Publications by authors named "Timo Krings"

265 Publications

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

Radiology 2021 Oct 26:204088. Epub 2021 Oct 26.

From the Department of Diagnostic and Interventional Neuroradiology, Montréal Neurologic Institute and Hospital, McGill University Health Centre, 3801 Rue University, Montréal, QC, Canada H3A 2B4 (J.M.K.); Department of Medical Imaging (J.M.K., D.V., K.D.B., H.G.J.K., T.K., K.P.M., K.G.t.B., D.J.M.), Department of Materials Science & Engineering, Faculty of Applied Science & Engineering (D.V.), and Division of Neurosurgery, Department of Surgery (T.K., K.G.t.B.), University of Toronto, Toronto, Canada; Division of Neuroradiology, Toronto Western Hospital, University Health Network, Toronto, Canada (J.M.K., D.V., K.D.B., H.G.J.K., T.K., K.P.M., K.G.t.B., D.J.M.); Centre Hospitalier de l'Université de Montréal (CHUM), Department of Radiology, Service of Neuroradiology, l'Université de Montréal, Montréal, Canada (J.M.K.); and Department of Medical Imaging, Sydney Children's Hospitals Network, Westmead, Australia (K.D.B.).

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.
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http://dx.doi.org/10.1148/radiol.2021204088DOI Listing
October 2021

The centrally restricted diffusion sign on MRI for assessment of radiation necrosis in metastases treated with stereotactic radiosurgery.

J Neurooncol 2021 Oct 24. Epub 2021 Oct 24.

Department of Medical Imaging, University of Toronto, Toronto, Canada.

Purpose: Differentiation of radiation necrosis from tumor progression in brain metastases treated with stereotactic radiosurgery (SRS) is challenging. For this, we assessed the performance of the centrally restricted diffusion sign.

Methods: Patients with brain metastases treated with SRS who underwent a subsequent intervention (biopsy/resection) for a ring-enhancing lesion on preoperative MRI between 2000 and 2020 were included. Excluded were lesions containing increased susceptibility limiting assessment of DWI. Two neuroradiologists classified the location of the diffusion restriction with respect to the post-contrast T1 images as centrally within the ring-enhancement (the centrally restricted diffusion sign), peripherally correlating to the rim of contrast enhancement, both locations, or none. Measures of diagnostic accuracy and 95% CI were calculated for the centrally restricted diffusion sign. Cohen's kappa was calculated to identify the interobserver agreement.

Results: Fifty-nine patients (36 female; mean age 59, range 40 to 80) were included, 36 with tumor progression and 23 with radiation necrosis based on histopathology. Primary tumors included 34 lung, 12 breast, 5 melanoma, 3 colorectal, 2 esophagus, 1 head and neck, 1 endometrium, and 1 thyroid. The centrally restricted diffusion sign was seen in 19/23 radiation necrosis cases (sensitivity 83% (95% CI 63 to 93%), specificity 64% (95% CI 48 to 78%), PPV 59% (95% CI 42 to 74%), NPV 85% (95% CI 68 to 94%)) and 13/36 tumor progression cases (difference p < 0.001). Interobserver agreement was substantial, at 0.61 (95% CI 0.45 to 70.8).

Conclusion: We found a low probability of radiation necrosis in the absence of the centrally restricted diffusion sign.
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http://dx.doi.org/10.1007/s11060-021-03879-4DOI Listing
October 2021

The cerebrofacial metameric syndromes: An embryological review and proposal of a novel classification scheme.

Interv Neuroradiol 2021 Oct 19:15910199211044938. Epub 2021 Oct 19.

Department of Radiology, 6915Mayo Clinic, USA.

The cerebrofacial metameric syndromes are a group of congenital syndromes that result in vascular malformations throughout specific anatomical distributions of the brain, cranium and face. Multiple reports of patients with high-flow or low-flow vascular malformations following a metameric distribution have supported this idea. There has been much advancement in understanding of segmental organization and cell migration since the concept of metameric vascular syndromes was first proposed. We aim to give an updated review of these embryological considerations and then propose a more detailed classification system for these syndromes, predominately incorporating the contribution of neural crest cells and somitomeres to the pharyngeal arches.
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http://dx.doi.org/10.1177/15910199211044938DOI Listing
October 2021

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

Radiology 2021 Oct 19:202043. Epub 2021 Oct 19.

From the Montreal Neurologic Institute and Hospital, Department of Diagnostic and Interventional Neuroradiology, McGill University Health Centre, 3801 Rue University, Montréal, QC, Canada H3A 2B4 (J.M.K.); Department of Medical Imaging, University of Toronto, Toronto, Canada (J.M.K., D.V., K.D.B., H.G.J.K., T.K., K.P.M., K.G.t.B., D.J.M.); Division of Neuroradiology, Toronto Western Hospital, University Health Network, Toronto, Canada (J.M.K., D.V., K.D.B., H.G.J.K., T.K., K.P.M., K.G.t.B., D.J.M.); Centre Hospitalier de l'Université de Montreal (CHUM), Department of Radiology, Service of Neuroradiology, l'Université de Montreal, Montréal, Canada (J.M.K.); Department of Materials Science & Engineering, Faculty of Applied Science & Engineering, University of Toronto, Toronto, Canada (D.V.); Department of Medical Imaging, Sydney Children's Hospitals Network, Westmead, Australia (K.D.B.); and Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada (T.K., K.G.t.B.).

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.
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http://dx.doi.org/10.1148/radiol.2021202043DOI Listing
October 2021

Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox-Gastaut syndrome.

Brain Commun 2021 14;3(3):fcab207. Epub 2021 Sep 14.

Adult Epilepsy Genetics Research Program, Krembil Neurosciences Institute, Toronto Western Hospital, University Health Network, Toronto, Canada.

Epilepsies are a group of common neurological disorders with a substantial genetic basis. Despite this, the molecular diagnosis of epilepsies remains challenging due to its heterogeneity. Studies utilizing whole-genome sequencing may provide additional insights into genetic causes of epilepsies of unknown aetiology. Whole-genome sequencing was used to evaluate a cohort of adults with unexplained developmental and epileptic encephalopathies ( = 30), for whom prior genetic tests, including whole-exome sequencing in some cases, were negative or inconclusive. Rare single nucleotide variants, insertions/deletions, copy number variants and tandem repeat expansions were analysed. Seven pathogenic or likely pathogenic single nucleotide variants, and two pathogenic deleterious copy number variants were identified in nine patients (32.1% of the cohort). One of the copy number variants, identified in a patient with Lennox-Gastaut syndrome, was too small to be detected by chromosomal microarray techniques. We also identified two tandem repeat expansions with clinical implications in two other patients with Lennox-Gastaut syndrome: a CGG repeat expansion in the 5'untranslated region of , and a CTG expansion in (previously implicated in spinocerebellar ataxia type 8). Three patients had pathogenic variants. One of them died of sudden unexpected death in epilepsy. The other two patients had, in addition to a variant, a second variant impacting potential epilepsy-relevant genes ( and ). Overall, whole-genome sequencing provided a genetic explanation in 32.1% of the total cohort. This is also the first report of coding and non-coding tandem repeat expansions identified in patients with Lennox-Gastaut syndrome. This study demonstrates that using whole-genome sequencing, the examination of multiple types of rare genetic variation, including those found in the non-coding region of the genome, can help resolve unexplained epilepsies.
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http://dx.doi.org/10.1093/braincomms/fcab207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491034PMC
September 2021

Feasibility of robot-assisted neuroendovascular procedures.

J Neurosurg 2021 Sep 24:1-13. Epub 2021 Sep 24.

1Division of Neuroradiology, Department of Medical Imaging, Toronto Western Hospital, University Health Network, University of Toronto; and.

Objective: Geographic factors prevent equitable access to urgent advanced neuroendovascular treatments. Robotic technologies may enable remote endovascular procedures in the future. The authors performed a translational, benchtop-to-clinical study to evaluate the in vitro and clinical feasibility of the CorPath GRX Robotic System for robot-assisted endovascular neurointerventional procedures.

Methods: A series of bench studies was conducted using patient-specific 3D-printed models to test the system's compatibility with standard neurointerventional devices, including microcatheters, microwires, coils, intrasaccular devices, and stents. Optimal baseline setups for various procedures were determined. The models were further used to rehearse clinical cases. Subsequent to these investigations, a prospective series of 6 patients was treated using robotic assistance for complex, wide-necked intracranial saccular aneurysms between November 2019 and February 2020. The technical success, incidence of periprocedural complications, and need for conversion to manual procedures were evaluated.

Results: The ideal robotic setup for treatment of both anterior and posterior circulation aneurysms was determined to consist of an 80-cm guide catheter with a 115-cm-long intermediate catheter, a microcatheter between 150 and 170 cm in length, and a microwire with a minimum length of 300 cm. All coils, intrasaccular devices, and stents tested were compatible with the system and could be advanced or retracted safely and placed accurately. All 6 clinical procedures were technically successful, with all intracranial steps being performed robotically with no conversions to manual intervention or failures of the robotic system. There were no procedure-related complications or adverse clinical outcomes.

Conclusions: This study demonstrates the feasibility of robot-assisted neurointerventional procedures. The authors' results represent an important step toward enabling remote neuroendovascular care and geographic equalization of advanced endovascular treatments through so-called telestroke intervention.
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http://dx.doi.org/10.3171/2021.1.JNS203617DOI Listing
September 2021

Dilated MMA sign in cDAVF and other arterial feeders on 3D TOF MRA.

Neuroradiol J 2021 Aug 27:19714009211041530. Epub 2021 Aug 27.

Division of Neuroradiology, Toronto Western Hospital (University Health Network), Canada.

Background: Among the varied causes of pulsatile tinnitus, the condition that can cause severe mortality and morbidity is a cranial dural arteriovenous fistula (cDAVF). This study aimed to assess the diagnostic accuracy of the dilated middle meningeal artery on three-dimensional time-of-flight magnetic resonance angiography in cranial dural arteriovenous fistula and to identify other feeders that can aid in the detection of these lesions.

Method: Magnetic resonance angiography and digital subtraction angiography data of all patients with cranial dural arteriovenous fistula treated in a single tertiary referral center between 2007-2020 were included. The middle meningeal artery and other feeders recorded from digital subtraction angiography were assessed on magnetic resonance angiography.

Results: The overall agreement between readers in identifying the dilated middle meningeal artery was substantial (κ = 0.878, 95% confidence interval: 0.775-0.982). The dilated middle meningeal artery indicated the presence of a cranial dural arteriovenous fistula with a sensitivity of 79.49% (95% confidence interval: 66.81-92.16), specificity of 100% (95% confidence interval: 100.00-100.00), and negative predictive value of 94.56% (95% confidence interval: 90.89-98.02). An area under the curve of 0.8341 was observed for the ipsilateral middle meningeal artery, with a sensitivity of 92.2% and a specificity of 75.0% at a cut-off of 0.30 mm for identifying a cranial dural arteriovenous fistula. Of 73 other feeders, the occipital, meningohypophyseal trunk, ascending pharyngeal, and posterior meningeal arteries contributed to a large proportion visualized on magnetic resonance angiography (83.6% (41/49)).

Conclusion: The dilated middle meningeal artery sign is useful for identifying a cranial dural arteriovenous fistula. Dilatation of the occipital and ascending pharyngeal arteries and meningohypophyseal trunk should be assessed to facilitate the detection of a cranial dural arteriovenous fistula, particularly in the transverse-sigmoid and petrous regions.
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http://dx.doi.org/10.1177/19714009211041530DOI Listing
August 2021

The Magnetic Resonance Imaging "Spot" Sign: A Sign of Imminent Intracranial Hemorrhage?

Can J Neurol Sci 2021 Jun 23:1-2. Epub 2021 Jun 23.

Division of Diagnostic and Interventional Neuroradiology, Departments of Radiology and Surgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1017/cjn.2021.144DOI Listing
June 2021

Improving long-term outcomes in pediatric torcular dural sinus malformations with embolization and anticoagulation: a retrospective review of The Hospital for Sick Children experience.

J Neurosurg Pediatr 2021 Jul 30;28(4):469-475. Epub 2021 Jul 30.

1Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto.

Objective: Torcular dural sinus malformations (tDSMs) are rare pediatric cerebrovascular malformations characterized by giant venous lakes localized to the midline confluence of sinuses. Historical clinical outcomes of patients with these lesions were poor, though better prognoses have been reported in the more recent literature. Long-term outcomes in children with tDSMs are uncertain and require further characterization. The goal of this study was to review a cohort of tDSM patients with an emphasis on long-term outcomes and to describe the treatment strategy.

Methods: This study is a single-center retrospective review of a prospectively maintained data bank including patients referred to and cared for at The Hospital for Sick Children for tDSM from January 1996 to March 2019. Each patient's clinical, radiological, and demographic information, as well as their mother's demographic information, was collected for review.

Results: Ten patients with tDSM, with a mean follow-up of 58 months, were included in the study. Diagnoses were made antenatally in 8 patients, and among those cases, 4 families opted for either elective termination (n = 1) or no further care following delivery (n = 3). Of the 6 patients treated, 5 had a favorable long-term neurological outcome, and follow-up imaging demonstrated a decrease or stability in the size of the tDSM over time. Staged embolization was performed in 3 patients, and anticoagulation was utilized in 5 treated patients.

Conclusions: The authors add to a growing body of literature indicating that clinical outcomes in tDSM may not be as poor as initially perceived. Greater awareness of the lesion's natural history and pathophysiology, advancing endovascular techniques, and individualized anticoagulation regimens may lead to continued improvement in outcomes.
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http://dx.doi.org/10.3171/2021.3.PEDS20921DOI Listing
July 2021

External Validation and Modification of Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Score.

Neurosurgery 2021 09;89(4):591-596

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.

Background: The Nationwide Inpatient Sample Subarachnoid Hemorrhage (SAH) Severity Score (NIS-SSS) was developed as a measure of SAH severity for use in administrative databases. The NIS-SSS consists of International Classification of Diseases Ninth Revision (ICD-9) diagnostic and procedure codes derived from the SAH inpatient course and has been validated against the Hunt-Hess score (HH).

Objective: To externally validate both the NIS-SSS and a modified version of the NIS-SSS (m-NIS-SSS) consisting of codes present only on admission, against the HH in a Canadian province-wide registry and administrative database of SAH patients.

Methods: A total of 1467 SAH patients admitted to Ontario stroke centers between 2003 and 2013 with recorded HH were included. The NIS-SSS and m-NIS-SSS were validated against the HH by testing correlation between the NIS-SSS/m-NIS-SSS and HH, comparing discriminative ability of the NIS-SSS/m-NIS-SSS vs HH for poor outcome by calculating area under the curve (AUC), and comparing calibration of the NIS-SSS, m-NIS-SSS, and HH by plotting predicted vs observed outcome.

Results: Correlation with HH was 0.417 (P ≤ .001) for NIS-SSS, and 0.403 (P ≤ .001) for m-NIS-SSS. AUC for prediction of poor outcome was 0.786 (0.764-0.808) for HH, 0.771 (0.748-0.793) for NIS-SSS, and 0.744 (0.721-0.767) for m-NIS-SSS. Calibration plots demonstrated that HH had the most accurate prediction of outcome, whereas the NIS-SSS and m-NIS-SSS did not accurately predict low risk of poor outcome.

Conclusion: The NIS-SSS and m-NIS-SSS have good external validity, and therefore, may be suitable to approximate traditional clinical scores of disease severity in SAH research using administrative data.
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http://dx.doi.org/10.1093/neuros/nyab237DOI Listing
September 2021

Clinical and Angioarchitectural Features of Hemorrhagic Brain Arterio-Venous Malformations in Adults and Children: Contrasts and Implications on Outcome.

Neurosurgery 2021 09;89(4):645-652

Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Canada.

Background: Hemorrhage from brain arteriovenous malformations (bAVMs) is estimated at 3% per annum. Features influencing risk of hemorrhage include perforator/posterior circulation supply, associated aneurysms, and deep drainage. Children are more likely to present with bAVM bleeds.

Objective: To analyze differences in bAVM angioarchitecture between children and adults and describe predictors of poor outcome.

Methods: Data were collected from adult and pediatric tertiary referral hospitals. Demographic data, bleed location, treatment, and follow-up modified Rankin Scale (mRS) were collected. Angioarchitectural assessment included aneurysm presence, nidus morphology, perinidal angiogenesis, intranidal shunting, steal phenomenon, venous ectasia, venous stenosis, venous reflux, and pseudophlebitic pattern. Regression analyses conducted to determine predictors of mRS > 2.

Results: A total of 270 adult and 135 pediatric ruptured bAVMs were assessed. Median age was 42 (adults) and 10.9 (children) yr. Intranidal aneurysms were more frequent in children (P = .012), whereas prenidal aneurysms were more common in adults (P < .01). Children demonstrated more perinidal angiogenesis (P = .04), whereas steal phenomenon was commoner in adults (P < .01). Venous ectasia (P < .01), reflux (P < .01), and pseudophlebitic pattern (P = .012) were more frequent in adults. Children had better outcome (mRS score ≤ 2) (P < .01). Older age (odds ratio [OR] = 1.02), eloquent location (OR = 2.5), multicompartmental hemorrhage (OR = 1.98), venous reflux (OR = 2.5), diffuse nidus (OR = 1.83), pseudophlebitic pattern (OR = 1.96), intranidal shunts (OR = 2), and no treatment (OR = 3.68) were significant predictors of mRS > 2.

Conclusion: Children are more likely to have intranidal aneurysms and perinidal angiogenesis, whereas adults have more prenidal aneurysms, venous ectasia, corticovenous reflux, and pseudophlebitic pattern. Eloquent location, diffuse nidus, intranidal shunts, venous reflux, and pseudophlebitic pattern predict poorer outcome.
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http://dx.doi.org/10.1093/neuros/nyab251DOI Listing
September 2021

When Two Is Better than One : The Buddy-wire Technique in Flow-diversion Procedures.

Clin Neuroradiol 2021 Jul 8. Epub 2021 Jul 8.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, Toronto, Ontario, Canada.

Background: Delivery of most flow diverters (FD) requires larger, and thus stiffer microcatheters (0.021-0.027in.) which can pose challenges to intracranial navigation. The concomitant use of two microwires within one microcatheter, also known as the buddy-wire technique, may be helpful for navigation and support in challenging situations.

Methods: We analyzed all flow diverter procedures in our prospectively collected database. We recorded all patient-related, anatomical and procedural information. We performed univariate statistics and technical descriptions.

Results: In total, 208 consecutive patients treated with a FD at our institution between July 2014 and August 2020 were retrospectively analyzed. In 17 patients the buddy-wire technique was used (mean age 63 years, range 31-87 years: 16 female). Aneurysms were located at the petrous, cavernous, supraophthalmic internal carotid artery, and a proximal M2 branch in 2, 7, 7 and 1 patient(s), respectively. In all cases a 0.027in. microcatheter was used for device deployment. In 14 patients with a wide-necked aneurysm the buddy-wire provided additional support to advance the microcatheter and mitigated the ledge between the aneurysm neck and the parent artery or a side branch. In two giant cavernous aneurysms treated with telescoping FDs, the buddy-wire was used to re-enter the proximal end of the foreshortened FD.

Conclusion: The buddy-wire is a useful technique in FD procedures to prevent herniation of the microcatheter into the aneurysm sack, in wide-necked aneurysms to mitigate the ledge effect between the aneurysm neck and the parent artery where the microcatheter tip may get stuck, or to enable re-entry into a foreshortened FD.
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http://dx.doi.org/10.1007/s00062-021-01053-xDOI Listing
July 2021

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation.

Acta Neurochir (Wien) 2021 09 29;163(9):2503-2514. Epub 2021 Jun 29.

Hemorrhagic Brain Pathology Research Group, NeuroCenter, Kuopio University Hospital, Kuopio, Finland.

Background: Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions.

Methods: Tissue was obtained from surgery of 139 bAVMs and 21 normal Circle of Willis samples. The samples were studied with immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR). Clinical data was collected from patient records.

Results: COX2 expression was found in 78% (109/139) of the bAVMs and localized to the vessels' lumen or medial layer in 70% (95/135) of the bAVMs. Receptors for prostaglandin E2, a COX2-derived mediator of vascular remodeling, were found in the endothelial and smooth muscle cells and perivascular inflammatory cells of bAVMs. COX2 was expressed by infiltrating inflammatory cells and correlated with the extent of inflammation (r = .231, p = .007, Spearman rank correlation). COX2 expression did not associate with haemorrhage.

Conclusion: COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodelling and ongoing inflammation. Role of COX2 signalling in the pathobiology and clinical course of bAVMs merits further studies.
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http://dx.doi.org/10.1007/s00701-021-04895-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357659PMC
September 2021

Symptomatic Unruptured Arteriovenous Malformations: Focal Edema, Thrombosis, and Vessel Wall Enhancement: A Retrospective Cohort Study.

World Neurosurg 2021 08 2;152:e467-e475. Epub 2021 Jun 2.

Division of Neuroradiology, JDMI, University Health Network, Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, University Health Network, Ontario, Canada.

Background: Focal brain edema in unruptured brain arteriovenous malformations (AVMs) is rare and associated with venous outflow abnormalities and aneurysm growth. These patients have an increased rate of progressive neurologic symptoms, as well as a potentially increased risk of hemorrhage. In this study, we aim to assess in further detail the relationship between perifocal edema and enhancement of the vessel wall in symptomatic patients with an unruptured brain AVM.

Methods: A single-center retrospective cohort study of all patients presenting with an unruptured AVM at Toronto Western Hospital from 2009 to 2019 was performed. Patients were included for review if they had focal edema surrounding an AVM on magnetic resonance imaging (MRI) and a contrast-enhanced MRI scan. Associated digital subtraction angiography studies were reviewed.

Results: A total of 122 patients presented with an unruptured AVM. Twelve symptomatic patients presented with focal edema surrounding the AVM. Six patients had focal edema and contrast-enhanced MRI performed. All 6 demonstrated luminal thrombosis at the level of the brain edema on MRI. Moreover, the vessel wall demonstrated enhancement at the level of the luminal thrombus in all.

Conclusions: Vessel wall enhancement, perifocal edema, and luminal thrombosis demonstrated in all patients with unruptured AVM points towards a common mechanism. We suspect an interplay between vascular hypoxia, the innate immune system, and thrombosis formation. Current research in the field of immunothrombosis supports this theory. Unravelling the mechanisms involved is important because it might guide therapy for patients with an unruptured AVM towards noninvasive options.
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http://dx.doi.org/10.1016/j.wneu.2021.05.116DOI Listing
August 2021

Embolization strategies for intracranial dural arteriovenous fistulas with an isolated sinus: a single-center experience in 20 patients.

J Neurointerv Surg 2021 Jun 3. Epub 2021 Jun 3.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Background: Intracranial dural arteriovenous fistulas (DAVFs) draining into an isolated sinus segment constitute a specific entity within the spectrum of cranial dural AV shunts, with under-reporting of their optimal treatment.

Objective: To describe the multimodal treatment approach to isolated sinus DAVFs in a large single-center cohort.

Methods: Retrospective analysis of adult patients with an isolated sinus DAVF treated at our institution between 2004 and 2020 was performed. Cases were analyzed for demographics, clinical presentation, angiographic findings, treatment techniques, angiographic and clinical outcomes, and complications.

Results: Of 317 patients with DAVFs, 20 (6.3%) with an isolated sinus DAVF underwent treatment. Transarterial embolization was performed through the middle meningeal artery in 9 of 12 procedures, with a success rate of 66.7%. Transarterial glue embolization proved successful in two of five procedures (40%) and Onyx in six of seven procedures (85.7%). Transvenous embolization (TVE) with navigation via the occlusion into the isolated sinus was successful in seven out of nine procedures (77.8%). All three open TVE and one pure open surgical procedure gained complete closure of the fistula. There were two major complications. Complete occlusion of the fistula was eventually obtained in all cases (100%).

Conclusions: Isolated sinus DAVFs are always aggressive and require a multimodal approach to guarantee closure of the shunt. Transarterial treatment with Onyx achieves good results. Transvenous treatment appears equally successful, navigating into the occluded segment across the occlusion or via burr hole as backup.
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http://dx.doi.org/10.1136/neurintsurg-2021-017652DOI Listing
June 2021

The safety profile and angioarchitectural changes after acute targeted embolization of ruptured arteriovenous malformations.

J Neurosurg 2021 May 7:1-10. Epub 2021 May 7.

2Division of Neuroradiology, Department of Medical Imaging, and.

Objective: The aim of this study was to 1) compare the safety and efficacy of acute targeted embolization of angiographic weak points in ruptured brain arteriovenous malformations (bAVMs) versus delayed treatment, and 2) explore the angioarchitectural changes that follow this intervention.

Methods: The authors conducted a retrospective analysis of a prospectively acquired database of ruptured bAVMs. Three hundred sixteen patients with ruptured bAVMs who presented to the hospital within 48 hours of ictus were included in the analysis. The first analysis compared clinical and functional outcomes of acutely embolized patients to those with delayed management paradigms. The second analysis compared these outcomes of patients with acute embolization to those with angiographic targets who did not undergo acute embolization. Finally, a subset of 20 patients with immediate postembolization angiograms and follow-up angiograms within 6 weeks of treatment were studied to determine the angioarchitectural changes after acute targeted embolization. Kaplan-Meier curves for survival between the groups were devised. Multivariate logistical regression analysis was conducted.

Results: There were three deaths (0.9%) and an overall rerupture rate of 4.8% per year. There was no statistical difference in demographic variables, mortality, and rerupture rate between patients with acute embolization and those with delayed management. Patients with acute embolization were more likely to present functionally worse (46.9% vs 69.8%, modified Rankin Scale score 0-2, p = 0.018) and to require an adjuvant therapy (71.9% vs 26.4%, p < 0.001). When comparing acutely embolized patients to those nonacutely embolized angiographic targets, there was a significant protective effect of acute targeted therapy on rerupture rate (annual risk 1.2% vs 4.3%, p = 0.025) and no difference in treatment complications. Differences in the survival curves for rerupture were statistically significant. Multivariate analyses significantly predicted lower rerupture in acute targeted treatment and higher rerupture in those with associated aneurysms, deep venous anatomy, and higher Spetzler-Martin grade. All patients with acute embolization experienced complete obliteration of the angiographic weak point with various degrees of resolution of the nidus; however, some had spontaneous recurrence of their bAVM, while others had spontaneous resolution over time. No patients developed new angiographic weak points.

Conclusions: This study demonstrates that acute targeted embolization of angiographic weak points, particularly aneurysms, is technically safe and protective in the early phase of recovery from ruptured bAVMs. Serial follow-up imaging is necessary to monitor the evolution of the nidus after targeted and definitive treatments. Larger prospective studies are needed to validate these findings.
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http://dx.doi.org/10.3171/2020.9.JNS201558DOI Listing
May 2021

Brain Arteriovenous Malformations: The Role of Imaging in Treatment Planning and Monitoring Response.

Neuroimaging Clin N Am 2021 May 24;31(2):205-222. Epub 2021 Mar 24.

Department of Neuroradiology, University of Toronto, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. Electronic address:

Brain arteriovenous malformations (AVMs) are characterized by shunting between pial arteries and cortical or deep veins, with the presence of an intervening nidus of tortuous blood vessels. These lesions present a therapeutic challenge, because their natural history entails a risk of intracranial hemorrhage, but treatment may cause significant morbidity. In this article, imaging features of AVMs on MR imaging and catheter angiography are reviewed to stratify the risk of hemorrhage and guide appropriate management. The angioarchitecture of AVMs may evolve over time, spontaneously or in response to treatment, necessitating ongoing imaging surveillance.
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http://dx.doi.org/10.1016/j.nic.2020.12.001DOI Listing
May 2021

Characteristics of pial brain arteriovenous malformations with transdural arterial supply.

Eur J Radiol 2021 Jun 8;139:109670. Epub 2021 Apr 8.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Purpose: Transdural blood supply (TDBS) to pial brain arteriovenous malformations (BAVM) is uncommon and believed to be related to vascular endothelial growth factor - induced angiogenesis. The aim of this study was to define the BAVM characteristics in relation to presence and volume of TDBS.

Methods: BAVMs managed at our institution between January 2006 and December 2016 who subsequently underwent complete digital subtraction angiography (DSA) were included. They were classified based on presence of TDBS as well as volume of TDBS.

Results: Of the 641 BAVM patients managed during the recruitment period, 387 (391 BAVMs) had complete pretreatment DSAs. Forty-three (11.0 %, 10 ruptured) BAVMs exhibited TDBS. With TDBS group had a significantly greater proportion of large nidus (> 3.1 cm) than the Without TDBS group (85.1 % vs 19.5 %, p < 0.01) and were more frequently temporal (32.6 % vs 14.7 %, p < 0.01) and occipital (25.6 % vs 13.5 %, p < 0.05) in location. In unruptured BAVMs, the presence of headaches was significantly more prevalent when the malformation harboured TDBS compared to not (57.6 vs 34.8 %, p < 0.05). The annual rupture rate among unruptured BAVMs treated by conservative management was 4.7 % in the With TDBS (n = 12) group and 0% (n = 21) in BAVMs with TDBS that underwent treatment including surgery, endovascular therapy, or radiosurgery.

Conclusion: BAVMs with TDBS are more likely to be associated with a large nidus and located in the temporal and occipital lobes. Headache is more frequently associated with the presence of TDBS. Rupture rate of unruptured BAVMS with TDBS can be effectively reduced following treatment.
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http://dx.doi.org/10.1016/j.ejrad.2021.109670DOI Listing
June 2021

Novel flat-panel cone-beam CT compared to multi-detector CT for assessment of acute ischemic stroke: A prospective study.

Eur J Radiol 2021 May 10;138:109645. Epub 2021 Mar 10.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, Toronto, Ontario, Canada.

Purpose: Cone beam CT (CBCT) imaging assessment of acute ischemic stroke (AIS) patients with large-vessel occlusion (LVO) in the angiosuite may improve stroke workflow and decrease time to recanalization. In order for this workflow to gain widespread acceptance, current CBCT imaging needs further development to improve image quality. Our study aimed to compare the image quality of a new CBCT protocol performed directly in the angiosuite with imaging from multidetector CT as a gold standard.

Methods: AIS patients with an LVO who were candidates for endovascular treatment were prospectively included in this study. Following conventional multidetector CT (MDCT), patients underwent unenhanced cone beam CT (XperCT, Philips) imaging in the angiosuite, using two different protocols: a standard 20.8 s XperCT and/or an improved 10.4 s XperCT protocol. Images were evaluated using both qualitative and quantitative methods.

Results: We included 65 patients in the study. Patients received CBCT imaging prior to endovascular treatment; 18 patients were assessed with a standard 20.8 s protocol scans and 47 with a newer 10.4 s scan. The quantitative analysis showed that the mean contrast-to-noise ratio (CNR) was significantly higher for the newer 10.4 s protocol compared with the 20.8 s protocol (2.08 +/- 0.64 vs. 1.15 +/- 0.27, p < 0.004) and the mean image noise was significantly lower for the 10.4 s XperCTs when compared with the 20.8 s XperCTs (6.30 +/- 1.34 vs. 7.82 +/- 2.03, p=<0.003). Qualitative analysis, including 6 measures of image quality, demonstrated that 74.1 % of the 10.4 s XperCT scans were ranked as 'Acceptable' for assessing parenchymal imaging in AIS patients(scoring 3-5 points on a 5-point Likert-scale), compared with 32.4 % of the standard 20.8 s XperCT and 100 % of the MDCT scans. Compared to the MDCT studies, 83 % of the 10.4 s XperCT scans were deemed sufficient image quality for a direct-to-angiosuite selection, compared to only 11 % for the standard 20.8 s scans. The largest image quality improvements included grey/white matter differentiation (59 % improvement), and reduction of image noise and artefacts (63 % & 50 % improvement, respectively).

Conclusions: Continued advances in cone-beam CT allow marked improvements in image quality for the assessment of brain parenchyma, which supports a direct-to-angiosuite approach for AIS patients eligible for thrombectomy treatment.
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http://dx.doi.org/10.1016/j.ejrad.2021.109645DOI Listing
May 2021

Clinical and Angioarchitectural Features of Ruptured Dural Arteriovenous Fistulas.

World Neurosurg 2021 03 29;147:e476-e481. Epub 2020 Dec 29.

Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.

Background: Hemorrhage is a feared complication of cranial dural arteriovenous fistulas (DAVFs). Traditional grading systems including the Cognard and Borden classifications assess for this risk. We sought to define the specific angioarchitecture of ruptured lesions.

Methods: A total of 41 cases between 2004 and 2019 with ruptured cranial DAVFs were retrospectively analyzed. Information reviewed from records and imaging included hematoma location, fistula anatomy and architecture, classification, venous pouches, common collecting veins, downstream stenosis, treatment, and outcomes.

Results: Mean age at presentation was 60 years, and 61% of patients were male. Hemorrhage was most commonly intraparenchymal, and the majority of fistulae were transverse-sigmoid, tentorial, or convexity. We noted that 71% of lesions had a multi-feeder-common-hole configuration. Venous aneurysms (present in 64% of patients) were in direct communication with the hematoma in 88%; 72% of cases were treated by endovascular means; 64% of patients were treated within 7 days. Five patients re-bled between diagnosis and treatment. A total of 83% of patients were functionally independent at last follow-up.

Conclusions: Hemorrhage from cranial DAVFs is mostly intraparenchymal. Venous aneurysms are common and very often responsible for the bleed. Embolization yields high cure rates and should be performed early because of risk of re-hemorrhage. However, in spite of hemorrhage, DAVFs have a relatively favorable clinical outcome.
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http://dx.doi.org/10.1016/j.wneu.2020.12.091DOI Listing
March 2021

Radial vs. Femoral Artery Access for Procedural Success in Diagnostic Cerebral Angiography : A Randomized Clinical Trial.

Clin Neuroradiol 2020 Dec 29. Epub 2020 Dec 29.

Division of Neuroradiology, Toronto Western Hospital, 399 Bathurst St., M5T 2S8, Toronto, Ontario, Canada.

Background And Purpose: Radial artery access has become the standard of care in percutaneous coronary procedures due to demonstrated patient safety and comfort benefits; however, uptake of radial access for diagnostic cerebral angiography has been limited by practitioner concerns over the ability to achieve procedural success. We aimed to provide randomized clinical trial evidence for the non-inferiority of radial access to achieve procedural success.

Material And Methods: Monocentric open label randomized controlled trial with a non-inferiority design and blinded primary outcome assessment. Adult patients referred in-hours for diagnostic cerebral angiography were eligible. Participants underwent permuted block randomization to radial or femoral artery access with an intention-to-treat analysis. The primary outcome was procedural success, defined as selective cannulation and/or diagnostic angiography of predetermined supra-aortic vessels of interest. The non-inferiority limit was 10.0%. Secondary outcomes included postprocedural complications, fluoroscopy and procedural times, radiation dose, contrast volume and rates of vertebral artery cannulation.

Results: A total of 80 participants were enrolled (female 42, male 38, mean age 47.0 years, radial access group n = 43, femoral n = 37). One patient in the radial group was excluded after enrollment due to insufficient sonographic radial artery internal diameter. Procedural success was achieved in 41 of 42 participants in the radial group (97.6%) and 36 of 37 in the femoral group (97.3%). The difference between groups was -0.3% (one-sided 95% confidence interval, CI 6.7%) and the null hypothesis was rejected.

Conclusion: Radial artery access is non-inferior to femoral artery access for procedural success in cerebral angiography. A large multicenter trial is recommended as the next step.
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http://dx.doi.org/10.1007/s00062-020-00984-1DOI Listing
December 2020

Endovascular Therapy of Acute Ischemic Stroke in Patients with Large-Vessel Occlusion Associated with Active Malignancy.

J Stroke Cerebrovasc Dis 2021 Feb 23;30(2):105455. Epub 2020 Nov 23.

Division of Neuroradiology, JDMI, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, Toronto, Ontario, M5T2S8, Canada; Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, Toronto, Ontario, M5T2S8, Canada. Electronic address:

Purpose: There is limited data on the effectiveness of endovascular therapy (EVT) in stroke patients with active malignancy. In this study, we investigated the outcome of EVT for acute ischemic stroke for patients with active malignancy compared to those without malignancy.

Methods: We selected patients who underwent EVT for acute ischemic stroke between January 2015 and July 2019. Patients were divided into two groups, those with active malignancy (oncology group - OG) and those without (non-oncology group, NOG).

Results: 300 patients were included in this study. There were 19 EVT procedures (18 patients) in the OG and 285 procedures (282 patients) in the NOG. There was no difference in recanalization success rate (mTICI 2b & 3) between the groups: 94.7% versus 80.9% in OG and NOG respectively (p = 0.13). Success rate using the direct aspiration (ADAPT) technique of EVT was not different between compared groups (42.9% versus 67.7%; p = 0.18). However, when using smaller-caliber aspiration devices, ADAPT was less successful in OG (0.0% versus 64.7%, p < 0.05). There was no difference in recanalization success rate of EVT when using a stent-retriever or combined technique. Patients in the OG had a less favorable functional outcome than in the NOG group (mRS 0-2 at 90-days post event: 22.2% versus 48.2%, p < 0.05) CONCLUSION: The technical success rate of EVT in patients with active malignancy is similar to the general population of stroke patients. Interestingly, the success rate of EVT using the ADAPT technique was lower in the OG when using smaller caliber aspiration devices.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105455DOI Listing
February 2021

Torrents of torment: turbulence as a mechanism of pulsatile tinnitus secondary to venous stenosis revealed by high-fidelity computational fluid dynamics.

J Neurointerv Surg 2021 Aug 20;13(8):732-737. Epub 2020 Nov 20.

Mechanical & Industrial Engineering, University of Toronto, Toronto, Ontario, Canada.

Background: Pulsatile tinnitus (PT) is a debilitating condition that can be caused by a vascular abnormality, such as an arterial or venous lesion. Although treatment of PT-related venous lesions has been shown to successfully cure patients of the associated 'tormenting' rhythmical sound, much controversy still exists regarding their role in the etiology of PT.

Methods: A patient presented with a history of worsening, unilateral PT. A partial venous sinus obstruction related to the large arachnoid granulation was detected on the right side, and subsequently stented at the right transverse sinus. High-fidelity computational fluid dynamics (CFD) was performed on a 3D model digitally segmented from the pre-stent venogram, with assumed pulsatile flow rates. A post-stent CFD model was also constructed from this. Data-driven sonification was performed on the CFD velocity data, blinded to the patient's self-reported sounds.

Results: The patient reported that the PT was completely resolved after stenting, and has had no recurrence of the symptoms after more than 2 years. CFD simulation revealed highly disturbed, turbulent-like flow at the sigmoid sinus close to auditory structures, producing a sonified audio signal that reproduced the subjective sonance of the patient's PT. No turbulence or sounds were evident at the stenosis, or anywhere in the post-stent model.

Conclusions: For the first time, turbulence generated distal to a venous stenosis is shown to be a cause of PT. High-fidelity CFD may be useful for identifying patients with such 'torrents' of flow, to help guide treatment decision-making.
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http://dx.doi.org/10.1136/neurintsurg-2020-016636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292577PMC
August 2021

Detection and Measurement of Intracranial Aneurysm Compared between Magnetic Resonance Intracranial Black Blood Vessel Imaging and Gold Standard Cerebral Digital Subtraction Angiography.

J Neurosci Rural Pract 2020 Oct 13;11(4):545-551. Epub 2020 Jul 13.

Department of Medical Imaging, Division of Neuroradiology, Faculty of Medicine, University of Toronto, Canada.

 Magnetic resonance intracranial black blood vessel imaging (MR-IBBVI) is a new noninvasive method for evaluating intracranial vessel wall pathology. No previous studies have investigated the efficacy of MR-IBBVI to determine aneurysm size. We aimed to identify the precise diagnosis of MR-IBBVI for the detection and measurement of intracranial aneurysm compared with gold standard cerebral digital subtraction angiography (cDSA).  The retrospective study collected patients of precoiled or postcoiled intracranial aneurysm who were treated at our institute from January 2012 to June 2019 and who had MR-IBBVI, cDSA imaging, and/or three-dimensional time-of-flight sequence of magnetic resonance angiography. The sensitivity and specificity of aneurysm detection by MR-IBBVI and the accuracy of MR-IBBVI for measuring the aneurysm and vessel size were calculated.  One hundred and twenty patients (61% female) with 132 aneurysms were included into this study. The mean aneurysm size was 5.3 mm (range: 2.2-22.6). Sensitivity and specificity of MR-IBBVI to detect a small aneurysm were 98.74 and 91.21%, respectively. No statistically significant results were observed between MR-IBBVI and DSA for aneurysm detection or any of the evaluated measurement parameters.  MR-IBBVI is an accurate and highly sensitive method to detect and evaluate the size of an intracranial aneurysm both before and after coiling.
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http://dx.doi.org/10.1055/s-0040-1714042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595774PMC
October 2020

Absence of pontine perforators in vertebrobasilar dolichoectasia on ultra-high resolution cone-beam computed tomography.

J Neurointerv Surg 2021 Jun 21;13(6):580-584. Epub 2020 Oct 21.

Department of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland.

Background: Vertebrobasilar dolichoectasia (VBDE) is a rare type of non-saccular intracranial aneurysm, with poor natural history and limited effective treatment options. Visualizing neurovascular microanatomy in patients with VBDE has not been previously reported, but may yield insight into the pathology, and provide important information for treatment planning.

Objective: To carry out a retrospective analysis of ultra-high resolution cone-beam computed tomography (UHR-CBCT) in patients with fusiform basilar aneurysms, visualizing neurovascular microanatomy of the posterior circulation with a special focus on the pontine perforators.

Methods: UHR-CBCT was performed in seven patients (mean age 59 years; two female) with a VBDE, and in 14 control patients with unrelated conditions.

Results: The mean maximum diameter of the fusiform vessel segment was 28 mm (range 19-36 mm), and the mean length of the segment was 39 mm (range 15-50 mm). In all patients with VBDE, UHR-CBCT demonstrated an absence of perforating arteries in the fusiform arterial segment and a mean of 3.7 perforators arising from the unaffected vessel segment. The network of interconnected superficial circumferential pontine arteries (brainstem vasocorona) were draping around the aneurysm sac. In controls, a mean of 3.6, 2.5, and 1.2 perforators were demonstrated arising from the distal, mid-, and proximal basilar artery, respectively.

Conclusions: The absence of pontine perforators in the fusiform vessel segment of VBDE is counterbalanced by recruitment of collateral flow from pontine perforators arising from the unaffected segment of the basilar artery, as well as collaterals arising from the anterior inferior cerebellar artery/posterior inferior cerebellar artery and superior cerebellar artery. These alternative routes supply the superficial brainstem arteries (brainstem vasocorona) and sustain brainstem viability. Our findings might have implications for further treatment planning.
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http://dx.doi.org/10.1136/neurintsurg-2020-016818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142461PMC
June 2021

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets.

Brain Stimul 2020 Nov - Dec;13(6):1668-1677. Epub 2020 Oct 6.

Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada. Electronic address:

Background: Endovascular delivery of current using 'stentrodes' - electrode bearing stents - constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.

Objective: To establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.

Methods: Neuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.

Results: Six out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0-17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.

Conclusions: While several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.
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http://dx.doi.org/10.1016/j.brs.2020.09.016DOI Listing
April 2021

Endovascular Treatment Versus Best Medical Therapy in Acute Ischemic Stroke Patients with Mild Symptoms.

World Neurosurg 2020 12 18;144:e837-e841. Epub 2020 Sep 18.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Background: The benefit of endovascular treatment (EVT) for acute ischemic stroke patients with mild deficits is unknown. We sought to evaluate the natural history of patients with a low National Institute of Health Stroke Score (NIHSS) and an intracranial occlusion.

Methods: We included patients with a computed tomography angiogram-proven intracranial arterial occlusion who presented within 24 hours of symptom onset with an NIHSS of ≤6. We compared outcomes of patients who were treated with EVT and those who were not by performing propensity score-matched analysis. Primary outcome was modified Rankin score (mRS) at 90 days.

Results: A total of 66 patients were included: 38 were men (57.6%) with a median age of 69 (interquartile range [IQR], 57-79.5) years. Median NIHSS was 3 (IQR, 2-5). Median time from symptom onset to presentation was 2.87 hours (IQR, 1.3-5.9). Forty of the total cohort underwent best medical therapy alone (60.6%), whereas 26 underwent EVT (39.4%). Nineteen of the 26 patients who underwent EVT had a good clinical outcome (mRS ≤2) (73.1%), compared with 29 of 40 best medical therapy patients (72.5%) (odds ratio, 0.833 with 95% confidence interval, 0.263-2.631; P = 0.755). Following propensity score adjustment there was a tendency toward lower mRS following EVT (P = 0.051).

Conclusions: Despite the higher number of proximal occlusions in the EVT group, overall outcomes were similar, with >70% of patients in each cohort having a good outcome at 90 days.
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http://dx.doi.org/10.1016/j.wneu.2020.09.080DOI Listing
December 2020

Contemporary Challenges of Acute Ischemic Stroke in Takayasu Arteritis.

Stroke 2020 10 21;51(10):e280-e284. Epub 2020 Aug 21.

Department of Interventional Neuroradiology, Neurosurgery & Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China (P.G., T.W., J.R., F.C., L.J.).

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http://dx.doi.org/10.1161/STROKEAHA.120.030249DOI Listing
October 2020

Not a String, not a Tangle, not an Aneurysm : Emerging Pattern of Large Parenchymal Bleeding in Younger Patients Associated with Abnormal Vessels on Imaging.

Clin Neuroradiol 2021 Sep 19;31(3):653-659. Epub 2020 Aug 19.

Division of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst, M5T 2S8, Toronto, Ontario, Canada.

Purpose: Intracerebral hemorrhage (ICH) accounts for up to 20% of all strokes, and there is a high rate of associated morbidity and mortality. Computed tomography (CT) findings, such as a spot sign have been shown to be an independent predictor of poor outcome. We have recently encountered a succession of ICH patients who presented with a peculiar imaging finding, which we term the spot on a string sign. This is a rare imaging finding, and interestingly, all these patients presented to our institution over the last few weeks.

Methods: This was a single high-volume center series of patients who presented to our institution between 1 April and 21 May 2020. All patients underwent initial non-contrast CT brain and subsequent CT angiography (CTA). We also present laboratory and clinical data. Our primary measure was the presence of the spot on a string sign on the CTA. We also report the clinical course of these patients.

Results: In this study seven large-volume ICH patients with this imaging sign were identified, with a median age of 48 years (range 30-68 years). All had tested negative for coronavirus disease 19 (COVID-19).

Conclusion: We have described an unusual imaging finding in a cohort of younger patients with large-volume ICH, all of whom presented in a 2-month period to a high-volume neurovascular unit. The cause of these ICH presentations and associated imaging findings are unclear, but we encourage other clinicians to be aware of and vigilant for this rare phenomenon, especially in younger patients with such a bleeding pattern.
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http://dx.doi.org/10.1007/s00062-020-00944-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437111PMC
September 2021

Acute Stroke Management During the COVID-19 Pandemic: Does Confinement Impact Eligibility for Endovascular Therapy?

Stroke 2020 08 1;51(8):2593-2596. Epub 2020 Jul 1.

Departments of Neurology and Neuroradiology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal (J.P.M., J.N.R.).

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (<0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time (<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.
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http://dx.doi.org/10.1161/STROKEAHA.120.030794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340133PMC
August 2020
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