Die Borna-Virus-Enzephalitis als Differenzialdiagnose zur seronegativen Autoimmunenzephalitis

Meier, H.; Bauer, Christina; Finkenzeller, W.; Nentwich, Jens; Städt, Michael; Steininger, Philipp; Korn, Klaus; Essner, A.; Erbguth, Frank

doi:10.1007/s00115-021-01259-x

Cited by 11 publications

(16 citation statements)

References 6 publications

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“…Absence of such antibodies in psychiatric patients was described years before [ 7 , 8 ] in times of scientific dispute about the controversial involvement of BoDV-1 in psychiatric disease [ 9 , 24 ], but testing had not been performed in an endemic area. Our negative findings do not rule out that BoDV-1 causes neuropsychiatric symptoms during encephalitis however; in the initial phase of BoDV-1 encephalitis, hallucinations and behavior changes are well noted [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 79%

Detection of bornavirus-reactive antibodies and BoDV-1 RNA only in encephalitis patients from virus endemic areas: a comparative serological and molecular sensitivity, specificity, predictive value, and disease duration correlation study

et al. 2023

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Purpose Human Borna disease virus (BoDV-1) encephalitis is an emerging disease in Germany. This study investigates the spectrum of human BoDV-1 infection, characterizes anti-BoDV-1-antibodies and kinetics, and compares laboratory test performances. Methods Three hundred four encephalitis cases, 308 nation-wide neuropsychiatric conditions, 127 well-defined psychiatric cases from Borna disease-endemic areas, and 20 persons with contact to BoDV-1 encephalitis patients or animals were tested for BoDV-1 infections by serology and PCR. Results BoDV-1 infections were only found in encephalitis patients with residence in, or recent travel to, virus-endemic areas. Antibodies were detected as early as 12 days after symptom onset. Serum antibody levels correlated with disease duration. Serology was ordered after 50% of the disease duration had elapsed, reflecting low awareness. BoDV-1-antibodies were of IgG1 subclass, and the epitope on BoDV-1 antigens was determined. Specificity of the indirect immunofluorescence antibody test (IFAT) and lineblot (LB) from serum and cerebrospinal fluid (CSF), as well as PCR testing from CSF, was 100%. Sensitivity, depending on first or all samples, reached 75–86% in serum and 92–94% in CSF for the IFAT, and 33–57% in serum and 18–24% in CSF for the LB. Sensitivity for PCR in CSF was 25–67%. Positive predictive values were 100% each, while negative predictive values were 99% (IFAT), 91–97% (LB), and 90% (PCR). Conclusions There is no hint that BoDV-1 causes other diseases than encephalitis in humans. Awareness has to be increased in virus-endemic areas. Tests are robust but lack sensitivity. Detection of IgG1 against specific peptides may facilitate diagnosis. Screening of healthy individuals is likely not beneficial.

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Section: Discussionmentioning

confidence: 79%

Detection of bornavirus-reactive antibodies and BoDV-1 RNA only in encephalitis patients from virus endemic areas: a comparative serological and molecular sensitivity, specificity, predictive value, and disease duration correlation study

et al. 2023

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“…To date, at least 23 human infections have been published, of which 22 patients died. 12,18,29,33,36,40,41,51,59 Three of these patients acquired the infection after receiving liver or kidney transplants from the same infected donor, 33,51 while the majority of the cases appear to be the result of sporadic spillover events directly from the reservoir host. 12,18,29,36,40,41,59 Viral antigen and RNA were localized mainly in the patients’ CNS, virtually identical to the other known dead-end hosts.…”

mentioning

confidence: 99%

“…12,18,29,33,36,40,41,51,59 Three of these patients acquired the infection after receiving liver or kidney transplants from the same infected donor, 33,51 while the majority of the cases appear to be the result of sporadic spillover events directly from the reservoir host. 12,18,29,36,40,41,59 Viral antigen and RNA were localized mainly in the patients' CNS, virtually identical to the other known dead-end hosts. 41,51 Generally, BD occurs sporadically in spillover hosts and is usually restricted to a few individuals or animals of a herd.…”

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confidence: 99%

Borna disease virus 1 infection in alpacas: Comparison of pathological lesions and viral distribution to other dead-end hosts

et al. 2023

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Borna disease is a progressive meningoencephalitis caused by spillover of the Borna disease virus 1 (BoDV-1) to horses and sheep and has gained attention due to its zoonotic potential. New World camelids are also highly susceptible to the disease; however, a comprehensive description of the pathological lesions and viral distribution is lacking for these hosts. Here, the authors describe the distribution and severity of inflammatory lesions in alpacas ( n = 6) naturally affected by this disease in comparison to horses ( n = 8) as known spillover hosts. In addition, the tissue and cellular distribution of the BoDV-1 was determined via immunohistochemistry and immunofluorescence. A predominant lymphocytic meningoencephalitis was diagnosed in all animals with differences regarding the severity of lesions. Alpacas and horses with a shorter disease duration showed more prominent lesions in the cerebrum and at the transition of the nervous to the glandular part of the pituitary gland, as compared to animals with longer disease progression. In both species, viral antigen was almost exclusively restricted to cells of the central and peripheral nervous systems, with the notable exception of virus-infected glandular cells of the Pars intermedia of the pituitary gland. Alpacas likely represent dead-end hosts similar to horses and other spillover hosts of BoDV-1.

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“…Single (in vitro or in vivo) experimental studies testing antiviral compounds (ribavirin [30,31] or favipiravir (T-705) [32]), cocktails of small interfering RNAs (siRNAs) [33] or combinations of those, have not clinically proven effective at the moment. Indeed, favipiravir or ribavirin administration in individual BoDV-1 cases was ineffective [2,22,34], maybe due to a delayed administration. Alternatively, as BoDV-1 induces a severe pro-in ammatory state [20], a combination of antiviral and anti-in ammatory could theoretically be bene cial.…”

Section: Discussionmentioning

confidence: 99%

A potential role for early hyponatremia in the diagnosis of Borna-virus encephalitis?

Lourbopoulos

Schnurbus

Guenther

et al. 2023

Preprint

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Background The first case of fatal Borna Virus-1 encephalitis (BoDV-1) was reported in 2018. Here, we report another fatal case of BoDV-1 encephalitis with early severe hyponatremia, indicative of neurohypophysial dysfunction. Case presentation: A 77-year-old female living in southern Germany was admitted to hospital in 2020 due to rapidly progressing word-finding difficulties, personality changes, global disorientation, diffuse cognitive slowness, and gait ataxia, initially without fever. After a rapid deterioration with fever, gait instability and ataxia, rapid cognitive decline, meningism, epileptic seizures, aphasia, and signs of latent right hemiparesis, the suspicion of a (meningo-)encephalitis was set. Furthermore, an unexplained, severe hyponatremia had been present since admission. Laboratory workup in cerebrovascular fluid (CSF) and serum as well as brain imaging was negative. Despite extensive empirical antiviral, antimicrobial, and immunosuppressive treatment efforts, the patient fell into coma (day 5), lost all brainstem functions (day 18), and remained fully dependent on invasive mechanical ventilation. Finally, she clinically developed a status of brain death and died 42 days after initial admission. Brain autopsy confirmed an extensive, diffuse, and severe affection of neocortical, subcortical and cerebellar structures as well as the neurohypophysis due to infection with BoDV-1. In light of the autopsy results, the hyponatremia could imply an early basal brain involvement, which could narrow down the initial differential diagnosis. Conclusion The diagnosis of BoDV-1 encephalitis remains clinically challenging. The disease progresses quickly to irreversible brain damage. An early, unexplained, hyponatremia in the presence of severe and rapidly evolving encephalitis may narrow down the diagnosis.

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Die Borna-Virus-Enzephalitis als Differenzialdiagnose zur seronegativen Autoimmunenzephalitis

Cited by 11 publications

References 6 publications

Detection of bornavirus-reactive antibodies and BoDV-1 RNA only in encephalitis patients from virus endemic areas: a comparative serological and molecular sensitivity, specificity, predictive value, and disease duration correlation study

Detection of bornavirus-reactive antibodies and BoDV-1 RNA only in encephalitis patients from virus endemic areas: a comparative serological and molecular sensitivity, specificity, predictive value, and disease duration correlation study

Borna disease virus 1 infection in alpacas: Comparison of pathological lesions and viral distribution to other dead-end hosts

A potential role for early hyponatremia in the diagnosis of Borna-virus encephalitis?

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