Advances in Acute Ischemic Stroke Treatment: Current Status and Future Directions.

The management of acute ischemic stroke has undergone a paradigm shift in the past decade. This has been spearheaded by the emergence of endovascular thrombectomy, along with advances in medical therapy, imaging, and other facets of stroke care. Herein, we present an updated review of the various stroke trials that have impacted and continue to transform stroke management. It is critical for the radiologist to stay abreast of the ongoing developments to provide meaningful input and remain a useful part of the stroke team.

Quantifying Intra-Arterial Verapamil Response as a Diagnostic Tool for Reversible Cerebral Vasoconstriction Syndrome.

BACKGROUND AND PURPOSE: There is mounting evidence supporting the benefit of intra-arterial administration of vasodilators in diagnosing reversible cerebral vasoconstriction syndrome. We prospectively quantified the degree of luminal diameter dilation after intra-arterial administration of verapamil and its accuracy in diagnosing reversible cerebral vasoconstriction syndrome. MATERIALS AND METHODS: Patients suspected of having intracranial arteriopathy on noninvasive imaging and referred for digital subtraction angiography were enrolled in a prospective registry. Intra-arterial verapamil was administered in vascular territories with segmental irregularities. The caliber difference (Caliberpost - Caliberpre) and the proportion of caliber change ([(Caliberpost - Caliberpre)/Caliberpre] × 100%) were used to determine the response to verapamil. The diagnosis of reversible cerebral vasoconstriction syndrome was made on the basis of clinical and imaging features at a follow-up appointment, independent of the reversibility of verapamil. Receiver operating characteristic curve analysis was performed to determine the best threshold. RESULTS: Twenty-six patients were included, and 9 (34.6%) were diagnosed with reversible cerebral vasoconstriction syndrome. A total of 213 vascular segments were assessed on diagnostic angiography. Every patient with a final diagnosis of reversible cerebral vasoconstriction syndrome responded to intra-arterial verapamil. The maximal proportion of change (P < .001), mean proportion of change (P = .002), maximal caliber difference (P = .004), and mean caliber difference (P = .001) were statistically different between patients with reversible cerebral vasoconstriction syndrome and other vasculopathies. A maximal proportion of change ≥32% showed a sensitivity of 100% and a specificity of 88.2% to detect reversible cerebral vasoconstriction syndrome (area under the curve = 0.951). The Reversible Cerebral Vasoconstriction Syndrome-2 score of ≥5 points achieved a lower area under the curve (0.908), with a sensitivity of 77.8% and a specificity of 94.1%. CONCLUSIONS: Objective measurement of the change in the arterial calibers after intra-arterial verapamil is accurate in distinguishing reversible cerebral vasoconstriction syndrome from other vasculopathies. A proportion of change ≥32% has the best diagnostic performance.

Retrospective, dual-centre review of imaging findings in neurosarcoidosis at presentation: prevalence and imaging sub-types.

AIM: To assess the prevalence of various imaging manifestations in neurosarcoidosis (NS) patients at presentation and to explore if specific imaging findings may cluster in different sub-groups. MATERIALS AND METHODS: A retrospective, dual-institution, systematic imaging review was undertaken of the magnetic resonance imaging (MRI) findings in 100 consecutive NS patients who presented over a 15-year period. Clustering analysis (k-mode) was performed to evaluate co-occurrence of imaging findings. RESULTS: Non-enhancing white matter (NEWM) lesions were the most common imaging abnormality (56%), followed by leptomeningeal (47%) and pachymeningeal (32%) involvement. Other common manifestations included cranial nerve involvement (30%), parenchymal granulomas (27%), hypothalamic-pituitary-adrenal axis involvement (26%), and hydrocephalus (14%). Additionally, a higher prevalence of perivascular enhancement (23%), cerebrovascular events (including ischaemic and haemorrhagic events; 17%), and ependymal involvement (20%) were noted than recognised previously. Additional k-mode analysis was performed to explore underlying disease sub-clusters. This was evaluated for clusters varying between two though five (k=2-5). For k=4, the analysis revealed that the imaging findings may possibly be divided into disease sub-sets of four groups, each with varying distribution of imaging manifestations and clinical manifestations. CONCLUSION: Overall, NEWM lesions and meningeal involvement are the most common imaging manifestations of NS. The prevalence of perivascular enhancement, cerebrovascular events, and ependymal involvement is likely higher than reported previously. Additionally, different imaging findings in NS may cluster together and imaging subtypes in NS possibly exist.

Preserving Access: A Review of Stroke Thrombectomy during the COVID-19 Pandemic.

Thrombectomy for large-vessel-occlusion stroke is a highly impactful treatment. The spread of coronavirus 19 (COVID-19) across the United States and the globe impacts access to this crucial intervention through widespread societal and institutional changes. In this document, we review the implications of COVID-19 on the emergency care of large-vessel occlusion stroke, reviewing specific infection-control recommendations, available literature, existing resources, and expert consensus. As a population, patients with large-vessel occlusion stroke face unique challenges during pandemics. These are broad in scope. Responses to these challenges through adaptation of stroke systems of care and with imaging, thrombectomy, and postprocedural care are detailed. Preservation of access to thrombectomy must be prioritized for its public health impact. While the extent of required changes will vary by region, tiered planning for both escalation and de-escalation of measures must be a part of each practice. In addition, preparations described serve as templates in the event of future pandemics.

Imaging of Patients with Suspected Large-Vessel Occlusion at Primary Stroke Centers: Available Modalities and a Suggested Approach.

The overwhelming benefit of endovascular therapy in patients with large-vessel occlusions suggests that more patients will be screened than treated. Some of those patients will be evaluated first at primary stroke centers; this type of evaluation calls for standardizing the imaging approach to minimize delays in assessing, transferring, and treating these patients. Here, we propose that CT angiography (performed at the same time as head CT) should be the minimum imaging approach for all patients with stroke with suspected large-vessel occlusion presenting to primary stroke centers. We discuss some of the implications of this approach and how to facilitate them.

Hemodynamic Impairment Measured by Positron-Emission Tomography Is Regionally Associated with Decreased Cortical Thickness in Moyamoya Phenomenon.

BACKGROUND AND PURPOSE: Impaired cerebrovascular reactivity has been associated with decreased cortical thickness in patients with arterial occlusive diseases. This study tests the hypothesis that severe hemodynamic impairment, indicated by increased oxygen extraction fraction ratios on positron-emission tomography with 15O tracers, is associated with decreased cortical thickness in patients with Moyamoya phenomenon. MATERIALS AND METHODS: Patients with unilateral or bilateral idiopathic Moyamoya phenomenon were recruited. Oxygen extraction fraction ratio maps were generated from cerebral images of O[15O] counts divided by H2[15O] counts with normalization by corresponding cerebellar counts. The normal range of the oxygen extraction fraction ratio was estimated from historically available healthy control subjects. Cortical thickness was estimated from T1-weighted MR imaging and FreeSurfer. Regional samples of oxygen extraction fraction ratios and cortical thicknesses were drawn using FreeSurfer parcellations, retaining only parcellations from the vascular territory of the middle cerebral artery. RESULTS: Complete MR imaging and PET datasets were available in 35 subjects, including 23 women; the mean age at scanning was 44 years. Patients with Moyamoya phenomenon had a significantly increased regional oxygen extraction fraction ratio compared with 15 healthy control subjects (P < .001). Regional oxygen extraction fraction ratio and age were significant predictors of cortical thickness (P < .001 for each) in a generalized linear mixed-effects model. Using hemisphere averages and patient averages, we found that only age was a significant predictor of cortical thickness (P < .001). CONCLUSIONS: Chronic hemodynamic impairment, as indicated by a higher regional oxygen extraction fraction ratio, was significantly predictive of reduced cortical thickness in mixed-effects analysis of FreeSurfer regions. This phenomenon may be related to reversible metabolic down-regulation.

Cerebrovascular manifestations in neurosarcoidosis: how common are they and does perivascular enhancement matter?

AIM: To determine the occurrence of ischaemic and haemorrhagic events in patients with neurosarcoidosis at presentation and follow-up and to evaluate its association with perivascular enhancement. MATERIALS AND METHODS: The MRI findings in patients with neurosarcoidosis who presented to our institute from 2002-2017 were retrospectively reviewed, with emphasis on cerebrovascular events. A chi-squared test was used to evaluate the statistical association with presence of perivascular enhancement. RESULTS: A total of 49 patients (32 females and 17 males) were analysed. Ischaemic events were noted in four patients at presentation while parenchymal haemorrhages occurred in three patients. The combined occurrence of cerebrovascular events (CVEs) at presentation was 14%. On follow-up, three additional patients developed ischaemic infarcts, of which, one patient had parenchymal haemorrhage at presentation. Additionally, one patient also developed new parenchymal haemorrhages. In total, 10 patients in current cohort developed CVEs, either at presentation or on follow-up. Perivascular enhancement was seen in 50% of patients with cerebrovascular events and 18% of patients with neurosarcoidosis, but no CVEs. This was statistically significant (p<0.05). CONCLUSION: CVEs in patients with neurosarcoidosis are more common than previously reported and appear to be significantly related to the presence of perivascular enhancement on imaging.

An Update on the Adjunctive Neurovascular Support of Wide-Neck Aneurysm Embolization and Reconstruction Trial: 1-Year Safety and Angiographic Results.

BACKGROUND AND PURPOSE: The safety and efficacy of the PulseRider for the treatment of wide-neck, bifurcation aneurysms at the basilar and carotid terminus locations were studied in a prospective trial, the Adjunctive Neurovascular Support of Wide-Neck Aneurysm Embolization and Reconstruction (ANSWER) trial, reporting on initial 6-month angiographic and clinical results. This report provides insight into the longer term durability and safety with 12-month data. MATERIALS AND METHODS: Aneurysms treated with the PulseRider among enrolled sites were prospectively studied. Updated 12-month data on clinical and imaging end points are included. RESULTS: Thirty-four patients were enrolled (29 women, 5 men) with a mean age of 60.9 years. The mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range, 2.3-11.6 mm). At 1 year, there were no device migrations or symptomatic in-stent stenoses. Raymond-Roy I occlusion was achieved in 53% of cases at the time of treatment and progressed to 61% and 67% at 6 and 12 months, respectively. Adequate occlusion (Raymond-Roy I/II) progressed from 88% at 6 months to 90% at 12 months. No recanalizations were observed. There was 1 delayed ischemic event. Good outcome (mRS 0-2) was achieved in 90% of patients. CONCLUSIONS: The updated 1-year results from the ANSWER trial demonstrate aneurysm stability and an acceptable safety profile for aneurysms treated at the basilar apex and carotid terminus. Prospective data from a larger set of aneurysms treated at other locations are required to assess how treatment with PulseRider compares with alternatives for treating wide-neck bifurcation aneurysms.

Blunt Cerebrovascular Injuries: Advances in Screening, Imaging, and Management Trends.

Blunt cerebrovascular injury is a relatively uncommon but sometimes life-threatening injury, particularly in patients presenting with ischemic symptoms in that vascular territory. The decision to pursue vascular imaging (generally CT angiography) is based on clinical and imaging findings. Several grading scales or screening criteria have been developed to guide the decision to pursue vascular imaging, as well as to recommend different treatment options for various injuries. The data supporting many of these guidelines and options are limited however. The purpose of this article is to review and compare these scales and criteria and the data supporting clinical efficacy and to make recommendations for future research in this area.

Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery.

SUMMARY: Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

Hemodynamic effects of developmental venous anomalies with and without cavernous malformations.

BACKGROUND AND PURPOSE: Association between developmental venous anomalies is well known, but remains unexplained. Our aim was to study possible hemodynamic differences around developmental venous anomalies with and without cavernous malformations. MATERIALS AND METHODS: In this prospective study approved by the institutional review board, PWI was performed in 24 patients with 25 DVAs (10 with and 15 without CMs) who consented to participate. We calculated relative cerebral blood volume, relative cerebral blood flow, and relative mean transit time for the brain surrounding the DVA tributaries in reference to contralateral mirror image locations. Corresponding control values (cCBV, cCBF, and cMTT) were generated in a similar fashion for remote ipsilateral regions with normal venous drainage, also in reference to contralateral mirror image locations. Perfusion parameters for DVAs and control regions were tested for differences between groups with the t test for independent or paired samples (or the nonparametric equivalents). Similar testing was done for perfusion parameters for DVAs with and without CMs. RESULTS: Normal-appearing brain surrounding DVAs showed increased rCBV (median = 2.98; range = 1.39-6.61), increased rCBF (median = 2.00, range = 0.79-4.43), and increased rMTT (mean = 1.46; 95% confidence interval, 1.32-1.59). These were significantly higher than median cCBV (0.99; 95% confidence interval, 0.89-1.06; P < .01), median cCBF (1.00; 95% confidence interval, 0.94-1.27; P < .01), and mean cMTT (1.00; 95% confidence interval, 0.98-1.02; P < .01), respectively. Mean rMTT (1.70; 95% confidence interval, 1.46-1.93) for DVAs with CMs was higher than mean rMTT (1.29; 95% confidence interval, 1.19-1.40; P < .01) for DVAs without CMs. CONCLUSIONS: DVAs are strongly associated with altered hemodynamics. Significant differences in these hemodynamic alterations for DVAs with and without CMs suggest their possible role in the formation of CMs.

Retrospective review of cerebral mycotic aneurysms in 26 patients: focus on treatment in strongly immunocompromised patients with a brief literature review.

BACKGROUND AND PURPOSE: Cerebral mycotic aneurysms are a rare and deadly type of aneurysm that have no definitive treatment guidelines. Our purpose was to retrospectively review known or suspected cases of CMA in order to identify patient populations that may be associated with higher morbidity and mortality. We hope that the identification of patients with these risk factors will lead to early stratification upon presentation, and more urgent treatment of their CMAs. We also hoped to identify any benefit or complication that was specific to either the endovascular or neurosurgical repair of CMAs. MATERIALS AND METHODS: A retrospective multi-institutional study was performed examining cases of CMA during a 15-year period. Patients were considered strongly immunocompromised if there were long-term severely immunocompromised states: AIDS, chemotherapy, or steroid immunosuppression. Patients were excluded if angiographic findings suggested an alternative diagnosis or if an infectious etiology was unknown. Antibiotics were considered "noninvasive treatment." Endovascular and neurosurgical repair were considered "invasive treatment." Data were recorded by reviewing electronic medical records and imaging reports. RESULTS: Twenty-six patients with 40 CMAs were included. Three patients were considered strongly immunocompromised and presented with 4 CMAs, which demonstrated larger average size and more rapid growth; 3 of these patients' aneurysms were treated invasively in the acute period, with the one that was not ruptured causing death. Technical success (aneurysm occlusion without rupture or recanalization) and clinical success (no neurologic complication attributable to the intervention) were obtained equally endovascularly and neurosurgically. Clipping was aborted in favor of coiling for 1 patient. Anticoagulation needed reversal before 2 patients underwent craniotomy for clipping after valve replacement. For CMAs treated with antibiotics alone with angiographic follow-up (n=11), initial aneurysm size was unrelated to persistence and 64% completely regressed. CONCLUSIONS: We recommend initial invasive treatment for CMAs in strongly immunocompromised patients. Testing for underlying immunocompromised states is warranted in patients with CMAs. Endovascular treatment is favored over neurosurgical treatment in patients requiring acute cardiac valve repair due to delays with anticoagulation reversal.

The Kety-Schmidt technique for quantitative perfusion and oxygen metabolism measurements in the MR imaging environment.

SUMMARY: The Kety-Schmidt technique provides quantitative measurement of whole-brain CBF. CBF is measured as the area between the arterial and venous washout curves of a diffusible tracer. Oxygen extraction and metabolism may be calculated from arterial and venous samples. In this report, we present a method for performing these measurements in an MR imaging environment. This technique could be useful for validation of MR imaging methods of hemodynamic and metabolic measurements in humans.

Susceptibility-weighted imaging: a new tool in the diagnosis and evaluation of abnormalities of the vein of Galen in children.

We retrospectively identified 9 consecutive children, 3 males and 6 females (age 5.2 ± 6.3 years, range 1 day to 18 years), with known or suspected AVGs who underwent MR imaging, including SWI, at our institution between January 2007 and March 2011. On the SWI sequence, arterialized blood flow was considered to be present in the vein of Galen or its tributaries when these showed abnormal signal hyperintensity from arteriovenous shunting. SWI findings were correlated with findings from DSA studies or findings from time-of-flight or contrast-enhanced MR angiography sequences. SWI was found to accurately differentiate between high-flow and low-flow AVGs and was also useful in characterizing the arterial supply and venous drainage patterns associated with high-flow AVGs.

Cerebral hemodynamics and cognitive impairment: baseline data from the RECON trial.

OBJECTIVE: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.

Improvement in angiographic cerebral vasospasm after intra-arterial verapamil administration.

BACKGROUND AND PURPOSE: Endovascular options for therapy for patients with vasospasm after SAH include angioplasty and intra-arterial vasodilator infusion. Preliminary studies of the effects of the calcium channel antagonist verapamil on angiographic vasospasm have yielded mixed and/or qualitative results. In this study, improvement in angiographic vasospasm after intra-arterial verapamil administration is demonstrated with quantitative, blinded methods. MATERIALS AND METHODS: This retrospective observational case series includes 12 patients with vasospasm after SAH who collectively received 16 treatments with intra-arterial verapamil during a 2-year period at our institution. The exclusion criterion was concurrent treatment with angioplasty. Blinded reviewers quantitatively evaluated angiograms from each patient and/or treatment after presentation with SAH and before and after intra-arterial treatment of vasospasm. RESULTS: Patients were treated with intra-arterial verapamil for vasospasm 9 ± 4 days after SAH with a range from 1 to 16 days. For the 34 arterial distributions treated, the segment with the worst angiographic vasospasm from each arterial distribution averaged 51 ± 13% stenosis, which improved to 29 ± 18% stenosis (P < .001). There was no significant difference in treatment effect in proximal arterial segments, which may be amenable to angioplasty, compared with distal segments (P > .05). There was no significant difference in treatment effect in arterial segments previously subjected to angioplasty compared with other segments (P > .05). CONCLUSIONS: Intra-arterially administered verapamil improves angiographic vasospasm after SAH when administered at 10 ± 3 mg per arterial distribution. Optimal dose, infusion rate, and retreatment interval remain to be determined. Randomized controlled trials are needed to prove efficacy in the treatment of clinical vasospasm.

Performance and training standards for endovascular ischemic stroke treatment.

Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial thrombolysis in selected patients. Intra-arterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.

Reporting standards for endovascular repair of saccular intracranial cerebral aneurysms.

BACKGROUND AND PURPOSE: The goal of this article is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting on the radiological evaluation and endovascular treatment of intracranial, cerebral aneurysms. These criteria can be used to design clinical trials, to provide uniformity of definitions for appropriate selection and stratification of patients, and to allow analysis and meta-analysis of reported data. METHODS: This article was written under the auspices of the Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1991 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data about the assessment and endovascular treatment of cerebral aneurysms useful as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This article offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of cerebral aneurysms. Included in this guidance article are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications. CONCLUSIONS: The evaluation and treatment of brain aneurysms often involve multiple medical specialties. Recent reviews by the American Heart Association have surveyed the medical literature to develop guidelines for the clinical management of ruptured and unruptured cerebral aneurysms. Despite efforts to synthesize existing knowledge on cerebral aneurysm evaluation and treatment, significant inconsistencies remain in nomenclature and definition for research and reporting purposes. These operational definitions were selected by consensus of a multidisciplinary writing group to provide consistency for reporting on imaging in clinical trials and observational studies involving cerebral aneurysms. These definitions should help different groups to publish results that are directly comparable.