Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study

PURPOSE:Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms.MATERIALS AND METHODS:In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0–5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement).RESULTS:A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation.CONCLUSIONS:The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019 and has rapidly spread around the world to become a pandemic.¹ Extensive studies have described chest and brain imaging characteristics associated with coronavirus disease 2019 (COVID-19).^2-13 The hallmarks of COVID-19 infection on chest imaging are now well-established, including bilateral and peripheral ground-glass and consolidative pulmonary opacities.^2-5 COVID-19-related brain imaging findings such as ischemic infarcts, hemorrhages, and multiple patterns of leukoencephalopathy^6-13 are also well-known. The clinical symptomatology has been linked to the imaging findings with up to 47% of patients with COVID-19 with neurologic symptoms demonstrating acute neuroimaging findings⁶ and patients with high lung severity scores being admitted to the intensive care unit.³ The incidence of neurologic symptoms is higher in patients with more severe respiratory disease.^10,13 There is increasing evidence that patients with acute lung injury are at risk of brain injury through hypoxemia and/or proinflammatory mediators that connect both the brain and the lungs.^14-17 However, little information is available on the potential association between the prevalence of neuroimaging abnormalities and the severity of CT lung findings in patients with COVID-19. The objective of this study was to examine the association between chest and brain imaging abnormalities in patients with COVID-19. We hypothesized that the severity of lung disease may predict acute abnormalities on neuroimaging in patients with COVID-19 with neurologic symptoms.     

Acute Ischemic Stroke or Epileptic Seizure? Yield of CT Perfusion in a “Code Stroke” Situation

BACKGROUND AND PURPOSE:The clinical differentiation between acute ischemic stroke and epileptic seizure may be challenging, and making the correct diagnosis could avoid unnecessary reperfusion therapy. We examined the accuracy of CTP in discriminating epileptic seizures from acute ischemic stroke without identified arterial occlusion.MATERIALS AND METHODS:We retrospectively identified consecutive patients in our emergency department who underwent CTP in the 4.5 hours following the development of an acute focal neurologic deficit who were discharged with a final diagnosis of acute ischemic stroke or epileptic seizure.RESULTS:Among 95 patients, the final diagnosis was epileptic seizure in 45 and acute ischemic stroke in 50. CTP findings were abnormal in 73% of the patients with epileptic seizure and 40% of those with acute ischemic stroke. Hyperperfusion was observed more frequently in the seizure group (36% versus 2% for acute ischemic stroke) with high specificity (98%) but low sensitivity (35%) for the diagnosis of epileptic seizure. Hypoperfusion was found in 38% of cases in each group and was not confined to a vascular territory in 24% of patients in the seizure group and 2% in the acute ischemic stroke group. The interobserver agreement was good (κ = 0.60) for hypo-, hyper-, and normoperfusion patterns and moderate (κ = 0.41) for the evaluation of vascular systematization.CONCLUSIONS:CTP patterns helped to differentiate acute ischemic stroke from epileptic seizure in a “code stroke” situation. Our results indicate that a hyperperfusion pattern, especially if not restricted to a vascular territory, may suggest reconsideration of intravenous thrombolysis therapy.

“Code stroke” status, a sudden-onset neurologic deficit, is a common cause of admission to emergency departments. Stroke is the first diagnosis to explore because it requires early reperfusion therapy such as thrombolysis and/or mechanical thrombectomy because as many as 30% of patients with code stroke involve conditions that mimic stroke,¹ with epileptic seizure being one of the most frequent (∼10%).² Up to 15% of patients receiving rtPA after NCCT have a stroke mimic.³ Although some studies have demonstrated that intravenous rtPA in stroke mimics is relatively safe,³ complications such as such hemorrhage or angioedema can occur in 1% of cases each⁴ and increase the cost and length of hospitalization.⁵Imaging modalities that can differentiate an acute ischemic stroke from an epileptic seizure could facilitate the appropriate choice of urgent treatment. Intracranial arterial imaging is insufficient to diagnose ischemic stroke because up to 40% of patients with stroke have no identified occlusion.⁶Although brain MR imaging with diffusion-weighted imaging is regarded as the criterion standard for detecting early ischemia, CTP is a more widely accessible imaging technique, with shorter acquisition times. In recent thrombectomy studies, CTP screening was performed 11 times more frequently than MR imaging screening.⁷Cerebral perfusion imaging related to acute ischemic stroke has been widely investigated,⁸ but few studies on the role of cerebral perfusion imaging in seizure diagnosis have been published.^9,10 During the ictal period, neuronal activation may be associated with an increase in regional brain perfusion, whereas the postictal period is characterized more frequently by hypoperfusion.^11,12The aim of our study was to identify cerebral perfusion imaging patterns that help differentiate an acute focal neurologic deficit related to an epileptic seizure from an acute ischemic stroke in code stroke alerts, in the absence of vessel occlusion or stenosis on CTA.     

Severity of Chest Imaging is Correlated with Risk of Acute Neuroimaging Findings among Patients with COVID-19

BACKGROUND AND PURPOSE:Severe respiratory distress in patients with COVID-19 has been associated with higher rate of neurologic manifestations. Our aim was to investigate whether the severity of chest imaging findings among patients with coronavirus disease 2019 (COVID-19) correlates with the risk of acute neuroimaging findings.MATERIALS AND METHODS:This retrospective study included all patients with COVID-19 who received care at our hospital between March 3, 2020, and May 6, 2020, and underwent chest imaging within 10 days of neuroimaging. Chest radiographs were assessed using a previously validated automated neural network algorithm for COVID-19 (Pulmonary X-ray Severity score). Chest CTs were graded using a Chest CT Severity scoring system based on involvement of each lobe. Associations between chest imaging severity scores and acute neuroimaging findings were assessed using multivariable logistic regression.RESULTS:Twenty-four of 93 patients (26%) included in the study had positive acute neuroimaging findings, including intracranial hemorrhage (n = 7), infarction (n = 7), leukoencephalopathy (n = 6), or a combination of findings (n = 4). The average length of hospitalization, prevalence of intensive care unit admission, and proportion of patients requiring intubation were significantly greater in patients with acute neuroimaging findings than in patients without them (P < .05 for all). Compared with patients without acute neuroimaging findings, patients with acute neuroimaging findings had significantly higher mean Pulmonary X-ray Severity scores (5.0 [SD, 2.9] versus 9.2 [SD, 3.4], P < .001) and mean Chest CT Severity scores (9.0 [SD, 5.1] versus 12.1 [SD, 5.0], P = .041). The pulmonary x-ray severity score was a significant predictor of acute neuroimaging findings in patients with COVID-19.CONCLUSIONS:Patients with COVID-19 and acute neuroimaging findings had more severe findings on chest imaging on both radiographs and CT compared with patients with COVID-19 without acute neuroimaging findings. The severity of findings on chest radiography was a strong predictor of acute neuroimaging findings in patients with COVID-19.

The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has now infected >40 million people worldwide, with >1 million deaths reported by the end of October 2020.¹ While COVID-19 is well-known for its pulmonary manifestations, it has been shown to involve other organs, including the heart, kidneys, liver, and central nervous system.^2-5 This involvement is consistent with viral entry through the angiotensin-converting enzyme 2 receptor, which is abundantly expressed on vascular endothelial cells of the lungs but also in other organs, including the central nervous system, heart, kidneys, intestines, and muscles.⁶ Reported neurologic manifestations of COVID-19 infection include ischemic and hemorrhage stroke, encephalitis, and leukoencephalopathy.^7-12It has been previously reported that patients with COVID-19 and severe respiratory distress have a relatively high rate of neurologic involvement.¹³ Furthermore, patients with COVID-19 and neurologic symptoms have been shown to have poorer outcomes than those without them.¹⁴ Thus, it would be important to identify clinical or imaging features in patients with COVID-19 that may help predict an increased risk of neurologic injury. Severity of disease on chest imaging is a strong predictor of clinical outcome and risk of complications.^15-17 The objective of our study was to identify whether the severity of chest imaging findings is correlated with the risk of positive neuroimaging findings in patients admitted for COVID-19 infection.     

MRI Brain Findings in 126 Patients with COVID-19: Initial Observations from a Descriptive Literature Review

BACKGROUND AND PURPOSE:Recently, numerous investigational studies, case series, and case reports have been published describing various MR imaging brain findings in patients with COVID-19. The purpose of this literature review was to compile and analyze brain MR imaging findings in patients with COVID-19-related illness.MATERIALS AND METHODS:Literature searches of PubMed, publicly available Internet search engines, and medical journal Web sites were performed to identify articles published before May 30, 2020 that described MR imaging brain findings in patients with COVID-19.RESULTS:Twenty-two articles were included in the analysis: 5 investigational studies, 6 case series, and 11 case reports, encompassing MR imaging of the brain in 126 patients. The articles originated from 7 different countries and were published in 14 medical journals. MR imaging brain findings included specific diagnoses (such as acute infarct, posterior reversible encephalopathy syndrome) or specific imaging features (such as cortical FLAIR signal abnormality, microhemorrhages).CONCLUSIONS:The most frequent diagnoses made on brain MR imaging in patients with COVID-19 were acute and subacute infarcts. Other common findings included a constellation of leukoencephalopathy and microhemorrhages, leptomeningeal contrast enhancement, and cortical FLAIR signal abnormality.

Growing evidence suggests that coronavirus disease 2019 (COVID-19), secondary to infection with Severe Acute Respiratory Syndrome coronavirus 2 can manifest with a multitude of neurologic conditions including ataxia, seizure, acute stroke, and impaired consciousness.^1,2 Since the World Health Organization declared coronavirus disease 2019 (COVID-19) a global pandemic on March 11, 2020,³ the medical literature describing COVID-19 mechanisms, manifestations, and treatments has expanded with extraordinary speed. In concordance with the World Health Organization’s efforts for rapid distribution of data by biomedical journals during public health emergencies,⁴ this rapid pace has been aided by the expedited peer-review processes instituted by multiple medical journals.⁵ Consequently, journals representing multiple disciplines simultaneously have published numerous articles describing imaging findings in COVID-19 illness. While pulmonary disease is the best recognized morbidity associated with COVID-19, there are many reported neurologic manifestations of this infection. The purpose of this literature review was to collect, analyze, and summarize the findings on brain MR imaging reported to date in patients with COVID-19.     

Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy

BACKGROUND AND PURPOSE:Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients.MATERIALS AND METHODS:This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy–positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20.RESULTS:Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71–0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1–2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0–1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8–0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5–1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84–0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%–67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement–positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%–84.0%) versus 32.2% (95% CI, 14.4%–62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0–12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9–7.0; P = .080).CONCLUSIONS:Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

Vessel wall enhancement (VWE) can be detected using vessel wall MR imaging (vwMRI) using flow-suppressed, contrast-enhanced black-blood T1-weighted sequences.^1,2 In the setting of intracranial atherosclerosis, VWE is a known independent risk factor for acute ischemic stroke (AIS).^3,4 Other pathologies also affect the vessel wall, including vasculitis, reversible cerebral vasoconstriction syndrome, and Moyamoya disease and their findings on vwMRI that have been previously described.^1,5,6 Very recently, a case series found VWE in 2 of 5 patients (40%) with cerebral amyloid angiopathy (CAA).⁷ Although this small study showed that VWE can occur in patients with noninflammatory CAA, its neurologic impact is unknown.In addition to lobar hemorrhage, CAA is an important cause of transient neurologic complaints (amyloid spells), cognitive impairment, and ischemic infarcts.^8-10 The pathogenesis of CAA is complex and related to amyloid-β deposition in the small- to medium-sized vessel walls, resulting in necrosis, vessel rupture, or thrombosis.^11-13 Because of this, imaging techniques that highlight vessel wall pathology, such as vwMRI, may have diagnostic and prognostic impact in patients with CAA. Brain imaging currently plays a vital role in CAA diagnosis using the modified Boston criteria.¹⁴ The most common acute imaging finding in patients with CAA is hemorrhage from vessel rupture.¹⁵ Microinfarcts can be seen in animal models of CAA¹⁶ and are present in 30%–60% of patients with CAA,^17,18 contributing to cortical thinning.¹⁹ CAA imaging criteria depend primarily on the presence of prior hemorrhage on susceptibility-weighted sequences,²⁰ including siderosis and microhemorrhages in lobar, cortical- or subcortical locations.¹⁴ CAA disproportionately affects older adults, with increasing prevalence after age 60 years.²¹ Because of this, the modified Boston criteria for CAA use a threshold of 55 years or older.Patients with CAA often undergo work-up for acute neurologic deficits concerning for ischemic stroke, which can be detected on MR imaging.²² Evaluation of ischemic stroke risk in patients with CAA has important diagnostic and prognostic impact because it is a significant contributor to cognitive decline.²³ These patients have complex medical histories, and because vessel wall pathology may not easily be seen with lumen imaging, this necessitates further evaluation with vessel wall imaging techniques. Because of their complicated nature, neurology consultation and vwMRI are often performed in the work-up of patients with CAA at our institution. In light of this and given the importance of VWE in a variety of intracranial vasculopathies, our goal was to determine the association of VWE with AIS in patients with CAA undergoing vwMRI during stroke work-up. In this study, we evaluated both acute concurrent and future ischemic stroke risk while controlling for potential cerebrovascular confounders. Our hypothesis was that in patients with CAA, VWE would be associated with both concurrent and future ischemic stroke.     

Fast Stent Retrieval during Mechanical Thrombectomy Improves Recanalization in Patients with the Negative Susceptibility Vessel Sign

BACKGROUND AND PURPOSE:In acute ischemic stroke, the negative susceptibility vessel sign on T2*-weighted images traditionally highlights fibrin-rich clots, which are particularly challenging to remove. In vitro, fast stent retrieval improves fibrin-rich clot extraction. We aimed to evaluate whether the speed of stent retrieval influences the recanalization and clinical outcome of patients presenting with the negative susceptibility vessel sign.MATERIALS AND METHODS:Patients were identified from a registry of patients with ischemic stroke receiving mechanical thrombectomy between January 2016 and January 2020. Inclusion criteria were the following: 1) acute ischemic stroke caused by an isolated occlusion of the anterior circulation involving the MCA (Internal Carotid Artery-L, M1, M2) within 8 hours of symptom onset; 2) a negative susceptibility vessel sign on prethrombectomy T2*-weighted images; and 3) treatment with a combined technique (stent retriever + contact aspiration). Patients were dichotomized according to retrieval speed (fast versus slow). The primary outcome was the first-pass recanalization rate.RESULTS:Of 68 patients who met inclusion criteria, 31 (45.6%) were treated with fast retrieval. Patients receiving a fast retrieval had greater odds of first-pass complete (relative risk and 95% confidence interval [RR 95% CI], 4.30 [1.80–10.24]), near-complete (RR 95% CI, 3.24 [1.57–6.68]), and successful (RR 95% CI, 2.60 [1.53–4.43]) recanalization as well as greater odds of final complete (RR 95% CI, 4.18 [1.93–9.04]), near-complete (RR 95% CI, 2.75 [1.55–4.85]), and successful (RR 95% CI, 1.52 [1.14–2.03]) recanalization. No significant statistical differences in procedure-related serious adverse events, distal embolization, or symptomatic intracranial hemorrhage were reported. No differences were noted in terms of functional independence (RR 95% CI, 1.01 [0.53–1.93]) and all-cause mortality (RR 95% CI, 0.90 [0.35–2.30]) at 90 days.CONCLUSIONS:A fast stent retrieval during mechanical thrombectomy is safe and improves the retrieval of clots with the negative susceptibility vessel sign.

In acute ischemic stroke, the susceptibility vessel sign (SVS) on T2*-weighted sequences is thought to highlight the red blood cells in the clot.^1-3 Histopathologic correlations of retrieved thrombi with MR imaging features showed that clots not visible on T2*-weighted images (negative SVS) contained a high proportion of fibrin,^1,2 which makes them particularly firm and sticky,^4,5 and thus very challenging to remove mechanically.^5-7 Approximately 20% of patients receiving bridging therapy cannot achieve recanalization,^7,8 possibly due, in part, to how difficult it is to tailor the retrieval technique to clot properties.⁹ Recent in vitro experiments have shown that fast retrieval of the clot using a combined technique (contact aspiration + stent retriever) can improve recanalization, especially with fibrin-rich clots.¹⁰ Currently, device manufacturers’ instructions advise operators to withdraw stent retrievers slowly to avoid potential artery dissection or rupture. Yet, the effect of retrieval speed on mechanical thrombectomy success in vivo has yet to be explored. A fast retrieval may mobilize the clot suddenly, enhance clot wedging, and minimize loss of apposition during retrieval.¹⁰ The present study aimed to evaluate whether stent-retrieval speed influences recanalization rates and clinical outcome in patients presenting with negative SVS clots.     

Clot Burden Score and Collateral Status and Their Impact on Functional Outcome in Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Collateral status and thrombus length have been independently associated with functional outcome in patients with acute ischemic stroke. It has been suggested that thrombus length would influence functional outcome via interaction with the collateral circulation. We investigated the individual and combined effects of thrombus length assessed by the clot burden score and collateral status assessed by a FLAIR vascular hyperintensity–ASPECTS rating system on functional outcome (mRS).MATERIALS AND METHODS:Patients with anterior circulation acute ischemic stroke due to large-vessel occlusion from the ASTER and THRACE trials treated with endovascular thrombectomy were pooled. The clot burden score and FLAIR vascular hyperintensity score were determined on MR imaging obtained before endovascular thrombectomy. Favorable outcome was defined as an mRS score of 0–2 at 90 days. Association of the clot burden score and the FLAIR vascular hyperintensity score with favorable outcome (individual effect and interaction) was examined using logistic regression models.RESULTS:Of the 326 patients treated by endovascular thrombectomy with both the clot burden score and FLAIR vascular hyperintensity assessment, favorable outcome was observed in 165 (51%). The rate of favorable outcome increased with clot burden score (smaller clots) and FLAIR vascular hyperintensity (better collaterals) values. The association between clot burden score and functional outcome was significantly modified by the FLAIR vascular hyperintensity score, and this association was stronger in patients with good collaterals, with an adjusted OR = 6.15 (95% CI, 1.03–36.81).CONCLUSIONS:The association between the clot burden score and functional outcome varied for different collateral scores. The FLAIR vascular hyperintensity score might be a valuable prognostic factor, especially when contrast-based vascular imaging is not available.

Therapeutic reperfusion with endovascular thrombectomy (EVT) is consistently associated with a better long-term functional outcome in anterior circulation acute ischemic stroke (AIS).¹ Early reperfusion is the mainstay of therapy because it strongly predicts functional outcome.² Many factors impact clinical outcomes, including the extent of clot and collateral supply.^3–7The clot burden score (CBS) assessed by the T2* MR imaging sequence (T2*-CBS), which was adapted from the CTA-CBS,⁸ has been used to assess the extent of the clot⁹ and has been independently associated with functional outcome in patients undergoing EVT.¹⁰Good collaterals have been related to better clinical outcome through 2 distinct mechanisms. First, collaterals are thought to contribute to prolonged penumbra sustenance.^11,12 Second, good retrograde collateral filling beyond the occlusion could promote successful reperfusion by providing more access to thrombolytics at the distal end of the clot and robust collaterals dissolving clot fragments in the distal vasculature.^13,14 The Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration analysis suggested a benefit with EVT across all strata of collateral circulation status;¹⁵ however, patients with poor collaterals are less likely to benefit from EVT than those with better collaterals.Most interesting, FLAIR vascular hyperintensity (FVH) on baseline MR imaging could indicate the formation of a leptomeningeal collateral circulation and serve as a prognostic marker for patients with AIS.^16-18 Both collaterals and the CBS were separately associated with functional outcome in patients undergoing EVT,^10,16 but their combined effect regarding clinical outcome is still poorly understood and has been assessed and quantified only with CTA or contrast-enhanced MRA in patients with AIS.^14,15 Furthermore, the lack of adjustment for possible confounders because of the small number of patients with very low collateral scores might also have influenced results in these studies.The purpose of this study was to determine whether there is an association between the CBS and FVH score and whether the association between the CBS and functional outcome is modified by the FVH score for patients who were treated by EVT for large-vessel occlusion within the framework of the Contact Aspiration versus Stent Retriever for Successful Revascularization (ASTER) and the THRombectomie des Artères CErebrales (THRACE) randomized trials.^19,20     

Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase

BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD_z). Through linear regression, we evaluated the relation between microbleed concentration and MD_z in predefined structures.RESULTS:In the cerebral hemispheres, MD_z at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MD_z in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MD_z in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.^1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).³ TAI is a major predictor of functional outcome,^4,5 but it is mostly invisible on CT and conventional MR imaging.^6,7DTI provides direct information on WM integrity and axonal injury.^5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).^4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).⁴ Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.^6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.^12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable¹ except in the hyperacute^14,15 and the late chronic phases.¹⁶ Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.¹⁷ Indeed, TAI is not invariably hemorrhagic.¹⁸ Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.¹⁸DTI is not only affected by pathophysiological changes but also by susceptibility.¹⁹ The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.^4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI^5,18,20 and it can reliably be evaluated with DTI,^5,21 and TAI in the corpus callosum is related to clinical prognosis.^6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.²² The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.²³ Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,^24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.     

Intra-Arterial Thrombolysis after Unsuccessful Mechanical Thrombectomy in the STRATIS Registry

BACKGROUND AND PURPOSE:Recent data suggest that intra-arterial thrombolytics may be a safe rescue therapy for patients with acute ischemic stroke after unsuccessful mechanical thrombectomy; however, safety and efficacy remain unclear. Here, we evaluate the use of intra-arterial rtPA as a rescue therapy in the Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry.MATERIALS AND METHODS:STRATIS was a prospective, multicenter, observational study of patients with acute ischemic stroke with large-vessel occlusions treated with the Solitaire stent retriever as the first-line therapy within 8 hours from symptom onset. Clinical and angiographic outcomes were compared in patients having rescue therapy treated with and without intra-arterial rtPA. Unsuccessful mechanical thrombectomy was defined as any use of rescue therapy.RESULTS:A total of 212/984 (21.5%) patients received rescue therapy, of which 83 (39.2%) and 129 (60.8%) were in the no intra-arterial rtPA and intra-arterial rtPA groups, respectively. Most occlusions were M1, with 43.4% in the no intra-arterial rtPA group and 55.0% in the intra-arterial rtPA group (P = .12). The median intra-arterial rtPA dose was 4 mg (interquartile range = 2–12 mg). A trend toward higher rates of substantial reperfusion (modified TICI  ≥ 2b) (84.7% versus 73.0%, P = .08), good functional outcome (59.2% versus 46.6%, P = .10), and lower rates of mortality (13.3% versus 23.3%, P = .08) was seen in the intra-arterial rtPA cohort. Rates of symptomatic intracranial hemorrhage did not differ (0% versus 1.6%, P = .54).CONCLUSIONS:Use of intra-arterial rtPA as a rescue therapy after unsuccessful mechanical thrombectomy was not associated with an increased risk of symptomatic intracranial hemorrhage or mortality. Randomized clinical trials are needed to understand the safety and efficacy of intra-arterial thrombolysis as a rescue therapy after mechanical thrombectomy.

Mechanical thrombectomy (MT) is a powerful therapy for patients with acute ischemic stroke with large-vessel occlusions. However, despite its proved success,^1-5 most patients do not achieve complete reperfusion^6-9 and only about half of all patients treated with MT achieve a good clinical outcome at 3 months.⁶ Because patients with complete reperfusion are 2 times more likely to have favorable outcomes than those with near-complete reperfusion,¹⁰ exploration of adjunctive or rescue therapies (RTs) to augment MT complete reperfusion is warranted.The role of intra-arterial (IA) thrombolysis has evolved from a primary therapy^11-17 to an adjunctive or RT to MT. Recently, a US survey indicated that 60.6% of neurointerventionalists use IA lytics in their practice, with the most common approach as an RT after MT.¹⁸ Previous studies on the use of IA rtPA in the context of MT either as an RT or adjunctive therapy have yielded promising data, but these studies are limited by their small sample sizes and retrospective design.^19-21 Here, in this subanalysis, we retrospectively evaluate the use of IA rtPA as an RT after unsuccessful MT in the multicenter, prospective, Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry (https://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02239640","term_id":"NCT02239640"}}NCT02239640?term=STRATIS&draw=2&rank=7).     

Postprocedural Antiplatelet Treatment after Emergent Carotid Stenting in Tandem Lesions Stroke: Impact on Stent Patency beyond Day 1

BACKGROUND AND PURPOSE:Postprocedural dual-antiplatelet therapy is frequently withheld after emergent carotid stent placement during stroke thrombectomy. We aimed to assess whether antiplatelet regimen variations increase the risk of stent thrombosis beyond postprocedural day 1.MATERIALS AND METHODS:Retrospective review was undertaken of all consecutive thrombectomies for acute stroke with tandem lesions in the anterior circulation performed in a single comprehensive stroke center between January 9, 2011 and March 30, 2020. Patients were included if carotid stent patency was confirmed at day 1 postprocedure. The group of patients with continuous dual-antiplatelet therapy from day 1 was compared with the group of patients with absent/discontinued dual-antiplatelet therapy.RESULTS:Of a total of 109 tandem lesion thrombectomies, 96 patients had patent carotid stents at the end of the procedure. The early postprocedural stent thrombosis rate during the first 24 hours was 14/96 (14.5%). Of 82 patients with patent stents at day 1, in 28 (34.1%), dual-antiplatelet therapy was either not initiated at day 1 or was discontinued thereafter. After exclusion of cases without further controls of stent patency, there was no significant difference in the rate of subacute/late stent thrombosis between the 2 groups: 1/50 (2%) in patients with continuous dual-antiplatelet therapy versus 0/22 (0%) in patients with absent/discontinued dual-antiplatelet therapy (P = 1.000). In total, we observed 88 patient days without any antiplatelet treatment and 471 patient days with single antiplatelet treatment.CONCLUSIONS:Discontinuation of dual-antiplatelet therapy was not associated with an increased risk of stent thrombosis beyond postprocedural day 1. Further studies are warranted to better assess the additional benefit and optimal duration of dual-antiplatelet therapy after tandem lesion stroke thrombectomy.

In around 15% of endovascular procedures for anterior circulation stroke,¹ there is a tight stenosis or occlusion of the cervical carotid artery in addition to the intracranial artery occlusion. The optimal endovascular management of tandem lesions has yet to be defined; however, there is mounting evidence^2,3 that emergent stent placement in the carotid artery associated with at least 1 antiplatelet agent could lead to better recanalization rates and improved clinical outcomes. A more definitive answer should be provided by the Thrombectomy In TANdem lesions (TITAN) randomized multicenter trial,⁴ designed to assess the safety and efficacy of emergent internal carotid artery stent placement in tandem lesion thrombectomy. This study recently enrolled the first patient in early 2020.In patients undergoing emergent carotid stent placement, there is no consensus regarding the optimal periprocedural antiplatelet therapy. Many groups^5,6 chose to avoid dual-antiplatelet therapy (DAPT) during the first 24 hours in an attempt to reduce the risk of hemorrhagic transformation. Conversely, less aggressive antiplatelet regimens might increase the risk of carotid stent thrombosis.Stent thrombosis was recently identified as a predictor of unfavorable clinical outcome.^7,8 To date, available data regarding stent patency rates remain scarce. Most case series of endovascular management for tandem lesions^5,9-11 do not report postprocedural stent patency, while some publications^12-15 offer partial data for a subgroup of patients for whom carotid imaging controls were available. Reported rates of stent thrombosis ranged between 1.2% and 22.0%.^{6-8,12-14,16,17}To date, no study has attempted to differentiate between early (first 24 hours) and subacute/late postprocedural stent thrombosis. During the first 24 hours, protection against stent thrombosis is conferred by antiplatelet agents administered during the procedure (periprocedural antiplatelets). Beyond 24 hours, the recommended antiplatelet regimen is DAPT for 4–12 weeks,^9,17 but in reality, antiplatelets are often tailored in view of neurological and extra-neurological hemorrhagic events. It is currently unknown whether discontinuation of DAPT is associated with an increased risk of late stent thrombosis.Thus, we aimed to describe the variations in the postprocedural antiplatelet regimen in a large consecutive cohort of tandem lesion thrombectomies with emergent carotid artery stent placement and to assess whether discontinuation of DAPT was associated with an increased risk of carotid stent thrombosis.     

Clinical,Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy

BACKGROUND AND PURPOSE:Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology.MATERIALS AND METHODS:Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included. Seven (7/27, 26%) developed an unusual pattern of “leukoencephalopathy with reduced diffusivity” on diffusion-weighted MR imaging. The remaining patients did not exhibit this pattern. Clinical and laboratory indices, as well as neuroimaging findings, were compared between groups.RESULTS:The reduced-diffusivity group had a significantly higher body mass index (36 versus 28 kg/m², P < .01). Patients with reduced diffusivity trended toward more frequent acute renal failure (7/7, 100% versus 9/20, 45%; P = .06) and lower estimated glomerular filtration rate values (49 versus 85 mL/min; P = .06) at the time of MRI. Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin levels (8.1 versus 10.2 g/dL, P < .05) and higher serum sodium levels (147 versus 139 mmol/L, P = .04) within 24 hours before MR imaging. The reduced-diffusivity group showed a striking and highly reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < .001).CONCLUSIONS:Our findings highlight notable correlations between severe COVID-19 leukoencephalopathy with reduced diffusivity and obesity, acute renal failure, mild hypernatremia, anemia, and an unusual brain MR imaging white matter lesion distribution pattern. Together, these observations may shed light on possible SARS-CoV-2 pathophysiologic mechanisms associated with leukoencephalopathy, including borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the known cytokine storm syndrome that accompanies severe COVID-19.

Among the neurologic disorders associated with Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2)^1-3 infection, there have been several reports of diffuse white matter abnormalities, including a “leukoencephalopathy with reduced diffusivity” on diffusion-weighted MR imaging.⁴ This pattern of severe, bilateral white matter involvement appears to develop late in the course of coronavirus disease 2019 (COVID-19) in critically ill patients and may be related to the prolonged hypoxemia that these patients experience, often even while asymptomatic.⁵Indeed, although leukoencephalopathy can result from a diverse group of genetic, toxic/metabolic, inflammatory, and infectious conditions, several well-described leukoencephalopathy syndromes may have direct relevance to COVID-19 pathophysiology. These disorders, which are associated with distinct clinical features, imaging patterns, and laboratory findings, include but are not limited to both delayed posthypoxic leukoencephalopathy (which often develops days or weeks following an initial, typically catastrophic, global hypoxic event, such as carbon monoxide poisoning, drowning, opioid overdose, or other causes of cardiac arrest)^6-9 and sepsis-related leukoencephalopathy (which occurs in critically ill patients and is likely due to deranged blood-brain barrier permeability caused by inflammatory mediators, allowing passage of cytokines and other neurotoxins into the cerebral white matter).^10-13Review of the current literature suggests possible roles for “silent hypoxia” and/or “cytokine storm” in the development of severe COVID-19-related leukoencephalopathy;^5,14,15 the paucity of postmortem studies to date contributes to this uncertainty.¹⁶ Our purpose, therefore, has been to characterize the clinical, imaging, and laboratory correlates of COVID-19 leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiologic mechanisms of severe white matter cellular injury.     

Delayed Contrast-Enhanced MR Angiography for the Assessment of Internal Carotid Bulb Patency in the Context of Acute Ischemic Stroke: An Accuracy,Interrater, and Intrarater Agreement Study

BACKGROUND AND PURPOSE:CTA has shown limited accuracy and reliability in distinguishing tandem occlusions and pseudo-occlusions on initial acute stroke imaging. The utility of early and delayed contrast-enhanced MRA in this setting is unknown. We aimed to assess the accuracy and reliability of early and delayed contrast-enhanced MRA for carotid bulb patency in patients with acute ischemic stroke.MATERIALS AND METHODS:We retrospectively reviewed patients who had ICA occlusion and underwent thrombectomy with preprocedural early and delayed contrast-enhanced MRA in a single comprehensive stroke center. During 2 sessions, 10 raters independently assessed 32 cases with early contrast-enhanced MRA (with an additional delayed contrast-enhanced MRA sequence during the second reading session). Their judgments were compared with DSA as a reference standard. Accuracy and interrater agreement were measured. Five raters undertook a third reading session to assess intrarater agreement.RESULTS:Accuracy for the assessment of carotid bulb patency with early contrast-enhanced MRA was limited (69%; 95% CI, 59%–79%), with moderate interrater agreement (κ = 0.42; 95% CI, 0.27–0.55). The second reading with an additional delayed contrast-enhanced MRA sequence improved both accuracy (82%; 95% CI, 73%–91%; P < .001) (raters corrected 43%–77% of incorrect diagnoses with early contrast-enhanced MRA alone; mean = 59%) and interrater agreement (κ = 0.56; 95% CI, 0.41–0.73; P = .07). Intrarater agreement was almost perfect, substantial, and moderate for 3, 1, and 1 raters.CONCLUSIONS:Early contrast-enhanced MRA has limited accuracy and repeatability for the evaluation of carotid bulb patency in acute ischemic stroke. The additional delayed contrast-enhanced MRA sequence may improve accuracy and reliability.

Several trials have demonstrated the benefit of mechanical thrombectomy in acute ischemic stroke (AIS) with anterior circulation large-vessel occlusion¹ depicted by noninvasive intracranial vascular imaging (CTA or MRA). However, in case of tandem occlusion (ie, an ICA occlusion with an intracranial large-vessel occlusion), there remains uncertainty regarding the optimal management of the carotid bulb lesion,² and the benefits of acute angioplasty/stent placement are controversial.^3,4 Randomized controlled trials are needed to determine the best strategy and will thus require an accurate and repeatable noninvasive imaging method to select patients with an intracranial large-vessel occlusion and an additional carotid bulb occlusion,⁵ which will typically appear as an absence of visualization of the whole symptomatic carotid artery from the bulb.However, in AIS, a single, large clot located above the ICA bulb can impede contrast ascension from the common carotid artery, leading to a false image of bulbar occlusion, an entity called ICA pseudo-occlusion (PO).^6-9 It can, thus, be challenging to distinguish tandem occlusions and POs on initial acute stroke imaging. A previous study has shown limited accuracy and reliability of CTA for this task.¹⁰ CTA might thus be limited for the detection of tandem occlusions, whether in clinical routine (for endovascular management planning) or in research settings (for patient selection in a randomized controlled trial).MR imaging offers several interesting features for acute stroke imaging and decision-making, including a high sensitivity for the detection of early ischemic lesions¹¹ and the ability to detect stroke mimics¹² and identify patients who will benefit from reperfusion therapy in case of unknown onset stroke.¹³ Noninvasive vascular imaging can then be performed with MRA: The TOF sequence is usually performed for the depiction of intracranial large-vessel occlusion, and early contrast-enhanced MRA (CE-MRA), for the assessment of the complete supra-aortic vasculature. As with CTA, cases with an intraluminal filling defect of the bulb on ICA on the stroke side might correspond to either a tandem occlusion or a PO. Delayed acquisition after gadolinium injection (delayed CE-MRA) might overcome this issue, but CE-MRA performance has not been thoroughly studied in this setting.In this study, we aimed to assess the accuracy and reliability of early and delayed CE-MRA for the assessment of carotid bulb patency in patients with AIS.     

Tissue at Risk and Ischemic Core Estimation Using Deep Learning in Acute Stroke

BACKGROUND AND PURPOSE:In acute stroke patients with large vessel occlusions, it would be helpful to be able to predict the difference in the size and location of the final infarct based on the outcome of reperfusion therapy. Our aim was to demonstrate the value of deep learning–based tissue at risk and ischemic core estimation. We trained deep learning models using a baseline MR image in 3 multicenter trials.MATERIALS AND METHODS:Patients with acute ischemic stroke from 3 multicenter trials were identified and grouped into minimal (≤20%), partial (20%-80%), and major (≥80%) reperfusion status based on 4- to 24-hour follow-up MR imaging if available or into unknown status if not. Attention-gated convolutional neural networks were trained with admission imaging as input and the final infarct as ground truth. We explored 3 approaches: 1) separate: train 2 independent models with patients with minimal and major reperfusion; 2) pretraining: develop a single model using patients with partial and unknown reperfusion, then fine-tune it to create 2 separate models for minimal and major reperfusion; and 3) thresholding: use the current clinical method relying on apparent diffusion coefficient and time-to-maximum of the residue function maps. Models were evaluated using area under the curve, the Dice score coefficient, and lesion volume difference.RESULTS:Two hundred thirty-seven patients were included (minimal, major, partial, and unknown reperfusion: n = 52, 80, 57, and 48, respectively). The pretraining approach achieved the highest median Dice score coefficient (tissue at risk = 0.60, interquartile range, 0.43–0.70; core = 0.57, interquartile range, 0.30–0.69). This was higher than the separate approach (tissue at risk = 0.55; interquartile range, 0.41–0.69; P = .01; core = 0.49; interquartile range, 0.35–0.66; P = .04) or thresholding (tissue at risk = 0.56; interquartile range, 0.42–0.65; P = .008; core = 0.46; interquartile range, 0.16–0.54; P < .001).CONCLUSIONS:Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods.

As demonstrated in recent Endovascular Therapy following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) and Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trials,^1,2 perfusion imaging can be used to triage patients with acute ischemic stroke to reperfusion therapy in addition to the original “time window.” The DWI/PWI mismatch paradigm is the most common way of triaging patients,³ especially in those exceeding 6 hours of stroke onset.The tissue at risk, sometimes called the penumbra, reflects the maximal extent of infarct if only minimal reperfusion is achieved, defined by time-to-maximum of the residue function (Tmax) > 6 seconds region using standard clinical software. Likewise, the ischemic core reflects the minimal ischemic lesion if major reperfusion is achieved, which has been defined by an ADC value < 620 × 10⁻⁶ mm²/s.⁴ Despite the simplicity and ease of use of single-value thresholds to identify salvageable tissue, such approaches have difficulty distinguishing benign hypoperfusion from tissue at risk⁵ and may fail to capture the complexity of the disease evolution.Machine learning is a class of algorithms that automatically learn from data and provide predictions. Studies have shown that machine learning can be used to predict final stroke lesions from acute imaging data.^6-13 Convolutional neural networks are a subtype of machine learning that do not require humans to define relevant features, instead extracting features automatically from images using many hidden layers (giving rise to the term “deep learning”).^14-16 One type of deep convolutional neural network known as a U-net has shown much promise for segmentation tasks in medical imaging.¹⁷The most obvious approach to define the ischemic core and tissue at risk is to train 2 separate models using patients with complete or no reperfusion. However, such patients account only for a small subgroup of all patients who undergo reperfusion therapy, and the performance of deep learning models improves with increased sample size.¹⁸ Therefore, the aim of this study was to explore whether deep learning could provide a more accurate estimation of tissue at risk and ischemic core, and what is the most efficient and accurate approach with limited clinical data.We evaluated 2 different approaches: training using targeted cases (patients with minimal and major reperfusion) only (separate training approach); or pretraining on a much wider cross-section of cases (including those with partial reperfusion) followed by fine-tuning on the targeted cases (pretraining approach). We hypothesized that the pretraining approach is superior to separate training and that both methods outperform the current clinical standard thresholding method based on the DWI/PWI mismatch.     

Longitudinal Assessment of Enhancing Foci of Abnormal Signal Intensity in Neurofibromatosis Type 1

BACKGROUND AND PURPOSE:Patients with neurofibromatosis 1 are at increased risk of developing brain tumors, and differentiation from contrast-enhancing foci of abnormal signal intensity can be challenging. We aimed to longitudinally characterize rare, enhancing foci of abnormal signal intensity based on location and demographics.MATERIALS AND METHODS:A total of 109 MR imaging datasets from 19 consecutive patients (7 male; mean age, 8.6 years; range, 2.3–16.8 years) with neurofibromatosis 1 and a total of 23 contrast-enhancing parenchymal lesions initially classified as foci of abnormal signal intensity were included. The mean follow-up period was 6.5 years (range, 1–13.8 years). Enhancing foci of abnormal signal intensity were followed up with respect to presence, location, and volume. Linear regression analysis was performed.RESULTS:Location, mean peak volume, and decrease in enhancing volume over time of the 23 lesions were as follows: 10 splenium of the corpus callosum (295 mm³, 5 decreasing, 3 completely resolving, 2 surgical intervention for change in imaging appearance later confirmed to be gangliocytoma and astrocytoma WHO II), 1 body of the corpus callosum (44 mm³, decreasing), 2 frontal lobe white matter (32 mm³, 1 completely resolving), 3 globus pallidus (50 mm³, all completely resolving), 6 cerebellum (206 mm³, 3 decreasing, 1 completely resolving), and 1 midbrain (34 mm³). On average, splenium lesions began to decrease in size at 12.2 years, posterior fossa lesions at 17.1 years, and other locations at 9.4 years of age.CONCLUSIONS:Albeit very rare, contrast-enhancing lesions in patients with neurofibromatosis 1 may regress over time. Follow-up MR imaging aids in ascertaining regression. The development of atypical features should prompt further evaluation for underlying tumors.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant tumor predisposition syndrome characterized by optic pathway gliomas, neurofibromas, skin manifestations, iris hamartomas, and bone lesions, affecting approximately 1 in 3000 individuals.^1,2 Foci of abnormal signal intensity, previously known as unidentified bright objects or neurofibromatosis bright objects of the brain, are not among the diagnostic criteria but can be found in 43%–95% of pediatric patients with NF-1.^3-7 On MR imaging, FASI appear as T2/FLAIR hyperintense lesions of the brain with a predilection for the basal ganglia, cerebellum, and brain stem. Although FASI are not completely understood, myelin vacuolization is commonly considered as an underlying feature of these lesions.^1,4,5,7-9Patients with NF-1 are at an increased risk of developing low- and high-grade brain tumors, including cerebral and cerebellar astrocytomas, ependymomas, and brain stem gliomas, many of which can mimic FASI on MR imaging.^3,10-14 On the other hand, FASI are known for their dynamic properties and may increase or decrease in size or resolve over time.⁸ Although the reference standard for differentiating brain lesions is transcranial biopsy with its own inherent risks, brain signal abnormalities in patients with NF-1 are primarily followed up by MR imaging to screen for possible tumors.^15-18 Contrast enhancement after administration of a gadolinium-based contrast agent is usually considered atypical for FASI and likely to indicate the presence of a brain tumor. Reports considering contrast enhancement in FASI are sparse, limited to case reports and small numbers in cohort studies.^3,6,19-29 We therefore aimed to characterize lesions considered to represent enhancing FASI based on location, volume of enhancement, and demographics to advance the understanding of these rare lesions.     

CTA Evaluation of Basilar Septations: An Entity Better Characterized as Aberrant Basilar Fenestrations

BACKGROUND AND PURPOSE:A basilar artery intraluminal septation is an exceedingly rarely reported, presumed congenital abnormality. In our clinical practice, we have occasionally noticed an intraluminal band within the inferior aspect of the basilar artery on CTA. Furthermore, we have noticed, at times, the presence of a punctate calcification associated with this finding. We hypothesized that what previous studies have called “basilar septations” in fact represent miniature and thus aberrant basilar fenestrations.MATERIALS AND METHODS:We retrospectively reviewed CTA studies obtained between January 1, 2017, and August 31, 2019. Identified intraluminal basilar abnormalities were classified as either basilar septations or basilar fenestrations. Association with other posterior circulation abnormalities was documented.RESULTS:A total of 3509 studies were examined. A basilar intraluminal abnormality was evident in 80 patients (2.3%). Of these 80 patients, 59 were classified as having a basilar fenestration (1.7%) and 21 were classified as having basilar septations (0.6%). Associated calcification was evident in 3 of the basilar fenestration cases and 13 of the basilar septation cases.CONCLUSIONS:Basilar septations most likely represent and should be referred to as aberrant basilar fenestrations. They should be interpreted as benign congenital incidental findings and should not be misinterpreted as focal dissections or arterial webs. Important variations in the morphology of aberrant basilar fenestrations exist, including areas of thinning, varying thickness, and nodularity. Therefore, when associated with calcification or nodularity, aberrant basilar fenestrations should not be confused with focal intraluminal thrombi or calcified or noncalcified emboli.

The most common congenital finding of the basilar artery is a fenestration (prevalence range, 0.28%–5.26% in postmortem series).^1-4 Other congenital intraluminal abnormalities of the basilar artery have been rarely reported in the literature. In particular, case reports of intraluminal basilar septations and basilar webs are exceedingly rare.^5,6 Although infrequently seen, these variations can be detected on routine vascular imaging.Arterial fenestrations are segmental duplications of the vessel lumen into 2 endothelial cell-lined ducts that share a common origin and reconnect distally.^7,8,9,10,11 Fenestrations result from an incomplete fusion in the early embryonic stage, yielding a developmental abnormality that can range in length from 1 mm to a near-complete doubling of the artery.¹⁰ A large fenestration appears like a “window” perforating the vessel, whereas a very small fenestration can look like a dimple in the vessel wall.¹⁰ Prevalence varies greatly between postmortem and imaging reports, with a reported angiographic prevalence of 1.1%.¹³ Additionally, prevalence based on 3D reconstruction of CT and MR angiography has been reported at 13%.^11,12 Although relationships between fenestration and neurovascular pathology are not well-defined, associations with aneurysms and ischemic stroke have been observed.^10,12-14A basilar intraluminal septation is an exceedingly rarely reported, presumed congenital abnormality. To our knowledge, only 2 published articles describe this entity. These articles describe them as intraluminal bands within the vessel.^6,15 The most frequent location for this variation is in close proximity to the junction of the vertebral arteries.^6,15 The initial study describing this finding was published by Davy,¹⁵ in 1839, in which he described 17 cases in 98 postmortem examinations (17.35%). The most recent article is a single cadaveric study that found 1 septation in a sample of 150 cadavers (0.67%).⁶ In this case, the septation measured 3 mm long and 1.5 mm wide.⁶ Tubbs et al⁶ have suggested that these septations may represent a form fruste of basilar fenestrations and may be misinterpreted as dissections or thrombus.¹⁶ A similar finding has been described in a few imaging case reports as a presumed basilar web when associated with thrombosis and infarction.⁵ However, only correlational evidence was reported. Of note, these findings were not present at a branching point and did not mirror the ledge-like imaging findings of a carotid web.^17,18 In fact, the imaging findings appear to be identical in location and morphology to the aforementioned basilar septations.In our clinical practice, we have occasionally noticed an intraluminal band within the inferior aspect of the basilar artery on routine CTA. Because there is no theoretic inferior limit to the size of a basilar fenestration, we hypothesized that what previous studies have called “basilar septations” or “basilar webs” in fact represent miniature and thus aberrant basilar fenestrations (aBFs).     

Time-to-Maximum of the Tissue Residue Function Improves Diagnostic Performance for Detecting Distal Vessel Occlusions on CT Angiography

BACKGROUND AND PURPOSE:Detecting intracranial distal arterial occlusions on CTA is challenging but increasingly relevant to clinical decision-making. Our purpose was to determine whether the use of CTP-derived time-to-maximum of the tissue residue function maps improves diagnostic performance for detecting these occlusions.MATERIALS AND METHODS:Seventy consecutive patients with a distal arterial occlusion and 70 randomly selected controls who underwent multimodal CT with CTA and CTP for a suspected acute ischemic stroke were included in this retrospective study. Four readers with different levels of experience independently read the CTAs in 2 separate sessions, with and without time-to-maximum of the tissue residue function maps, recording the presence or absence of an occlusion, diagnostic confidence, and interpretation time. Accuracy for detecting distal occlusions was assessed using receiver operating characteristic analysis, and areas under curves were compared to assess whether accuracy improved with use of time-to-maximum of the tissue residue function. Changes in diagnostic confidence and interpretation time were assessed using the Wilcoxon signed rank test.RESULTS:Mean sensitivity for detecting occlusions on CTA increased from 70.7% to 90.4% with use of time-to-maximum of the tissue residue function maps. Diagnostic accuracy improved significantly for the 4 readers (P < .001), with areas under the receiver operating characteristic curves increasing by 0.186, 0.136, 0.114, and 0.121, respectively. Diagnostic confidence and speed also significantly increased.CONCLUSIONS:All assessed metrics of diagnostic performance for detecting distal arterial occlusions improved with the use of time-to-maximum of the tissue residue function maps, encouraging their use to aid in interpretation of CTA by both experienced and inexperienced readers. These findings show the added diagnostic value of including CTP in the acute stroke imaging protocol.

Intravenous thrombolysis is the mainstay for treatment of arterial occlusions distal to the internal carotid artery, M1 segment of the MCA, and the vertebral and basilar arteries.¹ These occlusions are referred to as distal vessel occlusions (DVOs), to distinguish them from proximal large-vessel occlusions.² While demonstration of DVOs is not a requirement for thrombolysis,¹ their detection is becoming increasingly relevant to clinical decision-making. The main reason is that endovascular thrombectomy (EVT) can be used to treat occlusions involving large- and medium-sized distal arteries in carefully selected patients.² There is evidence of improved functional outcomes with EVT compared with standard medical management in patients with occlusion of the M2 segment of the MCA.^2-4 M2 occlusions are, therefore, increasingly considered for EVT, which is also safe and technically feasible for occlusions involving the M3 segment of the MCA, the anterior cerebral artery (ACA), or the posterior cerebral artery (PCA).^1,3,5,6Advances in endovascular device technology have led to the development of smaller and more navigable stent retrievers and thromboaspiration devices that can reach smaller distal arteries, including the M4 segment of the MCA and the A4 segment of the ACA.² Because these DVOs can cause severe neurologic deficits when eloquent brain regions are supplied, EVT may be justified to achieve rapid reperfusion.^4,7 It is also the only option for reperfusion in patients who are ineligible for thrombolysis. Thus, distal-vessel EVT is considered a “promising next potential frontier” for stroke therapy and is the subject of current research.² Because demonstration of a target arterial occlusion is required for triage to EVT, fast and accurate detection of DVOs is important to ensure timely treatment.Detecting DVOs also allows the correct diagnosis to be made. This, in turn, is important for prognostication and ongoing management such as work-up for an embolic source and secondary prevention. It is also possible that detection of a target DVO may become a requirement for thrombolysis if the treatment window is extended beyond 4.5 hours, to avoid futile treatment and justify the increased risk of thrombolysis.⁸CTA has become a routine part of the acute stroke imaging protocol.^9,10 Its main purpose is to identify patients with proximal large-vessel occlusions for triage to EVT. DVOs are more difficult to detect on CTA than these proximal occlusions, due to the smaller caliber, larger number, and poorer opacification of distal arteries. Reported sensitivity is as low as 33%, with 35% of M2-segment MCA occlusions missed at the time of initial CTA evaluation in 1 recent study.^11-13CTP is now widely included in acute stroke CT protocols.¹⁴ The time-to-maximum of the tissue residue function (Tmax) is a parameter that is routinely obtained from CTP when deconvolution-based postprocessing is used.¹⁵ Tmax is well-established for identifying salvageable ischemic penumbra in patients with proximal vessel occlusions.^16,17 We have observed, in our clinical practice, that Tmax delay within a vascular territory indicates severe stenosis or occlusion of the supplying artery. This information can, in turn, be used to detect and localize distal arterial occlusions on CTA. These occlusions may otherwise be missed or difficult to find. Despite its real-world value in routine clinical practice, no previous studies have assessed and quantified the diagnostic utility of Tmax for detecting intracranial arterial occlusions.The purpose of this study was to assess the added value of Tmax maps and verify our clinical impression that they facilitate detection of distal occlusions on CTA. We hypothesized that diagnostic accuracy, speed, and confidence for detecting DVOs on CTA would increase with the use of Tmax for readers with different levels of experience.     

Impact of SARS-CoV-2 Pandemic on “Stroke Code” Imaging Utilization and Yield

BACKGROUND AND PURPOSE:Indirect consequences of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic include those related to failure of patients to seek or receive timely medical attention for seemingly unrelated disease. We report our experience with stroke code imaging during the early pandemic months of 2020.MATERIALS AND METHODS:Retrospective review of stroke codes during the 2020 pandemic and both 2020 and matched 2019 prepandemic months was performed. Patient variables were age, sex, hospital location, and severity of symptoms based on the NIHSS. We reviewed the results of CT of the head, CTA, CTP, and MR imaging examinations and classified a case as imaging-positive if any of the imaging studies yielded a result that related to the clinical indication for the study. Both year-to-year and sequential comparisons were performed between pandemic and prepandemic months.RESULTS:A statistically significant decrease was observed in monthly stroke code volumes accompanied by a statistically significant increased proportion of positive imaging findings during the pandemic compared with the same months in the prior year (P < .001) and prepandemic months in the same year (P < .001). We also observed statistically significant increases in average NIHSS scores (P = .045 and P = .03) and the proportion of inpatient stroke codes (P = .003 and P = .03).CONCLUSIONS:During our pandemic period, there was a significantly decreased number of stroke codes but simultaneous increases in positivity rates, symptom severity, and inpatient codes. We postulate that this finding reflects the documented reluctance of patients to seek medical care during the pandemic, with the shift toward a greater proportion of inpatient stroke codes potentially reflecting the neurologic complications of the virus itself.

The impact of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease 2019 (COVID-19) pandemic has reverberated throughout virtually all facets of daily life, with implications beyond those associated with the viral infection itself. Within radiology, overall imaging use initially dropped sharply, largely due to suspension of elective clinical practice.¹ In addition, shifts in specific technique and subspecialty use have paralleled evolving recommendations regarding diagnosis, understanding of disease manifestations, and increasing recognition of delayed and chronic disease complications. For example, the role of chest CT during the pandemic underwent shifts from initial use for diagnosis, particularly when real-time polymerase chain reaction (RT-PCR) testing availability was limited, to later use primarily for assessment of patients with worsening or chronic respiratory failure.² At the time of this writing, at least partial recovery of imaging volumes has occurred in many centers.³In New York City, one of the early epicenters of COVID-19 in the world, this disease initially overtook all others in health care use, with concerns regarding the availability of hospital beds and supportive technology to accommodate the rapidly growing number of severely ill patients. Nevertheless, it was intuitively expected during the early stages of the pandemic that the frequency of other illnesses in the population would be unchanged by the presence of the virus. If anything, the multisystem strain of the disease seemed likely to exacerbate pre-existing morbidities, so that underlying neurologic, cardiovascular, metabolic, and other chronic conditions might worsen during viral infections, resulting in an increased incidence of acute events. In February, first reports of prothrombotic complications of SARS-CoV-2 were published, further supporting the likelihood of an increase in emergency presentation of vascular-related diseases such as pulmonary embolism, myocardial infarction, and stroke.⁴Paradoxically, however, reports in the cardiovascular literature showed a decrease in the incidence of diagnosed myocardial infarction during the initial weeks of the pandemic.⁵ At about the same time, reports in the media confirmed a growing suspicion that patients were choosing to stay home with cardiac and other acute symptoms that would have otherwise brought them to the emergency department due to fears of contracting the disease at health care facilities.⁶ Statistics compiled from the New York City Fire Department, which manages the city''s 911 emergency response system, showed a striking increase of emergency calls that resulted in “refusals of medical aid” during March (118%) and early April (235%).⁷ Furthermore, emergency departments noted early drops in census followed by progressive increases, the latter composed primarily of patients with COVID-19-related illness.⁸The first confirmed case of COVID-19 infection was diagnosed on RT-PCR testing at our 450-bed New York City hospital in early March 2020, with our peak occurring in early April (Fig 1). As both the emergency department and hospital censuses became dominated by patients positive for COVID-19, we noticed a trend toward a reduced frequency of stroke code–related imaging. This observed trend was later confirmed in a correspondence to the New England Journal of Medicine describing a concurrent 39% decrease in the use of the RApid processing of PerfusIon and Diffusion (RAPID; iSchemaView) software platform used at ours and many other US institutions to identify patients who might benefit from endovascular thrombectomy in the setting of acute stroke.⁹ Simultaneously, we began to note trends toward increased positivity rates of stroke code imaging, as well as shifts in patient demographics, including a greater proportion of stroke codes initiated in the inpatient setting. The purpose of this study was to retrospectively review our institution''s stroke codes during the early COVID-19 pandemic (March 1 to April 30, 2020) to quantify imaging use and further analyze the positive imaging findings.Open in a separate windowFIG 1.Hospital census March 13, 2020, through May 24, 2020, shows the timing of the COVID-19 surge. The turquoise line indicates total hospital census; the orange line, patients positive for COVID-19; and the yellow line, patients under investigation for COVID-19. N indicates the number of patients in each category.     

Arterial Spin-Labeling Perfusion for PHACE Syndrome

BACKGROUND AND PURPOSE:Arterial stroke is a rare-but-reported complication in patients with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome. Currently, stroke risk is inferred by the severity of arterial anomalies identified on MRA, though no evidenced-based data exist. The purpose of our study was to determine whether arterial spin-labeling MR imaging perfusion can detect alterations in CBF in patients with PHACE syndrome.MATERIALS AND METHODS:Records were reviewed from 3 institutions for all patients with PHACE syndrome who underwent arterial spin-labeling from 2000 to 2019. CBF was qualitatively investigated with arterial spin-labeling to determine whether there was decreased or normal perfusion. Arterial anomalies were characterized on MRA imaging, and parenchymal brain findings were evaluated on conventional MR imaging sequences.RESULTS:Forty-one patients with PHACE syndrome had arterial spin-labeling imaging. There were 30 females and 11 males (age range, 7 days to 15 years). Of the 41 patients, 10 (24%) had decreased CBF signal corresponding to a major arterial territory. Ten of 10 patients had decreased CBF signal in the anterior circulation, 2/10 had decreased anterior and posterior circulation CBF signal, 2/10 had decreased bilateral anterior circulation CBF signal, and 1/10 had globally decreased CBF signal. Forty of 41 (97.5%) patients had at least 1 arteriopathy, and in those with decreased CBF signal, the arteriopathy corresponded to the CBF signal alteration in 10/10 patients.CONCLUSIONS:Arterial spin-labeling can potentially characterize hemodynamic changes in patients with PHACE syndrome.

Arterial ischemic stroke is a rare-but-devastating complication in a minority of patients with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome. Stroke has been reported in multiple patients with PHACE syndrome,^1-6 but the etiology of stroke is poorly understood.¹ Possible mechanisms for stroke with PHACE include the following: 1) artery-to-artery embolisms, 2) ischemia from reduced blood flow, or 3) cardioembolism. These etiologies are predicated on arteriopathies in the brain, neck, and aortic arch, which are the most common extracutaneous finding in patients with PHACE syndrome.⁷ In 1 study, arteriopathies were observed in 91% of 33 patients⁸ and ranged from an anomalous course to marked stenosis with a Moyamoya pattern.³ Currently, stroke risk is only inferred by the severity of these arteriopathies identified on MRA imaging.⁹ Despite knowledge of the types of arteriopathies in PHACE,³ it is unclear why certain patients with arteriopathies experience a stroke and others do not, even if there are severe anomalies in both subsets. To date, no evidence-based data exist on stroke risk in PHACE syndrome.Arterial spin-labeling (ASL) is a noncontrast MR imaging perfusion sequence that has been studied in patients with stroke and vasculopathies, particularly with the Moyamoya pattern and has proved useful in analyzing CBF.^10,11 In the setting of PHACE syndrome, the concept of ASL imaging has been introduced^12,13 as well as for other cutaneous vascular anomalies.^12-14 The purpose of our study was to determine whether ASL perfusion can detect alterations in CBF in patients with PHACE syndrome.