrapelvic pressures in such patients added support to this hypothesis. ²⁶ Mathematical modeling by Bateman et al., showed a scenario in which an inciting central venous pressure leads to decreased CSF absorption by the veins, resulting in a Starling resistor-mediated feedback loop to reinforce elevated CSF pressure and intracranial venous pressures. ²⁷ Instructively, a series of patients in whom prolonged coughing or vomiting produced persistent IIH symptoms provides anecdotal support for this pathomechanistic theory. ²⁸ In addition, weight loss is a mainstay of medical management (Wall-Nordic Trial). Similarly, a meta-analysis of bariatric surgery in obese IIH patients suggests it is also effective in reducing the severity of symptoms and intracranial pressures (ICPs) with significant weight loss. ²⁹ However, many of us that measure venous pressures find that the central venous pressures in IIH patients are normal, but the intracranial venous sinus pressures are elevated. The presence of this gradient directly predicts the potential benefit of venous sinus stenting to restore the cerebral venous pressures to the level of the more ‘normal’ central venous pressures.^30,31

While the exact relationship between venous, CSF flow and pressures remain unclear, large published meta-analyses showed the effectiveness of venous sinus stenting in select patients with an obstructive venous flow pattern with a pressure gradient across the stenotic segment. A recent study showed that severe intracranial hypertension was more common with cerebral venous sinus stenosis than with IJV stenosis. The appearance of collateral venous vessels is a key feature in IJV stenosis. ³² As such, dural venous sinus stenting (DVSS) is efficacious and may be considered a first line treatment for medical failures when the predominant presenting symptom is headache when compared to ONSF and ventriculoperitoneal shunting for symptomatic relief and low periprocedural complications in IIH.^33,34

The abundance of venous pathology underpinning observed CSF hypertension suggests that the term ‘idiopathic’ may now be unnecessary given increasing data to support that, in many of these patients, a venous inciting mechanism can usually be found.^35,36 While venous congestion may not be the sole causal factor of CSF hypertension, it appears to be a pivotal factor.

Venous congestion: known parenchymal effects

The sequelae of venous congestion are clearly observed in the manifestation of venous infarction and hemorrhages in the setting of venous injury; for example, in the setting of dural sinus and cortical vein thrombosis.^37–39 While these are clinically apparent, studies into their underlying pathomechanisms remain infrequent,^40,41 and animal models, while established, are rare. ⁴²

The mechanistic pathway of such venous congestion is generally associated with complete or near complete restriction of venous outflow due to cortical or juxtacortical thrombosis.

The glymphatic system: bridging CSF and veins?

A glymphatic system has been described as a macroscopic waste clearance system making use of astroglial perivascular tunnels to allow for elimination of soluble proteins and metabolites.^43,44 There is continuous exchange between CSF and interstitial fluid (ISF) along the periarterial spaces, driven by arterial pulsation and mediated through aquaporin 4 channels in fluid transport. ⁴⁵ This interaction between CSF and interstitial spaces raises the possibility of another point of interaction between venous blood and CSF, given the interactions between interstitial spaces and intracellular spaces, and should be a consideration for pathomechanisms in hydrodynamic diseases of the brain.

From juxta-cardiac to cerebral: variations in venous pathology

While intracranial hypertension is commonly considered from the perspective of CSF dynamics, under the Monro–Kellie hypothesis, the possibility of venous etiologies in certain patients can drastically affect diagnostic work-up and management. Pathologies at nearly every venous level from intracranial to central can predispose a susceptible patient to venous hypertension.

One recent categorization scheme for patients with IIH divides patients into four distinct groups based on the primary drivers of intracranial venous hypertension: type 1 patients, defined by pathological venous stenosis as the primary driver; type 2, defined by elevated central venous pressures as the primary driver; type 3, defined by a mixed picture with both elevated central venous pressure and venous stenosis contributing; and type 4, a heterogenous group with a history of venous sinus thrombosis. ³⁴ This scheme is important in differentiating patients based on the etiology of venous congestion but does not identify the various locations for potential venous outflow obstruction or differentiate between patients with differing pathophysiologies.

To expand on this categorization, we briefly outline the various levels of contributory etiologies, with references from published literature, some of which relate to illustrative cases detailed in the subsequent section.

Central venous hypertension and congestion can result from increased body habitus with globally increased intrathoracic, intra-abdominal, and intrapelvic pressures. ⁴⁶ Furthermore, pulmonary hypertension and right heart failure are potential causes of central venous hypertension,^47,48 and sleep apnea has been associated with both pulmonary hypertension^48,49 and intracranial hypertension^50,51 as well as CSF leaks,^52,53 which may be secondary to chronic intracranial CSF hypertension from venous outflow stenosis.

As mentioned before, SVC syndrome can result in both communicating hydrocephalus and intracranial hypertension^54,55 as well as CSF leaks. ⁵⁶ The neurological symptoms are not generally a prominent feature of reported cases, instead demonstrating more of arm, neck and facial swelling. ⁵

The internal jugular valves can be incompetent, predisposing to greater reflux and less protection of the brain from central venous pressure; Nedelmann and colleagues have reported increased association of venous incompetence in patients with intracranial hypertension.^57,58 IJV stenosis and occlusion have been reported in association with intracranial hypertension after thrombosis ⁵⁹ as well as after radical neck dissection with jugular sacrifice. ⁶⁰ Given that these events are fairly rare, we hypothesize that affected patients have less venous reserve capacity.

Recent descriptions of styloid and C1 lateral mass compression of the high cervical IJV have also been associated with intracranial hypertension,^61–63 which has been treated with stenting in case series^17,64 and surgical decompression. ⁶⁵ Li et al. have described a subset of five patients with bilateral elongated styloid processes and severe narrowing of the jugular veins at the C1 level as stylo-jugular compression and Eagle syndrome. ⁶¹

Intracranially, transverse sinus stenosis may be intrinsic related to either thrombosis^66,67 and neoplasm, ⁶⁸ or extrinsic due to compression from CSF.^69,70 Transverse sinus stenting has been shown to be associated with high technical success and low complication rates. ³³ A 2018 meta-review of studies examining dural venous sinus stenting with focused review of few representative cases has demonstrated a clear role for dural venous sinus stenting for certain patients with IIH, with high technical success and symptomatic improvement. ⁷¹

Typically seen, developmental venous anomalies (DVAs), characterized by fusing large draining transmedullary venous networks into a single venous collector, can cause local venous congestion with abnormal mean transit time, cerebral blood volume and cerebral blood flow. ⁷² DVAs can become symptomatic by thrombosing and bleeding, as well as causing venous infarcts ⁷³ in much the same way as cortical or deep vein thrombosis can cause injury. ⁷⁴

In addition to these intrinsic and extrinsic venous pathologies, there is a spectrum of hydrovenous disorders, particularly in pediatric populations, associated with dural arteriovenous fistulae (DAVF) and arteriovenous malformations (AVMs), first described by Lasjaunias, as impaired resorption of CSF or interstitial fluid due to markedly severe venous hypertension, resulting in increased ICP, hydrocephalus, or syringomyelia. ⁷⁵ This peculiarly pediatric presentation is related to the immature CSF resorption system; these disorders are also well characterized in patients with vein of Galen malformations. In the latter pathology, high flow induces progressive jugular bulb stenosis and occlusion, with subsequent venous congestion and effects on brain parenchymal and child development if collateral networks are not adequately developed.

For example, it has been well established that the cause of hydrocephalus in vein of Galen malformations is not due to aqueductal obstruction, but secondary to venous hypertension restricted transmedullary CSF and interstitial fluid resorption, resulting in brain swelling and/or ventriculomegaly. Consequently, in cases of pediatric ventriculomegaly, alternative etiologies other than a focal CSF–flow obstruction (e.g. stenosis of the Sylvian aqueduct) should be considered. In line with this, multiple case series have shown poor results with shunting in these patients.^76,77 In adults, dementia/cognitive decline in AVM/arteriovenous fistulae patients due to ventricular dilation from chronic venous hypertension may be reversible with treatment of the fistula. ⁷⁸

DAVF cause venous hypertension and congestion with arterial shunting from dural vessels into a venous recipient pouch which may drain towards the heart. As such, DAVF can result in intracranial hypertension^79,80 as well as CSF leaks (Figure 1). ⁸¹

Figure 1.

Pathomechanism of hydrovenous disorders resulting from dural arteriovenous fistulae (DAVF) and arteriovenous malformations (AVMs).

Within the brain parenchyma, AVMs in adults may similarly cause local venous hypertension due to arterialization of a draining vein resulting in increased venous pressure for adjacent parenchyma.^82,83 Moreover, brain AVMs with a fistular component have been deemed as causative lesions for intracranial CSF hypertension via venous hypertension as reported by Chimowitz et al. ⁸⁴ and Rosenfeld et al. ⁸⁵ The treatment of the AVM resulted in cure of the intracranial hypertension. CSF leaks have also been reported as the presenting symptom for an AVM reflecting the propensity to cause CSF hypertension. ⁸⁶

Illustrative cases are shown in Figure 2.

Figure 2.

Legend of illustrative cases detailed below with respect to level of pathology.

Systemic

Patient 1: Body habitus associated IIH

A female patient in the second decade of life with neck and back pain, with progressive blurry vision for 2 weeks worse with lying down, presented with severe bilateral papilledema and bilateral cranial nerve (CN) VI palsies necessitating an emergency room visit. She had a 25 lb weight gain the past year and no history of vitamin A supplements. Magnetic resonance imaging (MRI) demonstrated typical findings of IIH. Opening pressure was greater than 60 cm H₂O with normal CSF analysis. Lumbar dural fenestration was performed and she was started on acetazolamide. Cerebral angiography performed 2 days after fenestration showed dominant right venous system with hypoplastic left and a high-grade stenosis in the distal right transverse sinus. The pressure gradient measured 10 mmHg, and the stenosis was stented. She reported immediate improvement in vision, diplopia, and headaches with slowly resolving papilledema over the subsequent 2 months. Lumbar puncture 3 months after stenting showed opening pressure of 13 cm H₂O and acetazolamide has been discontinued (Figure 3).

Figure 3.

(a) Magnetic resonance imaging (MRI) brain demonstrating findings compatible with idiopathic intracranial hypertension (IIH), including intraocular protrusion of the optic nerve head and nerve tortuosity. (b) Delayed phase MRI demonstrates stenosis of the distal right transverse sinus, which was also seen on (c) angiography. (d) and (e) After placement of stent, there is improved venous outflow and increased sinus caliber. Pre (f) and post (g) intervention ophthalmoscopic images demonstrate resolution of papilledema, decreased swelling of the optic discs, and resolving macular star of exudate in each eye (fundoscopic images courtesy of Jonathan Horton, MD).

Intracranial

Patient 2: Dural sinus thrombosis

A male patient in the fifth decade of life presented with headache and shortness of breath at another institution. Visual obscuration was noted without tinnitus. Further work-up demonstrated pulmonary emboli without pelvic deep vein thrombosis. Papilledema 3+ was seen and he was managed with 1000 mg acetazolamide daily. Brain MRI revealed right sigmoid sinus venous sinus thrombosis. Opening pressure was 35 cm H₂O. Venography demonstrated high torcular pressures and high gradient with a large thrombus in the right transverse and sigmoid sinuses (Figure 4). As the patient tolerated acetazolamide with manageable symptoms, conservative management was maintained with progressive reduction in clot burden. If he became intolerant or refractory to continued treatment, clot extraction and stenting may be considered.

Figure 4.

(a) Initial magnetic resonance imaging (MRI) demonstrating large right transverse and sigmoid sinus thrombosis with minimal opacification. (b) Follow-up MRI approximately 5 weeks after demonstrates partial recanalization of the right transverse and sigmoid sinuses. (c) Blooming artifacts (arrow) on susceptibility weighted imaging compatible with residual thrombus. (d) and (e) Venography shows filling defects in the right transverse and sigmoid sinuses compatible with residual thrombus (arrows).

Patient 3: Dural sinus thromboses and dural fistulae

A male patient in the sixth decade of life presented with severe obtundation. The patient had a history of prior deep vein thrombosis and Factor V Leiden, and was managed on rivaroxaban and acetazolamide 1000 mg QD for intracranial hypertension. Venography revealed bilateral venous sinus occlusions and multiple dural fistulae. The shunting lesions were obliterated by endovascular embolization (Figure 5) and the patient returned to his baseline on acetazolamide.

Figure 5.

(a) Multiple filling defects compatible with venous sinus thromboses. (b) Left internal carotid artery (ICA) arteriogram with early dural sinus filling. (c) Contrast opacification of dural arteriovenous fistula. (d) Embolization. (e) Pre-embolization lateral left ICA arteriogram with early venous opacification. (f) Post-embolization with no venous sinus opacification on similar early arterial phase.

Patient 4: Cerebellar DVA with outflow stenosis

A male patient in the fifth decade of life presented with new onset occipital headaches. MRI demonstrated a right cerebellar hemisphere DVA that drains nearly the entire hemisphere as well as a tight venous stenosis in the outflow vein (Figure 6). The remainder of his work-up was unrevealing. After multidisciplinary discussions with focus on mechanisms of DVA hemorrhage and thrombosis, the patient was started on a therapeutic dose of warfarin. Headaches resolved at 2 weeks, and the patient remained asymptomatic at 2-year follow-up.

Figure 6.

(a) T1 C+ magnetic resonance imaging (MRI) demonstrated R cerebellar developmental venous anomaly (DVA). (b) Lateral venogram demonstrating DVA with outflow high grade venous stenosis (arrow). (c) Frontal venogram with better visualization of the high-grade venous stenosis in the DVA outflow vein (arrow).

Patient 5: Acute iatrogenic sinus occlusion

A female patient in the third decade of life underwent occipital craniotomy for a pineal lesion, complicated by a tear of the posterior aspect of the superior sagittal sinus requiring sinus ligation after failed attempts to control bleeding. Over the subsequent 48–72 hours, she experienced intractable increase in ICP (25–40 mmHg) despite barbiturate coma and heparin anticoagulation. Shunt from superior sagittal sinus (SSS) (proximal to occlusion) to the ipsilateral IJV with bypass conduit of overlapping stent grafts and interposition Dacron graft was created (Figure 7). ICP immediately reduced in a sustained manner (<20 mmHg) with resolution of mental status.

Figure 7.

(a) Digital subtraction venography demonstrates abrupt occlusion of the superior sagittal sinus with clips compatible with surgical ligation. (b) Intraoperative image partially demonstrating the constructed shunt between the superior sagittal sinus proximal to the occlusion and the ipsilateral internal jugular vein.

Patient 6: Non-iatrogenic asymmetric cerebral venous outflow

A female patient in the third decade of life presented with severe bilateral retro-orbital headache, nausea, vomiting, and recurrent nose bleeds without a clear inciting event. After a year of initial symptoms, she started developing poor memory, fatigue, and positional confusion and dysphasia. Magnetic resonance venography and angiography were notable for dominance of left transverse sinus. Superior sagittal sinus pressure was 9 mmHg, and noted to be 11 mmHg with right jugular compression and 29 mmHg with left jugular compression, with neurological symptoms developing with left jugular compression. She was treated with stenting of the right transverse and sigmoid sinuses over three procedures. Post-procedurally, her superior sagittal sinus pressure increased by only 4 mmHg with left jugular compression. Her neurological symptoms have improved dramatically with no further episodes of epistaxis or confusion ⁸⁷ (Figure 8).

Figure 8.

(a) and (b) Magnetic resonance venography and venous phase angiography demonstrating dominant left-sided cerebral venous drainage with markedly narrowed right-sided dural venous sinuses. (c) and (d) Status post stenting of the right transverse and sigmoid sinuses with increased outflow through the stented segments. (Adapted from Higgins et al., 2014, with permission from the Journal of Observational Pain Medicine.)

Patient 7: Mass effect from vein of Galen malformation

A young male infant presented with marked supratentorial ventriculomegaly and interstitial edema. Anatomical evaluation demonstrated a dilated vein of Galen resulting in compression of the tectal plate and Sylvian aqueduct, resulting in communicating hydrocephalus (Figure 9).

Figure 9.

(a) Markedly dilated vein of Galen compresses the tectal plate and Sylvian aqueduct, resulting in supratentorial ventriculomegaly. (b) and (c) Susceptibility weighted imaging (SWI) images demonstrated hypointense and dilated subdural, subarachnoid, subependymal, and intramedullary veins compatible with venous hypertension.

C1–2 Level pathology

Patient 8: C1–2 IJV stenosis/occlusion

A female patient in the third decade of life with body mass index (BMI) 22.7, HLA B27 mutation, and history of amblyopia, presented with 1+ papilledema and intermittent tinnitus, but without headache. She had an opening pressure of 25 cm H₂O. Computed tomography venography (CVT) and digital subtraction venography (DSV) demonstrated a left IJV that is pulled laterally by the transverse process of C1 (Figure 10), resulting in apparent occlusion on CTV, with robust collaterals along the vertebral plexus bilaterally. Given her mild symptoms, the patient is currently being managed with acetazolamide 500 mg daily.

Figure 10.

(a) Computed tomography venography (CVT) demonstrating lateral displacement of the L internal jugular vein (IJV) (arrow), directly apposed by the left C1 transverse process. (b) Three-dimensional reconstruction of CTV demonstrating apparent narrowing and occlusion of the L IJV (arrow). (c) Venography above the level of apparent narrowing showing limited flow through the L IJV and opacification of numerous collateral vessels. (d) Venography below the level of occlusion showing retrograde filling of collaterals.

Patient 9: R C1–2 stenosis post stent and L C1–2 pseudo-occlusion

A female patient in the fourth decade of life with a history of Chiari malformation status post decompression and possible Ehlers–Danlos syndrome presented for evaluation of long-standing headaches and occasional blurry vision. Previously underwent right internal jugular stenting at outside institution, now noted to be distally narrowed and abutting the lateral mass of C1. Venogram showed right IJV stent and vein stenosis by 70% from styloid-C1 lateral mass compression. Left IJV, nonvisualized on CTV, was seen to be non-dominant with slow flow but patent, and also with 70% C1–2 level stenosis. She underwent C1 tubercle resection and right styloidectomy with symptomatic improvement, and is now pending contralateral surgery given prior venogram findings (Figure 11).

Figure 11.

(a) Coronal three-dimensional (3D) reconstruction of venous phase computed tomography (CT) neck demonstrates right internal jugular vein (IJV) with stent and proximally absent and distally narrowed and opacified L IJV. (b) Sagittal 3D reconstruction of venous phase CT neck at the level of the R IJV shows markedly narrowed stent. (c) Axial computed tomography venography (CVT) at the level of stent narrowing shows compression between the right styloid process and lateral mass of C1. (d) Frontal view left IJV venogram demonstrates widely patent vein, despite apparent non-visualization on CTV. (e) Lateral view left IJV venogram shows high grade stenosis at the level of C1–2 (arrow). (f) Post-surgical CTV after right styloidectomy and C1 lateral mass resection shows improved stent patency.

Patient 10: C1–2 IJV stenosis

A male patient in the sixth decade of life presented with worsening headaches, tinnitus and intermittent obtundation. Initial angiography 9 years prior performed for cephalgia and tinnitus revealed no causative abnormalities. Recent angiography demonstrated a new arachnoid granulation in the left transverse, non-dominant sinus, which was associated with left transverse sinus stasis and to-and-fro flow. After much discussion, the lesion was stented, resulting in resolution of intermittent obtundation, but did not resolve the tinnitus. Additional imaging revealed a left C1–2 IJV stenosis (Figure 12). The patient is presently awaiting surgical decompression of the styloid and transverse processes.

Figure 12.

(a) Right dominant transverse sinus on early venous phase imaging. (b) Later phases of venous imaging show to-and-fro flow in the left transverse sinus. (c) Residual to-and-fro flow still visualized in the left transverse sinus after right-sided contrast has cleared. (d) Venogram after stent placement, with to-and-fro flow still visualized (not depicted).

IJV/thoracic pathology

Patient 11: IJV valve incompetence, high BMI

A female patient in the third decade of life and BMI of 39 with right-sided facial fullness and headaches. Non-invasive imaging demonstrated moderate to severe left transverse sinus narrowing, presumed long-standing. Venography showed this focal stenosis, as well as stenosis at the level of the distal left IJV near the valve, at the level of the origin of the left brachiocephalic vein. The right IJV was seen to be markedly distended, with presumed valvular incompetence secondary to enlarged vessel diameter and contrast regurgitation. There was a pressure gradient of 7 mmHg in the right transverse sinus. She underwent left distal IJV stenting and angioplasty with improvement in headaches (Figure 13).

Figure 13.

(a) Stenosis visualized in the left transverse sinus, approximately 70%. (b) Distended right internal jugular vein (IJV) with regurgitating contrast, suggestive of valve incompetence. (c) High grade stenosis visualized at the distal left IJV, at the level of the valve, near the origin of the brachiocephalic vein. (d) Left IJV venogram after stent placement demonstrates robust flow across the previously noted area of stenosis.

Patient 12: IJV stenosis and sigmoid sinus occlusion

A male patient in the fifth decade of life with low BMI (18) and systemic lupus erythematosis, who presented with peripheral visual obscurations, headache, tinnitus, head ‘fullness’, and exercise intolerance, with remote R sigmoid occlusion 9 years prior. The patient had previously been managed with acetazolamide, which the patient was not now tolerating. Stenting had been performed on the left transverse sinus with pre-stenting gradient of 25 mmHg, presently 0. Post stenting, the patient’s visual obscurations, tinnitus, headaches, and facial pain resolved for 3 years. The patient returned with increasing exercise intolerance and headaches. Further work-up revealed left internal jugular C1–2 stenosis on CTV. Additional findings included progressive erosion of the clivus (Figure 14), which was concerning for a risk of CSF leak. Venography demonstrated IJV compression at C1–2 due to styloid and C1 lateral mass compression with a gradient of 10 mmHg. The patient is currently scheduled for surgical decompression of the left IJV at C1–2.

Figure 14.

(a) Venogram showing known old right sigmoid sinus abnormality. (b) Left internal jugular vein (IJV) stenosis at the C1–2 level. (c) Computed tomography venography (CVT) demonstrates left IJV narrowing due to close apposition between the left styloid process and lateral mass of C1. (d) and (e) Magnetic resonance imaging (MRI) and computed tomography (CT) demonstrating clivus erosion and cerebrospinal fluid (CSF) leak.

Patient 13: SVC syndrome

A female patient in the fourth decade of life who presented with a history of sickle cell disease, with a several year history of upper extremity swelling. Ultrasound demonstrated right IJV clot in the setting of prior venous catheter placement with subsequent left-sided port placement. Her port was removed after multiple malfunctions, and over the years has had progressive swelling of her hands and forearms, and head/neck swelling exacerbated by bending her neck forward. She underwent balloon venoplasty with stenting; however, had recurrent symptoms several months afterwards. An additional stent was placed in the cranial segment of the SVC, with resolution of facial and neck swelling (Figure 15).

Figure 15.

(a) and (b) Initial venogram demonstrating near complete occlusion at the level of the superior vena cava (SVC) (a) with subsequent balloon plasty and stent placement resulting in recanalization and robust flow through the SVC (b). The patient presented again one month later with recurrent symptoms with repeat venogram showing a high grade stenosis in the cranial segment of the SVC (c) with balloon plasty and stent placement (d) resulting in restoration of normal venous flow (e).

Patient 14: Posterior reversible encephalopathy syndrome induced by SVC stenosis

A patient with end-stage renal disease (ESRD) on hemodialysis with a right upper extremity fistula presented with hypertensive crisis to systolic 240 mmHg and imaging findings compatible with posterior reversible encephalopathy syndrome (PRES) after a dialysis session. Magnetic resonance angiography (MRA) raised concern for an arteriovenous fistula involving the right cavernous sinus to the right transverse sinus via the inferior petrosal vein. Catheter angiography performed to evaluate for possible hemorrhage did not show an arteriovenous fistula, but rather SVC stenosis with intracranial reflux of venous flow. Venoplasty of the stenotic SVC led to resolution of observed reflux and PRES symptomatology (Figure 16).

Figure 16.

(a) Magnetic resonance fluid-attenuated inversion recovery (FLAIR) imaging showing bilateral posterior hyperintensities compatible with posterior reversible encephalopathy syndrome (PRES). (b) Magnetic resonance angiography (MRA) shows a large vascular structure suggestive of early right-sided venous filling, suspicious for arteriovenous malformation. (c) Digital subtraction angiography demonstrates marked stenosis of the superior vena cava (SVC). (d) Venoplasty of the stenotic SVC with waisting of the balloon. (e) Pre-venoplasty angiography of the sagittal head shows significant venous reflux. (f) Similar sagittal view of the head after venoplasty with near complete resolution of venous reflux. (g) Post-venoplasty MRA shows reduction in size of the previously observed prominent right-sided venous vessels.

Patient 15: Venous hypertension secondary to tetralogy of Fallot

A neonate with tetralogy of Fallot presented with significant increased systemic pressures with progressive macrocephaly, increasing above the 97th percentile. MRI demonstrated multiple engorged and tortuous intracranial veins. Staged corrective surgery was performed with an initial 1.5 chamber Glenn procedure (bidirectional cavopulmonary anastomosis (BDCPA)), which did not correct the central venous hypertension. Subsequent surgery with biventricular repair resulted in a decrease of central venous pressures with stabilization of progressive macrocephaly (Figure 17).

Figure 17.

(a) Neonatal head ultrasound demonstrating subarachnoid space expansion and numerous dilated superficial veins. T2 (b), fluid-attenuated inversion recovery (FLAIR) (c), and susceptibility weighted imaging (SWI) (d)–(f) sequences showing numerous T2-hypointense, FLAIR mildly hyperintense, and prominent SWI hypointense dilated intramedullary, subependymal, subarachnoid, and subdural veins. (g) Head circumference percentile and central venous pressure over time, with indicators marking points of cardiac surgical intervention for tetralogy of Fallot repair, showing decrease in elevated central venous pressures and stabilization of head circumference enlargement.

Discussion

We propose cerebral venous congestion as a general term to capture the altered flow and drainage of both CSF and venous blood – in many patients these processes are deeply interrelated. The present article focuses on venous congestion, a term which firstly communicates insufficient outflow, rather than merely high pressure (venous hypertension) or reduction in caliber (venous stenosis). Much as ischemia reflects insufficient arterial inflow, congestion reflects insufficient outflow.

Arteries and veins differ fundamentally in that most arterial trees are in series with watershed zones at the margins, whereas venous blood can exit via multiple parallel channels should they exist. Pressure modeling is therefore quite different.

Resistors in series can be written:

$$\text{R}={\text{R}}_{\text{1}}+{\text{R}}_{\text{2}}+{\text{R}}_{\text{3}}+\dots$$

which is the case in most arteries.

Resistors in parallel can be modeled:

$$\text{1}/\text{R}=\text{1}/{\text{R}}_{\text{1}}+\text{ 1}/{\text{R}}_{\text{2}}+\text{ 1}/{\text{R}}_{\text{3}}+\dots$$

Another substantial difference is capacitance; arterial walls have a muscular layer and can constrict responding to stimuli. Veins lack that layer and tend to stretch readily. Arteries are lower compliance and veins are higher compliance to use intracranial balloon terminology. These features should be noted when considering pressure readings. Within the calvaria, certain venous elements are inelastic, namely the dural sinuses, and venous maximum compliance is constrained. Outside of the calvaria, compliance is high and flow resistance may be mitigated by venous engorgement, analogous to capacitors in electrical circuits.

A proposed classification scheme

From the afore-mentioned clinical examples and our experience, we categorize venous congestion based on location (Table 1) and severity (Table 2). Furthermore, classification should be characterized based on anatomical location: intra-axial, intracranial, jugular or central. This generates a matrix of combinations with unique patient symptomatology, clinical/radiological findings, and management considerations (Tables 3 and 4).

Table 1.

Anatomical site.

Site	Mechanisms	Treatments
A. Central, juxtacardiac	BMI related, thrombus, cardiac dysfunction	Weight loss, thrombectomy/stenting
B. Cervical (most often C1–2)	Styloid, C1 transverse process, muscular entrapment (lower pressure gradients observed)	*Stenting, *Surgical release
C. Intracranial, extra-axial	Transverse sinus compression (extrinsic) or thrombosis (intrinsic) superior sagittal sinus compression	Stenting Treatment of extracranial source of venous congestion*
D. Intracranial, intra-axial	Local venous anomaly DVA vs. shunting lesion pressurizing parenchyma such as an AVM	No known treatments for DVA. AVM obliteration for AVMs

*Denotes evolving approaches to treatment.

AVM: arteriovenous malformation; DVA: developmental venous anomaly.

Table 2.

Severity grade.

Grade	Symptoms	Clinical scenarios
4. Fulminant	Near lethal intracranial pressure	Pan sinus thrombosis Bilateral IJV ligation in a patient without collaterals, massive DAVF
3. Severe	Meets clinical criteria for idiopathic intracranial hypertension	BMI related IIH with elevated LP OP C1–2 Jugular venous compression with symptoms meeting IIH criteria
2. Moderate	Elements of IIH without full criteria Brain Fog, visual obscurations, photopsia, tinnitus, CN dysfunction	Venous congestion and/or hypertension due to venous stenosis or thrombosis between the brain and heart
1. Mild	Fewer elements of IIH May present with CSF leak	CSF leak from multiple diverticula CSF leak from skull base erosion
0. Asymptomatic	No detectable symptoms	Incidental finding in an asymptomatic patient

CN: cranial nerve; CSF: cerebrospinal fluid; DAVF: dural arteriovenous fistulae; IIH: idiopathic intracranial hypertension; IJV: internal jugular vein; LP=lumbar puncture; OP=opening pressure.

Table 3.

CSF pressure grade.

Pressure grade	CSF opening pressure when not demonstrably leaking
+	>25 mmHg
–	>10 mmHg, <25 mmHg

CSF: cerebrospinal fluid.

Table 4.

Patient cases, as organized by anatomical site and severity.

Patient	Anatomical site	Severity grade	Class
1	Central/juxtacardiac	3	3A
2	Intracranial/extra-axial	3	3C
3	Intracranial/extra-axial	4	4C
4	Intracranial/intra-axial	1	1D
5	Intracranial/extra-axial	4	4C
6	Intracranial/extra-axial	2	2C
7	Intracranial/intra-axial	3	3D
8	Cervical	2	2B
9	Cervical	2	2B
10	Cervical	2	2B
11	Central/juxtacardiac	2	2A
12	Central/juxtacardiac	3	3A
13	Central/juxtacardiac	2	2A
14	Central/juxtacardiac	2	2A
15	Central/juxtacardiac	3	3A

Other associations

Jugular venous stenosis and reflux have also been implicated in transient monocular blindness, ⁸⁸ hypothesizing that local venous pressure fluctuations may result in disruption in normal eye physiology. Incompetent jugular valves and jugular reflux have also been implicated in transient global amnesia,^89,90 noting that jugular valve incompetence was found in a greater proportion in patients with prior amnestic events. As alluded to in other portions of the review, CSF leaks have been associated with most of the entities described herein, and it may be reasonable to evaluate for cerebral venous abnormalities in the setting of a non-iatrogenic, non-traumatic CSF leak. Indeed, CSF leaks may be the result of CSF hypertension arising from venous congestion.^91–93 Improvement in Chiari tonsillar descent and syrinx has also been described post transverse sinus stenting with reduction of venous flow gradients. ⁹⁴

Finally, spaceflight associated neuro-ocular syndrome (SANS) has been described with IIH features in a microgravity environment. ⁹⁵ While the pathomechanisms are unclear, another possibility is altered venous return and stasis in a microgravity environment.

Future research

A better understanding of normal physiological cerebral venous flow and pressures is required to determine the complex interplay between the various compartments under the Monro–Kellie hypothesis. Aggregation of symptomatic patients with identifiable venous lesions through registries can allow for the identification of trends in both clinical manifestations of pathologies, as well as similarities in physiological pressure measurements at the time of angiography. Such models can support and ultimately augment existing recommendations for patient selection and treatment decision trees. ⁹⁶

A better understanding of normative and supplementary venous drainage pathways will also be essential for standardizing reporting on the venous networks of such patients. Subgroups of this disease family treated with transverse sinus stenting are highly amenable for study with randomized controlled trials. Similarly, other such subgroups as classified above, which have a reasonable history of medical and surgical intervention, should be further studied for determinations for optimal management.

Animal models to validate and characterize the neurosynaptic, intracellular, and pericellular environment in a state of venous congestion/stasis are necessary to understand better the molecular pathomechanisms and physiology underlying these observations.

Furthermore, non-invasive methods for assessing the extent of disease are needed. Innovative imaging techniques and protocols can be developed for better characterizing flow dynamics within the venous system. Mathematical modeling of patient-specific anatomy as defined by non-invasive imaging can describe pressure and flow dynamics in arterial and venous networks intracranially, with attention given to CSF spaces, under the Monro–Kellie hypothesis. ⁹⁷ Cerebral venous pathology has already been characterized mathematically from anatomical data derived from MRI studies. ⁹⁸

An important goal is a reliable metric and method by which treatable patients can be identified, and the probability of clinical improvement with a proposed treatment. Post-treatment flow changes have already been modeled mathematically for aneurysm stenting. ⁹⁹ However, further work is required to simulate the effects of venous congestion, particularly as it relates to chronic changes to affected venous networks and the formation of venous collaterals.

Limitations

The collection of cases presented was designed to highlight the wide spectrum of anatomical configurations that may result in venous congestion affecting the brain. The fact that the majority of patients are described in the literature as case reports and small case series indicate that these venous disease states are either rare, underrecognized, or both.

Without careful observation and a systematic approach, many patients may go unrecognized or misdiagnosed. Caution is warranted given prior attempts to link venous pathology to multiple sclerosis.^100,101 Given the infrequency and heterogeneity, it is unlikely that randomized trials will be feasible for many of the examples listed.

The anatomical configurations discussed may be non-pathological in many patients. Indeed, Jayaraman et al. ¹⁰² described CTA findings in 108 consecutive CTA angiograms that showed moderate narrowing of the IJV in up to 33.3% on the right and 25.9% of the left. Severe stenosis was seen in 24.1% on the right and 18.5% on the left. However, it should be mentioned that ‘normal’ in that study were patients without multiple sclerosis, presumably with headaches or other comorbidities that would prompt cerebrovascular imaging.

Conclusion

Venous pathology of the brain remains challenging to diagnose, define and study, but there is increasing experience that in carefully selected patients, intervention may be considered. A framework to approach venous lesions will help physician scientists organize their observations and research. The proposed framework considers the site of venous obstruction and severity of symptoms. The neurovascular community should consider venous pathology with greater attention, not merely as a route to address arterial pathology.

The presence of headaches, tinnitus, a sensation of fullness and ‘brain fog’ should prompt consideration of cerebral venous congestion and imaging of the venous network between the brain and heart. Medical therapy should be the first line therapy for such patients, particularly in patients with venous narrowing of the neck, but given that many asymptomatic patients have venous narrowing, operators should be judicious and cautious about recommending operative treatment. Rigorous selection criteria need to be established.