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Received: 9 February 2018    Revised: 17 March 2018    Accepted: 18 March 2018

DOI: 10.1111/cns.12859

REVIEW ARTICLE

Understanding jugular venous outflow disturbance

Da Zhou1,2,3  | Jia-Yue Ding1,2,3  | Jing-Yuan Ya1,2,3 | Li-Qun Pan1,2,3 | 

Feng Yan2,3,4 | Qi Yang3,5 | Yu-Chuan Ding3,6 | Xun-Ming Ji2,3,4 | Ran Meng1,2,3

1
Department of Neurology, Xuanwu Hospital, 
Capital Medical University, Beijing, China Summary
2
Advanced Center of Stroke, Beijing Institute Extracranial venous abnormalities, especially jugular venous outflow disturbance,
for Brain Disorders, Beijing, China
were originally viewed as nonpathological phenomena due to a lack of realization and
3
Department of China-America Institute
exploration of their feature and clinical significance. The etiology and pathogenesis
of Neuroscience, Xuanwu Hospital, Capital
Medical University, Beijing, China are still unclear, whereas a couple of causal factors have been conjectured. The clini-
4
Department of Neurosurgery, Xuanwu cal presentation of this condition is highly variable, ranging from insidious to sympto-
Hospital, Capital Medical University, Beijing,
China matic, such as headaches, dizziness, pulsatile tinnitus, visual impairment, sleep
5
Department of Radiology, Xuanwu disturbance, and neck discomfort or pain. Standard diagnostic criteria are not availa-
Hospital, Capital Medical University, Beijing, ble, and current diagnosis largely depends on a combinatory use of imaging modali-
China
6 ties. Although few researches have been conducted to gain evidence-­based
Department of Neurosurgery, Wayne State
University School of Medicine, Detroit, MI, therapeutic approach, several recent advances indicate that intravenous angioplasty
USA
in combination with stenting implantation may be a safe and efficient way to restore
Correspondence normal blood circulation, alleviate the discomfort symptoms, and enhance patients’
Ran Meng, Xuanwu Hospital, Capital
quality of life. In addition, surgical removal of structures that constrain the internal
Medical University, Beijing, China.
Email: ranmeng2011@pku.org.cn jugular vein may serve as an alternative or adjunctive management when endovascu-
lar intervention is not feasible. Notably, discussion on every aspect of this newly rec-
Funding information
National Key R&D Program, Grant/Award ognized disease entity is in the infant stage and efforts with more rigorous designed,
Number: 2017YFC1308401; National
randomized controlled studies in attempt to identify the pathophysiology, diagnostic
Natural Science Foundation, Grant/Award
Number: 8137289; Project of Beijing criteria, and effective approaches to its treatment will provide a profound insight into
Municipal Top Talent of Healthy Work,
this issue.
Grant/Award Number: 2014-2-015

KEYWORDS
diagnosis, jugular venous outflow disturbance, pathophysiology, tinnitus, treatment

1 |  I NTRO D U C TI O N
It is well acknowledged that cerebral arterial and venous diseases,
such as acute and chronic ischemic or hemorrhagic brain lesions,
cerebral venous thrombosis (CVT), and nonthrombotic cere-
bral venous sinus stenosis, have been commonly investigated.
However, the role of extracranial venous disorders in the central
nervous system (CNS), particularly the jugular vein abnormality,
is far from comprehensive. Recently, jugular venous outflow dis-
turbance secondary to various factors that interfere with normal
The first two authors equally contributed to this study.
cerebral blood drainage has gained a particular interest. In our
clinical practice, a cohort of nonthrombotic and nonosseous com-
pressive internal jugular vein (IJV) stenosis patients with idio-
pathic intracranial hypertension-­mimic presentations have been
noticed.7 Previous studies have also revealed that IJV anomalies
1-6 are probably related to a wide range of neurological diseases and
their corresponding clinical manifestations. 8-17 Herein, in this
review, we highlight the need for a better understanding of IJV
outflow disturbance-­related CNS disorders, and clinical aspects
of IJV anomalies regarding the etiology, proposed pathogenesis,
clinical manifestations, and diagnosis as well as therapeutic regi-
mens are recapitulated.

CNS Neurosci Ther. 2018;24:473–482. © 2018 John Wiley & Sons Ltd |  473
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474       ZHOU et al.
2 |  E TI O LO G Y
Based on the available evidence, a number of factors might be re-
sponsible for the abnormal IJV outflow and those can be briefly cat-
egorized as follows.
2.1 | Intraluminal anomalies
Intraluminal anomalies of the IJV refer to the innate defective or ac-
quired structures extending from the vessel wall, which may impair
the normal blood flow draining from the brain. These anomalies gen-
erally include membrane, web, multisepta, flaps, and malformed ve-
nous valves such as long, ectopic, accessory or fused leaflet, inverted
valves, and double valves (Figure 1).18-21 Anatomical conditions such
as arachnoid granulations may pose mass effect on venous vessels
and simulate focal thrombosis as well. Doppler ultrasonography and
intravascular ultrasound are two modalities that are able to clearly
visualize intraluminal structures. 21 Notably, the prevalence of intra-
luminal anomalies in the general population and their relevance to
the extent of IJV narrowing are currently unknown.
2.2 | Extraluminal anomalies
Anatomical variants and masses outside the IJV are vital factors
that can compress the IJV and narrow the venous lumen. It has been
proposed that mediastinal tumors or goiter, osseous impingement,
particularly bony structures between the styloid process and lateral
mass of cervical vertebra at C1 segment, and adjacent abnormally
engorged arteries as well as aneurysms are correlated with IJV ste-
22-25
nosis or occlusion (Figure 1). Compelling studies have also un-
raveled a link between neurogenic thoracic outlet syndrome and IJV
26
abnormalities.
F I G U R E   1   Proposed etiologies
of internal jugular vein (IJV) outflow
disturbance. IJV outflow disturbance
may be secondary to either extraluminal
compression or intraluminal anomalies.
Extraluminal compression can result
from enlarged thyroid gland (A), and
adjacent artery (B) or bony structures (C).
Intraluminal anomalies include thrombi
(D), septum (E), and elongated valve (F)
2.3 | Systemic factor-­related IJV anomalies
The origin of either intraluminal or extraluminal structural anoma-
lies may be a consequence of comorbidities including bacterial or
viral infections, inflammatory processes, and chronic cardiovascular,
renal osteodystrophy, or pulmonary diseases. 27
Jugular venous reflux (JVR) occurs when there exists an abnor-
mally elevated venous pressure gradient. Sustained JVR may render
the IJV valves incompetent and pose a retrograde transmitted pres-
sure into the CNS, whereby hampering the cerebral parenchyma and
circulation. 28,29 It seems that the prevalence of JVR increases with
age and the severity of JVR-­associated white matter lesions (WMLs)
is aging-­dependent. 29,30 Moreover, a couple of vascular risk factors
such as smoking, lack of exercise, and obesity have been reported in
association with the presence of venous abnormalities in the IJV.31,32
3 | PRO P OS E D PATH O PH YS I O LO G Y
So far, the understanding with regard to the underlying mechanisms
of IJV outflow disturbance-­induced brain structural and functional
disorders is limited. To the best of our knowledge, there are several
hypotheses that might help answer these conundrums.
3.1 | Anatomic characteristics of the IJV
The two IJVs are the largest cervical veins that play an indispen-
sable role in draining cerebral venous blood flow. Physiologically,
the paired IJVs can interconnect with each other via anastomosing
venous plexi, which are considered as main collateral channels that
maintain a fluent venous drainage when the IJVs are restricted.33-35
Communications are also present between the IJVs and the other
ZHOU et al.
extracranial cervical veins such as the anterior condylar confluent
and its branches. In the condition of significant IJV narrowing, extra-
jugular venous collaterals will remarkably generate to compensate
for the impeded primary venous outflow pathways. The IJV valve
functions as a buffer that can prevent sustained retrograde trans-
mitted venous blood and pressure into the cranium.
3.2 | Decreased cerebral perfusion
Hemodynamic alterations such as a decline in the cerebral perfusion
have been observed in patients with extracranial venous drainage
abnormalities.36,37 An association might be present between the
extent of hypoperfusion in the brain parenchyma and the severity
36
of IJV insufficiency. Additionally, there is evidence indicating that
correction of the abnormal flow due to nonmobile jugular leaflets in
the IJV is able to ameliorate cerebral hypoperfusion and decrease
38
enlarged brain ventricles. Reduced cerebral blood flow (CBF) can
result in the depletion of glucose and oxygen, followed by subse-
quent detrimental events such as neuronal mitochondrial dysfunc-
tion and neural cell death. Although it is still difficult to conclude
how the IJV abnormalities impact the brain hemodynamics, altered
vascular structure and compliance induced by elevated intracranial
venous pressure are assumed to play requisite roles. 20,39 It is note-
worthy that in the scenario of multiple sclerosis (MS) combined with
impaired extracranial venous drainage, CBF reduction might result
from vessel stenosis or occlusion secondary to iron overload, inflam-
matory cells, fibrin deposits, or others.40
3.3 | Cerebral microvascular structures impairment
It has been speculated that impaired venous outflow may weaken
the blood-­brain barrier (BBB), possibly via downregulating tight junc-
tion proteins and upregulating adhesion molecules in the vascular
41,42
endothelium. BBB damage enables the translocation of cells in-
cluding monocytes, erythrocytes, and other inflammatory cells into
the extracellular space, thus triggering cascades of responses such
as immunological or inflammatory reactions, cell injury, and fibrin or
iron deposition. Researchers also suggest that prolonged elevated
intracranial venous pressure can lead to hyalinosis and thickening of
venous vessel wall, endothelial dysfunction, and arteriolar regulation
43-46
impairment. Furthermore, in a previous study, it is interesting to
notice that patients with extracranial venous drainage abnormali-
ties displayed markedly decreased venous vasculature visibility on
susceptibility-­weighted imaging (SWI) venography.47
3.4 | Abnormal cerebrospinal fluid dynamics
Zamboni et al48 firstly reported a significantly lower net cerebrospi-
nal fluid (CSF) flow in MS patients with venous outflow disturbances,
the severity of which might be tightly correlated with the CSF flow.
Following this, Zivadinov et al49 further discovered that relieving the
impeded extracranial venous flow by percutaneous transluminal an-
gioplasty could promote the CSF flow while lower the CSF velocity.
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Increased CSF pulsatility was also observed in IJV abnormalities pa-
tients without any history of MS, implying that altered intracranial
CSF dynamics might primarily result from impaired cerebral venous
drainage instead of MS itself.50 Even though the precise mechanisms
involved are poorly understood, it is reasonable to postulate that
IJV outflow disturbance-­related intracranial venous hypertension,
particularly in the superior sagittal sinus, is capable of blunting the
absorption of CSF through the arachnoid villi, leading to abnormal
CSF dynamics.
3.5 | Aging and IJV
Advancing age has been shown to be associated with a group of
structural and functional changes of blood vessels, such as arteriolar
stiffness and tortuosity, endothelial dysfunction, decreased micro-
vascular density, and BBB impairment.51 Nevertheless, the extent
to which the morphology and function of the IJV alters with senes-
cence has not been fully explored. A high prevalence of JVR in the
elderly as well as more prominent age-­related WMLs among those
with severe JVR is suggestive of the role of aging in IJV disturbance-­
associated CNS disorders.30 In addition, the cross-­sectional area
(CAS) of the IJV in healthy volunteers seems to increase with aging
even after adjusting for vascular risk factors, indicating a propensity
to elevated venous pressure and vessel distension.52 Many ques-
tions remain unanswered at the moment, and it goes without saying
that much more work is required to validate the association between
aging and extracranial venous abnormalities.
4 | C LI N I C A L M A N I FE S TATI O N S
There is strong evidence showing that venous outflow abnormali-
ties can contribute to the development of intracranial hypertension.
The degree of clinical presentations of IJV outflow disturbance may
vary from none to severe based on individual variation and compen-
satory capability. Broadly speaking, these characteristics such as
headache, pulsatile tinnitus, visual impairment, sleep disturbance,
and neck discomfort or pain may mimic, at least partially, those of
idiopathic intracranial hypertension and chronic cerebral circulation
insufficiency. 2,7,53
Constant or intermittent head noises, known as intracerebral
noise and unilateral or bilateral tinnitus, are specific features of
the disease that are highly indicative of altered blood flow pat-
terns in the IJV lumen. Some of other prevalent symptoms include
headache, heavy-­h eadedness, dizziness, sleep disturbance, neck
discomfort, and back pain. Ophthalmological discomforts such as
eye soreness and eye dryness, dysmorphopsia, diplopia, blurred
vision, and even visual loss are frequently complained in a cer-
tain amount of patients. Patients may also have decreased cog-
nitive function and behavioral changes, which can be mistaken
for psychiatric issues. Physical findings are of limited localizing
value. Abducens nerve weakness and neck stiffness, although
not usual, may sometimes be detected in this condition. Notably,
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476       ZHOU et al.

abnormalities identified in the ophthalmic examination such as im-

paired visual acuity, visual field defects, and papilledema should
raise urgent suspicion.
5 |  D I AG N OS I S
So far, there are no established standardized diagnostic criteria for
extracranial venous abnormalities exist. Patients with unexplained
aforementioned clinical features, particularly in the absence of
obvious arterial vascular system-­related disorders, should be sus-
pected as likely being at risk of venous issues. It should be noted
that the IJV is easily influenced by a number of factors such as
respiration, posture, cardiac function, hemodynamic status, and
compression from surrounding structures. 54,55 More importantly,
it is arduous to clearly differentiate clinically significant abnormal-
ities form physiological variations considering the high anatomical
variability of the IJV. Therefore, single diagnostic modality is defi-
nitely far from enough, and it is likely that a more comprehensive
approach is warranted to screen, diagnose, and monitor these ve-
nous abnormalities.
5.1 | Doppler ultrasonography
Doppler ultrasonography is a widely used imaging technique that
has also been recently studied in the field of IJV abnormalities.56-60
Merits with respect to the noninvasiveness, free of ionizing radia-
tion, easy portability, and low expenditure render it the first option
for routine examination. Besides, it can provide dynamic hemody-
namic information such as blood flow and blood velocity with high
resolution and enable the assessment of intraluminal anomalies or
developmental variants. Major drawbacks of ultrasonography in-
clude poor visualization of some parts of the IJV such as the cer-
vical region and the jugular bulb, time-­
consuming, and operator
skill-­dependent.
5.2 | Magnetic resonance venography
Compared with Doppler ultrasonography, magnetic resonance ve-
nography (MRV) is capable of depicting a more comprehensive
view of the morphology of the head and neck veins, (Figure 2).61-67
Generally, it takes less time and is relatively operator-­independent,
enabling the possibility of being utilized in the blinded and multicenter

F I G U R E   2   Neuroimaging examples of patients with bilateral internal jugular vein (IJV) stenosis. Magnetic resonance venography (MRV)
images including (A,D) display the presence of bilateral IJV stenosis (short arrows) surrounded by abnormally engorged and tortuous
collaterals (long arrows). Three-­dimensional reconstruction images of CT including (B,C,E,F) further reveal the IJV stenosis might due to the
compression from nearby arteries
ZHOU et al.
clinical study design. In addition to the identification of luminal ste-
nosis, advanced MR sequences such as phase-­contrast MRV and
4D flow imaging hold the potential of evaluating intraluminal blood
flow patterns and more notably, the condition of collateral circula-
tion surrounding the IJV, which is viewed as a vital compensatory
65-67
mechanism for impaired venous outflow. However, MRV cannot
detect intraluminal anomalies such as malformed valves, membrane,
and septa in more detail, and it may sometimes even underestimate
the venous caliber.
5.3 | Computed tomography venography
Although the available evidence-­based literature regarding the
effectiveness of computed tomography venography (CTV) tech-
niques in the extracranial cervical veins is sparse, it may display
similar advantages as MRV for assessing the global status of the IJV.
Moreover, unlike MRV, CTV is able to visualize the conditions of the
azygos vein, which is an important component for the diagnosis of
chronic cerebrospinal venous insufficiency (CCSVI).7,68 Contrast CT,
usually performed along with CTV, is useful to help exclude the bony
impingement-­
associated IJV stenosis or occlusion (Figure 2). The
main disadvantages concentrate on the use of contrast agents and
exposure to low dose of radiation, both of which may limit the ap-
plication of CTV in a certain group of patients, including those who
have renal diseases or history of contrast allergy and get pregnant.
F I G U R E   3   Cather venography of unilateral internal jugular vein (IJV) stenosis. A, shows severe stenosis of the IJV on the right side (blue
arrow) and a significantly increased number of abnormal tortuous collateral veins (red arrows) before stenting. B, shows, after intervention
with stenting, the former stenotic lumen is recanalized (blue arrow) and the abnormal collaterals were distinctly reduced (red arrows)
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5.4 | Cervical plethysmography
Strain-­gauge cervical plethysmography (SGCP) is considered to be an
effective and noninvasive method that allows researchers to obtain
an overall view of venous function on the basis of venous capaci-
tance and resistance. Through a sensor encircling the cervical seg-
ment of the body, Zamboni et al69 discovered a profound difference
in the extracranial venous return-­associated parameters between
patients with CCSVI and healthy controls. In another study, Beggs
demonstrated that the mean hydraulic resistance of the extracranial
venous system measured by the means of SGCP in CCSVI patients
was significantly higher than controls.70 Nonetheless, whether or
not SGCP can be a complementary technique to other modalities for
diagnosing venous drainage abnormalities requires further studies
to validate.
5.5 | Catheter venography and ultrasonography
Despite being viewed as a gold standard imaging technique for
evaluating the degree of vascular stenosis and measuring the trans-­
stenotic pressure gradient for planning endovascular procedures,
catheter venography (CV) is unable to provide enough information
regarding the intraluminal anomalies that affect the regular venous
outflow (Figure 3). 20,71-73 Additionally, the features of invasive-
ness and being exposed to contrast agents or radiation render it a
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478       ZHOU et al.
suboptimal choice in a clinical scenario where the IJV outflow dis-
turbance is suspected.
Similar to the conventional sonography, intravascular ultraso-
nography (IVUS) is significantly superior to CV in detecting intralu-
minal malformations such as IJV valves and thrombi among patients
19-21
with abnormal extracranial venous abnormalities. Besides, IVUS
is capable of measuring venous vascular cross-­sectional area and cir-
cumference more accurately, whereby providing a relatively reliable
determination of the stenotic segments. 20 It also allows a better vi-
sualization of the whole course of the IJVs, which may be neglected
by the conventional sonography. These advantages might account
for the higher rate of venous (IJVs and azygos veins) abnormalities
measured by IVUS in comparison with CV. 21 Currently, IVUS is not a
routinely utilized modality for either the diagnosis of IJV outflow dis-
turbance or the guidance of selecting the most appropriate stenting/
angioplasty procedure, and there is no consensus available regarding
the optimal procedural endpoint.
5.6 | Other diagnostic techniques
MR black-­b lood thrombus imaging technique (MRBTI), as a novel
approach for the detection of CVT, has begun to garner an increas-
ingly attention of researchers. This noncontrast method could
suppress the blood signal and differentiate the thrombi from sur-
rounding structures, enabling a direct visualization and quantita-
74
tive measurement of intraluminal thrombi with high accuracy. To
be noted, a set of patients with IJV outflow disturbance display
thrombi inside the unilateral and/or contralateral IJV, and they
sometimes concomitantly have CVT as well. In this regard, MRBTI
may hold promise to serve as a valuable alternative to current
techniques.
Severe papilledema, secondary to elevated intracranial hyper-
tension, if not diagnosed and intervened promptly, may result in
permanent visual damage or even blindness. Optical coherence
tomography (OCT) has emerged as a noninvasive diagnostic tool
for evaluating optic nerve status by measuring parameters such as
retinal nerve fiber layer thickness and total retinal measurements.75
This kind of approach could be of interest in a wide cohort of pa-
tients who get admitted to medical facilities due to ophthalmological
complaints.
6 |  TR E ATM E NT
At present, there is no consensus among researchers with respect to
the optimal strategy for IJV outflow disturbance due to an absence
of robust evidence. The multidisciplinary team approach (a compre-
hensive strategy with two or more different techniques) has been
gradually accepted as a novel notion aiming at preventing and con-
trolling clinical manifestations as well as complications. The primary
goal of treating IJV outflow disturbance focuses on the restoration
of normal hemodynamics and relief of headaches, tinnitus, and other
symptoms associated with elevated intracranial pressure.
After excluding the likelihood of hemorrhage, standard anticoag-
ulant therapy, including subcutaneous low molecular weight or intra-
venous heparin for several days and subsequent bridging with oral
anticoagulants, is recommended for patients with IJV outflow distur-
bance either secondary to or in combination with the following condi-
tions: (i) thromboembolic events such as CVT and IJV thrombosis; (ii)
planning for surgical revascularization; and (iii) the presence of venous
valve malformation or other factor-­related IJV stenosis and coexisting
hypercoagulability state.76-79 Patients with IJV stenosis or thrombosis
originated from suspected bacterial infection should be administered
with antibiotics appropriately. Antiepileptic drugs are not indicated
unless there is evidence of seizures with or without parenchymal le-
sions. Despite the lack of high-­quality randomized controlled trials on
the effectiveness of carbonic anhydrase inhibitors or diuretics on the
functional outcomes of patients with impeded extracranial venous
outflow, acetazolamide is still a commonly utilized complementary
therapy for lowering intracranial hypertension in clinical practice.7
For those with thrombosis-­related venous stenosis, endovascu-
lar intervention including intravenous thrombolysis and mechanical
thrombectomy can be considered if aggravation of clinical symp-
toms occurs despite intensive medical treatment.79
Intraluminal defects are regarded as main etiologies, causing a sig-
nificant delay of jugular flow. Percutaneous transluminal balloon an-
gioplasty and stenting have been demonstrated to be feasible and safe
with low procedure-­related morbidity and mortality among patients
with CCSVI.80,81 Moreover, fixing the flow in the IJV via endophle-
bectomy of the jugular valve or septum together with patch angio-
plasty using the autologous great saphenous vein seems to robustly
ameliorate cerebral perfusion.38,82 Nevertheless, it is noteworthy that
not every venous valve malformations should be intervened surgically,
especially if there is no indication such as uncontrolled symptoms
and predicted severe complications of the lesions. These intraluminal
anomalies with obstructive nature like membrane, web, flaps, and mal-
formed venous valves may respond distinctly to different therapeutic
strategies as well.
To evaluate the safety and efficacy of venous percutaneous
transluminal angioplasty in patients with both relapsing-­remitting
MS and CCSVI, a multicenter, randomized, and controlled clinical
trial was conducted by Zamboni et al,83 who reported that this sur-
gical intervention should not be recommended for treating patients
with MS as there was no significant improvement on the functional
outcome or reduction in new combined brain lesions over 1-­year
follow-­up detected. A recent study concluded that nonthrombotic
unilateral or bilateral IJV stenosis in the absence of any intracranial
pathologies might account for a vital part of idiopathic intracranial
hypertension.7 Considerable resolution of the trans-­stenotic mean
pressure gradient and abnormal extracranial venous collaterals, re-
duction in intracranial pressure, and improvement of clinical mani-
festations including headache, tinnitus, and visual impairments were
achieved following the correction of the IJV with intravenous bal-
loon angioplasty combined with stenting (Figures 3 and 4). Of note,
no stenting-­related adverse events occurred in this group of patients
within 12 ± 5.6 months of follow-­up.
ZHOU et al. |
      479

(A) (B)

(C) (D)

F I G U R E   4   Fundal photographs and corresponding optical coherence tomography in a patient with bilateral internal jugular vein (IJV)
stenosis. Fundal photographs and corresponding optical coherence tomography (OCT) pictures of both eyes during hospital but before
stenting: (A) Right and (B) left show severe papilledema with disk elevation, periphery halo, and congested/tortuous retinal vessels;
hemorrhage is noticed in the right eye; the FPG scores are 5 and 4 for right and left eyes, respectively; OCT pictures show an significant
increase in retinal nerve fiber layer thickness. Fundal photographs and corresponding OCT pictures of both eyes at approximately 15 mo of
follow-­up after stenting: (C) Right and (D) left show remarkable improved papilledema with disappearance of tortuous vessels and optic disc
edema; the FPG scores were 0 for both eyes; the retinal nerve fiber layer thickness of each eye recovers to normal range

Extrinsic compression of the IJV secondary to the osseous and
muscular origins (such as the styloid process, the posterior belly of
the digastric muscle, and the transverse process of an adjacent ver-
tebra) has been found in a set of unselected patients who underwent
computed tomography angiography (CTA).84 However, some of the
IJV stenosis may not be taken as pathological considering no evi-
dence of abnormal collateral formation. Patients may display central
venous hypertension-­associated symptoms when this impingement
either occurs bilaterally or affects the dominant IJV. Surgical resec-
tion of culprit structures is gradually emerging as the choice of treat-
ment. Among patients with identified extrinsic impingement of the
IJV between the styloid process and the lateral mass of cervical ver-
tebra at C1 segment, venous stenting alone was deemed ineffective
given the compressive nature and delayed stenting complications
were also recorded. 24,25 In this setting, modified styloidectomy is
regarded as a potential adjunctive therapeutic approach, which not
only alleviates IJV stenosis-­associated intracranial hypertension but
salvages the probable complications of stenting.
Fulminant ophthalmological issues, in which severe deterioration
of the optic nerve function is rapid, occur in a few patients with IJV
stenosis. Optic nerve sheath fenestration (ONSF) may serve as an in-
triguing surgical intervention to improve or stabilize visual functions
when the origin of stenosis cannot be corrected as early as possible.85
7 | CU R R E NT C H A LLE N G E S
Unlike the arterial system, the role of extracranial venous drain-
age abnormalities is largely unknown and several conundrums lying
ahead await to be tackled.
The IJV is complicated with variability between individuals, and it
harbors the feature of asymmetry, where one IJV may be much larger
than the other as a result of preferential intracranial venous drainage.
IJV stenosis has also been reported in healthy subjects without any
disease history. The characteristics of venous wall predispose the IJV
to the impacts from a range of factors such as respiration, postural
alteration, hydration condition, and nearby structures. Accordingly,
differentiating what are physiological variants from what are truly
anomalies is a huge challenge. Abnormal formed intracranial or extra-
cranial collateral circulation is believed to be the most valuable evi-
dence, which suggests the presence of impaired venous outflow and
venous hypertension. To the best of our knowledge, it is necessary
to take both the status of collaterals and clinical symptoms/signs into
consideration when evaluating the IJV stenosis.
Current definition of venous stenosis is primarily based on the
experience from the arterial criteria, which are obviously not appro-
priate. The exact degree of IJV stenosis that could result in hemo-
dynamic alterations as well as increased cerebral venous pressure
is not as well understood. More comprehensive diagnostic criteria
derived from a combination of diverse imaging modalities and other
novel techniques need to be established.
It remains unclear the real contribution of intra-­or extraluminal
anomalies to the severity of IJV outflow disturbance. Additionally,
available data with respect to the association between the presence
of abnormalities in the IJV and confounders, such as aging, gender,
ethnicity, infection, immunological disorders, and other identified vas-
cular risk factors are scarce. Figuring out these puzzles may promote a
better understanding of the etiology of IJV outflow disturbance.
The proposed pathophysiology of impeded extracranial venous
drainage can be briefly summarized as following three aspects: (i) re-
duced cerebral blood perfusion; (ii) altered CSF dynamics; and (iii)
disrupted intracranial microvasculature. However, the detailed mecha-
nism through which venous drainage abnormalities affect the cerebral
circulation is basically unexplored that requires to be further addressed.
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480       ZHOU et al.
Given the complex and undetermined etiology and pathophys-
iology, treatment for IJV outflow disturbance remains a challenge. It
also raises intriguing questions as to whether venous outflow obstruc-
tion is correlated with some CNS disorders including MS, migraine,
Parkinson’s disease, cough syncope, Alzheimer’s disease, Meniere dis-
ease, transient global amnesia, transient monocular blindness, and leu-
koaraiosis, and if indeed a link exists, customized therapeutic regimens
must be designed for different groups of patients.10,12,13,16,17,29,30,86-90
Although preliminary findings regarding the efficacy of endovascular
therapy in relieving symptoms from IJV stenosis are a step forward,
further investigations are required to evaluate the short-­and long-­term
benefits of surgical interventions, as most of the pilot studies have been
single-­
center, retrospective, uncontrolled trials without quantifiable
endpoint measures. Moreover, successful establishment of collaterals
with nonsurgical maneuvers may be another novel direction for thera-
peutic intervention, particularly when there is no indication for surgery.
8 |  CO N C LU S I O N S
In summary, IJV outflow disturbance is an increasingly recognized
disease entity among patients with or without other CNS disorders.
The clinical manifestation of IJV outflow disturbance is heterogeneous
and sometimes even insidious. So far, the understanding regarding its
etiology, pathogenesis, diagnostic criteria, therapeutic strategies, and
long-­term clinical outcomes is far from enough, which may have clini-
cians underestimate the scale of the problem, resulting in misdiagno-
sis and treatment delay. Future efforts with more rigorous designed
clinical studies aiming at figuring out these unknown mysteries and
exploring either surgical or nonsurgical interventions to optimize the
treatment for IJV outflow disturbance will provide a profound insight
into this issue.
AC K N OW L E D G E M E N T S
The authors would like to thank the partial support from the National
Key R&D Program (2017YFC1308401), the National Natural Science
Foundation (81371289), and the Project of Beijing Municipal Top
Talent of Healthy Work (2014-­2-­015) of China. The funding agencies
had no role in the design and conduct of the study, in the collection,
analysis, and interpretation of the data, or in the preparation, review,
or approval of the manuscript.
C O N FL I C T O F I N T E R E S T
The authors declare no conflict of interest.
ORCID
Da Zhou  http://orcid.org/0000-0003-1376-4213
Jia-Yue Ding  http://orcid.org/0000-0003-3562-2187
Ran Meng  http://orcid.org/0000-0003-1190-4710
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How to cite this article: Zhou D, Ding J-Y, Ya J-Y, et al.
Understanding jugular venous outflow disturbance. CNS
Neurosci Ther. 2018;24:473–482.
https://doi.org/10.1111/cns.12859