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Background Technical improvements in magnetic resonance imaging (MRI) acquisition, such as higher field strength and optimized sequences, lead to better multiple sclerosis (MS) lesion detection and characterization. Multiplication of 3D-FLAIR with 3D-T2 sequences (FLAIR2) results in isovoxel images with increased contrast-to-noise ratio, increased white–gray-matter contrast, and improved MS lesion visualization without increasing MRI acquisition time. The current study aims to assess the potential of 3D-FLAIR2 in detecting cortical/leucocortical (LC), juxtacortical (JC), and white matter (WM) lesions. Objective To compare lesion detection of 3D-FLAIR2 with state-of-the-art 3D-T2-FLAIR and 3D-T2-weighted images. Methods We retrospectively analyzed MRI scans of thirteen MS patients, showing previously noted high cortical lesion load. Scans were acquired using a 3 T MRI scanner. WM, JC, and LC lesions were manually labeled and manually counted after randomization of 3D-T2, 3D-FLAIR, and 3D-FLAIR2 scans using the ITK-SNAP tool. Results LC lesion visibility was significantly improved by 3D-FLAIR2 in comparison to 3D-FLAIR (4 vs 1; p = 0.018) and 3D-T2 (4 vs 1; p = 0.007). Comparing LC lesion detection in 3D-FLAIR2 vs. 3D-FLAIR, 3D-FLAIR2 detected on average 3.2 more cortical lesions (95% CI − 9.1 to 2.8). Comparing against 3D-T2, 3D-FLAIR2 detected on average 3.7 more LC lesions (95% CI 3.3–10.7). Conclusions 3D-FLAIR2 is an easily applicable time-sparing MR post-processing method to improve cortical lesion detection. Larger sampled studies are warranted to validate the sensitivity and specificity of 3D-FLAIR2.

Background At patient-level, the prognostic value of several features that are known to be associated with an increased risk of converting from relapsing remitting (RR) to secondary phase (SP) multiple sclerosis (MS), remain limited. Methods Among 262 RRMS patients followed up for ten years, we assessed the probability of developing the SP course based on clinical and conventional and non-conventional magnetic resonance imaging (MRI) parameters at diagnosis and after two years. We used a machine learning method, the Random Survival Forests, to identify, according to their minimal depth (MD), the most predictive factors associated with the risk of SP conversion, which were then combined to compute the Secondary Progressive Risk Score (SP-RiSc). Results During the observation period, 69 (26%) patients converted to SPMS. The number of cortical lesions (MD=2.47) and age (MD=3.30) at diagnosis, the global cortical thinning (MD = 1.65), the cerebellar cortical volume loss (MD = 2.15) and the cortical lesion load increase (MD=3.15) over the first two years, exerted the greatest predictive effect. Three patients' risk-groups were identified; in the high-risk group, 85% (46 out of 55) of patients entered the SP phase in 7 median years. The SP-RiSc optimal cut-off estimated was 17.7 showing specificity and sensitivity of 87% and 92% respectively, and overall accuracy of 88%. Conclusions The SP-RiSc yielded a high performance in identifying MS patients with high probability to develop SPMS, which can help improve management strategies. These findings are the premise of further larger prospective studies to assess its use in clinical settings.

This study aimed to investigate at 7.0-T MRI a) the role of multiple sclerosis (MS) cortical lesions in cortical tissue loss b) their relation to neurological disability. In 76 relapsing remitting and 26 secondary progressive MS patients (N = 102) and 56 healthy subjects 7.0-T T2*-weighted images were acquired for lesion segmentation; 3.0-T T1-weighted structural scans for cortical surface reconstruction/cortical thickness estimation. Patients were dichotomized based on the median cortical lesion volume in low and high cortical lesion load groups that differed by age, MS phenotype and degree of neurological disability. Group differences in cortical thickness were tested on reconstructed cortical surface. Patients were evaluated clinically by means of the Expanded Disability Status Scale (EDSS). Cortical lesions were detected in 96% of patients. White matter lesion load was greater in the high than in the low cortical lesion load MS group (p = 0.01). Both MS groups disclosed clusters (prevalently parietal) of cortical thinning relative to healthy subjects, though these regions did not show the highest cortical lesion density, which predominantly involved frontal regions. Cortical thickness decreased on average by 0.37 mm, (p = 0.002) in MS patients for each unit standard deviation change in white matter lesion volume. The odds of having a higher EDSS were associated with cortical lesion volume (1.78, p = 0.01) and disease duration (1.15, p

Mechanisms initiated by traumatic brain injury (TBI), leading to the development of progressive secondary injury are poorly understood. MicroRNAs (miRNAs) have a proposed role in orchestrating the post-injury aftermath as a single miRNA can control the expression of several genes. We hypothesized that the post-injury level of circulating brain-enriched miR-124-3p explains the extent of post-TBI cortical lesion. Three separate cohorts of adult male Sprague-Dawley rats (total n = 57) were injured with lateral fluid-percussion-induced TBI. The miR-124-3p levels were measured in whole blood and/or plasma in cohorts 1 and 2 before TBI as well as at 2 d, 7 d, 2 months or 3 months post-TBI. The third cohort (22/57) was imaged with T2-weighted magnetic resonance imaging (MRI) at 2 months post-TBI to quantify cortical lesion area and perilesional T2-enhancement volume. Our data shows that miR-124-3p levels were elevated at 2 d post-TBI in both blood (FC 4.63, p 0.01) and plasma (FC 1.39, p 0.05) as compared to controls. Receiver operating curve (ROC) analysis indicated that plasma miR-124-3p level of 34 copies/µl or higher differentiated TBI animals from controls [area under curve (AUC) 0.815, p 0.05]. The data was validated in the third cohort (FC 1.68, p 0.05). T2-weighted MRI revealed inter-animal differences in cortical lesion area. Linear regression analysis revealed that higher the plasma miR-124-3p level at 2 d post-TBI, larger the lesion area at chronic time point (R

Disabilities resulting from traumatic brain injury (TBI) strongly correlate with the cytoarchitectonic part of the brain damaged, lesion area, and type of lesion. We developed a Web application to estimate the location of the lesion on mouse cerebral cortex caused by TBI induced by lateral fluid-percussion injury. The application unfolds user-determined TBI lesion measurements, e.g., from histologic sections to a reference template, and estimates the total lesion area, including the percentage of cortex damaged in different cytoarchitectural cortical regions. The resulting lesion can be visualized on a two-dimensional map of mouse cerebral cortex. The application also visualizes the development of the lesion over time when measurements from multiple time points are available. The web application was validated by comparing its performance to the manual method. The total area of the cortical lesion was similar between the manual (9.19 ± 0.66 mm2, range 4.25–14.93 mm2) and the automated analysis (9.27 ± 0.66 mm2, range 4.50–15.10 mm2) (p = 0.938). The results of the manual and automated analyses were strongly correlated (r = 0.999, p

Background and PurposeDoes the brain become more resilient after a first stroke to reduce the consequences of a new lesion? Although recurrent strokes are a major clinical issue, whether and how the brain prepares for a second attack is unknown. This is due to the difficulties to obtain an appropriate dataset of stroke patients with comparable lesions, imaged at the same interval after onset. Furthermore, timing of the recurrent event remains unpredictable.MethodsHere we used a novel clinical lesion simulation approach to test the hypothesis that resilience in brain networks increases during stroke recovery. 16 patients with a lesion restricted to the primary motor cortex were recruited. At 3 time points of the index event (10 days, 3 weeks, 3 months), we mimicked recurrent infarcts by deletion of nodes in brain networks (resting-state fMRI). Graph measures were applied to determine resilience (global efficiency) and wiring cost (mean degree) of the network.ResultsAt 10 days and 3 weeks after stroke, resilience was similar in patients and controls. However, at 3 months, while motor function had fully recovered, resilience to clinically representative simulated lesions was higher compared to controls (cortical lesion p=0.012; subcortical: p=0.009; cortico-subcortical: p=0.009). Similar results were found after random (p=0.012) and targeted (p=0.015) attacks.ConclusionOur results suggest that, after a lesion, brain networks reconfigure to increase resilience to future insults. Lesion simulation is an innovative approach, which may have major implications for stroke therapy. Individualized neuromodulation strategies could be developed to foster resilient network reconfigurations after a first stroke to limit the consequences of future attacks.

Aim: To compare the cognitive communicative performance of Stroke patients with that of normal subjects and also, to compare the cognitive communicative performance across stroke subgroups of cortical lesion and subcortical lesion. Materials and Methods: 15 stroke patients (experimental group) and 15 neurologically healthy individuals (control group) were taken. In the experimental group, 7 had cortical and 8 had subcortical lesion. Scale of Cognitive and Communicative Ability for Neurorehabilitation (SCCAN) test was used for assessing cognitive communicative abilities of all the subjects. Results: The stroke patients as a group performed significantly poorer when compared to that of control group on SCCAN. The performance of stroke patients was more impaired on memory scale compared to other scales of SCCAN. The cognitive communicative performance of patients within the experimental group showed that subcortical stroke patients performed poorer when compared to the cortical stroke patients on SCCAN. Conclusion: This study highlights on the nature of cognitive communicative deficits in stroke patients.

BACKGROUND Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations. PURPOSE The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T2*w magnetic resonance imaging. MATERIALS AND METHODS In this prospective study, a gradient-recalled echo sequence incorporating a navigator allowing for motion and B0 field correction was applied to collect T2*w images at 7 T from adults with MS between August 2019 and March 2020. T2*-weighted images were acquired in 1 to 3 partially overlapping scans per individual and were reconstructed using global average B0 correction ("uncorrected") or motion correction and spatially linear B0 correction ("corrected"). Image quality rating and manual segmentation of cortical lesions were performed on uncorrected and corrected images. Lesions seen on a single scan were retrospectively evaluated on the complementary scan. The association of cortical lesions with clinical disability was assessed. Mixed models were used to determine the effect of correction on lesion detection as well as on the relationship between disability and lesion count. RESULTS A total of 22 T2*w scans were performed on 11 adults with MS (mean [SD] age, 49 [11] years; 8 women). Quality improved for 20 of 22 scans (91%) after correction. A total of 69 cortical lesions were identified on uncorrected images (median per scan, 2; range, 0-11) versus 148 on corrected images (median per scan, 4.5; range, 0-25; rate ratio [RR], 2.1; P < 0.0001). For low-quality uncorrected scans with moderate to severe motion artifact (18/22, 82%), there was an improvement in cortical lesion detection with correction (RR, 2.5; P < 0.0001), whereas there was no significant change in cortical lesion detection for high-quality scans (RR, 1.3; P = 0.43). CONCLUSIONS Navigator-guided motion and B0 correction substantially improves the overall image quality of T2*w magnetic resonance imaging at 7 T and increases its sensitivity for cortical lesions.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

There is a large body of evidence suggesting that parasites could be a major preventable risk factor for epilepsy in low- and middle-income countries. We review potentially important substrates for epileptogenesis in parasitic diseases. Taenia solium is the most widely known parasite associated with epilepsy, and the risk seems determined mainly by the extent of cortical involvement and the evolution of the primary cortical lesion to gliosis or to a calcified granuloma. For most parasites, however, epileptogenesis is more complex, and other favorable host genetic factors and parasite-specific characteristics may be critical. In situations where cortical involvement by the parasite is either absent or minimal, parasite-induced epileptogenesis through an autoimmune process seems plausible. Further research to identify important markers of epileptogenesis in parasitic diseases will have huge implications for the development of trials to halt or delay onset of epilepsy.

Highlights • 7 T MRI improves cortical lesion detection compared to 3 T MRI. • Type II-IV intracortical lesion detection benefit most from 7 T MRI. • Progressive multiple sclerosis patients have four times more cortical lesions. • 7 T MRI has modest sensitivity towards cortical lesions compared with histopathology. • Guidelines for image acquisition and cortical lesion segmentation at 7 T are missing., Background Cortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7 T and above provides technological advances suited to optimize the detection of cortical lesions in MS. Purpose To provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS. Methods A systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3 T and 7 T MRI and between 7 T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology. Results 7 T MRI detected on average 52 ± 26% (mean ± 95% confidence interval) more cortical lesions than the best performing image contrast at 3 T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17 ± 6 per patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Yet, there was no difference in lesion type ratio between these MS subtypes. Furthermore, superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33 ± 6% and 71 ± 10%, respectively, with the highest sensitivity towards type I and type IV lesions. Conclusion UHF MRI improves cortical lesion detection in MS considerably compared to 3 T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7 T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed.

Background: Cortical lesions are highly inconspicuous on magnetic resonance imaging (MRI). Double inversion recovery (DIR) has a higher sensitivity than conventional clinical sequences (i.e. T1, T2, FLAIR) but is difficult to acquire, leading to overseen cortical lesions in clinical care and clinical trials. Objective: To evaluate the usability of artificially generated DIR (aDIR) images for cortical lesion detection compared to conventionally acquired DIR (cDIR). Methods: The dataset consisted of 3D-T1 and 2D-proton density (PD) T2 images of 73 patients (49RR, 20SP, 4PP) at 1.5 T. Using a 4:1 train:test-ratio, a fully convolutional neural network was trained to predict 3D-aDIR from 3D-T1 and 2D-PD/T2 images. Randomized blind scoring of the test set was used to determine detection reliability, precision and recall. Results: A total of 626 vs 696 cortical lesions were detected on 15 aDIR vs cDIR images (intraclass correlation coefficient (ICC) = 0.92). Compared to cDIR, precision and recall were 0.84 ± 0.06 and 0.76 ± 0.09, respectively. The frontal and temporal lobes showed the largest differences in discernibility. Conclusion: Cortical lesions can be detected with good reliability on artificial DIR. The technique has potential to broaden the availability of DIR in clinical care and provides the opportunity of ex post facto implementation of cortical lesions imaging in existing clinical trial data.

NLRP3 inflammasome has been considered as an important contributor to inflammation and neuronal death after traumatic brain injury (TBI). Oridonin (Ori), the major active ingredient of Chinese herbal medicine Rabdosia rubescens, has been proved to be a covalent NLRP3 inhibitor with strong anti-inflammation activity. The purpose of this study was to investigate the effect of Ori on inflammation and brain injury induced by TBI. Adult male C57BL/6 mice were subjected to closed-head injury using Hall’s weight-dropping method. Ori was injected directly intraperitoneally at a dose of 10 mg/kg within 30 min after TBI and injected once daily until the experiments ended. Our results showed that NLRP3 inflammasome was activated within 24 h post-TBI. The expression of NLRP3 inflammasome components (NLRP3, ASC, and caspase-1) was significantly decreased after treatment with Ori. Besides, the secretion of IL-1β and IL-18, downstream inflammatory factors of activated caspase-1, was reduced by Ori treatment. Importantly, Ori administration further protected the blood–brain barrier, alleviated brain edema, reduced cortical lesion volume, decreased cell death, and attenuated neurological deficits after TBI. Our findings indicate that NLRP3 inflammasome participated in the secondary injury after TBI and the application of Ori may provide neuroprotection via inhibiting NLRP3 inflammasome in animal models, suggesting that Ori might be a promising candidate for patients with TBI.

The automated detection of cortical lesions (CLs) in patients with multiple sclerosis (MS) is a challenging task that, despite its clinical relevance, has received very little attention. Accurate detection of the small and scarce lesions requires specialized sequences and high or ultra-high field MRI. For supervised training based on multimodal structural MRI at 7T, two experts generated ground truth segmentation masks of 60 patients with 2014 CLs. We implemented a simplified 3D U-Net with three resolution levels (3D U-Net-). By increasing the complexity of the task (adding brain tissue segmentation), while randomly dropping input channels during training, we improved the performance compared to the baseline. Considering a minimum lesion size of 0.75 {\mu}L, we achieved a lesion-wise cortical lesion detection rate of 67% and a false positive rate of 42%. However, 393 (24%) of the lesions reported as false positives were post-hoc confirmed as potential or definite lesions by an expert. This indicates the potential of the proposed method to support experts in the tedious process of CL manual segmentation., Comment: Accepted to MICCAI 2020

Background Both the type and severity of functional impairments caused by damage to the cerebral cortex depend on the functional cortical areas and networks affected, as well as the lesion extent and type. New method To accelerate the laborious quantitative analysis of cortical lesion location and size, we created user-friendly software that generates two-dimensional unfolded cortical maps of the lesions in adult rats. The program imports and superimposes simple user-made measurements, e.g., from histologic sections, on a template. The software then quantifies the total lesion area and the area of damage in each cortical cytoarchitechtonic region. To validate the accuracy of the software, we compared computer-generated maps with manually created unfolded maps from 32 rats with lateral fluid-percussion-induced traumatic brain injury. Results The total area of the cortical lesions varied from 7.37 to 38.45 mm2 in the automated analysis and from 7.26 to 38.97 mm2 in the manual analysis (p > 0.05). The Pearson correlation coefficient between the automated and manual analyses was 0.998 (p Comparison with existing methods Compared with the manual method, the automated method accurately and quickly generates unfolded cortical maps of lesioned cortical areas. Conclusions Application provides a novel tool for accurately positioning the lesioned area on the cortical mantle and quantifying the lesion area in histologic sections or magnetic resonance images.

Hemianopia can be rehabilitated by an auditory-visual “training” procedure, which restores visual responsiveness in midbrain neurons indirectly compromised by the cortical lesion and reinstates vision in contralesional space. Presumably, these rehabilitative changes are induced via mechanisms of multisensory integration/plasticity. If so, the paradigm should fail if the stimulus configurations violate the spatiotemporal principles that govern these midbrain processes. To test this possibility, hemianopic cats were provided spatially or temporally noncongruent auditory-visual training. Rehabilitation failed in all cases even after approximately twice the number of training trials normally required for recovery, and even after animals learned to approach the location of the undetected visual stimulus. When training was repeated with these stimuli in spatiotemporal concordance, hemianopia was resolved. The results identify the conditions needed to engage changes in remaining neural circuits required to support vision in the absence of visual cortex, and have implications for rehabilitative strategies in human patients.

In patients with cortical lesions, the structure of intelligence has never been studied as a function of age at lesion onset and presence vs absence of lesional epilepsy over the life span. Method Two thousand one hundred eighty-six cases were assembled bearing unilateral cortical lesions occurring at all ages (1301 with seizures) with postlesion verbal intelligence quotient (IQ) (VIQ) and performance IQ (PIQ). Results Global IQ significantly and constantly decreased as a function of age at lesion onset in the cases without epilepsy, and increased in the cases with epilepsy. Beyond the lesion onset age of 12 years, VIQ was significantly higher than PIQ in the cases without epilepsy, and lower in the cases with epilepsy. The VIQ/PIQ × lesion-side interaction indicative of hemispheric specialization increased significantly linearly with age at lesion onset in the patients without epilepsy but ceased to progress at the lesion-onset age of 30 years and beyond in the cases with epilepsy. Conclusion Postlesion global IQ, the difference between VIQ and PIQ, and the laterality index all vary significantly as a function of age at lesion onset. In addition, these changes over the life span are all quite different between cases with and without epilepsy.

Objective: To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). Methods: Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density–weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. Results: We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic volume, age at the time of the scan, or disease duration. The number of frontal CLs was associated with slower performance on the 9-HPT ( p = 0.05). Conclusion: Multi-contrast 3T MRI led to a high rate of CL detection, demonstrating that cortical pathology occurs even in pediatric-onset disease. Frontal lobe CL count was associated with reduced manual dexterity, indicating that these CLs are clinically relevant.

Objective To demonstrate the usefulness of early videofluoroscopic swallowing study (VFSS) and to investigate change patterns in dietary methods in stroke patients with dysphagia. Methods The VFSS was performed within 7 days of stroke onset in neurologically stable patients. The patients were divided into three groups according to type of brain lesion: cortical lesion (CL), subcortical lesion (SCL), and brainstem/cerebellar lesion (BCL). Based on the VFSS results, this study investigated change patterns in feeding method and discrepancies in the aspiration risk predicted by the Water Swallowing Test (WST) and the VFSS. Complications, such as aspiration pneumonia, were also evaluated. Results A total of 163 patients met the inclusion criteria and the VFSS was performed within 7 days of stroke. Patients considered at risk for aspiration (Penetration-Aspiration Scale [PAS] scores of 6 to 8) were found in all three groups using the VFSS (47.5% of the CL group, 59.3% of the SCL group, and 47.9% of the BCL group). After early VFSS, 79.7% of the patients were assessed to require restricted feeding methods. A 19.0% discrepancy was found between the WST and VFSS results. At 3-week follow-up after the VFSS, aspiration pneumonia was observed in 12 patients (7.4%) with restricted feeding methods. Conclusion Early VFSS during the acute period can facilitate determination of the most appropriate feeding method, and support effective dysphagia management for stroke patients.

Supratentorial cortical ependymoma is a rare primary brain tumor in adults. Only 50 cases are reported in the literature including pediatric and adult patients. We report a 30-year-old male with sensory-type seizures who was found to have a right posterior frontal cortical lesion with large cystic component. The lesion was resected completely and histopathology and immunohistochemistry examinations confirmed anaplastic ependymoma WHO grade III. The patient received radiotherapy treatment post-surgery, and he was tumor free one year after treatment.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls. Thirty-six patients with MS underwent 3T MR imaging, including 3D double inversion recovery and 3D-echo-planar SWI. RESULTS: Neuropathologic analysis revealed the presence of an intense band of microglia activation close to the pial membrane in subpial cortical lesions or to the WM border of leukocortical cortical lesions. The quantitative susceptibility mapping analysis revealed 131 cortical lesions classified as hyperintense; 33, as isointense; and 84, as hypointense. Quantitative susceptibility mapping hyperintensity edge found in the proximity of the pial surface or at the white matter/gray matter interface in some of the quantitative susceptibility mapping–hyperintense cortical lesions accurately mirrors the microglia activation observed in the neuropathology analysis. CONCLUSIONS: Cortical lesion susceptibility maps are highly heterogeneous, even at individual levels. Quantitative susceptibility mapping hyperintensity edge found in proximity to the pial surface might be due to the subpial gradient of microglial activation.

Environmental enrichment (EE) confers significant benefits after experimental traumatic brain injury (TBI). In contrast, the antipsychotic drug (APD) haloperidol (HAL) exerts deleterious effects on neurobehavioral and cognitive recovery. Neurorehabilitation and management of agitation, however, are integral components of the treatment strategy for patients with TBI. Hence, the goal of this study was to determine how the two therapeutic approaches interact and influence motor and cognitive recovery. Anesthetized adult male rats received a controlled cortical impact (2.8 mm tissue deformation at 4 m/sec) or sham injury and then were provided HAL (0.5 mg/kg; intraperitoneally [IP]) or vehicle (VEH; 1 mL/kg; IP) commencing 24 h after surgery and once daily for 19 days while housed in EE or standard (STD) conditions. Beam balance/walk and Morris water maze performance were assessed on post-injury days 1–5 and 14–19, respectively, followed immediately by quantification of cortical lesion volumes. The data revealed both expected and unexpected findings. It was not surprising that the TBI groups receiving EE performed significantly better than those in STD housing and that the TBI + STD + HAL group performed worse than the TBI + STD + VEH group (p 0.05). The potential clinical implications of these findings suggest that administering HAL to patients undergoing neurorehabilitation may be a double-edged sword because agitation must be controlled before rehabilitation can be safely initiated and executed, but its use may compromise therapeutic efficacy.

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Lastly, cortical lesions were assessed on phase-sensitive inversion recovery (PSIR) images and cortical thickness was quantified on volumetric T1 images. Our main result was the observation in the PPMS group of a significant correlation between periventricular NAWM MD values and cortical lesion load, with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation between cortical lesion load and deep NAWM MD values or periventricular WM lesions. Our data thus suggest that a common – and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS., Highlights • In PPMS, pathology is more frequent near the inner and outer brain surfaces. • We evaluated the association between cortical lesions and periventricular damage. • Cortical lesion load directly correlated with periventricular NAWM damage severity. • Cortical lesion load did not correlate with periventricular lesions. • A common factor seems to modulate cortical lesions and periventricular NAWM damage.

Cortical microstructural abnormalities are associated with clinical and cognitive deterioration in multiple sclerosis. Using diffusion tensor MRI, a higher fractional anisotropy has been found in cortical lesions versus normal-appearing cortex in multiple sclerosis. The pathological substrates of this finding have yet to be definitively elucidated. By performing a combined post-mortem diffusion tensor MRI and histopathology study, we aimed to define the histopathological substrates of diffusivity abnormalities in multiple sclerosis cortex. Sixteen subjects with multiple sclerosis and 10 age- and sex-matched non-neurological control donors underwent post-mortem in situ at 3 T MRI, followed by brain dissection. One hundred and ten paraffin-embedded tissue blocks (54 from multiple sclerosis patients, 56 from non-neurological controls) were matched to the diffusion tensor sequence to obtain regional diffusivity measures. Using immunohistochemistry and silver staining, cortical density of myelin, microglia, astrocytes and axons, and density and volume of neurons and glial cells were evaluated. Correlates of diffusivity abnormalities with histological markers were assessed through linear mixed-effects models. Cortical lesions (77% subpial) were found in 27/54 (50%) multiple sclerosis cortical regions. Multiple sclerosis normal-appearing cortex had a significantly lower fractional anisotropy compared to cortex from non-neurological controls (P = 0.047), whereas fractional anisotropy in demyelinated cortex was significantly higher than in multiple sclerosis normal-appearing cortex (P = 0.012) but not different from non-neurological control cortex (P = 0.420). Compared to non-neurological control cortex, both multiple sclerosis normal-appearing and demyelinated cortices showed a lower density of axons perpendicular to the cortical surface (P = 0.012 for both) and of total axons (parallel and perpendicular to cortical surface) (P = 0.028 and 0.012). In multiple sclerosis, demyelinated cortex had a lower density of myelin (P = 0.004), parallel (P = 0.018) and total axons (P = 0.029) versus normal-appearing cortex. Regarding the pathological substrate, in non-neurological controls, cortical fractional anisotropy was positively associated with density of perpendicular, parallel, and total axons (P = 0.031 for all). In multiple sclerosis, normal-appearing cortex fractional anisotropy was positively associated with perpendicular and total axon density (P = 0.031 for both), while associations with myelin, glial and total cells and parallel axons did not survive multiple comparison correction. Demyelinated cortex fractional anisotropy was positively associated with density of neurons, and total cells and negatively with microglia density, without surviving multiple comparison correction. Our results suggest that a reduction of perpendicular axons in normal-appearing cortex and of both perpendicular and parallel axons in demyelinated cortex may underlie the substrate influencing cortical microstructural coherence and being responsible for the different patterns of fractional anisotropy changes occurring in multiple sclerosis cortex.

Longitudinal 7.0-T MRI in multiple sclerosis demonstrates accrual rate of cortical lesions, which predominates over white matter lesion accumulation. Lesions occurs preferentially intracortically a...

Background The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. Aim To assess HLA-DRB * 1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Methods Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB * 1501 haplotype was determined by genotyping (rs3135388). Results No significant differences were observed in MRI measures between the HLA-DRB * 1501 subgroups. Conclusions The HLA-DRB * 1501 haplotype is not strongly associated with MRI-visible grey matter pathology.

Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto‐medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease‐like lesions of the nigro‐striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti‐Nogo‐A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti‐Nogo‐A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi‐section of the cervical cord (at C7 level) and anti‐Nogo‐A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery.

WOS: 000429001000004 The aim of this study is to investigate if the three-dimensional (3D) double inversion recovery (DIR) sequence is superior compared to the 3D fluid-attenuated inversion-recovery (FLAIR) sequence in detecting intracortical, mixed, juxtacortical (JX), and deep grey matter (GM) lesions in multiple sclerosis (MS) patients. The correlation between intracortical lesion load and disability status was also investigated. Magnetic resonance imaging examinations of 24 patients (9 males, 15 females; mean age 34.4 +/- 12.0 (16-69) were retrospectively evaluated from our database. Lesions were counted and classified according to anatomic regions as intracortical, mixed, JX, and deep GM on the 3D DIR and FLAIR sequences. The incidence of lesions on the two sequences were identified and compared. The relationship between the number of lesions and type of MS, patient age, gender, duration of the disease, disability, the mean number of attacks per year and Expanded Disability Status Scale (EDSS) score was also investigated. More lesions were detected by the DIR sequence compared to the FLAIR sequence in all regions except for thalamus (11/12). The lesion detection superiority of DIR was statistically significant for intracortical lesions (p

Rationale and Objectives Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance (MR) phase images. Our purpose was to evaluate if there is additional diagnostic value of QSM images in detecting the cortical gray matter involvement in multiple sclerosis (MS) patients. Materials and Methods Our institutional review board approved this study. Conventional MR imaging, including T2-weighted imaging and two- or three-dimensional fluid-attenuated inversion recovery images, and QSM imaging examinations were performed in 27 patients (19 male and eight female) with MS. Two radiologists (radiologists 1 and 2) assessed the MS lesions in the following 3 anatomic regions: intracortical, mixed white matter–gray matter (WM–GM), and juxtacortical regions. The numbers of lesions per region category were compared between conventional MR images with and without QSM images. Results For radiologists 1 and 2, QSM images identified 6 (50.0%) and 7 (50.0%) additional lesions that were not seen in the conventional MR images, respectively. In a lesion-by-lesion analysis, the substantial fraction (20 [25.3%] of 79 at radiologist 1, 22 [29.7%] of 74 at radiologist 2) of juxtacortical white matter lesions on the conventional MR images were scored as mixed WM–GM lesions with QSM images. Conclusions Our preliminary results suggest that the MR imaging with QSM may increase the sensitivity in cortical lesion detection in the MS brain and improved distinction between juxtacortical and mixed WM–GM lesions.

We report a 10-year-old boy with supratentorial cortical ependymoma that rapidly grew in the course of 3 years. He suffered generalized seizures when he was 5 years old; MRI showed a small cortical lesion in the right postcentral gyrus. MRI performed 2 years later revealed no changes. For the next 3 years he was free of seizures. However, at the age of 10 he again suffered generalized seizures and MRI disclosed a large parietal tumor. It was resected totally and he remains free of neurological deficits. The histopathological diagnosis was ependymoma. Pediatric supratentorial cortical ependymomas are extremely rare. We recommend including cortical ependymoma as a differential diagnosis in pediatric patients with cortical mass lesions presenting with seizures and careful follow-up even in the absence of symptoms because these tumors may progress.

Palinopsia, the persistence or recurrence of visual images after the stimulus has been removed, is a nonspecific term that describes multiple types of visual symptoms with a wide variety of etiologies. For example, palinopsia may be the presenting symptom of a potentially life-threatening posterior cortical lesion, yet it may also be a benign medication side effect. We comprehensively review all published cases and subdivide palinopsia into two clinically relevant categories: illusory palinopsia and hallucinatory palinopsia.

A cortical lesion of the tibial diaphysis in a young patient poses a diagnostic challenge to the clinician. Brown tumors, although not very common, may mimic malignancies on radiographs. Brown tumors are destructive lytic lesions of the bone due to increased osteoclastic activity and fibroblastic proliferation in patients with uncontrolled hyperparathyroidism (HPT). They occur after primary or secondary HPT due to renal failure but very rarely due to vitamin D deficiency. We report a rare case of a brown tumor of tibial diaphyses in a young female patient mimicking a locally aggressive tumor with secondary HPT due to a severe vitamin D deficiency. The effect of hyperparathyroidism on bone metabolism is clinically worse in the presence of vitamin D deficiency and, hence, it predisposes patients to brown tumors that can affect any bone in the body. They can be managed conservatively but may require prophylactic fixation in particular cases.

Background: Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients. Objective: To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients. Methods: Three-dimensional double inversion recovery imaging and clinical information were retrospectively obtained from 92 Japanese MS patients. Results: CLs of any type, intracortical lesions (ICLs), and leukocortical lesions (LCLs) were detected in 39.1%, 26.1%, and 28.3% of patients, respectively. MS patients with ICLs had a significantly higher frequency of secondary progression and greater Expanded Disability Status Scale (EDSS) scores than those without ICLs. Similar trends were observed with CLs and LCLs. The number of all three lesion types positively correlated with EDSS scores. The frequency and number of ICLs were significantly higher in HLA-DRB1*15:01 carriers than in HLA-DRB1*15:01 non-carriers, but significantly lower in HLA-DRB1*04:05 carriers than in HLA-DRB1*04:05 non-carriers. Multivariate logistic regression analysis revealed a negative association of HLA-DRB1*04:05 with ICLs. Conclusion: ICLs are associated with greater disease severity in Japanese MS patients and are partly suppressed by the HLA-DRB1*04:05 allele.

The autoimmune disease Multiple Sclerosis (MS) is characterized by relapses in the majority of patients. A definitive clinical diagnosis of relapse in MS can be complicated by the presence of an infection or comorbid disorder. In this mini-review, we describe efforts to develop enhanced imaging techniques and biomarker detection as future tools for relapse validation. There is emerging evidence of roles for meningeal inflammation, sex hormones, comorbid metabolic or mood disorders, and a dysregulated immune profile in the manifestation and severity of relapse. Specific subsets of immune cells likely drive the pathophysiology of relapse, and identification of a patient’s unique immunological signature of relapse may help guide future diagnosis and treatment. Finally, these studies highlight the diversity in terms of relapse presentation, immunological signature, and response in patients with MS, indicating that going forward the best approach to assessment and treatment of relapse will be multi-factorial and highly personalized.

Purpose In patients with multiple sclerosis (MS), Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to identify cortical lesions (CL). We sought to evaluate the reliability of CL detection on DIR longitudinally at multiple subsequent time-points applying the MAGNIMs scoring criteria for CLs. Methods 26 MS patients received a 3T-MRI (Siemens, Skyra) with DIR at 12 time-points (TP) within a 16 months period. Scans were assessed in random order by two different raters. Both raters separately marked all CLs on each scan and total lesion numbers were obtained for each scan-TP and patient. After a retrospective re-evaluation, the number of consensus CLs (conL) was defined as the total number of CLs, which both raters finally agreed on. CLs volumes, relative signal intensities and CLs localizations were determined. Both ratings (conL vs. non-consensus scoring) were compared for further analysis. Results A total number of n = 334 CLs were identified by both raters in 26 MS patients with a first agreement of both raters on 160 out of 334 of the CLs found (κ = 0.48). After the retrospective re-evaluation, consensus agreement increased to 233 out of 334 CL (κ = 0.69). 93.8% of conL were visible in at least 2 consecutive TP. 74.7% of the conL were visible in all 12 consecutive TP. ConL had greater mean lesion volumes and higher mean signal intensities compared to lesions that were only detected by one of the raters (p

Objective: We combined double inversion recovery (DIR) and diffusion tensor (DT) magnetic resonance imaging (MRI) to quantify the severity of cortical lesion (CL) microstructural tissue abnormalities in a large cohort of relapse-onset multiple sclerosis (MS) patients and its contribution to cognitive dysfunction. Methods: DIR, DT, dual-echo, and three-dimensional (3D) T1-weighted scans were acquired from 149 MS patients and 40 controls. Cognitively impaired (CI) patients had ⩾2 abnormal neuropsychological tests. Diffusivity values in CLs, cortex, white matter (WM) lesions, and normal-appearing (NA) WM were assessed. Predictors of cognitive impairment were identified using a random forest analysis. Results: Compared to controls, MS patients had lower normalized brain volume (NBV), gray matter volume (GMV), WM volume, lower fractional anisotropy (FA), and higher mean diffusivity in cortex and normal-appearing white matter (NAWM). A total of 44 (29.5%) patients were CI. Compared to cognitively preserved (CP), CI patients had higher T2 WM lesion volume (LV), lower NBV and GMV, and more severe diffusivity abnormalities in WM lesions, cortex, and NAWM. CL measures did not differ between CI and CP patients. Cortex FA, age, disease duration, T2 WM LV, and GMV best predicted MS-related cognitive impairment (C-statistic = 0.88). Conclusion: “Diffuse” GM and NAWM damage and WM lesions, rather than intrinsic CL damage, contribute to cognitive impairment in MS.

The role of different factors in influencing the risk of seizures during multiple sclerosis (MS) is not known. To perform a systematic review and meta-analysis of risk factors for epilepsy during MS. Pubmed, Google scholar, and Scopus databases were searched. Articles published in English (1986–2016) were included. Nine studies were included (3 retrospective cohort and 6 case–control) enrolling 2845 MS patients (217 with epilepsy; 7.6%). MS patients with epilepsy had a younger age at onset compared to MS patients without seizures (difference in means = −5.42 years, 95% CI −7.19 to −3.66, p

It is now well established that cortical lesion detection is important in the diagnosis and prognosis of neurological deficits in patients with multiple sclerosis (MS). In this chapter, the role of in vivo magnetic resonance imaging, both conventional and recently improved, as well as more versatile modalities, together with immunopathological studies to elucidate cortical pathology in MS are introduced. Emphasis is then shifted to the role of animal models of MS and the use of in vitro studies to further understand the cellular interactions between neural and both adaptive and innate arms of the immune system in mediating demyelination and the varying forms of neuronal damage involved in the evolution, progression, and potential remission of neuroinflammatory lesions in MS. The use of current disease-modifying drugs in the treatment of MS is put into context, along with perspectives on the future development of new more selective therapeutic interventions.

The purpose of the present study was to determine whether a unilateral photothrombotic brain lesion induces bilateral ischemic tolerance towards a subsequent severe ischemia performed 5 days later. Severe ischemia was induced by transient (1h; t) or permanent (p) occlusion of the middle cerebral artery (MCAO). Rats were sacrificed 24h later. Preconditioning reduced the size of subsequent infarcts in both hemispheres. This effect was most prominent with tMCAO, and ipsilateral preconditioning was more effective than contralateral preconditioning (% of hemispheric volume, mean ± SD: 31.9 ± 3.7 to 19.0 ± 10.3 with ipsilateral tMCAO; 31.9 ± 3.7 to 22.9 ± 4.9 with contralateral tMCAO; 64.7 ± 4.3% to 47.2 ± 12.5% with ipsilateral pMCAO; 64.7 ± 4.3% to 53.1 ± 8.9% with contralateral pMCAO). Ischemic preconditioning was associated with a successive bilateral up-regulation of superoxide dismutases which may be involved in the development of ischemic tolerance. Our data suggest that a focal ischemic brain lesion induces neuroprotective mechanisms in extensive brain areas and thus cause bilateral ischemic tolerance within a certain time window.

Background: Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration. Objective: The objective of this paper is to assess correlation between cortical lesion load and magnetisation transfer ratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration. Methods: Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearson correlation was calculated for NAWM MTR vs cortical lesion load, and WML volumes. Results: Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongest correlation was with cortical lesion volumes obtained using MTR images ( r = −0.6874, p = 0.0006). WML volume had no significant correlation with NAWM mean MTR ( r = −0.08706, p = 0.3615). Conclusion: Our findings are consistent with the hypothesis that cortical lesions cause NAWM degeneration. This implicates cortical lesions in the pathogenesis of NAWM axon loss, which underpins long-term disability and progression in MS.

BACKGROUND AND PURPOSE: Double inversion recovery has been suggested as the MR imaging contrast of choice for segmenting cortical lesions in patients with multiple sclerosis. In this study, we sought to determine the utility of double inversion recovery for cortical lesion identification by comparing 3 MR imaging reading protocols that combine different MR imaging contrasts. MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 3 with secondary-progressive MS were imaged with 3T MR imaging by using double inversion recovery, dual fast spin-echo proton-density/T2-weighted, 3D FLAIR, and 3D T1-weighted imaging sequences. Lesions affecting the cortex were manually segmented by using the following 3 MR imaging reading protocols: Protocol 1 (P1) used all available MR imaging contrasts; protocol 2 (P2) used all the available contrasts except for double inversion recovery; and protocol 3(P3) used only double inversion recovery. RESULTS: Six hundred forty-three cortical lesions were identified with P1 (mean = 22.96); 633, with P2 (mean = 22.6); and 280, with P3 (mean = 10). The counts obtained by using P1 and P2 were not significantly different (P = .93). The counts obtained by using P3 were significantly smaller than those obtained by using either P1 (P < .001) or P2 (P < .001). The intraclass correlation coefficients were P1 versus P2 = 0.989, P1 versus P3 = 0.615, and P2 versus P3 = 0.588. CONCLUSIONS: MR imaging cortical lesion segmentation can be performed by using 3D T1-weighted and 3D FLAIR images acquired with a 1-mm isotropic voxel size, supported by conventional T2-weighted and proton-density images with 3-mm-thick sections. Inclusion of double inversion recovery in this multimodal reading protocol did not significantly improve the cortical lesion identification rate. A multimodal approach is superior to using double inversion recovery alone.

We aimed to generate two-dimensional (2D) unfolded cortical maps from magnetic resonance (MR) images to delineate the location of traumatic brain injury (TBI)-induced cortical damage in functionally diverse cytoarchitectonic areas of the cerebral cortex, and to predict the severity of functional impairment after TBI based on the lesion location and extent. Lateral fluid-percussion injury was induced in adult rats and T2 maps were acquired with magnetic resonance imaging (MRI) at 3 days post-TBI. Somatomotor deficits were assessed based on the composite neuroscore and beam balance test, and spatial learning was assessed in the Morris water maze. Animals were perfused for histology at 13 days post-injury. A 2D template was generated by unfolding the cerebral cortex from 26 sections of the rat brain atlas, covering the lesion extent. Next, 2D unfolded maps were generated from T2 maps and thionin-stained histological sections from the same animals. Unfolding of the T2 maps revealed the lesion core in the auditory, somatosensory, and visual cortices. The unfolded histological lesion at 13 days post-injury was 12% greater than the MRI lesion at 3 days post-TBI, as the lesion area increased laterally and caudally; the larger the MRI lesion area, the larger the histological lesion area. Further, the larger the MRI lesion area in the barrel field of the primary somatosensory cortex (S1BF), upper lip of the primary somatosensory cortex (S1ULp), secondary somatosensory division (S2), and ectorhinal (Ect) and perirhinal (PRh) cortices, the more impaired the performance in the beam balance and Morris water maze tests. Subsequent receiver operating characteristic analysis indicated that severity of the MRI lesion in S1ULp and S2 was a sensitive and specific predictor of poor performance in the beam balance test. Moreover, MRI lesions in the S1ULp, S2, S1BF, and Ect and PRh cortices predicted poor performance in the Morris water maze test. Our findings indicate that 2D-unfolded cortical maps generated from MR images delineate the distribution of cortical lesions in functionally different cytoarchitectonic regions, which can be used to predict the TBI-induced functional impairment.

Background Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. Objectives To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Methods Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Results Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. Conclusion In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease.

Significant progress in our understanding and treatment of multiple sclerosis (MS) has been enabled by remarkable advances in genetics, expression profiling, proteomics, bioinformatics, and systems-biology tools. However, the successful application of these approaches to advancing the field is contingent upon an appreciation that MS is biologically diverse and histologically complex. MS pathology differs based on stage of demyelinating activity, topographical region, structural, and immunopathological features, disease phase, age at onset, course, and duration. This chapter will review the dynamic neuropathology of MS and discuss its clinical and pathogenic implications.

Purpose: To evaluate the inter-rater agreement of cortical lesion detection using 7 Tesla (T) FLASH-T2* and 3T DIR sequences. Materials and Methods: Twenty-six patients with multiple sclerosis were scanned on a human 7T (Siemens) and 3T MRI (TIM Trio, Siemens) to acquire 3T DIR/MEMPR and 7T FLASH-T2* sequences. Four independent reviewers scored and categorized cortical lesions in the bilateral precentral gyri (motor strips) as leukocortical, intracortical, or subpial. Inter-rater agreement was assessed according to lesion category using the kappa statistic. The sensitivity of recent MAGNIMS consensus guidelines for cortical lesion detection using 3T DIR was assessed with 7T FLASH-T2* as the reference gold standard. Results: Inter-rater agreement at 7T was excellent compared with 3T (k = 0.97 versus 0.12). FLASH-T2* at 7T detected subpial lesions while 3T DIR did not. The predicted sensitivity of 3T DIR sequence for cortical lesions in vivo is modest (range of 13.6 to 18.3%). Conclusion: The 7T FLASH-T2* detects more cortical—particularly subpial—lesions compared with 3T DIR. In the absence of DIR/postmortem data, 7T FLASH-T2* is a suitable gold-standard instrument and should be incorporated into future consensus guidelines. J. Magn. Reson. Imaging 2012;537-542. © 2011 Wiley Periodicals, Inc.

Ziel: Darstellung der seit Einfuhrung der MRT in 13 Jahren gewonnenen Erfahrungen in der neuroradiologischen Diagnostik bei Epilepsien und Vorstellung der typischen MRT- und CT-Befunde sowie geeigneter Untersuchungstechniken der haufigsten epileptogenen Strukturveranderungen des Gehirns. Material und Methoden: Analyse typischer Signal- bzw. Dichteabweichungen bei Ammonshornsklerose, glioneuronalen Tumoren und Hamartien (kortikalen Dysplasien), Migrations- und Gyrierungsstorungen, vaskularen und posttraumatischen epileptogenen Lasionen. Ergebnisse: Ammonshornsklerosen, die haufigste Ursache fokaler Epilepsien, werden bei Anwendung hochauflosender koronarer T2-gewichteter Sequenzen durch visuelle Beurteilung und quantitative Messungen von Signal und Volumen der Hippocampi mit 90-98 % Sensitivitat nachgewiesen. Gutartige Tumoren wie Gangliogliome und dysembryoplastische neuroepitheliale Tumoren (DNT) sowie glioneuronale Hamartien weisen gehauft zystische Komponenten neben soliden Anteilen und Verkalkungen, jedoch kein perifokales Odem auf. Storungen der Blut-Hirn-Schranke bei rund 40 % der Tumoren erlauben als einziges Kriterium eine Differenzierung dieser Lasionen gegenuber nicht-tumorosen Veranderungen. Total verkalkte Lasionen konnen gelegentlich der MRT entgehen; hier ist die CT additiv indiziert. Zur Erfassung solider kortikaler Komponenten sind MRT-Bilder in Protonendichte-Gewichtung oder FLAIR-Technik essentiell, um sie gegen Liquor abgrenzen zu konnen. Migrations- und Gyrierungsstorungen werden durch T1-gewichtete Inversion-Recovery (IR)-Techniken am sensitivsten erfast. Bei Verdacht auf vaskulare Lasionen mit Verkalkungen oder Hamosiderindepots und bei posttraumatischen Herden sind T2*-gewichtete Gradienten-Echo-Sequenzen zur Optimierung der Sensitivitat angezeigt. Schlusfolgerungen: Die MRT wird in naher Zukunft zeigen, das bei nahezu 100 % der Patienten mit fokalen Epilepsien strukturelle Parenchymlasionen ursachlich sind. Bereits heute liegt die Sensitivitat der neuroradiologischen Diagnostik bei Anwendung subtiler Untersuchungstechnik bei etwa 90 %. Sie ist damit der Schlussel zur epilepsiechirurgischen Therapieoption. Purpose: To communicate the experience in the neuroradiological evaluation of epilepsy gathered in 13 years since the introduction of MRI in this field and to present typical MRI- and CT-features and appropriate examination techniques for the most frequent epileptogenic structural brain abnormalities. Materials and Methods: Typical signal and density characteristics of hippocampal sclerosis, glioneural tumors and cortical dysplasia, migration- and gyration-abnormalities, and vascular and posttraumatic lesions are analysed. Results: Hippocampal sclerosis, the most frequent cause of focal epilepsy, can be detected with 90-98 % sensitivity by visual analysis and quantitative signal and volume measurement of the hippocampi in high-resolution coronal T2-weighted MR images. Benign tumors, such as gangliogliomas and dysembryoplastic neuoepithelial tumors (DNT), as well as cortical dysplasias are frequently composed of cystic and solid parts, which may show calcification, but never edema. Blood-brain-barrier disruption as seen in approximately 40 % of the benign tumors are the only feature that allows to differentiate them from non-neoplastic dysplasias. In rare cases of totally calcified lesions, CT may be the only diagnostic imaging modality. Proton-density-weighted or FLAIR imaging is essential for the detection of small solid cortical lesion components, because they provide sufficient contrast with adjacent CSF. T1-weighted inversion recovery images are most sensitive for the detection of migration and gyration abnormalities. The depiction of calcified lesions and hemosiderin deposits after trauma is most efficient with T2* weighted gradient echo sequences. Conclusions: With further rapid improvent of high resolution MRI techniques, the near future will probably show that nearly 100 % of focal epilepsies are caused by structural brain abnormalities. With refined imaging techniques applied, the sensitivity of neuroradiological evaluation is 90 % at present. Therefore presurgical MRI plays a key role in epilepsy surgery.

Cortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS) over 48 months. Patients (n=165) were randomized to sc IFNβ-1a 44 μg, im IFNβ-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFNβ-1a (1.4 ± 1.0, range 0–5) compared with im IFNβ-1a (2.3 ± 1.3, range 0–6,P=0.004) and glatiramer acetate (2.2 ± 1.5, range 0–7,P=0.03). Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 months, compared with the 24 months of no treatment. Concluding, this study confirms that DMDs significantly reduce CL development and cortical atrophy progression compared with no treatment.

We describe the clinical and electrophysiological features of an elderly woman presenting with persistent clonic twitching of the abdominal muscles that were considered to represent a rare manifestation of epilepsia partialis continua due to a metastatic cortical lesion.

BACKGROUND AND PURPOSE: In acute stroke with proximal artery occlusion, FLAIR vascular hyperintensities observed beyond the boundaries of the cortical lesion on DWI (newly defined “FLAIR vascular hyperintensity–DWI mismatch”) may be a marker of tissue at risk of infarction. Our aim was to compare the occurrence of FLAIR vascular hyperintensity–DWI mismatch relative to that of perfusion-weighted imaging–DWI mismatch in patients with proximal MCA occlusion before IV thrombolysis. MATERIALS AND METHODS: In 141 consecutive patients with proximal MCA occlusion, 2 independent observers analyzed FLAIR images for the presence of FLAIR vascular hyperintensity–DWI mismatch before IV thrombolysis. PWI-DWI mismatch was defined as Volume(hypoperfusion) > 1.8 × Volume(DWI), with Volume(hypoperfusion) > 6 seconds on time to maximum value of the residue function maps in the 94 patients with available PWI. The presence of FLAIR vascular hyperintensity–DWI mismatch, PWI-DWI mismatch, and infarct growth on 24-hour follow-up DWI was compared. RESULTS: A FLAIR vascular hyperintensity–DWI mismatch was present in 102/141 (72%) patients, with an excellent interobserver reliability (κ = 0.91), and a PWI-DWI mismatch, in 61 of the 94 (65%) patients with available PWI. FLAIR vascular hyperintensity–DWI mismatch predicted PWI-DWI mismatch with a sensitivity of 92% (95% CI, 85%–99%) and a specificity of 64% (95% CI, 47%–80%). Patients with FLAIR vascular hyperintensity–DWI mismatch had smaller initial DWI lesion and larger infarct growth (P < .001) than patients without FLAIR vascular hyperintensity–DWI mismatch, even though their final infarcts remained smaller (P < .001). CONCLUSIONS: Albeit being moderately specific, probably due to inclusion of oligemic tissue, the FLAIR vascular hyperintensity–DWI mismatch identifies large PWI-DWI mismatch with high sensitivity.