Unilateral Transverse Sinus Stenting of Patients with Idiopathic Intracranial Hypertension

Discussion

Distal TS stenoses are observed in a high proportion of patients with IIH.^11,12 Using 3D gadolinium-enhanced MR venography, bilateral sinovenous stenoses were seen in 27 of 29 patients with IIH but in only 4 of 59 controls.¹¹ In another study, absence of segmental flow (flow gaps) in both TSs was seen in 13 of 20 patients with IIH but not observed in 40 healthy headache-free controls by using phase-contrast and time-of-flight MR venography.¹² Consistent with these findings, direct intrasinus manometry has demonstrated elevated pressures in the superior sagittal and proximal TSs of patients with IIH, with a significant drop in venous pressures in the distal TS.^30,31 Taken together, these data suggest that TS stenoses may play a role in the pathophysiology of IIH in some patients by causing partial venous outflow obstruction. It is well known that the clinical presentation of other conditions that cause cerebral venous outflow obstruction, such as venous sinus thrombosis, can mimic IIH.

The etiology of lateral sinus stenoses in patients with IIH remains uncertain. Considerable congenital asymmetry between the TSs has been found in anatomic studies. The right lateral sinus is larger or dominant in up to 73% of cases, and partial or total agenesis of portions of a TS are observed in up to 23% of cases.³³ The cortical vein of L'Abbé drains into the distal third of the TS, in addition to several smaller tributaries from the inferolateral temporal lobe, occipital lobe, and cerebellum.³⁴ Arachnoid granulations are frequently seen in the lateral TS associated with these venous entry sites,³⁵ and if large may be a cause of venous outflow obstruction.³⁶ Large transversely oriented septations or fenestrations were present in 10% of TSs evaluated in 1 postmortem study and are postulated to be a cause of venographic cryptic stenosis.³⁷ Incomplete recanalization after thrombosis of a TS may occur causing filling defects and sinus narrowing due to residual chronic organized (fibrosed) thrombus.^38,39 There are also case reports of focal fatty deposits²¹ and heterotopic brain or small brain hernia^21,40 causing TS obstruction.

Other recent studies have suggested that the sinovenous stenoses seen in IIH may be manifestations of raised intracranial pressure. The Monro-Kellie hypothesis postulates that changes in CSF are in part compensated by changes in intracranial blood volume reflected primarily in the venous system.⁴¹ Raised intracranial pressure may therefore cause a collapse or extrinsic compression of the sinus walls. In agreement with this hypothesis, several authors have reported reversibility of lateral sinus stenoses by CSF removal or diversion procedures in patients with IIH.^12,14–18 Using a lateral C1–2 puncture to remove 20–25 mL of CSF, King et al¹⁵ demonstrated resolution of venous hypertension measured by intrasinus manometry in patients with IIH. Normalization of venous sinus caliber on MR venography after lumbar puncture¹⁷ or subsequent to ventriculo- or lumboperitoneal shunt surgery^13,14,16 has also been observed in selected patients with IIH. However, in a study by Bono et al,⁴² TS stenoses persisted after normalization of CSF pressure with acetazolamide and weight loss in 14 patients with IIH, suggesting either that some patients have fixed obstructions or that large acute shifts in CSF volume by lumbar puncture or CSF diversion procedures are required to produce changes in the caliber of sinuses.

The current case series adds to a small but growing body of evidence^14,19–27 suggesting that selected patients with IIH may benefit from TS stent placement. Higgins et al¹⁹ reported the first patient with refractory IIH and TS stenosis treated with a stent. They described a 30-year-old woman with a 22-month history of headache, visual disturbance, and papilledema and an MR venogram demonstrating bilateral TS stenosis. Direct cerebral venography and manometry confirmed the presence of the stenoses with raised pressures proximal to the obstructions. Dilation of 1 of the sinuses with a stent reduced the pressure gradient with dramatic symptomatic improvement. To date, 40 patients with IIH treated with sinovenous stent placement have been reported in the literature (on-line Table 2 and Table 2). Most of the patients were female (36/40), ranging in age from 15–65 years old. Symptom duration ranged from 2 weeks to 15 years. Clinical follow-up ranged from 4 to 60 months. After stent placement (Table 2), 33 of 40 (82.5%) patients reported their headaches as resolved or significantly improved and papilledema improved or resolved in 30 of 33 (91%) patients with active papilledema at presentation. Eight patients with active papilledema developed chronic optic nerve changes at follow-up. Periprocedural complications were infrequently reported. The most commonly reported adverse event was transient headache ipsilateral to the stent (>50% of patients). Transient unsteadiness and hearing loss were each reported in 1 patient.²⁰ Two patients in this series required thrombolysis for in-stent thrombosis.²⁰ The preprocedural antiplatelet regimen was not clearly described in this cohort, and lack of pretreatment may have contributed to thrombus development. There have been no reported cases to date of in-stent stenosis, though numbers are small and follow-up limited. Two patients had new stenoses develop proximal to the stent.^14,21 One of these patients was treated with a ventriculoperitoneal shunt due to persistent symptoms.²¹

Three patients in the present case series were not found to have significantly elevated pressures in the TS. Time-of-flight MR venography was used to image the cerebral veins in these patients. It is possible that the severity of the stenoses was overestimated due to the insensitivity of this technique to in-plane flow or due to its sensitivity to slow flow or turbulence.³⁹ Gadolinium-enhanced MR venography, which is not susceptible to in-plane saturation effects, may have resulted in more accurate estimation of sinus caliber^11,39 and improved patient selection for possible stent placement. Alternatively, these patients may have lacked a significant pressure gradient because the visualized stenosis may not be contributing to the pathophysiology of their symptoms, perhaps due to sufficient venous collateral drainage.

An increased incidence of prothrombotic factors or genetic thrombophilia has been recently described in patients with IIH.^43–48 This association has led to the hypothesis that microthrombus formation in arachnoid villi may impair CSF outflow and thereby contribute to the pathogenesis of IIH.^44,47,48 There is little evidence, however, to support this hypothesis. It has also been suggested that cranial venous outflow obstruction may occur due to unrecognized nonocclusive thrombus or due to incomplete recanalization of a previously occluded sinus.^38,39,46 In the present series, headaches and papilledema improved in all 3 patients with a history of thrombophilia subsequent to restoration of the diameter of the stenotic TS with a stent.

We acknowledge several limitations of this small retrospective case series. First, the clinical course of IIH is quite variable. It can be a subacute and remitting disorder or follow a more protracted course with delayed worsening occurring even years after a period of stability.⁶ Thus, although the response of this small group of patients to TS stent placement is encouraging, a true assessment of the efficacy and durability of any treatment for IIH would require a larger randomized controlled study. Second, weight fluctuations were not systematically recorded during follow-up. Weight loss on its own may result in clinical improvement in a proportion of patients with IIH. Third, the long-term risk of in-stent stenosis or delayed thrombosis of stents within dural venous sinuses in primarily young female patients is unknown.

Although most patients with IIH improve with conservative therapy, an estimated 18%–22% of patients are considered refractory with visual impairment and/or headaches persisting or progressing despite maximally tolerated treatment with acetazolamide, furosemide, and dietary counseling for weight loss.^49,50 Surgical procedures, such as optic nerve sheath fenestration, ventriculo- or lumboperitoneal shunt surgery, and subtemporal decompression are usually considered for such patients to prevent visual loss and treat intractable headaches. These procedures are not universally effective, however. Failure rates as high as 30% have been reported and complications are not infrequent.^50–53 Venous sinus stent placement may be an alternative treatment option for patients with IIH refractory to medical therapy. The safety and efficacy of this procedure, however, should be evaluated in a larger randomized controlled study before it is applied more widely.