1. Graff-Radford J, Lesnick T, Rabinstein AA, et al. Cerebral microbleeds: relationship to antithrombotic medications. Stroke 2021;52:2347–55. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031515

Cerebral microbleeds (CMBs) are a risk factor for intracerebral hemorrhage (ICH) and are associated with increased risk of dementia and mortality. The prevalence of CMBs increases significantly with age, approaching forty percent by the age of 80 years. Established risk factors for CMBs include age, male sex, and hypertension. Antithrombotic medications have also been associated with increased risk of developing CMBs, but few population-based studies have evaluated this association. The authors sought to determine in a population-based study whether antithrombotic medications correlate with CMBs and, if present, whether the association was direct or mediated by another variable.

The study consisted of 1253 participants from the population-based Mayo Clinic Study of Aging who underwent T2* gradient-recalled echo magnetic resonance imaging. They tested the relationship between antithrombotic medications and CMB presence and location, using multivariable logistic-regression models.

Two hundred ninety-five participants (26.3%) had CMBs. Among 678 participants taking only antiplatelet medications, 185 (27.3%) had CMBs. Among 95 participants taking only an anticoagulant, 43 (45.3%) had CMBs. Among 44 participants taking an anticoagulant and antiplatelet therapy, 21 (48.8%) had CMBs. Anticoagulants correlated with the presence and frequency of CMBs, whereas antiplatelet agents were not. Structural equation models showed that predictors for presence/ absence of CMBs included older age at magnetic resonance imaging, male sex, and anticoagulant use.

They conclude that anticoagulant use correlated with presence of CMBs in the general population.

4 tables, 2 figures, no imaging

2. Preziosa P, Rocca MA, Filippi M. Central vein sign and iron rim in multiple sclerosis: ready for clinical use? Curr Opin Neurol 2021;34:505–13. Available from: https://journals.lww.com/10.1097/WCO.0000000000000946

The pathological hallmark of MS is the formation of demyelinating white matter lesions around venules. Cerebral veins and their relations with white matter lesions can be detected using the combination of magnitude and phase images from high resolution 3D T2*-weighted GRE sequences or conventional SWI.

CVS has been detected in up to 92% of MS lesions, with a decreased gradient from the periventricular areas to the cortex, being less detectable in infratentorial regions and spinal cord, although they have been described in 70% of infratentorial lesions.

To discriminate MS from other conditions, different criteria have been proposed, including a minimum threshold of percentage of CVS+ lesions (from 35 to 60%), or simplified approaches based on the presence of three (3-lesion rule) or six (6-lesion rule) CVS+ lesions.

By evaluating 35 eligible studies, a meta-analysis showed that the pooled proportion of CVS+ lesions was 73% in MS patients. 1.5-T scanners detected a significantly lower pooled proportion of CVS+ lesions (58%) vs. 3T (74%) and 7T (82%), without significant difference between 3T and 7T. 3D T2* EPI was superior in detecting CVS+ lesions vs. other sequences (82 vs. 71%), whereas postprocessing did not significantly influence the detection of CVS+ lesions. Finally, 40% was identified as the optimal threshold to differentiate MS from non-MS patients, with sensitivity =90%, specificity =89% and AUC =0.946.

Iron rim lesions are specific for MS, they develop mainly in the relapsing-remitting phase and persist in progressive forms, increasing in size in the first few years after their formation and then stabilizing, often losing the iron rim. The presence of at least four iron rim lesions is associated with an earlier and more severe clinical disability, a higher prevalence of clinical progressive MS and more severe brain atrophy.

1 table, 2 figures including MR

3. Wattjes MP, Ciccarelli O, Reich DS, et al. 2021 MAGNIMS–CMSC–NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol 2021;20:653–70. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1474442221000958

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centers guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centers, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. They recommend changes in MRI acquisition protocols, such as emphasizing the value of three-dimensional FLAIR as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and they provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, they extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period.

2 tables, 3 figures with MR, and 6 summary panels regarding specific recommendations of 1) establishing MS diagnosis, 2) gad use in the diagnosis and monitoring of MS, 3) indications for spinal cord and optic nerve imaging, 4) monitoring treatment effectiveness and assessment of disease activity, 5) use of MR for monitoring treatment safety, and 6) use of MR with contrast in pregnancy and lactation

4. Buchanan CR, Muñoz Maniega S, Valdés Hernández MC, et al. Comparison of structural MRI brain measures between 1.5 and 3 T: data from the Lothian Birth Cohort 1936. Hum Brain Mapp 2021;42:3905–21. Available from: https://onlinelibrary.wiley.com/doi/10.1002/hbm.25473

In one of the largest between-scanner comparisons to date, the authors report previously lacking information on a wide range of structural brain measures in an exclusively older group of participants. They found excellent levels of consistency (ICC > ~.75) between the 1.5 and 3 T scanners for the largest brain structures (whole-brain, ventricular and tissue volumes; global dMRI measures in WM; and global network metrics) that were similar to same-scanner test–retest studies. They noted that there were overall mean shifts in the absolute levels of most measures between 1.5 and 3 T: volumetric measures and thickness appeared larger at 3 T, RD, and MD were lower, and AD and FA were higher at 3 T, consistent with prior observations from smaller studies on single metrics. Regression-based correction for scanner (using intercept differences) effectively eliminated scanner differences in unseen (hold-out) data for global brain measures, giving similar (and sometimes higher) agreement than might be expected from same scanner test–retest data: global measures could be accurately predicted in line with 1.5 T values from 3 T data using 10-fold cross validation.

Interestingly, both GM and WM tissue volumes appeared larger at 3 T than at 1.5 T, but CSF volume was smaller. Contributing factors are likely to include a combination of higher tissue contrast (resulting in differences in the tissue-CSF boundary), different scanner-specific geometric distortions and a slight difference in T1-weighted voxel dimensions. More numerous sampling instances along a complex surface may result in both superior estimation, and the “coastline paradox,” whereby complex shapes appear larger when measured with greater fidelity. As would be expected, between-scanner agreement decreased as the granularity increased from large brain structures to include smaller regional imaging variables. Scanner agreement at the regional level was similar or slightly lower than prior same-scanner work, such as for cortical regional measures. They also found that smaller GM regions typically had poorer between-scanner agreement than large regions; this between-scanner finding corresponds well with the known relationship between reliability and region size observed in same-scanner work.

7 figures, 2 tables

5. Guglielmi V, Compagne KCJ, Sarrami AH, et al. Assessment of recurrent stroke risk in patients with a carotid web. JAMA Neurol 2021;78:826. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2779918

A comparative cohort study used data from the MR CLEAN trial (from 2010-2014) and MR CLEAN Registry (from 2014-2017). Data were analyzed in September 2020. The MR CLEAN trial and MR CLEAN Registry were nationwide prospective multicenter studies on endovascular treatment (EVT) of large vessel occlusion (LVO) stroke in the Netherlands. Baseline data were from 3439 consecutive adult patients with anterior circulation LVO stroke and available computed tomography (CT)–angiography of the carotid bulb. Two neuroradiologists reevaluated CT-angiography images for presence or absence of CW and identified 30 patients with CW ipsilateral to the index stroke. For these 30 eligible CW participants, detailed follow-up data regarding stroke recurrence within 2 years were acquired. These 30 patients with CW ipsilateral to the index stroke were compared with 168 patients without CW who participated in the MR CLEAN extended follow-up trial and who were randomized to the EVT arm.

Of 3439 patients with baseline CT-angiography assessed, the median age was 72 years and 1813 (53%) were men. Patients with CW were younger (median age, 57 years vs 66 years; P = .02 and more often women (22 of 30 [73%] vs 67 of 168 [40%]; P = .001) than patients without CW. Twenty-eight of 30 patients (93%) received medical management after the index stroke (23 with antiplatelet therapy and 5 with anticoagulant therapy). During 2 years of follow-up, 5 of 30 patients (17%) with CW had a recurrent stroke compared with 5 of 168 patients (3%) without CW.

In this study, 1 of 6 patients with a symptomatic CW had a recurrent stroke within 2 years, suggesting that medical management alone may not provide sufficient protection for patients with CW.

2 tables, 3 figures with CT angiograms

6. Luetzen N, Dovi-Akue P, Fung C, et al. Spontaneous intracranial hypotension: diagnostic and therapeutic workup. Neuroradiology 2021 Jul 23. [Epub ahead of print]. Available from: https://doi.org/10.1007/s00234-021-02766-z

Spontaneous intracranial hypotension (SIH) is an orthostatic headache syndrome with typical MRI findings among which engorgement of the venous sinuses, pachymeningeal enhancement, and effacement of the suprasellar cistern have the highest diagnostic sensitivity. SIH is in almost all cases caused by spinal CSF leaks. Spinal MRI scans showing so-called spinal longitudinal extradural fluid (SLEC) are suggestive of ventral dural tears (type 1 leak) which are located with prone dynamic (digital subtraction) myelography. As around half of the ventral dural tears are located in the upper thoracic spine, additional prone dynamic CT myelography is often needed. Leaking nerve root sleeves typically associated with meningeal diverticulae (type 2 leaks) and CSF-venous fistulas (type 3 leaks) are proven via lateral decubitus dynamic digital subtraction or CT myelography: type 2 leaks are spinal longitudinal extradural fluid -positive if the tear is proximal and spinal longitudinal extradural fluid -negative if it is distal, and type 3 leaks are always spinal longitudinal extradural fluid -negative. Although 30–70% of SIH patients show marked improvement following epidural blood patches applied via various techniques definite cure mostly requires surgical closure of ventral dural tears and surgical ligations of leaking nerve root sleeves associated with meningeal diverticulae or CSF-venous fistulas. For the latter, transvenous embolization with liquid embolic agents via the azygos vein system is a novel and valuable therapeutic alternative.

6 figures including MR, dynamic CT and digital subtraction myelography

7. Oesch G, Perez FA, Wainwright MS, et al. Focal cerebral arteriopathy of childhood. Stroke 2021;52:2258–65. Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.120.031880

Focal Cerebral Arteriopathy is a common cause of childhood ischemic stroke, historically accounting for approximately one-quarter of arteriopathies causing stroke. Focal Cerebral Arteriopathy is typically diagnosed in a previously healthy child presenting with an acute stroke but has also been described in young adults. Estimates of the incidence of Focal Cerebral Arteriopathy in childhood stroke range from 20% to 26% in European cohorts from 1984 to 2007, to 12% to 13% in predominantly North American cohorts from 2003 to 2014. Focal Cerebral Arteriopathy can initially progress over days to weeks, and children with this short term progressive arteriopathy appear to have a higher risk of recurrent ischemia. Recurrent stroke within 1 year has been reported in up to 25% of patients. There is increasing evidence that FCA is an inflammatory process, either infectious or postinfectious. Arterial inflammation may lead to further arterial narrowing as well as thrombus formation on inflamed and damaged endothelium. Vessel wall imaging studies using MRI have demonstrated enhancement of affected arterial segments suggestive of inflammation. However, the role of vessel wall imaging to categorize and predict clinical course in pediatric arteriopathies including FCA remains unclear. The optimal diagnostic imaging remains uncertain, as FCA can be missed on initial imaging, and can be mimicked by other entities such as intracranial dissection and embolus.

Focal Cerebral Arteriopathy occurring within a year of primary varicella infection (chicken pox) is called post varicella arteriopathy and has been previously reported in up to half of patients with FCA. There is overlap of post varicella arteriopathy with varicella vasculopathy, which is due to recent infection, and confirmed by demonstrating intrathecal varicella-zoster virus (VZV) antibody production or VZV DNA in the cerebrospinal fluid. Routine immunizations appear to be protective against stroke in childhood, however, the specific impact of routine VZV immunization is unknown.

Although FCA is typically described as occurring in previously healthy children, 6 of 15 children in the current cohort had acute illnesses requiring treatment, including intravenous antibiotics, surgical sinus drainage, acyclovir, and red blood cell transfusion. The authors found sensorimotor sequelae in 2/3 of their patients. The frequent sensorimotor involvement is not unexpected as the most common location of arteriopathy involved the M1 segment in this cohort resulting in middle cerebral artery distribution infarcts.

2 tables, 1 figure with MR and MRA

8. Aoki J, Sakamoto Y, Suzuki K, et al. Fluid-attenuated inversion recovery may serve as a tissue clock in patients treated with endovascular thrombectomy. Stroke 2021;52:2232–40

Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome.

Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older (P=0.011), the onset-to-image time was shorter (P<0.001), the frequency of cardioembolic stroke was higher (P=0.006), and the rate of intravenous thrombolysis was higher (P<0.001) in comparison to the FLAIR-positive group. Although the rate of complete recanalization after EVT did not differ between the 2 groups (P=0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group (P=0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change (P=0.047), while the onset-to-image time was not significant. A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome.

The major finding in this study was that the absence of FLAIR signal change was independently associated with a good outcome at 3 months in patients with EVT, regardless of the onset-to-image time.

3 tables, 3 figures

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.

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