Table_1_Case report: Fatal Borna virus encephalitis manifesting with basal brain and brainstem symptoms.XLSX

BackgroundSince the first report of fatal Borna virus-1 (BoDV-1) encephalitis in 2018, cases gradually increased. There is a lack of diagnostic algorithm, and there is no effective treatment so far.Case presentationWe report an acute BoDV-1 encephalitis in a 77-year-old female with flu-like onset, rapid progression to word-finding difficulties, personality changes, global disorientation, diffuse cognitive slowness, and gait ataxia and further deterioration with fever, meningism, severe hyponatremia, epileptic seizures, cognitive decline, and focal cortical and cerebellar symptoms/signs. The extensive diagnostic workup (cerebrovascular fluid, serum, and MRI) for (meningo-)encephalitis was negative for known causes. Our empirical common antiviral, antimicrobial, and immunosuppressive treatment efforts failed. The patient fell into coma 5 days after admission, lost all brainstem reflexes on day 18, remained fully dependent on invasive mechanical ventilation thereafter and died on day 42. Brain and spinal cord autopsy confirmed an extensive, diffuse, and severe non-purulent, lymphocytic sclerosing panencephalomyelitis due to BoDV-1, affecting neocortical, subcortical, cerebellar, neurohypophysis, and spinal cord areas. Along with our case, we critically reviewed all reported BoDV-1 encephalitis cases.ConclusionThe diagnosis of acute BoDV-1 encephalitis is challenging and delayed, while it progresses to fatal. In this study, we list all tried and failed treatments so far for future reference and propose a diagnostic algorithm for prompt suspicion and diagnosis.</p

Additional file 1: Figure S1. of Nogo receptor complex expression dynamics in the inflammatory foci of central nervous system experimental autoimmune demyelination

Bielschowsky staining, immunofluorescence, and real-time PCR quality controls. (A1–4) Typical images of scores 0–3 in Bielschowsky silver staining. (B, C) Preabsorption assay for LINGO-1 and TROY in serial sections of chronic and acute phases, respectively (the phase where signal is most abundant). (B1) LINGO-1 antibody specifications: rabbit polyclonal, Abcam ab23631, LOT N/A, dilution 1:300. (B2) LINGO-1 peptide specifications: rabbit, Abcam ab25890, LOT #GR41007-1, incubation with ab in 10× molecular ratio. (C1) TROY antibody specifications: goat polyclonal, Santa Cruz sc-13711 (E-19), LOT #H0707, epitope mapping near the C-terminus of TROY of mouse origin, dilution 1:100. (C2) TROY peptide specifications: goat, Santa Cruz sc-13711 P, LOT #B0402, incubation with ab in 10× molecular ratio. (D, E) Antibody specificity test for p75 and NgR with the use of another antibody (different company) recognizing a different epitope in serial sections of chronic and acute phases, respectively (the phase where signal is most abundant). (D1) p75 antibody #1 specifications: mouse monoclonal, Abcam ab8877, LOT GR136825-1, ME20.4, dilution 1:400. (D2) p75 antibody #2 specifications: mouse monoclonal, Santa Cruz p75 (B-1) sc-271708, LOT #J0611, epitope mapping between amino acids 393–427 at the C-terminus of NGFR p75 of human origin, 1:100. (E1) NgR antibody #1 specifications: rabbit polyclonal, Santa Cruz sc-25659 (H-120), LOT E1209, epitope corresponding to amino acids 31–150 mapping near the N-terminus of Nogo-R of human origin, dilution 1:100. (E2) NgR antibody #2 specifications: rabbit polyclonal, Abcam ab26291, LOT N/A, epitope from within residues 150–250 of rat Nogo receptor, dilution 1:100. (F) β-actin real-time PCR quality control showing the specific amplification products on agarose gel and the melting curves of their respective genes; curve identifier: light green TROY, orange p75, dark green LINGO-1. (G) mRNA levels of coreceptors LINGO-1, p75, and TROY in the spinal cord of EAE animals by real-time PCR analysis using GAPDH as a second, quality control, house-keeping gene. The levels of mRNA expression for the coreceptors (G1) LINGO-1, (G2) p75, and (G3) TROY, followed the same pattern with those that underwent β-actin analysis. Error bars indicate the standard statistical error of the mean (SEM), ***p < 0.001, **p < 0.01. Black scale bar = 20 μm