Cerebral microstructural alterations in Post-COVID-condition are related to cognitive impairment, olfactory dysfunction and fatigue.

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.

Clinical value of neuroimaging indicators of intracranial hypertension in patients with cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.

Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms.

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value <26/30 points) underwent DMI in the subacute stage of the disease (29.3 ± 14.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n = 35) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r = -0.64, P = 0.006) but not with olfactory performance (r = 0.29, P = 0.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r = 0.48, P = 0.068), a prominent marker of the COVID-19 related inflammatory response. In 14/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r = 0.57; P = 0.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase. In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Novel anti-cytoplasmic antibodies in cerebrospinal fluid and serum of patients with chronic severe mental disorders.

OBJECTIVES: There is an emerging role of autoimmune causes related to severe mental disorders (SMD). The clinical approach in patients with chronic SMD and novel anti-central nervous system antibodies is complex. METHODS: Two corresponding cumulative cases are presented. Cerebrospinal fluid (CSF) and serum were investigated using tissue-based assays. RESULTS: Both patients suffered from chronic SMD and were negative for well-characterized neuronal antibodies. Patient 1 suffered from a dysexecutive and neurocognitive syndrome with mild abnormalities in automated electroencephalography analysis, elevated CSF protein levels, several serum autoantibodies (including antibodies against endothelial cells), and novel antibodies with a "dotted/scalloped" binding against cytoplasmic structures in CSF. Patient 2 with obsessive-compulsive disorder had left temporal abnormalities on automated magnetic resonance imaging analysis, an elevated CSF/serum albumin quotient, and novel atypical cytoplasmic "spotted" antibody staining in the serum. Patient 1 improved with immunotherapy using high-dose steroids, but patient 2 did not improve under the same treatment. CONCLUSIONS: The detection of autoantibodies in CSF of chronic SMD may be beneficial in selecting some patients for immunotherapy. The possible impact of novel anti-cytoplasmic antibodies in this context is critically discussed. Further research is needed to establish the underlying pathophysiological processes as well as their diagnostic and therapeutic implications.

Mesoscopic imaging of glioblastomas: Are diffusion, perfusion and spectroscopic measures influenced by the radiogenetic phenotype?

The purpose of this study was to identify markers from perfusion, diffusion, and chemical shift imaging in glioblastomas (GBMs) and to correlate them with genetically determined and previously published patterns of structural magnetic resonance (MR) imaging. Twenty-six patients (mean age 60 years, 13 female) with GBM were investigated. Imaging consisted of native and contrast-enhanced 3D data, perfusion, diffusion, and spectroscopic imaging. In the presence of minor necrosis, cerebral blood volume (CBV) was higher (median ± SD, 2.23% ± 0.93) than in pronounced necrosis (1.02% ± 0.71), pcorr = 0.0003. CBV adjacent to peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity was lower in edema (1.72% ± 0.31) than in infiltration (1.91% ± 0.35), pcorr = 0.039. Axial diffusivity adjacent to peritumoral FLAIR hyperintensity was lower in severe mass effect (1.08*10-3 mm2/s ± 0.08) than in mild mass effect (1.14*10-3 mm2/s ± 0.06), pcorr = 0.048. Myo-inositol was positively correlated with a marker for mitosis (Ki-67) in contrast-enhancing tumor, r = 0.5, pcorr = 0.0002. Changed CBV and axial diffusivity, even outside FLAIR hyperintensity, in adjacent normal-appearing matter can be discussed as to be related to angiogenesis pathways and to activated proliferation genes. The correlation between myo-inositol and Ki-67 might be attributed to its binding to cell surface receptors regulating tumorous proliferation of astrocytic cells.

Anatomical shape analysis of the mandible in Caucasian and Chinese for the production of preformed mandible reconstruction plates.

PURPOSE: The purpose of this study was to evaluate and analyze statistical shapes of the outer mandible contour of Caucasian and Chinese people, offering data for the production of preformed mandible reconstruction plates. METHODS: A CT-database of 925 Caucasians (male: n=463, female: n=462) and 960 Chinese (male: n=469, female: n=491) including scans of unaffected mandibles were used and imported into the 3D modeling software Voxim (IVS-Solutions, Chemnitz, Germany). Anatomical landmarks (n=22 points for both sides) were set using the 3D view along the outer contour of the mandible at the area where reconstruction plates are commonly located. We used morphometric methods for statistical shape analysis. RESULTS: We found statistical relevant differences between populations including a distinct discrimination given by the landmarks at the mandible. After generating a metric model this shape information which separated the populations appeared to be of no clinical relevance. The metric size information given by ramus length however provided a profound base for the production of standard reconstruction plates. CONCLUSION: Clustering by ramus length into three sizes and calculating means of these size-clusters seem to be a good solution for constructing preformed reconstruction plates that will fit a vast majority.