Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
We have an obligation to our patients to prove that what we do works—that the benefits of our procedures outweigh their risks. That evidence base is notably lacking for dural sinus stenting for patients with idiopathic intracranial hypertension (IIH).
We do not dispute that many patients with IIH have a pressure gradient in their dural sinuses, typically due to what is almost certainly extrinsic compression of their transverse sinuses.1 Stenting of these patients reduces central venous and intracranial pressure, conclusively and dramatically.2 This is generally accompanied by improvement in many of the symptoms reported by these patients.3 We also do not dispute that it is reasonable to offer stenting to some patients, but with the caveat that the evidence regarding many aspects of this procedure is weak.
There is a long list of unanswered questions regarding venous sinus stenting for patients with IIH. The sum of our knowledge regarding the risks and benefits of this procedure are from case series: no randomized trial has been reported to date. While the risk of complications from this procedure is low in terms of frequency (2–3%), some can be catastrophic.4 Many studies to date have lacked objective or quantifiable measurements of outcome, such as stabilization or improvement in visual fields, for example. There is uncertainty regarding indications for treatment. Is headache alone an indication? Should we be using an objective threshold value for visual loss? If failed medical treatment is an indication, how should we define that? Is intractable pulse synchronous tinnitus in the setting of IIH an indication? We do not have clear guidance on length of follow-up and risk for recurrence. Finally, it must be recognized we are not treating the cause of the intracranial pressure increase: the underlying pathologic reason remains present and likely accounts for many of the treatment failures or recurrences.5 Owing to all these factors, this is a procedure that must be subjected to a randomized clinical trial against best medical therapy. In the following paragraphs we will provide more information supporting the statements above.
IIH is a disorder affecting primarily overweight women of childbearing age. It manifests as symptoms of increased intracranial pressure and can result in permanent vision loss if untreated. Weight loss, with as little as a 6% weight reduction, is an effective treatment.6 Bariatric surgery is superior to a dietary weight loss intervention for both weight loss and a sustained reduction in intracranial pressure.7 Acetazolamide and diet is also an effective treatment.8 The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) demonstrated that acetazolamide combined with a low-sodium weight-reduction diet was superior to diet alone for improvement in vision in patients with IIH and mild visual loss.8 Mild vision loss was defined as perimetric mean deviation (PMD), a measure of global visual field loss relative to normal age-corrected values, between −2 dB and −7 dB. The scale is logarithmic, so a PMD of −10 dB indicates a 10-fold loss in retinal sensitivity. The study was double-masked and placebo-controlled. One hundred and sixty-five subjects were enrolled. The primary outcome was the change in PMD from baseline to 6 months in the most affected eye. Acetazolamide dose was 2 to 4 g/day. The active treatment group had more improvement in PMD, papilledema and vision-related quality of life. About half of the enrolled subjects agreed to a follow-up lumbar puncture at 6 months, and intracranial pressure was significantly lower in the active treatment group. They also had more weight loss, and the benefit with acetazolamide was shown to be independent of weight loss. A phase 3 trial is currently underway for newly diagnosed IIH patients for oral exenatide, a glucagon-like peptide (GLP-1) receptor agonist that increases insulin secretion, after very promising phase 1 studies showed reductions in intracranial pressure.9
It should be noted that the IIHTT study excluded patients with severe vision loss, and those with medically refractory, rapidly progressive vision loss. These patients have been treated in the past with optic nerve fenestration and surgical shunting procedures, and more recently, dural sinus stenting.3 This group of patients will be hard to study owing to challenges related to recruitment and equipoise, but a trial comparing these three interventions with each other and medical therapy including weight loss would be of great value. In the absence of a trial, it is reasonable to offer stenting to these patients, just as it is reasonable to offer shunting or fenestration.
The more frequent and perhaps more important question is what to do with the patients without severe or rapidly-deteriorating vision. Medical management—high dose acetazolamide and a low-sodium weight-reduction diet as established by the IIHTT study—should be the first line treatment. Visual fields should be carefully monitored.
A randomized clinical trial of stenting for the IIHTT population is clearly the next step. The stenting procedure is relatively mature in terms of devices and technique. Periprocedural complications are unlikely to see much reduction from any kind of technological, patient selection, or pharmacological advance. Acetazolamide is generally well tolerated but the maximum tolerated dosage occasionally will not give the desired outcome. Stenting may be more effective than acetazolamide.
Why are case series insufficient to answer these questions? Case series, particularly single institution retrospective studies, are at risk for underestimating complications. In addition, many of these studies lack objective criteria to define eligibility or measure outcome, and these outcomes are not done in an independent or masked manner. Our field, and related ones, have many examples of case series data not being validated by subsequent randomized controlled studies. These include jugular venous stenting for multiple sclerosis,10 warfarin for symptomatic intracranial atherosclerotic disease,11 vertebroplasty for osteoporotic compression fractures,12 stenting for intracranial atherosclerotic disease,13 optic nerve sheath fenestration for anterior ischemic optic neuropathy,14 and angioplasty and stenting for chronic stable angina.15 Many of these negative trials have been criticized for many reasons—poor operators, poor technology and wrong patient population, for example. However, if these trials were not done, we would still be treating many of these patients and causing more harm than benefit. These negative trials also help us identify the next steps—better patient selection, subgroups, better technology and complication avoidance.
In summary, objective data from a well-executed randomized trial showing a benefit of stenting for recovery or preservation of vision in a well-defined patient cohort would be of great value, particularly one that accurately documents complications and has visual field testing as a major outcome measure. All one has to do is look at thrombectomy for patients with acute ischemic stroke and large vessel occlusion to see what kind of impact randomized trials can have on our patients and the field.16 It is our obligation to answer these questions and put our procedures to the test.
Patient consent for publication
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 Consulting (Data and Safety Monitoring Committee): Silkroad (NITE trial); Penumbra (Thunder Trial); NoNO (Escape NEXT, Frontier trials). Equity (Pulse Therapeutics - Stock Options).
Provenance and peer review Not commissioned; internally peer reviewed.