Epstein-Barr Virus-Associated Smooth-Muscle Tumor of the Brain.

Epstein-Barr virus, a herpesvirus, has been associated with a variety of cancers, including Burkitt, Hodgkin, and non-Hodgkin lymphomas; posttransplant lymphoproliferative disorders; gastric carcinoma; and nasopharyngeal carcinoma, in both immunocompetent and immunocompromised individuals. Previous studies have established a connection between Epstein-Barr virus and the development of smooth-muscle tumors. Smooth-muscle tumors of the brain are very rare and are often misdiagnosed as meningiomas on imaging. To our knowledge, advanced imaging findings such as MR perfusion of smooth-muscle tumors of the brain have never been reported. We describe the radiologic and pathologic features of the Epstein-Barr virus-associated smooth-muscle tumors of the brain in a person with newly diagnosed advanced HIV.

Limited utility of adding 3T cervical spinal cord MRI to monitor disease activity in multiple sclerosis.

BACKGROUND: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable. OBJECTIVE: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value. METHODS: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI. RESULTS: In 1285 pwMS (median interval: 13-14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses (p = 0.04), no disease-modifying therapy (DMT) use (p = 0.048), and ⩾ 3 new BLs (p < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3-11.7, p < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months). CONCLUSION: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity.

Plasma glial fibrillary acidic protein levels correlate with paramagnetic rim lesions in people with radiologically isolated syndrome.

BACKGROUND: There are no specific, evidence-based recommendations for the management of individuals with radiologically isolated syndrome. Imaging and blood biomarkers may have prognostic utility. OBJECTIVE: To determine whether plasma neurofilament light protein (NfL) or glial fibrillary acidic protein (GFAP) levels in people with radiologically isolated syndrome correlate with imaging measures that have been shown to be associated with negative clinical outcomes in people with multiple sclerosis. METHODS: Cross-sectional analysis of people with radiologically isolated syndrome. Participants underwent magnetic resonance imaging (MRI) of the brain and cervical spinal cord, and plasma was collected. Plasma NfL and GFAP levels were measured with a single-molecule array, and correlations with MRI measures were assessed, including the number of: T1-black holes, white-matter lesions demonstrating the central vein sign, paramagnetic rim lesions, cervical spinal cord lesions and infratentorial lesions. RESULTS: Plasma GFAP levels, but not NfL levels, showed correlations with the number of T1-black holes, white matter lesions demonstrating the central vein sign and paramagnetic rim lesions (all p < 0.05). CONCLUSION: We found correlations between plasma GFAP levels and imaging measures associated with poor clinical outcomes and chronic inflammation in individuals with radiologically isolated syndrome. Plasma GFAP may have prognostic utility in clinical trials and clinical practice.

Delayed Gadolinium Leakage in Ocular Structures on Brain MR Imaging: Prevalence and Associated Factors.

BACKGROUND AND PURPOSE: Gadolinium leakage in ocular structures (GLOS) is characterized by hyperintense signal in the chambers of the eye on FLAIR and has been reported in association with blood-ocular barrier breakdown in patients with ischemic strokes. The underlying mechanism of GLOS remains poorly understood; however, some studies suggest it may be part of a physiologic excretion pathway of gadolinium. This study aimed to determine the prevalence of GLOS in an unselected patient population. MATERIALS AND METHODS: A retrospective analysis was conducted on 439 patients who underwent brain MR imaging within 7 days of receiving a gadolinium-based contrast agent injection for a prior MR imaging study. Clinical, imaging, and laboratory data were collected. Descriptive and logistic regression analyses were performed. RESULTS: GLOS was observed in 26 of 439 patients (6%). The occurrence of GLOS varied with time, with 3 (12%), 14 (54%), 8 (31%), and 1 (4%) patient showing GLOS within 24, 25-72, 73-120, and >120 hours after gadolinium-based contrast agent injection, respectively. Patients with GLOS were older (median age: 72 versus 55 years, P = .001) and had higher median serum creatinine levels (73 versus 64 µmol/L, P = .005) and a lower median estimated glomerular filtration rate (84 versus 101 mL/min/1.73 m2, P < .001). A shorter median time interval between gadolinium-based contrast agent injection and the index brain MR imaging was observed in the group positive for GLOS (62 versus 91 hours, P = .003). Multivariable regression analysis identified the estimated glomerular filtration rate (OR = 0.970; 95% CI, 0.049-0.992; P = .008) and time interval since gadolinium-based contrast agent injection (OR = 0.987; 95% CI, 0.977-0.997; P = .012) as independent factors associated with GLOS. CONCLUSIONS: GLOS was observed in only a small percentage of patients receiving gadolinium-based contrast agent within 7 days before brain MR imaging. This phenomenon was noted in patients with normal findings on brain MR imaging and those with various CNS pathologies, and it was associated with lower estimated glomerular filtration rates and shorter time intervals after gadolinium-based contrast agent injection. While GLOS may be a physiologic gadolinium-based contrast agent excretion pathway, the presence of ocular disease was not formally evaluated in the included population. Awareness of GLOS is nonetheless useful for appropriate radiologic interpretation.

Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis.

BACKGROUND. The central vein sign (CVS) is a proposed MRI biomarker of multiple sclerosis (MS). The impact of gadolinium-based contrast agent (GBCA) administration on CVS evaluation remains poorly investigated. OBJECTIVE. The purpose of this study was to assess the effect of GBCA use on CVS detection and on the diagnostic performance of the CVS for MS using a 3-T FLAIR* sequence. METHODS. This study was a secondary analysis of data from the pilot study for the prospective multicenter Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS), which recruited adults with suspected MS from April 2018 to February 2020. Participants underwent 3-T brain MRI including FLAIR and precontrast and post-contrast echo-planar imaging T2*-weighted acquisitions. Postprocessing was used to generate combined FLAIR and T2*-weighted images (hereafter, FLAIR*). MS diagnoses were established using the 2017 McDonald criteria. Thirty participants (23 women, seven men; mean age, 45 years) were randomly selected from the CAVS-MS pilot study cohort. White matter lesions (WMLs) were marked using FLAIR* images. A single observer, blinded to clinical data and GBCA use, reviewed marked WMLs on FLAIR* images for the presence of the CVS. RESULTS. Thirteen of 30 participants had MS. Across participants, on precontrast FLAIR* imaging, 218 CVS-positive and 517 CVS-negative WMLs were identified; on post-contrast FLAIR* imaging, 269 CVS-positive and 459 CVS-negative WMLs were identified. The fraction of WMLs that were CVS-positive on precontrast and postcontrast images was 48% and 58% in participants with MS and 7% and 10% in participants without MS, respectively. The median patient-level CVS-positivity rate on precontrast and postcontrast images was 43% and 67% for participants with MS and 4% and 8% for participants without MS, respectively. In a binomial model adjusting for MS diagnoses, GBCA use was associated with an increased likelihood of at least one CVS-positive WML (odds ratio, 1.6; p < .001). At a 40% CVS-positivity threshold, the sensitivity of the CVS for MS increased from 62% on precontrast images to 92% on postcontrast images (p = .046). Specificity was not significantly different between precontrast (88%) and postcontrast (82%) images (p = .32). CONCLUSION. GBCA use increased CVS detection on FLAIR* images, thereby increasing the sensitivity of the CVS for MS diagnoses. CLINICAL IMPACT. The postcontrast FLAIR* sequence should be considered for CVS evaluation in future investigational trials and clinical practice.

Quantitative spinal cord MRI and sexual dysfunction in multiple sclerosis.

Background: Sexual dysfunction (SD) is frequently reported in multiple sclerosis (MS) and is likely related to MS-related damage to the spinal cord (SC). Objective: To assess associations between SD and quantitative MRI measures in people with MS (pwMS). Methods: This pilot study included 17 pwMS with SD who completed questionnaires assessing SD, mood, and fatigue. All participants underwent brain, cervical, and thoracic SC-MRI at 3T. Quantitative brain and SC-MRI measures, including brain/SC atrophy, SC lesion count, diffusion-tensor imaging (DTI) indices (fractional anisotropy [FA], mean, perpendicular, parallel diffusivity [MD, λ⊥, λ||]) and magnetization-transfer ratio (MTR) were obtained. Associations between quantitative MRI measures and SD were assessed while controlling for the extent of mood and fatigue symptomatology. Results: Subjects were a mean age of 46.9 years and 29% female. All subjects had self-reported SD (MSISQ-19 = 40.7, SQoL: 55.9) and 65% had a concurrent psychiatric diagnosis. When correlations between SD severity were assessed with individual brain and SC-MRI measures while controlling for psychiatric symptomatology, no associations were found. The only variables showing independent associations with SD were anxiety (p = 0.03), depression (p = 0.05), and fatigue (p = 0.04). Conclusion: We found no correlations between quantitative MRI measures in the brain and SC and severity of SD in pwMS, but psychiatric symptomatology and fatigue severity demonstrated relationships with SD. The multifactorial nature of SD in pwMS mandates a multidisciplinary approach.

Empty Sella in Neuro-Ophthalmology Patients Without Raised Intracranial Pressure.

BACKGROUND: Empty sella often supports a diagnosis of raised intracranial pressure (ICP) but is also seen in normal individuals. This study's objective was to determine the prevalence of empty and partially empty sella in neuro-ophthalmology patients undergoing MRI for indications other than papilledema or raised ICP. METHODS: Consecutive patients without papilledema or suspected raised ICP who underwent brain MRI between August 2017 and May 2021 were included in this study. Sagittal T1 images were evaluated by 2 independent, blinded neuroradiologists who graded the sella using the published criteria (Categories 1-5, with 1 being normal and 5 showing no visible pituitary tissue). Clinical parameters were also collected. RESULTS: A total of 613 patients (309 men; average age 56.69 ± 18.06 years) were included in this study with optic neuropathy as the most common MRI indication. A total of 176 patients had moderate concavity of the pituitary gland (Category 3), 81 had severe concavity (Category 4), and 26 had no visible pituitary tissue (Category 5). Sella appearance was mentioned in 92 patients' radiology reports (15%). There was a statistically significant difference in age between composite Categories 1 and 2 (mean 52.89 ± 18.91; P < 0.001) and composite Categories 4 and 5 (mean 63.41 ± 15.44), but not the other clinical parameters. CONCLUSION: Empty sella is common in neuro-ophthalmology patients without raised ICP; 17.4% of patients have severe concavity or no pituitary tissue visible. An isolated finding of empty or partially empty sella on imaging is therefore of questionable clinical value in this patient population.

A real-world demonstration of machine learning generalizability in the detection of intracranial hemorrhage on head computerized tomography.

Machine learning (ML) holds great promise in transforming healthcare. While published studies have shown the utility of ML models in interpreting medical imaging examinations, these are often evaluated under laboratory settings. The importance of real world evaluation is best illustrated by case studies that have documented successes and failures in the translation of these models into clinical environments. A key prerequisite for the clinical adoption of these technologies is demonstrating generalizable ML model performance under real world circumstances. The purpose of this study was to demonstrate that ML model generalizability is achievable in medical imaging with the detection of intracranial hemorrhage (ICH) on non-contrast computed tomography (CT) scans serving as the use case. An ML model was trained using 21,784 scans from the RSNA Intracranial Hemorrhage CT dataset while generalizability was evaluated using an external validation dataset obtained from our busy trauma and neurosurgical center. This real world external validation dataset consisted of every unenhanced head CT scan (n = 5965) performed in our emergency department in 2019 without exclusion. The model demonstrated an AUC of 98.4%, sensitivity of 98.8%, and specificity of 98.0%, on the test dataset. On external validation, the model demonstrated an AUC of 95.4%, sensitivity of 91.3%, and specificity of 94.1%. Evaluating the ML model using a real world external validation dataset that is temporally and geographically distinct from the training dataset indicates that ML generalizability is achievable in medical imaging applications.

Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS.

OBJECTIVE: The central vein sign (CVS) and "paramagnetic rim lesions" (PRL) are emerging imaging biomarkers in multiple sclerosis (MS) reflecting perivenular demyelination and chronic, smoldering inflammation. The objective of this study was to assess relationships between cognitive impairment (CI) and the CVS and PRL in radiologically isolated syndrome (RIS). METHODS: Twenty-seven adults with RIS underwent 3.0 T MRI of the brain and cervical spinal cord (SC) and cognitive assessment using the minimal assessment of cognitive function in MS battery. The CVS and PRL were assessed in white-matter lesions (WMLs) on T2*-weighted segmented echo-planar magnitude and phase images. Multivariable linear regression evaluated relationships between CI and MRI measures. RESULTS: Global CI was present in 9 (33%) participants with processing speed and visual memory most frequently affected. Most participants (93%) had ⩾ 40% CVS + WML (a threshold distinguishing MS from other WM disorders); 63% demonstrated PRL. Linear regression revealed that CVS + WML predicted performance on verbal memory(ß =-0.024, p = 0.03) while PRL predicted performance on verbal memory (ß = -0.040, p = 0.04) and processing speed (ß = -0.039, p = 0.03). CONCLUSIONS: CI is common in RIS and is associated with markers of perivenular demyelination and chronic inflammation in WML, such as CVS + WML and PRL. A prospective follow-up of this cohort will ascertain the importance of CI, CVS, and PRL as risk factors for conversion from RIS to MS.

Five-year longitudinal changes in quantitative spinal cord MRI in multiple sclerosis.

BACKGROUND: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). OBJECTIVES: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. METHODS: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3-C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. RESULTS: SC-CSA and MTR decreased (p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson's r with FA = -0.23 (p < 0.001); MD = 0.31 (p < 0.001); λ⊥ = 0.34 (p < 0.001); λ|| = -0.12 (p = 0.05), MTR = -0.37 (p < 0.001); SC-CSA = -0.47 (p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated (r = 0.93-0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). CONCLUSION: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.

Computed tomography angiography lightbulb sign: Characteristic enhancement pattern on neck computed tomography angiography in differentiating paraganglioma from schwannoma of the carotid space.

It is important to correctly distinguish paragangliomas from other tumors such as schwannomas in the preoperative assessment of head and neck tumors because paragangliomas have a propensity to bleed profusely during surgery. Therefore, preoperative embolization is often required while with schwannomas preoperative embolization is generally not required. Occasionally, schwannomas can mimic paragangliomas on routine computed tomography and magnetic resonance imaging of the neck. In this study, we retrospectively evaluated the computed tomography angiography of the neck of 10 patients with carotid space tumors. Seven patients had pathologically proven paraganglioma while three patients had schwannomas. We describe the "computed tomography angiography lightbulb sign" as avid homogeneous enhancement in the arterial phase which can accurately distinguish these entities.

High-Resolution MRI Vessel Wall Imaging in Acute Aneurysmal Subarachnoid Hemorrhage : Spatiotemporal Pattern and Clinicoradiologic Implications.

PURPOSE: The spatiotemporal pattern of vessel wall changes was investigated on two time point magnetic resonance images (MRI) in patients with aneurysmal subarachnoid hemorrhages (aSAH) and its association with clinicoradiologic severity score and delayed cerebral ischemia (DCI) was analyzed. METHODS: A total of 32 prospectively enrolled patients with aSAH (mean age 56.94 years; 9 male and 23 female) underwent vessel wall imaging (VWI) MRI. Of the patients 20 completed two time point MRIs early and late during the admission, 10 patients only had early MRI and 2 patients only had late MRI. Timing of early MRI had a mean of 2.5 days (range 1-6 days) and late MRI had a mean of 10.5 days (range 7-16 days) from time of admission. Spatiotemporal pattern of vessel wall enhancement (VWE), vasospasm, diffusion-weighted imaging (DWI) lesion burden (grade 0-III) and infarcts were analyzed against the clinicoradiologic severity score (high-risk: vasograde red and yellow, low-risk: vasograde green) and DCI. RESULTS: On the early MRI, mild VWE alone was significantly more frequent in the high-risk group (36.7% versus 20.0%; P = 0.024). On the late MRI, vasospasm was significantly more frequent in the high-risk group (27.2% versus 4.5%; P = 0.022). Vasospasm infrequently showed mild VWE (6.67% on early MRI and 9.09% on late MRI). Both mild VWE alone on early MRI and on late MRI were significantly associated with development of DCI during the admission (P = 0.034 and P = 0.035, respectively). CONCLUSION: Mild VWE on early MRI and vasospasm on late MRI were significantly more prevalent in high-risk and DCI patients suggesting VWI might enable imaging of early neuroinflammatory changes which are part of the pathomechanism of vasospasm and DCI.

Delayed presentation of cerebral schistosomiasis presenting as a tumor-like brain lesion.

Schistosomiasis is the second most common parasitic infection worldwide. North America is a nonendemic area. However, there are occasional case reports among travelers and immigrants from endemic regions. We describe a case of a 55-year-old Canadian woman who presented with first episode of seizure. Her magnetic resonance imaging scan revealed a mass-like lesion involving the left anterior temporal lobe. The lesion showed T1 hypo- and T2 hyperintense with perilesional brain edema. On post-gadolinium-enhanced T1-weighted sequence, the lesion showed multiple small nodular and linear enhancements, also called an "arborized" appearance. Initially, the lesion was thought to be a malignant tumor. She underwent left anterior temporal lobe resection. Histologic examination showed parasitic eggs with a characteristic lateral spine consistent with Schistosoma mansoni infection. Upon subsequent questioning, it was revealed that the patient lived in Ghana from the ages of 8-10 years and she visited Ghana again 10 years prior for two weeks. She recalled swimming in beaches and rivers. Latent disease, as in this case with presentation, many years or decades after presumed exposure is rare but has been reported. Characteristic magnetic resonance imaging findings may suggest the diagnosis and facilitate noninvasive work-up.

Clinical pitfall: false-positive aquaporin-4 IgG leading to misdiagnosis of neuromyelitis optica spectrum disorder in patient with spinal arteriovenous fistula.

INTRODUCTION: We report the cases of a 68-year-old male with a filum terminale arteriovenous fistula (AVF) who was initially misdiagnosed with neuromyelitis optica spectrum disorder (NMOSD) based on imaging findings and false-positive aquaporin-4 IgG (AQP4-IgG). CASE PRESENTATION: A 68-year-old male presented with slowly progressive weakness and numbness in his bilateral lower extremities. He was initially diagnosed with NMOSD and treated with immunosuppressive therapy based on findings of extensive spinal cord edema on magnetic resonance imaging (MRI) and initial negative spinal angiography as well as positive AQP4-IgG. Despite immunosuppressive treatment, his symptoms progressed slowly. He repeated MRI that showed persistent abnormal signal within the spinal cord. Second spinal angiography revealed filum terminale dural arteriovenous fistula (AVF). Finally, he underwent surgical disconnection of the fistula. Repeated AQP-IgG was reported negative. DISCUSSION: Although NMOSD and spinal AVFs can share imaging findings on spinal cord MRI, typical clinical features of each disorder are distinct. Identification of AQP4-IgG is the hallmark to confirm a clinical diagnosis of NMOSD; however, different assays can vary in sensitivity and specificity. Although it is rare, false positives can occur especially at low titers. A misdiagnosis of NMOSD and delayed diagnosis of spinal AVF had significant clinical implications because the treatment of spinal AVF is surgical disconnection or endovascular embolization, whereas the treatment for NMOSD includes long-term immunosuppressive therapy. Clinicians should be aware of the potential technical issues in detecting AQP4-IgG especially in the context of patients with atypical presentations for NMOSD.

Imaging Markers for Monitoring Disease Activity in Multiple Sclerosis.

OPINION STATEMENT: Multiple sclerosis (MS) is an immune-mediated disease affecting the central nervous system (CNS). Magnetic resonance imaging (MRI) has long been recognized as an important tool in the diagnosis of MS. It is increasingly recognized that in addition to its role in diagnosis, MRI can play a key role as a noninvasive tool for prognostication, disease monitoring, assessment of treatment efficacy, and safety monitoring of disease-modifying therapies (DMTs). A confluence of factors, including increased availability of MRI, development of improved MRI techniques, and increased availability of DMTs have contributed to the expanding role of MRI in MS clinical care. As the clinical use of MRI in MS expands, it is important that MRI protocols amongst clinical centers are standardized. Here, we summarize recent evidence supporting the use of MRI in clinical practice, summarize various clinical guidelines and recommendations for the use of MRI in MS disease monitoring, and provide our recommendations for standardized MRI protocols.