LAUSR

The underlying cause of encephalitis and other inflammatory diseases of the human central nervous system remains unclear in a substantial number of cases. Not infrequently, these cases are then assigned an “autoimmune” or “probably infectious” etiology. Two species of bornaviruses are currently unequivocally associated with encephalitis in mammals including humans. Mammalian 2 orthobornavirus (variegated squirrel bornavirus, VSBV) was identified as the cause of encephalitis in breeders of imported squirrels [2]; Mammalian 1 orthobornavirus (BoDV-1 and -2) is the agent of zoonotic borna disease, an encephalitic disease characterized by disturbances of behavior and movements in warm-blooded animals [4] that is most often diagnosed in horses and sheep. Recently, we detected BoDV-1 as the cause of fatal encephalitis in a previously healthy young man [3], and it was found in a cluster of encephalitic disease in organ recipients that received organs of a single donor from southern Bavaria [6]. Due to these new findings, BoDV-1 has now to be considered in the differential diagnosis of human encephalitic CNS diseases. After metagenomic sequencing led us to discover BoDV-1 in the CNS of a young patient who had died of encephalitis, we set out to test for the presence of this pathogen in other patients. For this purpose, we used real-time PCR to test brain biopsies and autopsy materials from cases with CNS disease of putative infectious origin that had been preserved at – 80 °C for years to decades. We detected high copy numbers of BoDV-1 RNA (10e7 copies BoDV-1 per ~ 2000 cells) in a brain biopsy obtained in 1996 from a 31-year-old female patient, whereas samples from four other patients remained negative. After about 10 days of non-specific prodromi (back pain; repeated vomiting attributed to antibiotic treatment for suspected kidney infection), the patient developed paraesthesias in hands, numbness in both legs, absent peripheral reflexes, and during the course paresis of both distal lower extremities. She was then admitted to a local hospital for possible Guillain–Barré-syndrome (GBS)/acute polyradiculitis. CSF analysis initially showed 10 leukocytes/μl and 90 mg/ dl protein on day 1 with a clear albuminocytologic dissociation (total CSF protein up to 3050 mg/dl in follow-up lumbar punctures). Correspondingly, neurographical analysis revealed prolonged distal motor latency in lower extremities in the context of a demyelinating neuropathy. Cranial MRI was normal on admission, but EEG showed general nonfocal abnormalities; with phases of frontal 3/s delta waves. She was treated with plasmapheresis (day 1 and 2), intravenous immunoglobulins (day 1 and 11, 25 g qd), intravenous aciclovir 250 mg t.i.d, ciprofloxacin 2 × 200 mg b.i.d, and amantadine-hemisulfate 200 mg/500 ml qd (for 12 days). On day 2, fever > 39 °C developed, intravenous ceftriaxone 2 g qd was given for 5 days and temperature was normalizing; on day 5/6 she was moved to ICU, and on day 14 she was transferred to our University hospital where she arrived in an unresponsive state. Various diagnostic procedures and laboratory tests were performed but did not reveal an underlying cause. Biopsy of left N. suralis and M. gastrocnemius showed axonal Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0040 1-019-02005 -z) contains supplementary material, which is available to authorized users.