The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 Ϯ 9 years old; 109 women; monthly attack frequency: 3.2 Ϯ 2.5; disease duration: 14 Ϯ 8.4 years) and 115 matched healthy subjects (29 Ϯ 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p Ͻ 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F (1,233) ϭ 6.79), anterior nucleus (F (1,237) ϭ 7.38), and lateral dorsal nucleus (F (1,238) ϭ 6.79). Moreover, reduced striatal volume (F (1,238) ϭ 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.

Background Several previous studies have investigated cortical abnormalities, specifically cortical thickness, in patients with migraine, with variable results. The relatively small sample sizes of most previous studies may partially explain these inconsistencies. Objective To investigate differences of cortical thickness between control subjects and migraineurs in a large cohort. Methods Three Tesla MRI data of 131 patients (38 with and 93 without aura) and 115 control subjects were analysed. A vertex-wise linear model was applied controlling for age, gender and MRI scanner to investigate differences between groups and determine the impact of clinical factors on cortical thickness measures. Results Migraineurs showed areas of thinned cortex compared with controls bilaterally in the central sulcus, in the left middle-frontal gyrus, in left visual cortices and the right occipito-temporal gyrus. Frequency of migraine attacks and the duration of the disorder had a significant impact on cortical thickness in the sensorimotor cortex and middle-frontal gyrus. Patients without aura showed thinner cortex than controls bilaterally in the central sulcus and in the middle frontal gyrus, in the left primary visual cortices, in the left supramarginal gyrus and in the right cuneus. Patients with aura showed clusters of thinner cortex bilaterally in the subparietal sulcus (between the precuneus and posterior cingulate cortex), in the left intraparietal sulcus and in the right anterior cingulate. Conclusion These results indicate cortical abnormalities in specific brain regions in migraineurs. Some of the observed abnormalities may reflect a genetic susceptibility towards developing migraine attacks, while others are probably a consequence of repeated head pain attacks.

Background and ObjectivesThe choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, the aim of this study was to compare the choroid plexus volume in MS and NMOSD.MethodsIn this retrospective, cross-sectional study, patients were included by convenience sampling from 4 international MS centers. The choroid plexus of the lateral ventricles was segmented fully automatically on T1-weighted MRI sequences using a deep learning algorithm (Multi-Dimensional Gated Recurrent Units). Uni- and multivariable linear models were applied to investigate associations between the choroid plexus volume, clinically meaningful disease characteristics, and MRI parameters.ResultsWe studied 180 patients with MS and 98 patients with NMOSD. In total, 94 healthy individuals and 47 patients with migraine served as controls. The choroid plexus volume was larger in MS (median 1,690 µL, interquartile range [IQR] 648 µL) than in NMOSD (median 1,403 µL, IQR 510 µL), healthy individuals (median 1,533 µL, IQR 570 µL), and patients with migraine (median 1,404 µL, IQR 524 µL; all p < 0.001), whereas there was no difference between NMOSD, migraine, and healthy controls. This was also true when adjusted for age, sex, and the intracranial volume. In contrast to NMOSD, the choroid plexus volume in MS was associated with the number of T2-weighted lesions in a linear model adjusted for age, sex, total intracranial volume, disease duration, relapses in the year before MRI, disease course, Expanded Disability Status Scale score, disease-modifying treatment, and treatment duration (beta 4.4; 95% CI 0.78–8.1; p = 0.018).DiscussionThis study supports an involvement of the choroid plexus in MS in contrast to NMOSD and provides clues to better understand the respective pathogenesis.

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.

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The choroid plexus (CP) is an organoid structure located in the ventricles of the brain that produces CSF and serves as a port of entry for lymphocytes into the CNS. In multiple sclerosis (MS), the CP acts as an important modulator and target of inflammatory activity, as shown in postmortem studies.1-3 Recently, new evidence has emerged highlighting the importance of in vivo CP measurements for understanding MS pathogenesis. The first study, published in 2020, showed gadolinium enhancement in the CP of patients with MS who had recently experienced a clinical relapse.4 Subsequent work demonstrated that CP volume was larger in patients with RRMS than in healthy controls, particularly in those with radiologically active disease, in whom it also correlated with clinical relapses.5 Clinical relevance of the finding was suggested when it was shown that CP volume correlated with the expanded disability status scale (EDSS).6 CP volume also predicted future EDSS development over a follow-up of 4 years, more than conventional MRI markers, such as the number of T2 or gadolinium-enhancing lesions at baseline. The enlargement of the CP is MS-specific because it was not observed in patients with neuromyelitis optica spectrum disorder or migraine.7 Most recently, CP enlargement in MS was associated with the expansion of chronic lesions and lesion severity measured with diffusion MRI8 and with remyelination failure in periventricular areas quantified with 11C-PiB-PET.9

ObjectiveCortical lesions are common in multiple sclerosis (MS), but their visualization is challenging on conventional magnetic resonance imaging. The uniform image derived from magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGEuni) detects cortical lesions with a similar rate as the criterion standard sequence, double inversion recovery. Fluid and white matter suppression (FLAWS) provides multiple reconstructed contrasts acquired during a single acquisition. These contrasts include FLAWS minimum image (FLAWSmin), which provides an exquisite sensitivity to the gray matter signal and therefore may facilitate cortical lesion identification, as well as high contrast FLAWS (FLAWShco), which gives a contrast that is similar to one of MP2RAGEuni. In this study, we compared the manual detection rate of cortical lesions on MP2RAGEuni, FLAWSmin, and FLAWShco in MS patients. Furthermore, we assessed whether the combined detection rate on FLAWSmin and FLAWShco was superior to MP2RAGEuni for cortical lesions identification. Last, we compared quantitative T1 maps (qT1) provided by both MP2RAGE and FLAWS in MS lesions.Materials and MethodsWe included 30 relapsing-remitting MS patients who underwent MP2RAGE and FLAWS magnetic resonance imaging with isotropic spatial resolution of 1 mm at 3 T. Cortical lesions were manually segmented by consensus of 3 trained raters and classified as intracortical or leukocortical lesions on (1) MP2RAGE uniform/flat images, (2) FLAWSmin, and (3) FLAWShco. In addition, segmented lesions on FLAWSmin and FLAWShco were merged to produce a union lesion map (FLAWSmin + hco). Number and volume of all cortical, intracortical, and leukocortical lesions were compared among MP2RAGEuni, FLAWSmin, and FLAWShco using Friedman test and between MP2RAGEuni and FLAWSmin + hco using Wilcoxon signed rank test. The FLAWS T1 maps were then compared with the reference MP2RAGE T1 maps using relative differences in percentage. In an exploratory analysis, individual cortical lesion counts of the 3 raters were compared, and interrater variability was quantified using Fleiss ϰ.ResultsIn total, 633 segmentations were made on the 3 contrasts, corresponding to 355 cortical lesions. The median number and volume of single cortical, intracortical, and leukocortical lesions were comparable among MP2RAGEuni, FLAWSmin, and FLAWShco. In patients with cortical lesions (22/30), median cumulative lesion volume was larger on FLAWSmin (587 μL; IQR, 1405 μL) than on MP2RAGEuni (490 μL; IQR, 990 μL; P = 0.04), whereas there was no difference between FLAWSmin and FLAWShco, or FLAWShco and MP2RAGEuni. FLAWSmin + hco showed significantly greater numbers of cortical (median, 4.5; IQR, 15) and leukocortical (median, 3.5; IQR, 12) lesions than MP2RAGEuni (median, 3; IQR, 10; median, 2.5; IQR, 7; both P < 0.001). Interrater agreement was moderate on MP2RAGEuni (ϰ = 0.582) and FLAWShco (ϰ = 0.584), but substantial on FLAWSmin (ϰ = 0.614). qT1 in lesions was similar between MP2RAGE and FLAWS.ConclusionsCortical lesions identificati...

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