Dataset Information

In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping.

ABSTRACT: A 35-year-old man with an enhancing tumefactive brain lesion underwent biopsy, revealing inflammatory demyelination. We used quantitative Gradient-Recalled-Echo (qGRE) MRI to visualize and measure tissue damage in the lesion. Two weeks after biopsy, qGRE showed significant R2t* reduction in the left optic radiation and surrounding tissue, consistent with the histopathological and clinical findings. qGRE was repeated 6 and 14 months later, demonstrating partially recovered optic radiation R2t*, in concert with improvement of the hemianopia to ultimately involve only the lower right visual quadrant. These results support qGRE metrics as in vivo biomarkers for tissue damage and longitudinal monitoring of demyelinating disease.

SUBMITTER: Xiang B

PROVIDER: S-EPMC7317639 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping.

Xiang Biao B Wen Jie J Lu Hsiang-Chih HC Schmidt Robert E RE Yablonskiy Dmitriy A DA Cross Anne H AH

Annals of clinical and translational neurology 20200504 6

A 35-year-old man with an enhancing tumefactive brain lesion underwent biopsy, revealing inflammatory demyelination. We used quantitative Gradient-Recalled-Echo (qGRE) MRI to visualize and measure tissue damage in the lesion. Two weeks after biopsy, qGRE showed significant R2t* reduction in the left optic radiation and surrounding tissue, consistent with the histopathological and clinical findings. qGRE was repeated 6 and 14 months later, demonstrating partially recovered optic radiation R2t*, i ...[more]

PMID: 32367692

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Project description:Background: There is still no consensus about the coronavirus disease 2019 (COVID-19) vaccine-associated glomerular disease (CVAGD). Given the large number of vaccinations administered and the variations in glomerulopathy observed across different countries and regional environments, CVAGD remains an important area of concern. Aim of study: We aimed to elucidate the findings of CVAGD within a Taiwanese cohort using biopsy data. Additionally, we endeavored to clarify the presentation of CVAGD. Methods: We collected data from patients who underwent renal biopsy from June 2021 to October 2022 at Taichung Veterans General Hospital. Two independent nephrologists meticulously reviewed the charts to exclude cases unrelated to vaccination. Results: Initially, a total of 286 patients underwent renal biopsy at our institute. Ultimately, we identified 14 patients with highly suspected CVAGD. All 14 patients exhibited proteinuria and hematuria. The urinary protein-to-creatinine ratio was elevated (median of 2012.1 mg/g; interquartile range (IQR) 25%-IQR 75%: 941.85-3884.1 mg/g) with a median serum creatinine level of 1.71 mg/dL (0.79-5.35). The majority of CVAGD cases were diagnosed as immunoglobulin A (IgA) nephropathy (n = 5, 35.7%), followed by antineutrophil cytoplasmic antibody (ANCA)-related rapidly progressive glomerulonephritis (RPGN) (n = 4, 28.6%). There were only three cases of minimal change disease each: one case of focal segmental glomerulosclerosis, one of membranous glomerulonephritis, and one of lupus nephritis. The culprit of COVID-19 vaccinations was 35.7% (n = 5) of Oxford-AstraZeneca (ChAdOx1-S), 42.9% (n = 6) of Moderna, and 21.4% (n = 3) of BNT162b2. Most patients experienced improvements in renal function. Only two cases of P-ANCA RPGN and one case of IgA nephropathy did not recover. Eighty percent of IgA nephropathy cases had favorable outcomes, but none of the patients with P-ANCA RPGN achieved full recovery. Conclusions: IgA nephropathy and ANCA-related RPGN were the most common CVAGD, and all types of COVID-19 vaccines posed a risk for CVAGD. However, further studies are required to confirm causality.

Project description:Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail.Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS. Demyelination and inflammation were assessed by real-time polymerase chain reaction and immunohistochemistry. Synaptic changes associated with inflammatory demyelination in the dorsal lateral geniculate nucleus (dLGN) were determined by immunohistochemistry, Western blot analysis, and electrophysiological field potential recordings.In the cuprizone model, demyelination was observed in retinorecipient regions of the subcortical visual system, in particular the dLGN, where it was found accompanied by microglia activation and astrogliosis. In contrast, anterior parts of the pathway, i.e., the optic nerve and tract, appeared largely unaffected. Under the inflammatory demyelinating conditions, as seen in the dLGN of cuprizone-treated mice, there was an overall decrease in excitatory synaptic inputs from retinal ganglion cells. At the same time, the number of synaptic complexes arising from gamma-aminobutyric acid (GABA)-generating inhibitory neurons was found increased, as were the synapses that contain the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B and converge onto inhibitory neurons. These synaptic changes were functionally found associated with a shift toward an overall increase in network inhibition.Using the cuprizone model of inflammatory demyelination, our data reveal a novel form of synaptic (mal)adaption in the CNS that is characterized by a shift of the excitation/inhibition balance toward inhibitory network activity associated with an increase in GABAergic inhibitory synapses and a possible increase in excitatory input onto inhibitory interneurons. In addition, our data recognize the cuprizone model as a suitable tool in which to assess the effects of inflammatory demyelination on subcortical retinorecipient regions of the visual system, such as the dLGN, in the absence of overt optic neuritis.

Dataset Information

In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping.

Publications

In vivo evolution of biopsy-proven inflammatory demyelination quantified by R2t* mapping.

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