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Review
Recommendations for the selection and treatment of patients with idiopathic intracranial hypertension for venous sinus stenting
  1. Kyle M Fargen1,
  2. Kenneth Liu2,
  3. Rebecca M Garner1,
  4. Garret P Greeneway1,
  5. Stacey Q Wolfe1,
  6. R Webster Crowley3
  1. 1 Department of Neurological Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
  2. 2 Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA
  3. 3 Department of Neurosurgery, Rush Medical College, Chicago, Illinois, USA
  1. Correspondence to Dr Kyle M Fargen, WakeForest University School of Medicine, Winston-Salem, NC 27013, USA; kfargen{at}wakehealth.edu

Abstract

Introduction Although venous sinus stenting (VSS) has emerged as a promising treatment option for patients with idiopathic intracranial hypertension (IIH) and associated venous sinus stenosis, there is considerable ambiguity regarding patient selection criteria, treatment protocols, and management strategies.

Methods An extensive literature review was performed to identify all reports of VSS in patients with IIH using PubMed. Recommendations for the selection and treatment of patients with IIH with VSS are outlined as determined based on author opinion from supporting studies. Due to the lack of randomized trials and few published prospective studies, standard grading scales for recommendations and level of evidence are not fully applicable and therefore a revised grading scale has been provided for recommendations.

Results The literature review identified a total of eight systematic reviews or meta-analyses and 29 published patient series on VSS. Recommendations for patient selection for diagnostic catheter angiography, angiography procedural considerations, stenting procedural considerations, and retreatment are provided based on the literature. Recommendations that were considered strong included: performance of venous sinus manometry to assess candidacy for treatment prior to stenting; administration of antiplatelet agents prior to stenting and for a follow-up period of at least 3–6 months; performance of post-stenting manometry to confirm resolution of pressure gradient; and performance of repeat angiography and manometry on patients with recurrence of symptoms after resolution with stenting to evaluate for recurrent stenosis.

Conclusion VSS for patients with IIH with venous sinus stenosis is now an established and effective treatment option. These recommendations have been provided, based on a summative review of the available published literature, to assist in standardizing care for patients with IIH undergoing VSS.

  • angiography
  • stent

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Introduction

Idiopathic intracranial hypertension (IIH), previously referred to as pseudotumor cerebri, is a medical condition characterized by a combination of intractable headaches, papilledema, visual symptoms, tinnitus, and an elevated cerebral spinal fluid (CSF) opening pressure on lumbar puncture in the absence of an intracranial mass. According to baseline characteristics of untreated patients with IIH enrolled in the IIH Treatment Trial, headache was the most commonly reported symptom, followed by transient visual obscurations, pulsatile synchronous tinnitus, back pain, and double vision.1 The incidence of IIH in the general North American population is roughly 1–2 per 100 000.2 3 IIH is frequently seen in obese women aged 22–44 years, with an incidence in this population of 14.9–19.3 per 100 000.3 Due to the refractory nature of the disease, the treatment strategy for patients with IIH is often multimodal. Historically, such treatment strategies have included weight loss, carbonic anhydrase inhibitors, and therapeutic lumbar punctures. However, 38–45% of patients experience eventual worsening or recurrence of symptoms within 6–10 years despite these strategies.4 5 Permanent CSF diversion and optic nerve sheath fenestration have also been explored as treatment options. However, these strategies have limitations.6

More recently, venous sinus stenting has matured as a promising treatment for IIH patients with associated venous sinus stenosis.7 Venous sinus stenosis can result in cerebral venous outflow obstruction that subsequently results in elevated intracranial pressure. Some studies have shown areas of focal stenosis in the venous sinuses in roughly 30–93% of patients diagnosed with IIH.8 The effect of stenting on intracranial pressure (ICP) is well known. Fargen et al reported a case of a woman undergoing ICP monitoring with an immediate decrease in ICP following venous sinus stenting.9 In a prospective case series of 10 patients, Liu et al reported an immediate decrease in ICP in patients who underwent venous sinus stenting while undergoing ICP monitoring.10 Similarly, in a series of 10 patients, Matloob et al reported an immediate decrease in ICP that was maintained over a 24-hour period in patients with concomitant ICP monitoring.11

Venous sinus stenting has been associated with significant symptomatic improvement. Systematic reviews and meta-analyses have been conducted to evaluate symptom improvement in patients following venous sinus stenting. These studies demonstrated 78–83% improvement in headache, 87–97% improvement in papilledema, 74–85% improvement in visual symptoms, and 95% improvement in tinnitus following stenting.7 12–17 The reported complication rates associated with stenting vary in the literature but are low, with an overall complication rate of 1.4–7.4% (major complications 1.6–2.9% and minor complications 1.6–4.4%).7 12–17

Although venous sinus stenting has emerged as a promising treatment option for IIH patients with venous sinus stenosis, there is considerable ambiguity regarding patient selection criteria, treatment protocols, and management strategies. This review aims to synthesize the literature into recommendations for the selection and treatment of patients with idiopathic intracranial hypertension with venous sinus stenting.

Methods

An extensive literature review was performed to identify all reports of venous sinus stenting in patients with IIH prior to February 2018. Using PubMed, a search was performed of the scientific literature using a combination of the keywords ‘Dural venous sinus stent’, ‘Venous sinus stent’, ‘Idiopathic intracranial hypertension’, and ‘Pseudotumor cerebri,’ in order to identify a comprehensive list of literature articles of patients with IIH undergoing venous sinus stent placement. The results of this literature search were used to establish recommendations and best practices for the selection and treatment of patients with IIH with venous sinus stenting. Some studies were excluded due to inadequate or irrelevant data. Included meta-analyses and systemic reviews are listed in table 1.

Table 1

Systematic reviews and meta-analyses reporting on treatment of idiopathic intracranial hypertension with venous sinus stent placement

Recommendations for the selection and treatment of patients with IIH using venous sinus stenting are outlined as determined based on expert opinion from supporting studies. Due to the lack of randomized trials and few published prospective studies, standard grading scales for recommendations and level of evidence are not fully applicable. For the purposes of this review, a revised grading scale has been provided for recommendations (table 2).

Table 2

The United States Preventative Services Task Force (USPSTF) and American Heart Association (AHA)/American Stroke Association (ASA) grading scales for recommendations and level of evidence. Due to the lack of published supportive randomized or prospective evidence, a revised scoring system is provided for establishing recommendations

Recommendations

Patient selection for diagnostic catheter angiography

Imaging-based selection

In general, most studies report using non-invasive imaging-based selection criteria to determine patient selection to undergo diagnostic catheter angiography. The reasons most commonly cited for obtaining non-invasive imaging prior to the venogram are to exclude other causes of ICP, and evaluation of stenosis prior to performing angiography. The most frequently used non-invasive imaging techniques in patients with IIH for diagnostic angiography are CT venography (CTV), magnetic resonance venography (MRV), or both.10 11 18–32 Multiple studies use demonstrated stenosis on CTV or MRV as criteria for proceeding with diagnostic catheter angiography, and three studies specifically cite requiring stenosis >50% when deciding whether or not to proceed with stenting.18 19 33MRI and CT scans are frequently used to rule out other potential causes of increased ICP such as a mass lesion.20 21 Some studies also use magnetic resonance angiography (MRA) to rule out other potential causes.10 19 22–24 Of the studies reviewed, 23 out of 29 (79%) obtained non-invasive imaging prior to having patients proceed with diagnostic angiography. Of the 23 studies that utilized imaging-based selection criteria, 20 (87%) used CTV, MRV, or both in search of radiographic signs of venous sinus stenosis prior to stenting patients. Six of the 29 studies did not use imaging-based selection criteria for angiography.

Studies have suggested, however, that transverse sinus hypoplasia or stenosis are found at relatively high frequencies in the normal population. Durst et al found the prevalence of unilateral transverse sinus stenosis or hypoplasia in the normal population to be 33% and the prevalence of bilateral transverse sinus stenosis to be 5%.25 Radvany et al observed in a study of 12 patients that two patients who underwent catheter venography had no pressure gradient, despite apparent transverse sinus stenosis on CTV.26 These findings suggest that CTV and MRV may have suboptimal sensitivity or specificity in predicting symptomatic venous outflow obstruction. Ultimately, CTV or MRV may be worthwhile to diagnose an area of anatomical stenosis but are unable to determine whether that is associated with a physiologic gradient. In one study where all medically refractory patients underwent catheter angiography regardless of MRV findings at time of referral, MRV sensitivity was <0.5 in detecting a significant stenosis associated with a pressure gradient.27 In a second retrospective study of venograms with manometry, Levitt et al found that only 65% of patients with prior non-invasive imaging (CTV/MRV) demonstrated dural venous sinus abnormalities on imaging.28

It is reasonable to suggest that providers obtain non-invasive imaging prior to having patients with IIH undergo diagnostic angiography, as imaging findings of stenosis in the setting of IIH are highly associated with pressure gradient findings on diagnostic angiography and manometry. In addition to the presence or absence of stenosis, non-invasive imaging can provide other information that may be useful to know prior to performing a cerebral angiogram. For instance, a dural arteriovenous fistula can present with some of the symptoms of IIH, particularly those with pulse-synchronous tinnitus. It is also useful in identifying a hypoplastic or atretic sinus. If the subsequent catheter angiography includes arterial imaging, this may not be critical information to know ahead of time. However, if the planned catheter angiography is limited to venous imaging and pressure measurements, knowledge of a hypoplastic transverse sinus may influence the subsequent intracranial catheterization and limit the associated risks. While MRV can be useful, it is also reasonable to use catheter angiography with manometry without prior non-invasive venographic imaging based on the conflicting evidence regarding incidence of stenosis in the normal population and lack of gradient with evidence of stenosis. It is possible to find a pressure gradient in the absence of stenosis on non-invasive imaging, and therefore one could argue that a diagnostic venogram should be performed on patients with IIH regardless of MRV or CTV findings.

Recommendations
  • Many authors support using non-invasive venous imaging to detect sinus stenosis and determine candidacy for angiography. However, the high rate of venous sinus variability in normal patients suggests that the utility of non-invasive venous imaging is questionable. It is reasonable to use non-invasive venous imaging as a screening tool to determine candidacy for catheter angiography (Moderate).

  • Given that a proportion of patients that undergo angiography and manometry without pre-imaging studies or without a demonstrated stenosis on MRV or CTV are found to have significant pressure gradients, it is reasonable to suggest that IIH patients without previous imaging studies or with studies demonstrating no evidence of sinus stenosis undergo diagnostic venography regardless (Weak).

Medically refractory symptoms

Failed medical treatment for IIH is one of the most consistent indications for a patient with IIH to undergo diagnostic catheter angiography. According to Donnet et al, failed medical treatment is defined as persistent visual symptoms or persistent headaches in spite of treatment with acetazolamide.22 Most of the studies reviewed report performing angiography in patients who have failed medical treatment and thus have persistent visual symptoms or persistent headaches in spite of treatment with acetazolamide.10 18 19 21 22 24 26 29 31 34–36 Of the studies reviewed, 18 out of 29 (62%) mentioned using a medically refractory disease course as an indication for a patient to undergo diagnostic angiography. Of the meta-analyses that were reviewed, none specifically mentioned using medically refractory symptoms as an indication for patients to proceed with angiography. Two studies reported using fulminant vision loss as an indication regardless of whether the patient was medically refractory.29 30

Given that the majority of studies reviewed used medically refractory symptoms as selection criteria, it is likely reasonable to proceed with diagnostic angiography in patients with IIH who meet medically refractory selection criteria.

Recommendations
  • The available literature suggests that it is reasonable to perform diagnostic catheter angiography on patients who continue to have symptoms while on medical therapy or who are intolerant of medical therapy (Moderate).

Intracranial pressure

Elevated ICP, most commonly documented by an elevated opening pressure on lumbar puncture, is a fundamental diagnostic criterion for IIH. There is some speculation that higher levels of opening pressures on lumbar puncture may correlate with a higher likelihood of finding venous sinus stenosis on angiography. However, there is little published literature that investigates this correlation. Ahmed et al found that patients with higher opening pressures were more likely to require additional stenting than those with lower opening pressures. For example, of the 52 patients in the study’s cohort, all of which received one stent initially, six ended up needing an additional stent placed. The six patients that required additional stenting had a mean opening pressure of 35 cm H2O compared with a mean opening pressure of 31 cm H2O in the group that did not require additional stenting.31 A similar study by Goodwin et al also showed that patients with a higher opening pressure were associated with needing a shunt placement post venous sinus stenting.32 In addition, Kumpe et al showed that patients with higher mean opening pressures were also more likely to have hemodynamic failure and require retreatment.37 It remains uncertain what specific angiographic findings or stenting outcomes can be elucidated from higher mean opening pressures. Future studies should aim to investigate further the role of mean opening pressures as an isolated variable and its role in venographic findings and stenting outcomes.

Many of the studies involved in the literature review included patients with elevated intracranial pressures on lumbar puncture. However, the intracranial pressure threshold that each study used was not generally mentioned. According to the accepted modified Dandy criteria, a patient must have a CSF opening pressure of at least 25 cm H2O to meet the diagnosis of IIH, thus suggesting that most studies performed venography on patients with CSF opening pressures greater than 25 cm H2O. In addition, Levitt et al found that 35% of patients with IIH undergoing venous manometry had a venous sinus pressure gradient of ≥8 mm Hg and that 0% of patients with normal ICP had a venous sinus pressure gradient of ≥8 mm Hg, suggesting that a normal ICP indicates a very low likelihood of detecting a significant pressure gradient.28

Recommendations
  • It is reasonable to perform venography on patients with intracranial pressures greater than or equal to 25 cm H2O (Moderate) and in select cases where pressures are below 25 cm H2O (Weak).

Body mass index

IIH is often found in overweight and obese women, with many studies reporting body mass index (BMI) in patients undergoing venous sinus stenting.14 Raper et al found that higher BMI was associated with higher pressure gradients as well as greater improvement in pressure gradient after treatment.38 However, there are no studies reporting whether BMI is correlated with the likelihood of venous sinus stenosis.

Recommendations
  • There are no data to support BMI as a predictive factor for symptomatic venous sinus stenosis in IIH and therefore BMI should not be used to influence candidacy for diagnostic catheter angiography (Weak).

Angiography procedural considerations

Manometry

Venous manometry is frequently used in detecting a pressure gradient in the venous sinuses in patients with IIH. All available studies, 29 out of 29 (100%), support the use of venous manometry to detect a pressure gradient across the region of sinus stenosis prior to stenting to assess candidacy for treatment. Of the 29 studies, the average pressure gradient found in study patients ranged from 12.4 to 30.0. Given its ability to accurately detect physiologically-relevant venous outflow obstruction, manometry is an invaluable technique in assessing whether or not a patient is a candidate for treatment prior to undergoing venous sinus stenting.

While there are no data supporting a threshold in the literature, most studies report using a pressure gradient >8 mm Hg for consideration of venous sinus stenting.29 31 34 35 39 40 The original 8 mm Hg gradient reported by Ahmed et al was arbitrarily selected as a reasonable threshold and was not generated based on scientific or empiric testing or observations.31 Other studies have reported using gradients as low as >4 mm Hg26 30 32 36 or as high as >10 mm Hg.33 37 41 42 A recent systematic review showed that higher pressure gradients are associated with higher rates of clinical success, with 94% of patients with a pressure gradient of 22 mm Hg or more having favorable outcomes compared with 82% of patients with gradients of 21 mm Hg or less.15

In theory, complete correction of a 7 mm Hg gradient with stenting would result in an approximate decrease in ICP of 9–10 cm H2O. Therefore, it seems reasonable to use a pressure gradient threshold of 6–8 mmH g when assessing candidacy for stenting.

Recommendations
  • Venous sinus manometry should be performed to assess candidacy for treatment prior to stenting (Strong).

  • A pressure gradient of 8 mm Hg or higher should be present when selecting candidacy for stenting (Moderate). A pressure gradient threshold of 4–7 mm Hg may show benefit in select cases (Weak).

Arteriography

Diagnostic catheter angiography often includes selective catheterization and angiography of bilateral internal and external carotid (or common carotid) and vertebral arteries to evaluate cerebral venous anatomy, venous outflow patterns, and to rule out arteriovenous shunting or fistulae. While all authors have supported venography and venous manometry as the primary method for establishing candidacy for stenting, there are no published data to suggest that arteriography is necessary in assessing candidacy for stenting. Given the practical diagnostic capabilities of arteriography as well as its high sensitivity in ruling out arteriovenous fistulae as a confounder, performing concomitant selective arteriography is reasonable and probably should be performed as part of the diagnostic process for patients with IIH. This may be particularly important in patients who have not had preoperative non-invasive venous or arterial imaging.

Recommendations
  • It is reasonable to perform selective catheter arteriography in conjunction with venography and manometry to evaluate venous anatomy and outflow patterns (Moderate).

Anesthesia choice during angiography

Anesthesia during angiography is a topic of current debate. In addition, there is currently no consensus among reports on the type of anesthetic used during venography. Of the 29 studies reviewed, seven (24%) were found to use general anesthesia when performing venography. Several authors have reported performing concomitant diagnostic venography and stenting under general anesthesia as a single procedure.23 42–44 Patients were awake during venography in 14 out of the 29 studies reviewed (48%).

Recently, two retrospective series have shown that there are significant differences in venous sinus pressure measurements when under general anesthesia compared with when awake. These studies both discovered that general anesthesia tends to underestimate pressure gradients across regions of stenosis compared with values obtained while awake.45 46 Based on these factors, authors have recommended that diagnostic venography be performed with the patient awake or under conscious sedation as opposed to general anesthesia.

Recommendations
  • Diagnostic venography and manometry should be performed with the patient awake (Moderate).

Microcatheter for manometric evaluation

The choice of microcatheter for manometric recording is often not reported in the literature. Some studies report using a 0.027 inch Renegade Hi-Flo microcatheter.10 31 40 41 A study comparing the accuracy and precision of microcatheters found that the Echelon 10, Prowler Select Plus, and Marksman 27 met ICP device monitoring standards while Excelsior SL-10 did not meet the standards and Excelsior 1018 met the standards variably.47

Recommendations
  • A large diameter microcatheter is recommended, or a smaller diameter catheter which is shown to be more accurate in the literature such as the Echelon 10 or Prowler Select Plus (Weak).

Stenting procedural considerations

Stent

There is no recommendation for the type of stent device implanted, as a variety are reported in the literature. These include Zilver,18 19 33 35 37 38 40 41 Precise,8 10 19 24 33–35 38 Wallstent,30 38 44 Protégé,10 24 38 43 and SMART,41 44 48 among others. There are no studies in the literature comparing the type of stent used with clinical outcomes and complication rates, therefore there is no evidence to support the use of a certain stent. An ongoing study, OPEN-UP (NCT number NCT01003639), which is looking at venous sinus stenting versus ventriculoperitoneal (VP) shunt placement, uses the Zilver stent.

Recommendations
  • There are no data to suggest superiority or inferiority of different stent devices in venous sinus stenting (Weak).

Unilateral versus bilateral stenting

There are no studies reporting specifically on synchronous bilateral transverse sinus stenting for patients with IIH. The vast majority of published series performed unilateral stenting with good procedural outcomes.

Recommendations
  • There are no data to support a benefit to upfront bilateral transverse sinus stenting over unilateral stenting (Weak).

Number of stents

The number of stents used per patient appears to be variable and is not often reported in the literature. Some report using a single stent per patient19 31 48 while others report numbers as high as an average of 1.4 stents per patient.11 38 Of interest is whether higher numbers of initial stents placed is associated with better outcomes. However, review of the literature found no studies investigating whether the initial number of stents is associated with a lower need for retreatment or with failure of treatment.

Recommendations
  • There are no data to suggest the use of multiple stents to reduce the risk of retreatment or treatment failure (Weak).

Antiplatelet agents

In general, most studies report using dual antiplatelet therapy of aspirin and clopidogrel for varying durations.10 18 26 29 33 35 36 39 40 Many studies report using heparin during the procedure.19 22 30 31 41 42 44 Teleb et al reported that the most common antiplatelet regimen was aspirin and clopidogrel 3–5 days pretreatment, heparin during treatment, and aspirin and clopidogrel for 3–6 months post treatment, followed by aspirin for a year or more. Teleb et al reported that, of the 207 patients treated, there were two reports of in-stent thrombosis.13 The two reports of in-stent thrombosis occurred in the same study where aspirin alone was used as antiplatelet therapy.21 No studies using dual antiplatelets reported intraluminal thrombotic complications. Two other studies reported using single agent antiplatelet therapy with aspirin or clopidogrel alone, encompassing a total of 20 patients, with no reported complications.11 22 There is not sufficient evidence in the literature to suggest the inferiority of using a single antiplatelet regimen.

Recommendations
  • Antiplatelet agents should be administered prior to stenting and in the follow-up period for at least 3–6 months following stenting (Strong).

  • There are no data to support inferiority of single antiplatelet agents over dual antiplatelet agents, although thromboembolic complications have been reported with aspirin use only (Weak).

Post-stent manometry

Post-stenting manometry was performed immediately after stenting in 26 of the 29 (90%) reviewed studies in order to confirm resolution of a pre-procedural pressure gradient. The three studies that did not specifically mention performing post-stenting manometry document performing post-stenting angiography in order to confirm patency of a post-procedural stent.18 19 33 There has yet to be an independent assessment of the necessity of post-stent manometry in confirming treatment success. In the absence of such a study, the literature strongly supports using post-stent manometry based on its use in the overwhelming majority of studies.

Recommendations
  • It is important to perform post-stenting manometry to confirm resolution of the pressure gradient after stenting to document procedural success (Strong).

Consideration of retreatment

Recurrence of symptoms and stent adjacent stenosis can occur following stenting. Two meta-analyses report repeat procedure rates of approximately 10%.13 14 Other studies suggest retreatment rates ranging from 0% to 20%.29 37 Ahmed et al reported that patients needing retreatment had higher opening lumbar pressures and higher initial pressure gradients.31 Mekabaty et al found that the need for retreatment was correlated with BMI.40 Kumpe et al reported that the need for retreatment was correlated with female gender, younger age, and higher opening lumbar pressures.37 Therefore, there is evidence to indicate that the need for retreatment is correlated with certain risk factors such as BMI, increased pre-stent intracranial pressure, and age.

There are few studies reporting on the criteria for retreatment and/or retreatment strategy following stenting. Many authors have recommended repeating angiography with manometry for evaluation of recurrent stenosis.8 10 11 21–24 26 29–32 34–44 46 48 Alternatively, CSF shunting is an option in refractory patients.33

Recommendations

  • There are limited data on the criteria for retreatment or for the optimal retreatment strategy. It is reasonable to repeat angiography and manometry on patients with recurrence of symptoms after resolution with stenting to evaluate for recurrent stenosis (Strong).

Conclusions

Venous sinus stenting for patients with IIH with venous sinus stenosis is now an established and effective treatment option. These recommendations have been provided, based on a summative review of the available published literature (table 3), to assist in standardizing care for patients with IIH undergoing venous sinus stenting.

Table 3

Summary of recommendations

References

View Abstract

Footnotes

  • Contributors KMF: conception, study design, data collection, data analysis, manuscript preparation. KL: data analysis, manuscript preparation. RMG: data collection, data analysis, manuscript preparation. GPG: data collection, data analysis, manuscript preparation. SQW: conception, design, data collection, manuscript preparation. RWC: data analysis, manuscript preparation.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There are no unpublished data available.

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