Central Vein Sign Research Articles

Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis.

The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications. In this workshop, experts were tasked with reviewing the current literature and proposing a series of consensus statements, which were reviewed and approved by the NAIMS. In this review and consensus paper, we provide background on the use of 7T MRI in MS research, highlighting this technology's promise for identification and quantification of aspects of MS pathology that are more difficult to visualize with lower-field MRI, such as grey matter lesions, paramagnetic rim lesions, leptomeningeal enhancement and the central vein sign. We also review the promise of 7T MRI to study metabolic and functional changes to the brain in MS. The NAIMS provides a series of consensus statements regarding what is currently known about the use of 7T MRI in MS, and additional statements intended to provide guidance as to what work is necessary going forward to accelerate 7T MRI research in MS and translate this technology for use in clinical practice and clinical trials. This includes guidance on technical development, proposals for a universal acquisition protocol and suggestions for research geared towards assessing the utility of 7T MRI to improve MS diagnostics, prognostics and therapeutic efficacy monitoring. The NAIMS expects that this article will provide a roadmap for future use of 7T MRI in MS.

Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis

Background: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) are a diagnostic biomarker in multiple sclerosis (MS). The central vein sign (CVS) is an imaging biomarker for MS that may improve diagnostic accuracy. Objectives: The objective of the study is to examine the diagnostic performance of simplified CVS methods in comparison to OCB in participants with clinical or radiological suspicion for MS. Methods: Participants from the CentrAl Vein Sign in MS (CAVS-MS) pilot study with CSF testing were included. Select-3 and Select-6 (counting up to three or six CVS+ lesions per scan) were rated on post-gadolinium FLAIR* images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for Select-3, Select-6, OCB, and combinations thereof were calculated for MS diagnosis at baseline and at 12 months. Results: Of 53 participants, 25 were OCB+. At baseline, sensitivity for MS diagnosis was 0.75 for OCB, 0.83 for Select-3, and 0.71 for Select-6. Specificity for MS diagnosis was 0.76 for OCB, 0.48 for Select-3, and 0.86 for Select-6. At 12 months, PPV for MS diagnosis was 0.95 for Select-6 and 1.00 for Select-6 with OCB+ status. Discussion: Results suggest similar diagnostic performance of simplified CVS methods and OCB. Ongoing studies will refine whether CVS could be used in replacement or in conjunction with OCB.

Typical and Emerging Diagnostic MRI Features in Multiple Sclerosis.

Magnetic resonance imaging (MRI) stands as the most sensitive paraclinical technique for detecting the demyelinating lesions characteristic of multiple sclerosis (MS). Consequently, MRI plays a pivotal role in establishing an accurate and timely diagnosis of the disease, ultimately based on the application of the McDonald criteria. Early diagnosis is particularly important as it facilitates the prompt initiation of disease-modifying treatments, deemed most effective during the initial phases of MS. This review article examines the recommended standardized MRI protocol, as well as the classic imaging features of MS in the brain, optic nerve, and spinal cord, capable of discriminating, in most cases, MS from other disorders that can mimic this disease. Additionally, novel MR imaging findings, such as the central vein sign and paramagnetic rim lesion, which have been proposed as new imaging biomarkers to enhance diagnostic specificity for MS, are also discussed. These emerging features are likely to be incorporated in the future iterations of the McDonald criteria, and therefore, radiologists should be familiar with their appearance and with the optimal MRI protocols required for their detection.

Paramagnetic rim lesions as a biomarker to discriminate between multiple sclerosis and cerebral small vessel disease.

Multiple sclerosis (MS) and Cerebral Small Vessel Disease (CSVD) exhibit some similarities in Magnetic resonance imaging (MRI), potentially leading to misdiagnosis and delaying effective treatment windows. It is unclear whether CSVD can be detected with Paramagnetic Rim Lesions (PRL), which is special in MS. We aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD. In this retrospective study, 49 MS and 104 CSVD patients underwent 3.0 T Magnetic resonance imaging (MRI). Visual assessment of 37 MS patients and 89 CSVD patients with or without lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), central vein sign (CVS), and PRL. The distribution and number of PRL were then counted. Our study found that PRL was detected in over half of the MS patients but was entirely absent in CSVD patients (78.38 vs. 0%, p < 0.0001), and PRL showed high specificity with good sensitivity in discriminating between MS and CSVD (sensitivity: 78.38%, specificity: 100%, AUC: 0.96). Paramagnetic Rim Lesions is a special imaging feature in MS, absent in CSVD. Detection of PRL can be very helpful in the clinical management of MS and CSVD.

Central vein sign and trigeminal lesions of multiple sclerosis visualised by 7T MRI

BackgroundAlthough trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site...

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

Central Vein Sign and Paramagnetic Rim Lesions: Susceptibility Changes in Brain Tissues and Their Implications for the Study of Multiple Sclerosis Pathology.

Multiple sclerosis (MS) is the most common acquired inflammatory and demyelinating disease in adults. The conventional diagnostic of MS and the follow-up of inflammatory activity is based on the detection of hyperintense foci in T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and lesions with brain-blood barrier (BBB) disruption in the central nervous system (CNS) parenchyma. However, T2/FLAIR hyperintense lesions are not specific to MS and the MS pathology and inflammatory processes go far beyond focal lesions and can be independent of BBB disruption. MRI techniques based on the magnetic susceptibility properties of the tissue, such as T2*, susceptibility-weighted images (SWI), and quantitative susceptibility mapping (QSM) offer tools for advanced MS diagnostic, follow-up, and the assessment of more detailed features of MS dynamic pathology. Susceptibility-weighted techniques are sensitive to the paramagnetic components of biological tissues, such as deoxyhemoglobin. This capability enables the visualization of brain parenchymal veins. Consequently, it presents an opportunity to identify veins within the core of multiple sclerosis (MS) lesions, thereby affirming their venocentric characteristics. This advancement significantly enhances the accuracy of the differential diagnostic process. Another important paramagnetic component in biological tissues is iron. In MS, the dynamic trafficking of iron between different cells, such as oligodendrocytes, astrocytes, and microglia, enables the study of different stages of demyelination and remyelination. Furthermore, the accumulation of iron in activated microglia serves as an indicator of latent inflammatory activity in chronic MS lesions, termed paramagnetic rim lesions (PRLs). PRLs have been correlated with disease progression and degenerative processes, underscoring their significance in MS pathology. This review will elucidate the underlying physical principles of magnetic susceptibility and their implications for the formation and interpretation of T2*, SWI, and QSM sequences. Additionally, it will explore their applications in multiple sclerosis (MS), particularly in detecting the central vein sign (CVS) and PRLs, and assessing iron metabolism. Furthermore, the review will discuss their role in advancing early and precise MS diagnosis and prognostic evaluation, as well as their utility in studying chronic active inflammation and degenerative processes.

Enlarged perivascular spaces are associated with brain microangiopathy and aging in multiple sclerosis

Background: Growing evidence links brain-MRI enlarged perivascular spaces (EPVS) and multiple sclerosis (MS), but their role remains unclear. Objective: This study aimed to investigate the cross-sectional associations of EPVS with several neuroinflammatory and neurodegenerative features in a large multicentric-MS cohort. Methods: In total, 207 patients underwent 3T axial-T2-weighted brain-MRI for EPVS assessment (EPVS dichotomized into high/low according to ⩾ 2/< 2 rating categories). MRI biomarkers included brain-predicted age and brain-predicted age difference (brain-PAD), central vein sign (CVS)-positive lesion percentage (CVS%), paramagnetic rim and cortical lesions, T2-lesion load, and brain volumetry. The variable relative importance for EPVS-category prediction was explored using a classification random forest approach. Results: High EPVS patients were older (49 vs 44 years, p = 0.003), had ⩾ 1 vascular risk factors (VRFs; p = 0.005), lower CVS% (67% vs 78%, p < 0.001), reduced brain volumes (whole brain: 0.63 vs 0.73, p = 0.01; gray matter: 0.36 vs 0.40; p = 0.002), and older brain-predicted age (58 vs 50 years, p < 0.001). No differences were found for neuroinflammatory markers. After adjusting for age and VFRs (multivariate analyses), the high EPVS category correlated with lower CVS% (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96–0.99; p = 0.02), lower whole brain (OR = 0.01, 95% CI = 0.0003–0.5; p = 0.02), gray matter (OR = 0.0004, 95% CI = 0.0000004–0.4; p = 0.03) volumes, and higher brain-PAD (OR = 1.05, 95% CI = 1.01–1.09; p = 0.02). Random forest identified brain-PAD as the most important predictor of high EPVS. Conclusion: EPVS in MS likely reflect microangiopathic disease rather than neuroinflammation, potentially contributing to accelerated neurodegeneration.

Clinical correlation between disease progression and central vein sign in pediatric onset multiple sclerosis: A binational study

BackgroundThe central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered. ObjectivesTo investigate the appearance of CVS and its correlation with POMS disease progression. MethodsOne hundred fifty-six POMS from two MS centers in Israel and Czech Republic MS centers were followed for five years. Patient assessment was performed by the Expanded Disability Status Scale (EDSS) and Annual Relapse Rate (ARR). Patients in whom at least 40 % of brain MRI lesions had CVS (“rule of 40”) were determined as CVS-positive. ResultsThe total group of POMS consisted of 96 CVS-negative (61.5 %), aged 14.6 ± 1.9 years, EDSS 2.0, 75 % Interquartile Range (IQR) 1.0–3.0, disease duration (DD) 6.28 ± 0.38 years, and 60 CVS-positive (38.5 %), aged 15.1 ± 0.3 years, EDSS 2.0, IQR 1.5–3.0, DD 5.62 ± 0.13 years, were analyzed. After a three and five-year follow-up, the CVS-positive patients had higher EDSS scores than those who were CVS-negative, 2.0, IQR 1.0–2.5, vs 1.0, IQR 1.0–2.0, (p = 0.009) and 2.0, IQR 1.0–3.25 vs 1.0, IQR 1.0–2.0, (p = 0.0003), respectively. Patients with CVS-positive POMS were characterized by a significantly higher ARR (0.78 ± 0.08 vs 0.57 ± 0.04, p = 0.002). These results were confirmed in subgroups of Disease Modifying Treatments (DMT) untreated and treated patients. ConclusionCVS-positive POMS is characterized by higher disability progression than CVS-negative, indicating the importance of CVS in disease pathogenesis.

The central vein sign in the diagnosis of multiple sclerosis

Objective: to determine the specificity and sensitivity of the central vein sign (CVS) for the diagnosis of multiple sclerosis (MS). Material and methods. We analyzed 76 patients. The main group consisted of 40 patients with a confirmed diagnosis of MS according to the McDonald criteria, 2017. The comparison group included 20 patients with migraine and 16 patients with cerebral microangiopathy. All patients underwent a standardized MRI scan of the brain, including 3D FLAIR and SWI modes. The total number of T2/FLAIR hyperintense lesions in the brain and the number of lesions with CVS were calculated. Results. In the group of MS patients, the total and relative number of lesions with CVS was higher than in the comparison group (p&lt;0.001). The 40% lesion rule had a sensitivity of 97.5% and a specificity of 94.4%. The sensitivity of the 3-lesion rule was 92.5% and the specificity 66.7%. The use of the 5-lesion rule had a sensitivity of 75% and a specificity of 83.7%. Conclusion. The data obtained indicate a significant diagnostic role for SCV in MS. The use of the 5-lesion rule provides high sensitivity and specificity with relative ease of use.

Serum Glial Fibrillary Acidic Protein as a Predictive Marker for Developing Central Vein Sign Lesions in Radiologically Isolated Syndrome (P7-6.002)

Serum Glial Fibrillary Acidic Protein as a Predictive Marker for Developing Central Vein Sign Lesions in Radiologically Isolated Syndrome (P7-6.002)

A central vein sign in the magnetic resonance diagnosing of multiple sclerosis

Background. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease, which is characterized by the inevitable disability of patients in the long term, which determines the relevance of this problem. Currently, active improvements are being made in the methods of diagnosing multiple sclerosis, which include the use of the central vein sign in magnetic resonance imaging (MRI) as a neuroimaging biomarker of MS with high sensitivity and specificity.Aim of study. Determination of the possibility of assessing the central vein sign (CVS) according to MRI data as a potential diagnostic biomarker of MS.Object and methods. An open single-center prospective study of brain MR data was conducted in 55 patients with a verified diagnosis of MS (EDSS 1.0-6.5) aged 19 to 72 years. MR-images were obtained on a tomograph with a magnetic field induction force of 3.0 T. Patients underwent MRI of the brain according to the standard protocol: T2-VI, FLAIR, T1-VI (before and after administration of contrast agent), SWI. A comprehensive statistical analysis and evaluation of the obtained MRI data was performed using the Statistica 12 program.Result. During the evaluation of MR-tomograms, all patients with a verified diagnosis in the foci of MS were found to have CVS. In 14.5 % of patients, CVS was detected in 10-30 % of foci, in 61.8 % of patients in 30-60 %, in 23.6 % of patients, from 60 to 95 % was detected. Accordingly, 52.7 % of patients overcame the threshold value of 45 % required for the differential diagnosis of MS from other conditions.Conclusion. The use of CVS in MRI helps to solve the problem of differential diagnosis of MS from other demyelinating diseases when using its threshold criterion – the percentage of foci containing central veins.

Emerging imaging markers in radiologically isolated syndrome: implications for earlier treatment initiation.

The presence of central nervous system lesions fulfilling the criteria of dissemination in space and time on MRI leads to the diagnosis of a radiologically isolated syndrome (RIS), which may be an early sign of multiple sclerosis (MS). However, some patients who do not fulfill the necessary criteria for RIS still evolve to MS, and some T2 hyperintensities that resemble demyelinating lesions may originate from mimics. In light of the recent recognition of the efficacy of disease-modifying therapy (DMT) in RIS, it is relevant to consider additional imaging features that are more specific of MS. We performed a narrative review on cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL) in patients with RIS. In previous RIS studies, the reported prevalence of CLs ranges between 20.0 and 40.0%, CVS + white matter lesions (WMLs) between 87.0 and 93.0% and PRLs between 26.7 and 63.0%. Overall, these imaging findings appear to be frequent in RIS cohorts, although not consistently taken into account in previous studies. The search for CLs, CVS + WML and PRLs in RIS patients could lead to earlier identification of patients who will evolve to MS and benefit from DMTs.

The diagnostic value of the central vein sign in radiologically isolated syndrome.

The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS. Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions. 180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis. This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS.

Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

The central vein sign in the differential diagnosis of multiple sclerosis

To carry out a clinical and radiological assessment of the central vein sign (CVS) as a diagnostic marker for multiple sclerosis (MS) and other demyelinating and non-demyelinating diseases with focal brain damage, using clinical and laboratory examination data, as well as MRI. The results of clinical and neuroradiological examination of 107 patients diagnosed with MS or with other diseases accompanied by focal brain damage according to MRI data were analyzed. CVS is a sensitive but low-specific diagnostic marker of MS. According to our data, the sensitivity and specificity of 40 and 50% of the threshold of perivenular lesions in the diagnosis of MS are the same and amount to 100% and 39.4%, respectively. Neither the type of MS course, nor the severity of the course, nor the intake of DMT (disease modifying treatment), affect the proportion of foci with CVS. The spread of the proportion of foci with CVS in patients with MS was 60-100%. The proportion of foci with CVS is below 40 and 50% of the threshold in patients with demyelinating and non-demyelinating diseases (NMOSD, migraine, systemic lupus erythematosus, Susak disease, CLIPPERS), which allows for differential diagnosis with MS. The proportion of foci with CVS comparable to MS in patients with acute disseminated encephalomyelitis, small vessel disease, as well as in patients with radiologically isolated syndrome does not allow using this symptom in the differential diagnosis of these conditions. The use of CVS as a diagnostic marker of MS is possible only in combination with the already existing diagnostic criteria of MS.

Central Vein Sign in Multiple Sclerosis: A Comparison Study of the Diagnostic Performance of 3T versus 7T MRI.

An early and accurate diagnosis of multiple sclerosis remains challenging in clinical neurology. Established diagnostic methods have less than desirable sensitivity and specificity. An accurate, noninvasive diagnostic test for MS could have a major impact on diagnostic criteria. We compared the frequency of detection of the central vein sign (CVS) in white matter lesions of MS and controls on 7T T2*-weighted and SWI to 3T SWI. Additionally, we assessed the diagnostic performance of 7T T2*, 7T SWI, and 3T SWI for MS. A retrospective case-control study was performed of patients with MS having both 7T MRI and 3T MRI. A control group of patients without MS was selected. Diagnosis of MS was established by board-certified neurologists with fellowship training in autoimmune neurology in line with the 2017 McDonald criteria. Percentage of lesions with a CVS was blindly measured for each technique. Diagnostic performance was computed by sensitivity, specificity, and positive and negative likelihood ratios (LRs). Sixty-one patients with MS (903 lesions) and 39 controls (1088 lesions) were included. 7T T2* showed significantly more CVS (87%) than both 7T SWI (73%) and 3T SWI (31%) (all P < .001). CVS was identified in the control group in ≤6% of lesions on all sequences. Using a threshold of >40% of lesions with CVS on 7T T2* and >15% on 7T SWI, both sequences had an accuracy = 100%, sensitivity = 100%, specificity = 100%, infinite positive LR, and zero negative LR. Using an optimal threshold of >12%, 3T SWI had an accuracy = 96.0%, sensitivity = 93.4%, specificity = 100%, infinite positive LR, and negative LR = 0.066. 7T MRI had 100% sensitivity and specificity for the diagnosis of MS and is superior to 3T. Future revisions to MS diagnostic criteria may consider recommendations for 7T MRI and inclusion of CVS as a biomarker.

Susceptibility-weighted image features in AQP4-negative-NMOSD versus MS

ObjectiveTo characterize the susceptibility-weighted image (SWI) features including paramagnetic rim and nodular lesions with signal intensity changes and central vein sign (CVS) associated with aquaporin 4 (AQP4)-immunoglobulin G (IgG)-negative neuromyelitis optica spectrum disorder (NMOSD), and explore whether they can be used as potential imaging biomarkers for differentiating multiple sclerosis (MS) from this disorder. MethodsWe prospectively recruited NMOSD with AQP4-IgG-negative (AQP4- NMOSD) and IgG-positive (AQP4+ NMOSD), and MS subjects from the Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE) project (NCT0410683) between 2019 and 2021. The SWI features including paramagnetic rim and nodular lesions with signal intensity changes and CVS were analyzed and compared among groups, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for distinguishing MS from AQP4- NMOSD. ResultsWe enrolled a total of 160 consecutive patients (22 AQP4- NMOSD, 65 AQP4+ NMOSD, and 73 MS). We observed paramagnetic rim lesion (0/120 lesions, 0 %) and nodular (1/120, 1 %) lesions with hypointense signals on SWI in the AQP4- NMOSD group. These characteristics were similar to those recorded from AQP4+ NMOSD patients (rim: 0/369 lesions, 0 %, P = 1.000; nodular: 10/369 lesions, 2.7 %, P = 1.000), but differed significantly from those observed in the MS group (rim: 162/1665 lesions, 9.7 %, P<0.001; nodular: 392/1665 lesions, 23.5 %, P < 0.001). AQP4- NMOSD patients had fewer average CVS+ rate (12 %) than MS patients (46 %, p<0.001), similar to AQP4+ NMOSD (13 %, p = 1.000). The SWI imaging features denoting lesions with paramagnetic rim or nodular hypointense SWI signals showed 90.4 % sensitivity, 95.5 % specificity, 98.5 % PPV, and 75 % NPV, and the criteria with≥3 CVS lesions showed sensitivity of 91.8 %, specificity of 90.9 %%, PPV of 97.1 %, and NPV of 76.9 % in distinguishing MS from AQP4- NMOSD. DiscussionThe SWI imaging features including lesions with paramagnetic rim or nodular hypointense SWI signals and 3 CVS lesions carries useful information in distinguishing MS from AQP4- NMOSD.

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

There are no specific, evidence-based recommendations for the management of individuals with radiologically isolated syndrome. Imaging and blood biomarkers may have prognostic utility. 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. 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. 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). 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.