Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part I-Anatomy and Physiology.

Normal physiologic function of organs requires a circulation of interstitial fluid to deliver nutrients and clear cellular waste products. Lymphatic vessels serve as collectors of this fluid in most organs; however, these vessels are absent in the central nervous system. How the central nervous system maintains tight control of extracellular conditions has been a fundamental question in neuroscience until recent discovery of the glial-lymphatic, or glymphatic, system was made this past decade. Networks of paravascular channels surrounding pial and parenchymal arteries and veins were found that extend into the walls of capillaries to allow fluid transport and exchange between the interstitial and cerebrospinal fluid spaces. The currently understood anatomy and physiology of the glymphatic system is reviewed, with the paravascular space presented as an intrinsic component of healthy pial and parenchymal cerebral blood vessels. Glymphatic system behavior in animal models of health and disease, and its enhanced function during sleep, are discussed. The evolving understanding of glymphatic system characteristics is then used to provide a current interpretation of its physiology that can be helpful for radiologists when interpreting neuroimaging investigations.

Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part II-Imaging Techniques and Clinical Applications.

The glymphatic system is a recently discovered network unique to the central nervous system that allows for dynamic exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF). As detailed in part I, ISF and CSF transport along paravascular channels of the penetrating arteries and possibly veins allow essential clearance of neurotoxic solutes from the interstitium to the CSF efflux pathways. Imaging tests to investigate this neurophysiologic function, although challenging, are being developed and are reviewed herein. These include direct visualization of CSF transport using postcontrast imaging techniques following intravenous or intrathecal administration of contrast material and indirect glymphatic assessment with detection of enlarged perivascular spaces. Application of MRI techniques, including intravoxel incoherent motion, diffusion tensor imaging, and chemical exchange saturation transfer, is also discussed, as are methods for imaging dural lymphatic channels involved with CSF efflux. Subsequently, glymphatic function is considered in the context of proteinopathies associated with neurodegenerative diseases and traumatic brain injury, cytotoxic edema following acute ischemic stroke, and chronic hydrocephalus after subarachnoid hemorrhage. These examples highlight the substantial role of the glymphatic system in neurophysiology and the development of certain neuropathologic abnormalities, stressing the importance of its consideration when interpreting neuroimaging investigations. © RSNA, 2021.

Thrombectomy Outcomes of Intracranial Atherosclerosis-Related Occlusions.

Background and Purpose- Intracranial atherosclerosis (ICAS) is an important cause of large vessel occlusion and poses unique challenges for emergent endovascular thrombectomy. The risk factor profile and therapeutic outcomes of patients with ICAS-related occlusions (ICAS-O) are unclear. We performed a systematic review and meta-analysis of studies reporting the clinical features and thrombectomy outcomes of large vessel occlusion stroke secondary to underlying ICAS (ICAS-O) versus those of other causes (non-ICAS-O). Methods- A literature search on thrombectomy for ICAS-O was performed. Random-effect meta-analysis was used to analyze the prevalence of stroke risk factors and outcomes of thrombectomy between ICAS-O and non-ICAS-O groups. Results- A total of 1967 patients (496 ICAS-O and 1471 non-ICAS-O) were included. The ICAS-O group had significantly higher prevalence of hypertension (odds ratio [OR] 1.46; 95% CI, 1.10-1.93), diabetes mellitus (OR, 1.68; 95% CI, 1.29-2.20), dyslipidemia (OR, 1.94; 95% CI, 1.04-3.62), smoking history (OR, 2.11; 95% CI, 1.40-3.17) but less atrial fibrillation (OR, 0.20; 95% CI, 0.13-0.31) than the non-ICAS-O group. About thrombectomy outcomes, ICAS-O had higher intraprocedural reocclusion rate (OR, 23.7; 95% CI, 6.96-80.7), need for rescue balloon angioplasty (OR, 9.49; 95% CI, 4.11-21.9), rescue intracranial stenting (OR, 14.9; 95% CI, 7.64-29.2), and longer puncture-to-reperfusion time (80.8 versus 55.5 minutes, mean difference 21.3; 95% CI, 11.3-31.3). There was no statistical difference in the rate of final recanalization (modified Thrombolysis in Cerebral Infarction score of 2b/3; OR, 0.67; 95% CI, 0.36-1.27), symptomatic intracerebral hemorrhage (OR, 0.79; 95% CI, 0.50-1.24), good functional outcome (modified Rankin Scale score of 0-2; OR, 1.16; 95% CI, 0.85-1.58), and mortality (OR, 0.94; 95% CI, 0.64-1.39) between ICAS-O and non-ICAS-O. Conclusions- Patients with ICAS-O display a unique risk factor profile and technical challenges for endovascular reperfusion therapy. Intraprocedural reocclusion occurs in one-third of patients with ICAS-O. Intraarterial glycoprotein IIb/IIIa inhibitors infusion, balloon angioplasty, and intracranial stenting may be viable rescue treatment to achieve revascularization, resulting in comparable outcomes to non-ICAS-O.

Cerebral neurovascular embryology, anatomic variations, and congenital brain arteriovenous lesions.

Cerebral neurovascular development is a complex and coordinated process driven by the changing spatial and temporal metabolic demands of the developing brain. Familiarity with the process is helpful in understanding neurovascular anatomic variants and congenital arteriovenous shunting lesions encountered in endovascular neuroradiological practice. Herein, the processes of vasculogenesis and angiogenesis are reviewed, followed by examination of the morphogenesis of the cerebral arterial and venous systems. Common arterial anatomic variants are reviewed with an emphasis on their development. Finally, endothelial genetic mutations affecting angiogenesis are examined to consider their probable role in the development of three types of congenital brain arteriovenous fistulas: vein of Galen malformations, pial arteriovenous fistulas, and dural sinus malformations.

Accelerated ethanol elimination via the lungs.

Ethanol poisoning is endemic the world over. Morbidity and mortality depend on blood ethanol levels which in turn depend on the balance between its rates of absorption and clearance. Clearance of ethanol is mostly at a constant rate via enzymatic metabolism. We hypothesized that isocapnic hyperpnea (IH), previously shown to be effective in acceleration of clearance of vapour anesthetics and carbon monoxide, would also accelerate the clearance of ethanol. In this proof-of-concept pilot study, five healthy male subjects were brought to a mildly elevated blood ethanol concentration (~ 0.1%) and ethanol clearance monitored during normal ventilation and IH on different days. IH increased elimination rate of ethanol in proportion to blood levels, increasing the elimination rate more than three-fold. Increased veno-arterial ethanol concentration differences during IH verified the efficacy of ethanol clearance via the lung. These data indicate that IH is a nonpharmacologic means to accelerate the elimination of ethanol by superimposing first order elimination kinetics on underlying zero order liver metabolism. Such kinetics may prove useful in treating acute severe ethanol intoxication.

First clinical experience with the new Surpass Evolve flow diverter: technical and clinical considerations.

OBJECTIVE: To describe the results in patients treated with the Surpass Evolve (SE) device, the new generation of Surpass flow diverters. METHODS: Twenty-five consecutive patients (20 women, average age 58 years), with anterior or posterior circulation aneurysms treated with SEs in two early-user centers, were included. Device properties and related technical properties, imaging and clinical follow-up data, and intraprocedural, early (<30 days) and delayed (>30 days) neurological complications, further divided into minor (silent/non-permanent) and major (permanent) complications, were recorded and analyzed. RESULTS: Twenty-nine SEs were successfully implanted in all subjects to treat 26 aneurysms using an 0.027" microcatheter with an average of 1.2 stents per patient. No intraprocedural thromboembolic or hemorrhagic complications were seen. At clinical follow-up, 24/25 (96%) patients had a modified Rankin Score of 0-2. Mortality was 0%. Imaging follow-up, available in 22/25 (88%) patients (median follow-up time 4 months), showed a complete aneurysm occlusion in 13/23 (57%) imaged lesions. Minor, transitory neurological deficits were recorded in 5/25 (20%) patients. One (4%) major complication was seen in one patient (4%) with a left-sided hemispheric stroke on postprocedural day 4 due to an acute stent thrombosis. CONCLUSIONS: Preliminary experience in patients demonstrates a good performance of the SE. This newly designed implant maintains the engineering characteristics of Surpass flow diverters, including precise placement due to its lower foreshortening and a high mesh density, yet can be deployed through a significantly lower-profile delivery system.

Transradial approach in the treatment of a sacral dural arteriovenous fistula: a technical note.

Sacral dural arteriovenous fistulas (SDAVFs) are rare, constituting no more than 10% of all spinal dural fistulas. They are most commonly fed by the lateral sacral artery (LSA), a branch of the internal iliac artery (IIA). Catheterization of this vessel requires either a crossover at the aortic bifurcation in cases of right femoral access or retrograde catheterization from the ipsilateral common femoral artery. We present the case of a 79-year-old man with tethered cord syndrome and a symptomatic SDAVF fed by two feeders from the left LSA. Spinal diagnostic angiography was made exceptionally challenging by an aorto-bi-iliac endograft, and selective catheterization of the left IIA was not possible. The patient could not undergo surgery due to multiple comorbidities, therefore embolization was considered the best approach. The procedure was carried out through a transradial access (TRA) with Onyx and n-butyl cyanoacrylate. The SDAVF was successfully treated and the patient made a full neurological recovery.

Republished: Transradial approach in the treatment of a sacral dural arteriovenous fistula: a technical note.

Sacral dural arteriovenous fistulas (SDAVFs) are rare, constituting no more than 10% of all spinal dural fistulas. They are most commonly fed by the lateral sacral artery (LSA), a branch of the internal iliac artery (IIA). Catheterization of this vessel requires either a crossover at the aortic bifurcation in cases of right femoral access or retrograde catheterization from the ipsilateral common femoral artery. We present the case of a 79-year-old man with tethered cord syndrome and a symptomatic SDAVF fed by two feeders from the left LSA. Spinal diagnostic angiography was made exceptionally challenging by an aorto-bi-iliac endograft, and selective catheterization of the left IIA was not possible. The patient could not undergo surgery due to multiple comorbidities, therefore embolization was considered the best approach. The procedure was carried out through a transradial access (TRA) with Onyx and n-butyl cyanoacrylate. The SDAVF was successfully treated and the patient made a full neurological recovery.

Periprocedural complications of second-generation flow diverter treatment using Pipeline Flex for unruptured intracranial aneurysms: a systematic review and meta-analysis.

BACKGROUND: Flow diverters are a breakthrough treatment for large and giant intracranial aneurysms but carry a risk of periprocedural death or major stroke. Pipeline Flex is a second-generation device that is thought to have lower complication rates because of improvements in the delivery system as well as increased operator experience. Our objective was to analyze the risk of periprocedural death or major complications using Pipeline Flex for unruptured intracranial aneurysms. METHODS: A systematic search of three databases was performed for studies of ≥10 treatments using Pipeline Flex for unruptured intracranial aneurysms (2014-2019) using PRISMA guidelines. Random effects meta-analysis was used to pool the rates of periprocedural (<30 days) death, major ischemic stroke, symptomatic intracranial hemorrhage, and minor stroke/transient ischemic attack. RESULTS: We included eight studies reporting 901 treatments in 879 patients. Periprocedural mortality (<30 days) was 0.8% (5/901; 95% CI 0.4% to 1.5%; I2=0%). Rate of major complications (death, major ischemic stroke, or symptomatic intracranial hemorrhage) was 1.8% (14/901; 95% CI 1.0% to 2.7%; I2=0%). Aneurysm size ≥10 mm was a statistically significant predictor of a major complication (OR 6.4; 95% CI 2.0 to 20.7; p=0.002). Risk of a major complication in aneurysms <10 mm was 0.9% (95% CI 0.3% to 1.7%; I2=0%). The meta-analysis was limited by the predominance of anterior circulation aneurysms. CONCLUSION: Treatment of unruptured intracranial aneurysms using the Pipeline Flex flow diverter has a low periprocedural risk of death (0.8%) or major complication (1.8%). The risk of a major complication is significantly higher for large/giant aneurysms (4.4%) and is very low for aneurysms <10 mm (0.9%).

A theory for polymicrogyria and brain arteriovenous malformations in HHT.

Hereditary hemorrhagic telangiectasia (HHT) is generally considered a disorder of endothelial dysfunction, characterized by the development of multiple systemic arteriovenous malformations (AVMs), including within the brain. However, there have recently been a number of reports correlating HHT with malformations of cortical development, of which polymicrogyria is the most common type. Here we present 7 new cases demonstrating polymicrogyria in HHT, 6 of which demonstrate a brain AVM (bAVM) in close spatial proximity, with the aim of providing a common origin for the association. Upon reviewing patient genetics and imaging data and comparing with previously reported findings, we form 2 new conclusions: (1) polymicrogyria in HHT appears exclusively associated with a subset of mutations in the transmembrane protein endoglin that is involved with blood flow-related mechanotransduction signaling during angiogenesis and (2) the polymicrogyria is characteristically unilateral, typically focal, and correlates with vascular regions experiencing low fluid shear stress during corticogenesis in utero. Integrating these with findings in the literature from genetics and molecular biology experiments, we propose a theory suggesting haploinsufficient endoglin mutations, especially those that are dominant-negative, may predispose focal, aberrant hypersprouting angiogenesis during corticogenesis that leads to the production of polymicrogyria. This hypoxic insult may further serve as the revealing trigger for later development of a spatially coincident bAVM. This hypothesis suggests an essential role for endoglin-mediated hemodynamic mechanotransduction in normal corticogenesis.

Optical Topographic Imaging for Spinal Intraoperative Three-Dimensional Navigation in Mini-Open Approaches: A Prospective Cohort Study of Initial Preclinical and Clinical Feasibility.

OBJECTIVE: Computer-assisted three-dimensional navigation often guides spinal instrumentation. Optical topographic imaging (OTI) offers comparable accuracy and significantly faster registration relative to current navigation systems in open posterior thoracolumbar exposures. We validate the usefulness and accuracy of OTI in minimally invasive spinal approaches. METHODS: Mini-open midline posterior exposures were performed in 4 human cadavers. Square exposures of 25, 30, 35, and 40 mm were registered to preoperative computed tomography imaging. Screw tracts were fashioned using a tracked awl and probe with instrumentation placed. Navigation data were compared with screw positions on postoperative computed tomography imaging, and absolute translational and angular deviations were computed. In vivo validation was performed in 8 patients, with mini-open thoracolumbar exposures and percutaneous placement of navigated instrumentation. Navigated instrumentation was performed in the previously described manner. RESULTS: For 37 cadaveric screws, absolute translational errors were (1.79 ± 1.43 mm) and (1.81 ± 1.51 mm) in the axial and sagittal planes, respectively. Absolute angular deviations were (3.81 ± 2.91°) and (3.45 ± 2.82°), respectively (mean ± standard deviation). The number of surface points registered by the navigation system, but not exposure size, correlated positively with the likelihood of successful registration (odds ratio, 1.02; 95% confidence interval, 1.009-1.024; P < 0.001). Fifty-five in vivo thoracolumbar pedicle screws were analyzed. Overall (mean ± standard deviation) axial and sagittal translational errors were (1.79 ± 1.41 mm) and (2.68 ± 2.26 mm), respectively. Axial and sagittal angular errors were (3.63° ± 2.92°) and (4.65° ± 3.36°), respectively. There were no radiographic breaches >2 mm or any neurovascular complications. CONCLUSIONS: OTI is a novel navigation technique previously validated for open posterior exposures and in this study has comparable accuracy for mini-open minimally invasive surgery exposures. The likelihood of successful registration is affected more by the geometry of the exposure than by its size.

Endovascular treatment of debilitating tinnitus secondary to cerebral venous sinus abnormalities: a literature review and technical illustration.

BACKGROUND AND OBJECTIVE: Pulsatile tinnitus (PT) can be debilitating and lead to significant morbidity. Cerebral venous sinus lesions, such as venous sinus stenosis, diverticula, and high-riding jugular bulb, are uncommon causes of PT, for which there is no standard treatment. Endovascular interventions have shown promising results for PT secondary to idiopathic intracranial hypertension, and may be a valid therapeutic option for isolated venous PT. METHODS: We conducted a systematic literature review on the outcome and safety of endovascular treatment for patients with isolated, debilitating venous PT. The venous lesion characteristics, endovascular techniques, complications, and clinical outcomes were assessed. In addition, an illustrative case of endovascular stenting for PT caused by venous sinus stenosis was included. RESULTS: A total of 41 patients (90.2% female) from 26 papers were included. The median age was 46 years (IQR 23; range 25-72 years). Focal venous sinus stenosis (20 patients) and sinus diverticula (14 patients) were the most common culprit lesions. Endovascular treatment included venous sinus stenting in 35 patients, 11 of whom had adjuvant coil embolization, and coil embolization alone in six patients. Complete resolution of the tinnitus was achieved in 95.1% of patients. There was one complication of cerebellar infarct, and no procedure-related mortality. CONCLUSIONS: In patients with debilitating PT secondary to venous sinus lesions, endovascular treatment by stenting and/or coil embolization appears to be safe and effective. Prospective randomized studies with objective outcome assessments are needed to confirm the treatment benefits.

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy.

BACKGROUND CONTEXT: Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy. PURPOSE: This study aimed to characterize the correlation between clinical pedicle screw accuracy, based on postoperative imaging, and absolute quantitative navigation accuracy. DESIGN/SETTING: This is a retrospective review of a prospectively collected cohort. PATIENT SAMPLE: We recruited 30 patients undergoing first-time posterior cervical-thoracic-lumbar-sacral instrumented fusion±decompression, guided by intraoperative three-dimensional CAN. OUTCOME MEASURES: Clinical or radiographic screw accuracy (Heary and 2 mm classifications) and absolute quantitative navigation accuracy (translational and angular error in axial and sagittal planes). METHODS: We reviewed a prospectively collected series of 209 pedicle screws placed with CAN guidance. Each screw was graded clinically by multiple independent raters using the Heary and 2 mm classifications. Clinical grades were dichotomized per convention. The absolute accuracy of each screw was quantified by the translational and angular error in each of the axial and sagittal planes. RESULTS: Acceptable screw accuracy was achieved for significantly fewer screws based on 2 mm grade versus Heary grade (92.6% vs. 95.1%, p=.036), particularly in the lumbar spine. Inter-rater agreement was good for the Heary classification and moderate for the 2 mm grade, significantly greater among radiologists than surgeon raters. Mean absolute translational-angular accuracies were 1.75 mm-3.13° and 1.20 mm-3.64° in the axial and sagittal planes, respectively. There was no correlation between clinical and absolute navigation accuracy. CONCLUSIONS: Radiographic classifications of pedicle screw accuracy vary in sensitivity across spinal levels, as well as in inter-rater reliability. Correlation between clinical screw grade and absolute navigation accuracy is poor, as surgeons appear to compensate for navigation registration error. Future studies of navigation accuracy should report absolute translational and angular errors. Clinical screw grades based on postoperative imaging may be more reliable if performed in multiple by radiologist raters.

Comparison of aortic arch and intravenous contrast injection techniques for C-arm cone beam CT: implications for cerebral perfusion imaging in the angiography suite.

RATIONALE AND OBJECTIVES: The ability to perform cerebral perfusion imaging (CPI) in the angiography suite has provided a new tool for diagnosis and treatment of neurovascular patients but requires comparable contrast perfusion to each cerebral hemisphere. In the angiography suite, contrast injection may be performed via an intra-arterial or intravenous (IV) route. The purpose of this study was to investigate whether a difference exists between contrast injection in the aortic arch (AA) and a peripheral vein (IV), particularly in the setting of stroke. MATERIALS AND METHODS: Using three canines, both AA and IV injection protocols compatible with CPI were performed prospectively at three time points after creation of a stroke. The common carotid arteries in the resulting image data sets were segmented and the means and distributions of corresponding pixel intensities analyzed with Student's t-test. Using similar techniques, the internal carotid arteries of three patients (one female, two males, ages 69, 29, and 20) undergoing AA contrast injection with cone beam computed tomography (CBCT) cerebral imaging were analyzed and compared retrospectively with those of three random patients (one female, two males, ages 19, 57, and 35) undergoing standard head CT scans using IV contrast administration. All acquisitions followed institutionally approved protocols and informed consent. RESULTS: No statistical significance (P < .05) was found when mean values for the right and left carotid artery pixel intensities were compared in the canine model or the clinical studies in which patients underwent imaging after AA or IV contrast administration. CONCLUSIONS: No statistically significant difference exists between right and left carotid artery filling density using either AA or IV contrast injection methods, making both suitable for CPI in the angiography suite.

Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughput infectious disease diagnostics.

Through the convergence of nano- and microtechnologies (quantum dots and microfluidics), we have created a diagnostic system capable of multiplexed, high-throughput analysis of infectious agents in human serum samples. We demonstrate, as a proof-of-concept, the ability to detect serum biomarkers of the most globally prevalent blood-borne infectious diseases (i.e., hepatitis B, hepatitis C, and HIV) with low sample volume (<100 microL), rapidity (<1 h), and 50 times greater sensitivity than that of currently available FDA-approved methods. We further show precision for detecting multiple biomarkers simultaneously in serum with minimal cross-reactivity. This device could be further developed into a portable handheld point-of-care diagnostic system, which would represent a major advance in detecting, monitoring, treating, and preventing infectious disease spread in the developed and developing worlds.