Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.

Combined microsurgical PICA-PICA bypass and endovascular parent artery occlusion for a ruptured dissecting vertebral artery aneurysm.

Dissecting vertebral artery (VA) aneurysms are difficult to obliterate when the parent artery cannot be safely occluded. In this video, we demonstrate a combined microsurgical and endovascular treatment technique for a ruptured, dissecting VA aneurysm incorporating the origin of the posterior inferior cerebellar artery (PICA). We first performed a PICA-PICA side-to-side bypass to preserve flow through the right PICA. An endovascular approach was then utilized to embolize the proximal portion of the aneurysm from the right VA and the distal portion of the aneurysm from the left VA. The video can be found here: http://youtu.be/dkkKsX2BiJI .

Endovascular Treatment of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension: Complications, Neurological Outcomes, and Radiographic Results.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) may result in a chronic debilitating disease. Dural venous sinus stenosis with a physiologic venous pressure gradient has been identified as a potential etiology in a number of IIH patients. Intracranial venous stenting has emerged as a potential treatment alternative. METHODS: A systematic review was carried out to identify studies employing venous stenting for IIH. RESULTS: From 2002 to 2014, 17 studies comprising 185 patients who underwent 221 stenting procedures were reported. Mean prestent pressure gradient was 20.1 mmHg (95% CI 19.4-20.7 mmHg) with a mean poststent gradient of 4.4 mmHg (95% CI 3.5-5.2 mmHg). Complications occurred in 10 patients (5.4%; 95% CI 4.7-5.4%) but were major in only 3 (1.6%). At a mean clinical follow-up of 22 months, clinical improvement was noted in 130 of 166 patients with headaches (78.3%; 95% CI 75.8-80.8%), 84 of 89 patients with papilledema (94.4%; 95% CI 92.1-96.6%), and 64 of 74 patients with visual symptoms (86.5%; 95% CI 83.0-89.9%). In-stent stenosis was noted in six patients (3.4%; 95% CI 2.5-4.3%) and stent-adjacent stenosis occurred in 19 patients (11.4%; 95% CI 10.4-12.4), resulting in restenting in 10 patients. CONCLUSION: In IIH patients with venous sinus stenosis and a physiologic pressure gradient, venous stenting appears to be a safe and effective therapeutic option. Further studies are necessary to determine the long-term outcomes and the optimal management of medically refractory IIH.

Multimodal MR imaging model to predict tumor infiltration in patients with gliomas.

INTRODUCTION: Gliomas remain difficult to treat, in part, due to our inability to accurately delineate the margins of the tumor. The goal of our study was to evaluate if a combination of advanced MR imaging techniques and a multimodal imaging model could be used to predict tumor infiltration in patients with diffuse gliomas. METHODS: Institutional review board approval and written consent were obtained. This prospective pilot study enrolled patients undergoing stereotactic biopsy for a suspected de novo glioma. Stereotactic biopsy coordinates were coregistered with multiple standard and advanced neuroimaging sequences in 10 patients. Objective imaging values were assigned to the biopsy sites for each of the imaging sequences. A principal component analysis was performed to reduce the dimensionality of the imaging dataset without losing important information. A univariate analysis was performed to identify the statistically relevant principal components. Finally, a multivariate analysis was used to build the final model describing nuclear density. RESULTS: A univariate analysis identified three principal components as being linearly associated with the observed nuclear density (p values 0.021, 0.016, and 0.046, respectively). These three principal component composite scores are predominantly comprised of DTI (mean diffusivity or average diffusion coefficient and fractional anisotropy) and PWI data (rMTT, Ktrans). The p value of the model was <0.001. The correlation between the predicted and observed nuclear density was 0.75. CONCLUSION: A multi-input, single output imaging model may predict the extent of glioma invasion with significant correlation with histopathology.

Venous stenting with concurrent intracranial pressure monitoring for the treatment of pseudotumor cerebri.

Increasing evidence supports dural venous sinus stenosis as the patho-etiology of pseudotumor cerebri (PTC) in a subset of affected patients. In this video, we demonstrate our technique for 1) diagnostic venous manometry to identify a flow-limiting stenosis of the transverse sinus in a PTC patient; and 2) successful treatment of the patient with venous stenting across the structural and physiological stricture in the dural sinus. The pressure gradient decreased from 20 mmHg pre-stent to 3 mmHg post-stent. In order to further quantify the effect of our intervention, concurrent intracranial pressure monitoring was performed. The video can be found here: http://youtu.be/auxRg17F8yI .

Pituitary insufficiency from large unruptured supraclinoid internal carotid artery aneurysm.

A 59-year-old female presented with headache and fatigue. Angiography revealed a giant superior hypophyseal aneurysm with intrasellar extension. Serum endocrine panel demonstrated pituitary insufficiency. The aneurysm was treated with a pipeline flow-diverting stent and the hypopituitarism was treated with hormone replacement. Pituitary insufficiency from aneurysmal compression is extremely rare.

Applications of stenting for intracranial atherosclerosis.

Intracranial atherosclerosis presents a therapeutic challenge to medical and surgical physicians alike. Despite maximal medical therapy, the stroke rate from this disease is still high, especially when arterial stenosis is severe and patients are symptomatic. Open surgical therapy has yet to be shown to be a more efficacious treatment than medical therapy alone, largely due to the relatively high rates of perioperative complications. Angioplasty has a similar fate, with the risk of periprocedural complications outweighing the overall benefit of treatment. With the advent of stents for use in intracranial vasculature, new hope has arisen for the treatment of intracranial atherosclerosis. The NEUROLINK system, the drug-eluting stents Taxus and Cypher, the flexible Wingspan stent, the Apollo stent, and the Pharos stent have all been used in various prospective and retrospective clinical studies with varying technical and clinical results. The authors' objective is to review and loosely compare the data presented for each of these stenting systems. While the Wingspan stent appears to have somewhat of an advantage with regard to technical success in comparison with the other stenting systems, the clinical follow-up time of its studies is too short to properly compare its complication rates with those of other stents. Before we continue to move forward with stenting for intracranial stenosis, a randomized prospective trial is ultimately needed to directly compare intracranial stenting to medical therapy.

Dural venous sinus stenting for treatment of pediatric idiopathic intracranial hypertension.

BACKGROUND: Dural venous sinus stenting (VSS) is an effective treatment for idiopathic intracranial hypertension (IIH) in adult patients. There are no published series to date evaluating safety and efficacy of VSS in pediatric patients. OBJECTIVE: To report on procedural device selection and technique as well as safety and efficacy of VSS for pediatric patients with medically refractory IIH due to underlying venous sinus stenosis. METHODS: A multi-institutional retrospective case series identified patients with medically refractory IIH aged less than 18 years who underwent VSS. RESULTS: 14 patients were identified at four participating centers. Patient ages ranged from 10 to 17 years, and 10 patients (71.4%) were female. Mean body mass index was 25.7 kg/m2 (range 15.8-34.6 kg/m2). Stenting was performed under general endotracheal anesthesia in all except two patients. The average trans-stenotic gradient during diagnostic venography was 10.6 mm Hg. Patients had stents placed in the superior sagittal sinus, transverse sinus, sigmoid sinus, occipital sinus, and a combination. Average follow-up was 1.7 years after stenting. Six patients out of 10 (60%) had reduced medication dosing, 12 of 14 patients (85.7%) had improvements in headaches, two patients (100%) with pre-stent tinnitus had resolution of symptoms, and four (80%) of five patients with papilledema had improvement on follow-up ophthalmological examinations. Two patients (14.3%) developed postprocedural groin hematomas, one patient (7.1%) developed a groin pseudoaneurysm, and one patient (7.1%) had postprocedural groin bleeding. No other procedural complications occurred. Four patients (28.6%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in a pediatric population with IIH and has a low complication rate and good clinical outcomes.

The SMART Registry: Long-Term Results on the Utility of the Penumbra SMART COIL System for Treatment of Intracranial Aneurysms and Other Malformations.

Introduction: Penumbra SMART COIL® (SMART) System is a novel generation embolic coil with varying stiffness. The study purpose was to report real-world usage of the SMART System in patients with intracranial aneurysms (ICA) and non-aneurysm vascular lesions. Materials and Methods: The SMART Registry is a post-market, prospective, multicenter registry requiring ≥75% Penumbra Coils, including SMART, PC400, and/or POD coils. The primary efficacy endpoint was retreatment rate at 1-year and the primary safety endpoint was the procedural device-related serious adverse event rate. Results: Between June 2016 and August 2018, 995 patients (mean age 59.6 years, 72.1% female) were enrolled at 68 sites in the U.S. and Canada. Target lesions were intracranial aneurysms in 91.0% of patients; 63.5% were wide-neck and 31.8% were ruptured. Adjunctive devices were used in 55.2% of patients. Mean packing density was 32.3%. Procedural device-related serious adverse events occurred in 2.6% of patients. The rate of immediate post-procedure adequate occlusion was 97.1% in aneurysms and the rate of complete occlusion was 85.2% in non-aneurysms. At 1-year, the retreatment rate was 6.8%, Raymond Roy Occlusion Classification (RROC) I or II was 90.0% for aneurysms, and Modified Rankin Scale (mRS) 0-2 was achieved in 83.1% of all patients. Predictors of 1-year for RROC III or retreatment (incomplete occlusion) were rupture status (P < 0.0001), balloon-assisted coiling (P = 0.0354), aneurysm size (P = 0.0071), and RROC III immediate post-procedure (P = 0.0086) in a model that also included bifurcation aneurysm (P = 0.7788). Predictors of aneurysm retreatment at 1-year was rupture status (P < 0.0001). Conclusions: Lesions treated with SMART System coils achieved low long-term retreatment rates. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT02729740.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

Microvascular decompression of the posterior cerebral artery for treatment of oculomotor nerve palsy.

Oculomotor nerve palsy resulting from non-aneurysmal vascular compression is extremely rare. Microvascular decompression (MVD) has been previously shown to improve oculomotor nerve palsy (ONP) secondary to arterial compression. A 71-year-old female, with a history of Cushing's disease previously treated with two transsphenoidal resections and Gamma Knife radiosurgery, presented with one year of progressive left eye diplopia and was diagnosed with a partial left oculomotor nerve palsy. We performed an orbitozygomatic craniotomy for MVD of the left posterior cerebral artery, which was found to be compressing the oculomotor nerve against the tentorium. Unfortunately, the patient's partial ONP remained unchanged at one year follow-up. The present case suggests inconsistent outcomes of MVD for ONP. Patients with prior sellar or parasellar irradiation may be less likely to benefit from this treatment approach.

Intracranial Venous Sinus Stenting: A Review of Idiopathic Intracranial Hypertension and Expanding Indications.

Idiopathic intracranial hypertension (IIH) is a functionally limiting disorder secondary to increased intracranial pressures (ICPs) with a prevalence of one per 100,000 persons. It is estimated to cost >$400 million per year in productively. Symptoms classically consist of chronic headaches, papilledema, and visual loss. The pathophysiology is unknown but postulated to involve increased resistance to cerebrospinal fluid (CSF) absorption. Traditional treatments involve weight loss, acetazolamide, CSF diversion, or optic nerve fenestration. More recent technology has allowed exploration of venous sinus stenosis. Through venous sinus stenting (VSS), the ICPs and venous sinus pressures decrease. After treatment, >75% exhibit an improvement in headaches, ~50% improvement in tinnitus, and ~50 % improvement in ophthalmologic testing. Complications are rare but involve stent stenosis, femoral pseudoaneurysm, and hemorrhages. Future studies will look into controlled studies for VSS as well as expansion to other venous structures of the intracranial circulation.

Idiopathic Intracranial Hypertension Masking as Obstructive Hydrocephalus: A Case Report.

Idiopathic intracranial hypertension (IIH) is a poorly understood phenomenon and its presentation can both mimic and co-exist with other intra-cranial processes. Accurate diagnosis is imperative as ongoing advancements in treatment can yield dramatic positive results. Here we present the case of an individual with signs and symptoms of obstructive hydrocephalus who was ultimately found to have IIH secondary to venous sinus stenosis. After correction of the venous sinus stenosis, resolution in the patient's symptoms was noted. The case highlights some of the unique considerations in approaching patients with IIH and provides a framework for review of current literature related to IIH and venous sinus stenosis.

Microsurgery Versus Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Matched Cohort Study.

BACKGROUND: Microsurgery (MS) and stereotactic radiosurgery (SRS) remain the preferred interventions for the curative treatment of brain arteriovenous malformations (AVM), but their relative efficacy remains incompletely defined. OBJECTIVE: To compare the outcomes of MS to SRS for AVMs through a retrospective, matched cohort study. METHODS: We evaluated institutional databases of AVM patients who underwent MS and SRS. MS-treated patients were matched, in a 1:1 ratio based on patient and AVM characteristics, to SRS-treated patients. Statistical analyses were performed to compare outcomes data between the 2 cohorts. The primary outcome was defined as AVM obliteration without a new permanent neurological deficit. RESULTS: The matched MS and SRS cohorts were each comprised of 59 patients. Both radiological (85 vs 11 mo; P < .001) and clinical (92 vs 12 mo; P < .001) follow-up were significantly longer for the SRS cohort. The primary outcome was achieved in 69% of each cohort. The MS cohort had a significantly higher obliteration rate (98% vs 72%; P = .001), but also had a significantly higher rate of new permanent deficit (31% vs 10%; P = .011). The posttreatment hemorrhage rate was significantly higher for the SRS cohort (10% for SRS vs 0% for MS; P = .027). In subgroup analyses of ruptured and unruptured AVMs, no significant differences between the primary outcomes were observed. CONCLUSION: For patients with comparable AVMs, MS and SRS afford similar rates of deficit-free obliteration. Nidal obliteration is more frequently achieved with MS, but this intervention also incurs a greater risk of new permanent neurological deficit.

SMART coils for intracranial aneurysm embolization: Follow-up outcomes.

The SMART coil (Penumbra Inc., Alameda, CA, USA) is a new microcoil designed to enhance deliverability. Although prior studies have described its perioperative safety and efficacy, the follow-up outcomes after embolization of intracranial aneurysms using SMART coils have not been reported. Therefore, the aim of this retrospective cohort study is to assess the angiographic outcomes at interim follow-up after aneurysm embolization with SMART coils. We reviewed data from consecutive patients with intracranial aneurysms who underwent endovascular treatment using SMART coils between June 2016 and August 2017. Baseline data and follow-up angiographic outcomes using the modified Raymond-Roy classification (MRRC) were recorded. The study cohort comprised 33 patients with 34 aneurysms who underwent SMART coil embolization and had sufficient follow-up data. The mean age was 57 years, and 82% were female. The mean aneurysm maximum diameter and neck width were 6.1 ±â€¯2.2 mm and 3.2 ±â€¯1.2 mm, respectively, and 14.7% of aneurysms were ruptured. The overall complication rate was 12%. Initial mean coil packing density was 26%, and the initial MRRC was I, II, IIIa, and IIIb in 24%, 26%, 35%, and 15%, respectively. At last follow-up (mean duration 7.7 ±â€¯3.2 months), the MRRC was I, II, IIIa, and IIIb in 62%, 26%, 3%, and 9%, respectively. The retreatment rate was 14.7%. The SMART coil is efficacious for the treatment of appropriately selected aneurysms, with an acceptable risk profile. The majority of residual aneurysms after the initial embolization procedure will progress to complete or near-complete occlusion at interim follow-up.

High-Grade Aneurysmal Subarachnoid Hemorrhage: Predictors of Functional Outcome.

BACKGROUND: Because the prognosis of high-grade aneurysmal subarachnoid hemorrhage (aSAH), classified as World Federation of Neurosurgical Societies (WFNS) grade IV-V, is generally poor, the functional outcomes of survivors have not been thoroughly explored. The aim of this retrospective cohort study is to determine predictors of functional independence in patients who survive a high-grade aSAH. METHODS: We retrospectively evaluated consecutive patients with aSAH admitted to a single institution from January 2000 to April 2015. Adult (age ≥18 years) patients with WFNS grade IV-V aSAH were included for analysis. Patients without sufficient baseline data, those who died before discharge, and those without follow-up data were excluded. Univariable and multivariable logistic regression analyses were used to identify factors associated with functional independence, defined as a modified Rankin Scale score of 0-2, at last follow-up. RESULTS: Of the 260 patients with a WFNS grade IV-V aSAH during the study period, 139 met the inclusion criteria. After a mean follow-up of 6.3 months, functional independence was achieved in 73% of high-grade aSAH survivors (101/139 patients) and in 39% of all high-grade aSAH cases (101/260 patients). Only a lack of cerebrospinal fluid shunt placement was found to be an independent predictor of functional independence in the multivariable analysis (odds ratio 0.28 [0.109-0.722]; P = 0.008). CONCLUSIONS: Because functional independence can be achieved in the majority of high-grade aSAH survivors, aggressive initial management of high-grade aSAH is warranted. Strategies that reduce the need for permanent cerebrospinal fluid diversion may improve functional outcomes in survivors of high-grade aSAH.

Concurrent Venous Stenting of the Transverse and Occipito-Marginal Sinuses: An Analogy with Parallel Hemodynamic Circuits.

Nonthrombotic intracranial venous occlusive disease (NIVOD) has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH) and various non-IIH headache syndromes. Endovascular stenting of stenotic, dominant transverse sinuses (TSs) may reduce trans-stenosis pressure gradients, decrease intracranial pressure, and alleviate symptoms in a subset of NIVOD patients. We present a case in which concurrent stenting of the occipito-marginal sinus obliterated the residual trans-stenosis pressure gradient across an initially stented dominant TS. We hypothesize that this observation may be explained using an electric-hydraulic analogy, and that this patient's dominant TS and occipito-marginal sinus may be modeled as a parallel hemodynamic circuit. Neurointerventionalists should be aware of parallel hemodynamic drainage patterns and consider manometry and possibly additional stenting of stenotic, parallel venous outflow pathways if TS stenting alone fails to obliterate the trans-stenosis pressure gradient.