Background
Growing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and ...long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects. Additionally, we analyzed the cortical features and the association with inflammatory biomarkers in the cerebrospinal fluid (CSF) and plasma.
Materials and methods
Thirty-three patients were selected from a prospective cross-sectional study cohort during the ongoing pandemic (August 2020–April 2021) at the university hospitals of Basel and Zurich (Switzerland). The group included patients with different neurological symptom severity (Class I: nearly asymptomatic/mild symptoms, II: moderate symptoms, III: severe symptoms). Thirty-three healthy age and sex-matched subjects that underwent the same MRI protocol served as controls. For each anatomical T1w MPRAGE image, regional cortical gray matter volume, thickness, and surface area were computed with FreeSurfer. Using a linear regression model, cortical measures were compared between groups (patients vs. controls; Class I vs. II–III), with age, sex, MRI magnetic field strength, and total intracranial volume/mean thickness/total surface area as covariates. In a subgroup of patients, the association between cortical features and clinical parameters was assessed using partial correlation adjusting for the same covariates.
P
-values were corrected using a false discovery rate (FDR).
Results
Our findings revealed a lower cortical volume in COVID-19 patients’ orbitofrontal, frontal, and cingulate regions than in controls (
p
< 0.05). Regional gray matter volume and thickness decreases were negatively associated with CSF total protein levels, the CSF/blood-albumin ratio, and CSF EN-RAGE levels.
Conclusion
Our data suggest that viral-triggered inflammation leads to neurotoxic damage in some cortical areas during the acute phase of a COVID-19 infection in patients with neurological symptoms.
Abstract
Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, ...posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.
To assess the effects of a change from free text reporting to structured reporting on resident reports, the proofreading workload and report turnaround times in the neuroradiology daily routine.
Our ...neuroradiology section introduced structured reporting templates in July 2019. Reports dictated by residents during dayshifts from January 2019 to March 2020 were retrospectively assessed using quantitative parameters from report comparison. Through automatic analysis of text-string differences between report states (i.e. draft, preliminary and final report), Jaccard similarities and edit distances of reports following read-out sessions as well as after report sign-off were calculated. Furthermore, turnaround times until preliminary and final report availability to clinicians were investigated. Parameters were visualized as trending line graphs and statistically compared between reporting standards.
Three thousand five hundred thirty-eight reports were included into analysis. Mean Jaccard similarity of resident drafts and staff-reviewed final reports increased from 0.53 ± 0.37 to 0.79 ± 0.22 after the introduction of structured reporting (p < .001). Both mean overall edits on draft reports by residents following read-out sessions (0.30 ± 0.45 vs. 0.09 ± 0.29; p < .001) and by staff radiologists during report sign-off (0.17 ± 0.28 vs. 0.12 ± 0.23, p < .001) decreased. With structured reporting, mean turnaround time until preliminary report availability to clinicians decreased by 20.7 minutes (246.9 ± 207.0 vs. 226.2 ± 224.9; p < .001). Similarly, final reports were available 35.0 minutes faster on average (558.05 ± 15.1 vs. 523.0 ± 497.3; p = .002).
Structured reporting is beneficial in the neuroradiology daily routine, as resident drafts require fewer edits in the report review process. This reduction in proofreading workload is likely responsible for lower report turnaround times.
Objective
Intrathecal Immunoglobulin M synthesis (IgMIntrathecal Fraction (IF)+) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple ...sclerosis (MS). We investigated whether IgMIF+ is associated with spinal cord manifestation and higher neuroaxonal damage in early MS.
Methods
In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non‐spinal clinical syndrome (2) spinal vs cerebral T2‐weighted (T2w) and (3) contrast‐enhancing (CE) lesion counts with IgGIF+ (vs IgGIF−) or IgMIF+ (vs IgMIF−) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgGIF and IgMIF (>0% vs 0%, respectively): (1) OCGB−/IgGIF−/IgMIF−; (2) OCGB+/IgGIF−/IgMIF−; (3) OCGB+/IgGIF+/IgMIF−; and (4) OCGB+/IgGIF+/IgMIF+. Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters.
Results
Patients with a spinal syndrome had a 8.36‐fold higher odds of IgMIF+ (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgMIF+ (but not of IgGIF+); this was not the case for cerebral lesions. OCGB+/IgGIF+/IgMIF+ category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01).
Interpretation
Intrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022;91:814–820
The optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). ...Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort.
MAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the fifth area of the CNS. A risk assessment analysis and the performance of the different DIS criteria were analyzed using the diagnosis of MS according to the 2017 McDonald criteria as the primary outcome and new T2 lesions and/or a second relapse as the secondary outcome.
We included 157 patients with CIS from 5 MAGNIMS centers; 60/157 (38.2%) patients presented with optic neuritis. Optic nerve involvement on ON-MRI was found in 40.2% patients at study entry and in 72.5% of those with optic neuritis.At follow-up (mean 27.9 months, SD 14.5), 111/157 patients (70.7%) were diagnosed with MS according to the 2017 McDonald criteria. Fulfilling either 2017 DIS or any modified DIS criteria conferred a similar high risk for reaching primary and secondary outcomes. The modified DIS criteria had higher sensitivity (92.5% with ON-MRI vs 88.2%), but slightly lower specificity (80.0% with GCIPL IEA ≥4 μm vs 82.2%), with overall similar accuracy (86.6% with ON-MRI vs 86.5%) than 2017 DIS criteria. Consistent results were found for secondary outcomes.
In patients with CIS, the presence of an optic nerve lesion defined by MRI, OCT, or VEP is frequently detected, especially when presenting with optic neuritis. Our study supports the addition of the optic nerve as a fifth topography to fulfill DIS criteria.
Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients ...experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS). Last, we explored the value of cross-sectional brain and spinal cord volumetric measurements in predicting PIRA.
From an ongoing multicentric cohort study, we selected patients with MS with (1) availability of a susceptibility-based MRI scan and (2) regular clinical and conventional MRI follow-up in the 4 years before the susceptibility-based MRI. Comparisons in spinal cord atrophy rates (explored with linear mixed-effect models) and PRL count (explored with negative binomial regression models) were performed between: (1) relapsing-remitting (RRMS) and PMS phenotypes and (2) patients experiencing PIRA and patients without confirmed disability accumulation (CDA) during follow-up (both considering the entire cohort and the subgroup of patients with RRMS). Associations between baseline MRI volumetric measurements and time to PIRA were explored with multivariable Cox regression analyses.
In total, 445 patients with MS (64.9% female; mean SD age at baseline 45.0 11.4 years; 11.2% with PMS) were enrolled. Compared with patients with RRMS, those with PMS had accelerated cervical cord atrophy (mean difference in annual percentage volume change MD-APC -1.41;
= 0.004) and higher PRL load (incidence rate ratio IRR 1.93;
= 0.005). Increased spinal cord atrophy (MD-APC -1.39;
= 0.0008) and PRL burden (IRR 1.95;
= 0.0008) were measured in patients with PIRA compared with patients without CDA; such differences were also confirmed when restricting the analysis to patients with RRMS. Baseline volumetric measurements of the cervical cord, whole brain, and cerebral cortex significantly predicted time to PIRA (all
≤ 0.002).
Our results show that PIRA is associated with both increased spinal cord atrophy and PRL burden, and this association is evident also in patients with RRMS. These findings further point to the need to develop targeted treatment strategies for PIRA to prevent irreversible neuroaxonal loss and optimize long-term outcomes of patients with MS.
A change in MRI hardware impacts brain volume measurements. The aim of this study was to use MRI data from multiple sclerosis (MS) patients and healthy control subjects (HCs) to statistically model ...how to adjust brain atrophy measures in MS patients after a major scanner upgrade.
We scanned 20 MS patients and 26 HCs before and three months after a major scanner upgrade (1.5 T Siemens Healthineers Magnetom Avanto to 3 T Siemens Healthineers Skyra Fit). The patient group also underwent standardized serial MRIs before and after the scanner change. Percentage whole brain volume changes (PBVC) measured by Structural Image Evaluation using Normalization of Atrophy (SIENA) in the HCs was used to estimate a corrective term based on a linear model. The factor was internally validated in HCs, and then applied to the MS group.
Mean PBVC during the scanner change was higher in MS than HCs (-4.1 ± 0.8 % versus −3.4 ± 0.6 %). A fixed corrective term of 3.4 (95% confidence interval: 3.13–3.67)% was estimated based on the observed average changes in HCs. Age and gender did not have a significant influence on this corrective term. After adjustment, a linear mixed effects model showed that the brain atrophy measures in MS during the scanner upgrade were not anymore associated with the scanner type (old vs new scanner; p = 0.29).
A scanner change affects brain atrophy measures in longitudinal cohorts. The inclusion of a corrective term based on changes observed in HCs helps to adjust for the known and unknown factors associated with a scanner upgrade on a group level.
In the work-up of patients presenting with a clinically isolated syndrome (CIS), 3T MRI might offer a higher lesion detection than 1.5T, but it remains unclear whether this affects the fulfilment of ...the diagnostic criteria for multiple sclerosis (MS).
We recruited 66 patients with CIS within 6 months from symptom onset and 26 healthy controls in 6 MS centers. All participants underwent 1.5T and 3T brain and spinal cord MRI at baseline according to local optimized protocols and the MAGNIMS guidelines. Patients who had not converted to MS during follow-up received repeat brain MRI at 3-6 months and 12-15 months. The number of lesions per anatomical region was scored by 3 raters in consensus. Criteria for dissemination in space (DIS) and dissemination in time (DIT) were determined according to the 2017 revisions of the McDonald criteria.
Three-Tesla MRI detected 15% more T2 brain lesions compared to 1.5T (
0.001), which was driven by an increase in baseline detection of periventricular (12%,
0.015), (juxta)cortical (21%,
0.005), and deep white matter lesions (21%,
0.001). The detection rate of spinal cord lesions and gadolinium-enhancing lesions did not differ between field strengths. Three-Tesla MRI did not lead to a higher number of patients fulfilling the criteria for DIS or DIT, or subsequent diagnosis of MS, at any of the 3 time points.
Scanning at 3T does not influence the diagnosis of MS according to McDonald diagnostic criteria.
Accurate detection of cerebral microbleeds (CMBs) on susceptibility-weighted (SWI) magnetic resonance imaging (MRI) is crucial for the characterization of many neurological diseases. Low-field MRI ...offers greater access at lower costs and lower infrastructural requirements, but also reduced susceptibility artifacts. We therefore evaluated the diagnostic performance for the detection of CMBs of a whole-body low-field MRI in a prospective cohort of suspected stroke patients compared to an established 1.5 T MRI.
A prospective scanner comparison was performed including 27 patients, of whom 3 patients were excluded because the time interval was >1 h between acquisition of the 1.5 T and 0.55 T MRI. All SWI sequences were assessed for the presence, number, and localization of CMBs by two neuroradiologists and additionally underwent a Likert rating with respect to image impression, resolution, noise, contrast, and diagnostic quality.
A total of 24 patients with a mean age of 74 years were included (11 female). Both readers detected the same number and localization of microbleeds in all 24 datasets (sensitivity and specificity 100%; interreader reliability ϰ = 1), with CMBs only being observed in 12 patients. Likert ratings of the sequences at both field strengths regarding overall image quality and diagnostic quality did not reveal significant differences between the 0.55 T and 1.5 T sequences (
= 0.942;
= 0.672). For resolution and contrast, the 0.55 T sequences were even significantly superior (
< 0.0001;
< 0.0003), whereas the 1.5 T sequences were significantly superior (
< 0.0001) regarding noise.
Low-field MRI at 0.55 T may have similar accuracy as 1.5 T scanners for the detection of microbleeds and thus may have great potential as a resource-efficient alternative in the near future.
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