case_images: PMC10850352_01
case_images: (A) Clinical course of the patient, shown as an arbitrary line of her neurological/clinical status decline (y-axis) against time (x-axis): grey arrows indicate running of main diagnostics as described in the text, dotted gray vertical lines indicate milestones of her disease course (onset, admission, intubation, and loss of respiratory center). (B1) The brain MRI on day 12 was mainly unremarkable, except for mild FLAIR signal increase in both insular cortexes (arrows). (B2) The MRI scan on day 28 showed age-related likely mineralization alterations in the basal ganglia (T2*GRE: arrows, present also in MRI of day 12, not shown here), diffuse and punctual gadolinium enhancement (T1 + Gd: arrowheads), and subtle expansion of increased FLAIR signal (FLAIR: arrows). (C) EEG on day 21 shows spontaneous burst suppression (red line) between theta-delta diffuse slowing, while the patient was clinically comatose. (D) On day 41, there is a complete absence of EEG-activity.
case_images: fneur-14-1305748-g001.jpg
case_images: PMC10850352_01_fneur-14-1305748-g001.jpg
case_images: fig1
case_images: The contrasted brain MRI scan on day 12 (Figure 1B1) revealed a discretely increased signal in the insula on the FLAIR sequence and discrete punctuate gadolinium enhancement in the frontal and temporal lobes without corresponding correlates in FLAIR sequences. Her EEG continued to deteriorate, showing a generalized theta-delta rhythm with spontaneous burst suppression on day 21 (Figure 1), indicating severe encephalopathy. A contrasted MRI brain scan performed on day 28 (Figure 1B2) did not correlate with the severity of her clinical status, showing only a subtle expansion of increased FLAIR signal compared to previous scans, some new punctual or diffuse gadolinium enhancement, and a diffuse increase of T2* signal in basal ganglia probably attributed to normal aging.
case_images: Pathology of our Borna-virus case in neocortical (A-C), cerebellar (D-F), pituitary (G-I), and upper cervical spinal cord (L-O) areas. J,K show selected cellular magnifications of brain areas. Hematoxylin-eosin or CD3 (for T lymphocytes) and Borna-virus-type-1 immunohistochemistry are illustrated here. Prominent perivascular as well as diffuse lymphocytic infiltration was found in all neocortical areas (A,B, asterisks at indicative infiltrations). This was accompanied by marked reactive astrogliosis with bizarrely enlarged reactive astrocytes (indicative of sclerosing encephalomyelitis), some of them with eosinophilic intranuclear inclusions (A-inset, arrows point at Joest-Degen bodies, i.e., distinct eosinophilic intranuclear inclusions). Borna disease virus 1 (BoDV-1) immunohistochemistry revealed strong positivity in neurons as well as the surrounding neuropil (C). Distinct inflammatory infiltration was also seen in the cerebellum (D,E, indicative asterisks) though reactive changes were less pronounced. The BoDV-1 signal was primarily visible in the white matter (F). The neurohypophysis (G-I, lower half) demonstrated massive lymphocytic infiltration (G,H) and presence of viral BoDV-1 antigens (I) in contrast to a relative absence of inflammatory infiltrates in the adenohypophysis (G-I upper half). J shows the negative control (frontal cortex of a patient with progressive supranuclear palsy) of our staining. Photos in K demonstrate selected cellular magnifications from lesioned areas, indicating Borna virus positivity in neurons, oligodendrocytes, and astrocytes. Finally, L-N show severe upper spinal cord pathology as well: severe inflammation (indicative asterisks of smaller or larger inflammatory foci) affected and indistinct borders between the gray and white matter (dotted lines in L and O), neuronal loss, and strong reactive astrogliosis (arrowheads pointing at glial cells) indicative of sclerosing encephalitis; N and O show BoDV-1+ signal in the spinal cord. M and N are magnifications of hematoxylin-eosin and BoDV-1 staining, respectively. Cumulatively, the pathology indicated a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest-Degen inclusion bodies in accordance with previous neuropathology studies.
case_images: fneur-14-1305748-g002.jpg
case_images: PMC10850352_01_fneur-14-1305748-g002.jpg
case_images: fig2
case_images: The sclerosing aspect is represented by the strong glial, primarily astrocytic activation with enlarged hypertrophic astrocytes in both brain and spinal cord (Figure 2). "Joest-Degen bodies" [i.e., distinct eosinophilic intranuclear inclusions, considered typical in BoDV-1 infection ] were also found in brain and spinal cord (Figure 2). Bavaria in other cases. BoDV-1 antigens and severe related pathology were detected in multiple areas in the brain, such as neocortical (e.g., frontal and occipital cortexes), hippocampus, subcortical (putamen and basal ganglia), cerebellar (nuclei and cortex), brainstem nuclei (e.g., pons nuclei, substantia nigra, and locus coeruleus) and neurohypophysial areas, as well upper cervical spinal cord (see Figure 2), explaining the clinical presentation of the patient.