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Abstract
Background Pulsatile tinnitus (PT) can be a disabling clinical condition, which may be caused by a sigmoid/transverse sinus stenosis (STSS). Intracranial venous stenting with off-label carotid or peripheral venous stents has been used successfully to treat this condition. We present the results of a cohort of patients presenting with PT treated with a novel, dedicated, braided stent for the endovascular treatment of STSS.
Methods Twelve patients presenting with PT and associated STSS were treated at our institution (December 2022–June 2023). All clinical and procedural variables were prospectively collected. We used the Tinnitus Function Index (TFI) and the Tinnitus Handicap Inventory (THI) scores to assess the impact of PT on quality of life before and after the treatment (mean follow-up: 10.3 months).
Results Twelve women (mean age: 44±16.5 years) presenting with PT and STSS were treated. Mean pretreatment TFI/THI scores were 78.8/77. The BosStent was successfully deployed in all patients. We experienced no intraprocedural/postoperative complications. Intra-stent angioplasty was performed in three cases. All patients reported a complete resolution of PT symptoms within 1 month and remained stable and PT-free at the last follow-up (mean posttreatment TFI/THI score: 7.1/5, p<0001).
Conclusions The BosStent was successfully used in a cohort of patients with PT without any intraprocedural complications. All the patients experienced a complete resolution of PT symptoms after 1 month, which was stable during the follow-up period. Further studies with larger populations will be necessary to investigate the safety and effectiveness of this novel stent for the treatment of PT with STSS.
- Stent
- Stenosis
- Vein
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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What is already known on this topic
Pulsatile tinnitus (PT) represents a disabling clinical condition with a remarkable impact on quality of life. It can be associated with a sigmoid/transverse sinus stenosis (STSS). Previous studies provided encouraging results for cerebral venous stenting, although the currently available devices used are not specifically designed for this purpose.
What this study adds
This study provides the long-term results of the first-in-human cohort of patients with PT and STSS treated with a novel, braided, self-expandable stent, the BosStent, which was specifically designed for this type of treatment.
How this study might affect research, practice or policy
These preliminary results show that the use of a dedicated device for this type of procedure can lead to PT resolution with substantial technical advantages. The design of the BosStent allows treatment of difficult and long stenoses with a relevant impact on patients’ quality of life after treatment and during follow-up.
Introduction
Sigmoid/transverse sinus stenosis (STSS) as well as other structural and anatomical variations (diverticula and abnormal arachnoid granulations) may cause pulsatile tinnitus (PT). Indeed, these abnormalities can cause a turbulent flow in the vascular structures adjacent to the inner ear which is subjectively experienced with an unexpected and unpleasant auditory perception synchronized with the pulsatile blood flow.1 This condition can present a remarkable burden on patients’ lives.2–4 The outflow obstruction can also cause ‘cerebral venous congestion’, thus producing idiopathic intracranial hypertension (IIH)-like symptoms, cognitive disorders, local alterations of the white matter,5 chronic headaches, and altered intracranial pressure.6 7 This presentation can occur in isolation or in combination, and these symptoms are associated with a significant negative impact on quality of life, high levels of anxiety and depression, as well as significant sleep disturbance.1 Venous stenting has been proposed to treat venous narrowing with promising clinical outcomes for both PT and IIH.8 9 However, the devices that are classically used in this context, such as carotid or venous stents, can be cumbersome to navigate to the targeted venous segment to be treated. Additionally, the transitions between the jugular bulb and sigmoid sinus can be tortuous and challenging to navigate stent-mounted devices. Also, classic off-label devices may lack radiopacity for visualization during deployment, could have unfit radial force for the cerebral venous system, and may have limited available lengths which are insufficient to cover the entirety of long stenotic segments and thus require the use of multiple overlapping devices.10 We aim to report a feasibility study of a new, dedicated device for the treatment of venous sinus stenosis, the BosStent. In this study, we discuss the technical and long-term clinical outcomes in a cohort of patients with STSS presenting with PT.
Methods
Patient population and initial assessment
Twelve female patients presenting with PT, with or without venous congestion or IIH symptoms, and STSS were treated at our institution with the BosStent between December 2022 and June 2023. The local institutional review board (St Michael’s Hospital IRB, IRB No. 23–056) approved the study. All patients were fully informed and gave their consent to participate in the study.
All patients were admitted to our institution for PT assessment and underwent diagnostic imaging and multidisciplinary clinical discussion (Ear, Nose, and Throat (ENT) and Neurovascular team). Demographic data (age, sex) and clinical items were collected and evaluated through anamnesis and examination. Anamnestic data included side, type (whooshing, heartbeat-type, buzz, hum, ringing), duration of the tinnitus (days, months, or years), and associated symptoms (headache, visual impairment, hearing loss, treatment for anxiety/depression). Patients were also evaluated by a neuro-ophthalmologist and optical coherence tomography (OCT) and visual fields were performed systematically for all patients. Medical management was the first-line choice according to the patients’ symptoms; however, PT persisted despite the initial medical treatment. The impact of PT on patients’ quality of life was assessed by means of the Tinnitus Functional Index (TFI)11 and Tinnitus Handicap Index (THI).12 The clinical examination included ipsilateral and contralateral internal jugular vein (IJV) compression, Valsalva manoeuvre, and extreme neck flexion and extension in the different axes to characterize a vascular origin of the PT. Auscultation of the IJV, mastoid, and occipital bones was also performed.
CT and/or MRI were used for baseline assessment. CT-venograms of the head and neck were mainly used to assess an eventual dominance of the venous drainage, the presence of transverse sinus stenosis and its cause (extrinsic or intrinsic), the presence of arachnoid granulations, diverticula/dehiscence, high-riding jugular bulb, the prominence of emissary veins, and IJV compression or Eagle syndrome.
Endovascular procedures
All procedures were performed using a biplane angiographic unit (Philips Azurion, Best, The Netherlands) with all patients under general anesthesia and systemic heparinization with seriate activated clotting time values (ACT >300 s) monitoring. All patients were premedicated with ticagrelor 90 mg ×2/day and acetylsalicylic acid (ASA) 5 days before the procedure. Dual antiplatelet therapy was maintained for 3 months and then ASA alone for 1 year. An arterial (5 Fr, femoral or radial) and a venous (8 Fr, femoral) access, obtained under ultrasound guidance, were used in all the procedures. A complete diagnostic angiogram was performed to confirm the absence of arteriovenous shunts and for morphological evaluation of the venous system. Pressure measurements were obtained from 12 positions between the superior sagittal sinus to the right atrium for evaluation of potential gradients across stenoses. Three-dimensional (3D)-rotational angiography was acquired in order to complete the diagnostic workup and choose the proper size of stent according to the diameter of the venous sinus and the extension and nature (monofocal or multifocal) of the stenosis. We used the largest of the mean of three diameters in a cross-section and the perimeter divided by three, in the case of a triangular shaped sinus, or by radius (if circumferential) at the proximal, distal, and largest segment to use as a reference to calculate the stent diameter. The stent length was chosen based on 3D digital subtraction angiography (3D-DSA) since 2D-DSA may underestimate the extent of the flattened segments. We used a stent size table with a vessel range recommendation per size and the expected length in each diameter. The aim of the procedure was to treat the stenosis ipsilateral to the symptoms. A Benchmark BMX96 guiding catheter (Penumbra Inc., Alameda, CA, USA) was navigated and placed in both IJVs and pressure measurements were performed through a Progreat 2.8 Fr (Terumo, Somerset, NJ, USA) over a Traxcess-14 microwire (Microvention, Aliso Viejo, CA, USA). The same pressure measurements were repeated after the positioning of the stent to compare pre- and post-stent pressure gradients when a pre-stent gradient was observed. A ConeBeam CT (VasoCT, Philips, Best, The Netherlands) acquisition was used to assess the patency and the wall apposition of the BosStent (Sonorous, Irvine, CA, USA) and Copernic (Balt Extrusion, Montmorency, France) or Sterling (Boston Scientific Corporation, Natick, MA, USA) balloons were used to perform pre- or intra-stent angioplasty manoeuvres, when necessary. The decision to treat these patients was based on the presence of a venous stenosis, a dehiscence or diverticula, and impact on quality of life, regardless of the presence of a pressure gradient. At the end of each procedure, the final angiograms of the injection of the ipsilateral internal carotid artery was performed in order to assess the post-stenting angiographic result, any intraprocedural complications, and potential impairments of the cortical veins tributaries of the transverse and sigmoid sinuses.
The BosStent
The BosStent is a novel, braided, closed-cell, self-expandable stent composed of nitinol DTF wires specifically designed for the treatment of venous sinus stenosis in patients with PT or IH (figure 1). The stent was designed to reach optimal radial force even in very small diameters to allow expansion without necessarily using balloon angioplasty in every case. The device is delivered through a 5 Fr distal access catheter after having crossed the stenosis with the delivery system. Stents sizes are available in two diameters (7 and 9 mm) and lengths (60 and 80 mm) for the treatment of venous stenoses. The percent surface area of the stent is <20% for all four sizes. In our cohort, a 90 cm Benchmark BMX96 and a 115 cm Navien 5 Fr (Medtronic, Irvine, CA, USA) or CAT 5 distal access catheter (Stryker Neurovascular, Fremont, CA, USA) were used as the guiding and delivery catheters, respectively.
Illustrative case: a middle-aged patient presenting with left-sided, heart-beating, pulsatile tinnitus and headaches. The pretreatment CT-venogram axial plane showed a left sigmoid-transverse sinus stenosis (STSS) with associated mastoid bone dehiscence (A, white arrows). Subtracted digital subtraction angiography (DSA) anteroposterior projection (B, black arrowhead) and the reconstruction of the pretreatment 3D-rotational acquisition (C) confirmed the presence of an intrinsic, left STSS. Posttreatment results after stent positioning were observed on the reconstruction of the cone beam CT (VasoCT) acquisition after deployment of the BosStent showing the optimal patency and wall apposition of the stent (D), and final subtracted DSA (E) anteroposterior projection showing the successful treatment of the right STSS. The 3-month CT-venogram (F) showed the correct positioning of the BosStent. The patient reported a complete resolution of pulsatile tinnitus and headaches.
Follow-up
A clinical follow-up was conducted with in-hospital visits or through telephone interviews. A clinical examination was performed during the hospitalization and at the time of discharge, whereas the THI/TFI used to assess impact on quality of life were administered before the endovascular treatment and 12 (±2) months after the procedure. Clinical assessment was independently performed through in-person clinical examinations at 6 and 12 (±2) months by an expert neuroradiologist (>15 years’ experience) not involved in the procedures. Also imaging assessment of the procedures and follow-up was independently performed by an expert neuroradiologist who was not involved in the procedures or in clinical management. Follow-up imaging was performed with CT-venograms on day 1, at 3 months, and 1 year post-procedure.
Statistical analysis
A statistical descriptive analysis of this cohort is presented considering the limited number of patients included in this preliminary study. Mean values were reported as continuous variables with ranges and Student’s t-test was performed to assess the differences between independent means.
Results
In our cohort, 12 females (mean age: 44±16.5 years) presenting initially with PT were included in this study. Other associated symptoms were visual impairment (mostly blurred vision) and headaches (5 cases). The main pattern of PT was described as a whooshing sound and/or heartbeat. In most cases (11 patients), PT had been present for years as well as headache, whereas visual impairment had appeared more recently. Four patients (33%) were under medical treatment for anxiety or depression associated with PT. Patient characteristics are summarized in table 1.
Patient characteristics
Imaging
Bilateral STSS was observed in 10 cases and unilateral STSS in two cases. In eight patients the stenosis was located at the distal segment of the transverse sinus, in one case it extended to the sigmoid sinus (patient 1), while in three cases (patients 8, 9, 10) it was located at the transverse-sigmoid junction after the confluence of the Labbe’s vein. A co-dominance of the venous drainage was observed in four cases. Other imaging findings included ipsilateral bony dehiscence (7 cases), abnormal arachnoid granulations (4 cases), and the presence of large condylar or suboccipital emissary veins (2 cases). Empty sella and tortuosity of the optic nerve were observed in five patients. The BosStent system was used for the endovascular treatment of STSS in all the cases. In one case, additional to the stenosis there was a large petro-sigmoid dehiscence and therefore an associated coiling was used additional to the stenting in a jailing technique. A 7 mm diameter device was implanted in seven patients and a 9 mm diameter device in the remaining five patients. In nine cases, VasoCT showed very good BosStent patency and wall apposition without the need for intra-stent angioplasty, whereas in three cases angioplasty was used to improve stent patency across the stiff stenosis. In two cases, angioplasty prior to the stent deployment was performed in order to allow the 5 Fr Navien to navigate through the stenosis. Two patients treated with BosStent were rescheduled after an initial failed treatment session attempted with a Carotid Wallstent (Boston Scientific, Boston, MA, USA). In all cases the STSS was successfully treated without intraprocedural complications. Median pre-stent pressure gradient was 7 (IQR: 3.5–8.75) mmHg which improved to 2 (IQR: 0–2.25) mmHg after stent deployment.
Impact on quality of life
Median length of clinical follow-up was 10.3 (range: 9–12) months. All patients reported a complete resolution of PT and associated symptoms either immediately after the stent deployment and prior to discharge (10 cases) or within 1 month afterwards on follow-up (2 patients). We observed the effect of the treatment of STSS in terms of impact on patients’ quality of life in all patients, with the mean TFI score improving from 78.8 (range: 58–100) before treatment to 7.1 (range 0–64.4) after treatment at the time of the last follow-up (p<0001). We observed the same results when considering the mean THI score, which dropped from 77 (range: 56–100, median grade: 4) before treatment to 5 (range: 0–50, median grade: 1) at the last follow-up (p<0001). No procedure-related, retro-auricular headaches were observed during the entire follow-up, except in one patient (case 3) who experienced mild retro-auricular pain after 3 months. After 6 months and at the last follow-up, all clinical outcomes were stable and unchanged without any recurrence of symptoms. All technical and clinical outcomes are summarized in table 2. The follow-up CT-venograms showed the patency of the implanted stents without any further modifications or in-stent stenosis.
Clinical and technical outcomes
Discussion
We report the first experience of a dedicated, self-expandable, nitinol stent specifically designed to treat PT related to venous sinus stenosis. The device uses an empty catheter deployment technique with a 5 Fr distal access catheter as delivery catheter. This initial experience with a long-term follow-up (median length: 10.3 months) demonstrated that this new approach is safe and effective for treating patients with PT.
Clinical considerations
Previously published series reported promising clinical outcomes after stent deployment with an improvement in the burden of symptoms for these patients following complete resolution of PT, ranging between 90% and 93% in recent systematic reviews.9 13–15 In our cohort, we observed a significant reduction of the THI/TFI scores and the complete resolution of PT in all cases, which represents a high success rate compared with other previously reported series, where PT resolution was described in 81% in a cohort of 168 patients treated with the Wallstent (Boston Scientific, Marlborough, MA, USA),8 in 90% in 29 patients16 and in 95% (44/46) patients within the first 3 months treated with the Precise Pro stent (Cordis, Miami Lakes, FL, USA).17
The effectiveness of venous stenting in improving the symptoms of IIH has also been reported, although these results may vary according to the type of symptoms. Indeed, Kalyvas et al reported in an extensive systematic review describing a clinical improvement after venous stenting for papilledema in 87%, visual deficits in 72.7%, and headaches in 72.1% of patients.18 In our cohort, associated symptoms that could be related to IIH were completely resolved in five patients, whereas in the others a visual impairment (blurred vision or diplopia). A recent, ongoing study focusing on the treatment of venous stenosis in patients with IIH using the River stent (Serenity Medical Inc., Redwood City, CA, USA) reported encouraging interim results in terms of safety and efficacy.19
The majority of patients awoke after the procedure no longer hearing the PT and two patients observed an improvement after a few days and reported this at the clinic follow-up. We did not observe any recurrence of PT nor associated symptoms, unlike other previously reported studies that describe recurrences and worsening of symptoms in about 10% of cases. Notably, these have been reported from 7 months to 4 years after treatment and were associated with stent restenosis.8 Moreover, we strongly believe that for patients presenting with PT, an extensive clinical and physical examination remains an essential step in order to precisely characterize and select patients for the appropriate treatment20 and neck compression should be mandatory for a complete assessment of treatable etiologies.21
Technical considerations
The technical success and the safety profile of venous stenting have been extensively reported in the literature.8 9 Although not yet widely used, this type of endovascular approach allows the treatment of dural sinus stenosis restoring the venous outflow and the possibility of ‘targeted’ treatment by stent-assisted coiling of some venous malformations (such as sigmoid sinus diverticula) that could be responsible for PT sound production.
In our study population, the use of the BosStent allowed for proper positioning of the stents and resolution of the STSS in all cases, while in one case it allowed for successful coiling of a venous diverticulum. Indeed, the stent structure allows easily navigation of the cells and provides a solid base for the jailing technique. One of the main advantages we observed with use of the BosStent, compared with off-label stents used for treatment of STSS, is its dedicated delivery system. It can be delivered through a 5 Fr delivery catheter, is resheathable, and supports smooth and easy deployment of the stent (online supplemental video 1). Furthermore, although long stents are already available (Zilver 518; Cook Medical, Bloomington, IN, USA), these are stiffer and have larger diameters, which could be difficult to navigate in tortuous anatomies. The BosStent was designed for treatment of venous sinus stenoses, which balances the need for restoring the diameter of the venous sinus while maintaining superior wall apposition and patency. Indeed, VasoCT acquisition after stent deployment showed optimal patency and wall apposition without the need for intra-stent angioplasty in the majority of cases. Two of the cases had a severe stenosis that no device was able to cross and therefore we performed pre-stent angioplasty. Post-stent angioplasty was also performed mainly to improve stent patency and apposition on the post-stenotic dilatation in the sigmoid area (figure 2). Interestingly, in our cohort we observed persistent retro-auricular headaches in only one case, which is a sensibly lower rate compared with other series previously reported in the literature.22 We hypothesize that this may be attributed to the braided design of the stent.
Supplementary video
Illustrative case 2: a patient in her 40s with right pulsatile tinnitus for 15 years worsening in recent years. Jugular compression test was positive. Concomitant holocranial headaches symptoms were recorded and papilledema was not observed. (A) CT-venography demonstrated dominant right-sided venous drainage, with severe intrinsic narrowing of the right transverse/sigmoid junction and a hypoplastic left dural venous sinus. (B) Venous phase timed 3D-rotational angiography: confirmation of the severe intrinsic stenosis on the right transverse sinus. (C) Digital subtraction angiography (DSA), lateral view/working projection baseline imaging showing the same severe narrowing on the 2D images. Since the vessel has a triangular shape and the narrowing is flat, the stenosis appears as a narrowing, low-density image (arrow). (D) DSA lateral/working projection: BosStent deployment through a 5 Fr Navien catheter. (E) DSA unsubtracted image of the post-procedure angioplasty to improve the apposition of the device at the level of the post-stenotic dilatation/dehiscence of the sigmoid sinus. (F) DSA unsubtracted image of the BosStent fully opened and deployed. (G) CT-venogram at 24 h showing the stent deployed over the stenotic segment, the apposition of the device over the segment with different diameters, and the lumen correction at the level of the stenosis.
We did not observe any peri- or postoperative complications, neither during the navigation and the deployment of the stent nor during hospitalization recovery. In the literature, major intraprocedural complications (such as subdural hematoma or subarachnoid haemorrhage immediately after or during stent deployment) have been reported as low-rate events (1.9–2%), while minor complications represent about 7.6% and are mainly characterized by stent thrombosis, post-stenting headaches, and groin hematomas. Postoperative complications including late subarachnoid hemorrhage and subdural hematoma account for less than 1%.7 8 Furthermore, we did not observe any impairment of the drainage of the vein of Labbé.23
Limitations
The limited study sample and the monocentric nature of the study represent the main limitations, whereas the angiographic results were independently adjudicated.
Conclusions
The BosStent achieved good technical results in terms of stent deployment and angiographic resolution of STSS in patients with PT without any intraprocedural complication. Long-term clinical results showed the complete and persistent resolution of PT after a median follow-up duration of 10.3 months in all patients with a significant impact on the severity of the PT and improvement of associated symptoms in all patients. Although these are promising preliminary results, future investigations of the use of BosStent in larger populations with longer clinical and imaging follow-up will be necessary to determine long-term effectiveness.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by St Michael’s Hospital Institutional Review Board (IRB No. 23-056). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
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Footnotes
X @NMCancelliere, @gcharbonnier, @VitorMendesPer1
Contributors All authors met all the criteria for authorship. In particular, VMP and NMC made substantial contributions to the conception and design of the study. VMP, NMC and AC were the guarantors for the study. AC was responsible for drafting the work, data acquisition, and analysis and interpretation of the data. HN and GC helped with data acquisition, and analysis and interpretation of the data. TRM, IV, and JS revised the work critically for important intellectual content. All authors participated in the critical revision of the drafts, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors gave final approval of the version to be published.
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 Professor Vitor Mendes Pereira is a consultant for Sonorous.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.