Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis.

Objective: To investigate the association between blood-brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC). Methods: In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores. Results: At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans). Interpretation: PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.

Early onset mixed cryoglobulinemia in hepatitis C.

Cryoglobulinemia is one of the most common forms of extrahepatic manifestation of chronic hepatitis infection. The phenomenon is generally seen after several years of chronicity predominantly in the female population resulting in arthralgias, purpuras, and other symptoms, due to vasculitis. Here we present a case of incomplete mixed cryoglobulinemia Type III (as per Brouet's classification) in a young boy aged 13 years who presented with an unusual symptom of pruritus. Diagnosis was confirmed by cryoprecipitation test followed by immunofixation. We aim to highlight the difficulty in diagnosis of this rare case/presentation, important investigation pitfalls and how to avoid them.