@article{GolombeckWessigMonoranuetal.2013,
  author    = {Golombeck, Stefanie Kristin and Wessig, Carsten and Monoranu, Camelia-Maria and Sch{\"u}tz, Ansgar and Solymosi, Laszlo and Melzer, Nico and Kleinschnitz, Christoph},
  title     = {Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report},
  series = {Journal of Medical Case Reports},
  volume    = {7},
  journal   = {Journal of Medical Case Reports},
  number    = {14},
  doi       = {10.1186/1752-1947-7-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135517},
  year      = {2013},
  abstract  = {Introduction: Reversible posterior leukoencephalopathy syndrome - a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures - is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.},
  language  = {en}
}
@article{CadarJellingerRiedereretal.2021,
  author    = {Cadar, D{\´a}niel and Jellinger, Kurt A. and Riederer, Peter and Strobel, Sabrina and Monoranu, Camelia-Maria and Tappe, Dennis},
  title     = {No metagenomic evidence of causative viral pathogens in postencephalitic parkinsonism following encephalitis lethargica},
  series = {Microorganisms},
  volume    = {9},
  journal   = {Microorganisms},
  number    = {8},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms9081716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245074},
  year      = {2021},
  abstract  = {Postencephalitic parkinsonism (PEP) is a disease of unknown etiology and pathophysiology following encephalitis lethargica (EL), an acute-onset polioencephalitis of cryptic cause in the 1920s. PEP is a tauopathy with multisystem neuronal loss and gliosis, clinically characterized by bradykinesia, rigidity, rest tremor, and oculogyric crises. Though a viral cause of EL is likely, past polymerase chain reaction-based investigations in the etiology of both PEP and EL were negative. PEP might be caused directly by an unknown viral pathogen or the consequence of a post-infectious immunopathology. The development of metagenomic next-generation sequencing in conjunction with bioinformatic techniques has generated a broad-range tool for the detection of unknown pathogens in the recent past. Retrospective identification and characterization of pathogens responsible for past infectious diseases can be successfully performed with formalin-fixed paraffin-embedded (FFPE) tissue samples. In this study, we analyzed 24 FFPE brain samples from six patients with PEP by unbiased metagenomic next-generation sequencing. Our results show that no evidence for the presence of a specific or putative (novel) viral pathogen was found, suggesting a likely post-infectious immune-mediated etiology of PEP.},
  language  = {en}
}
@article{BohnertWirthSchmitzetal.2021,
  author    = {Bohnert, Simone and Wirth, Christoph and Schmitz, Werner and Trella, Stefanie and Monoranu, Camelia-Maria and Ondruschka, Benjamin and Bohnert, Michael},
  title     = {Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury},
  series = {International Journal of Legal Medicine},
  volume    = {135},
  journal   = {International Journal of Legal Medicine},
  number    = {4},
  issn      = {1437-1596},
  doi       = {10.1007/s00414-021-02606-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266929},
  pages     = {1525-1535},
  year      = {2021},
  abstract  = {The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.},
  language  = {en}
}
@article{BohnertTrellaPreissetal.2022,
  author    = {Bohnert, Simone and Trella, Stefanie and Preiß, Ulrich and Heinsen, Helmut and Bohnert, Michael and Zwirner, Johann and Tremblay, Marie-{\`E}ve and Monoranu, Camelia-Maria and Ondruschka, Benjamin},
  title     = {Density of TMEM119-positive microglial cells in postmortem cerebrospinal fluid as a surrogate marker for assessing complex neuropathological processes in the CNS},
  series = {International Journal of Legal Medicine},
  volume    = {136},
  journal   = {International Journal of Legal Medicine},
  number    = {6},
  doi       = {10.1007/s00414-022-02863-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325009},
  pages     = {1841-1850},
  year      = {2022},
  abstract  = {Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction.},
  language  = {en}
}
@article{BohnertGeorgiadesMonoranuetal.2021,
  author    = {Bohnert, Simone and Georgiades, Kosmas and Monoranu, Camelia-Maria and Bohnert, Michael and B{\"u}ttner, Andreas and Ondruschka, Benjamin},
  title     = {Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications},
  series = {International Journal of Legal Medicine},
  volume    = {135},
  journal   = {International Journal of Legal Medicine},
  number    = {6},
  issn      = {1437-1596},
  doi       = {10.1007/s00414-021-02699-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266934},
  pages     = {2315-2322},
  year      = {2021},
  abstract  = {The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse.},
  language  = {en}
}