This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12044
Fungal encephalitis in human autopsy cases is associated with extensive neuronal damage but only minimal repair
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
- Accepted manuscript online: 21 MAR 2013 04:44AM EST
- Manuscript Accepted: 15 FEB 2013
- Cited By
- fungal infection;
- axonal injury;
- neuronal apoptosis;
The present study aimed at examining neuronal injury and repair in post mortem brain sections of humans who died from fungal CNS infections.
Histological and immunohistochemical abnormalities in 15 autopsy cases with fungal CNS infections from 1990 to 2008 were compared to findings in 10 age- und sex-matched control cases that died from acute non-neurological causes. The fungal pathogens were identified by culture or PCR and morphology in post mortem tissue. Seven patients with fungal encephalitis had either an organ transplantation or a malignant haematological disorder; 5 out of 15 did not have a classical pre-disposing illness but suffered from severe septic infections as the principal cause of immunosuppression, and 3 from alcoholism.
Fungal organisms detected were Aspergillus spp. and other moulds, Candida spp. and black yeast-like fungi including Cladosporium spp.. Histological analyses identified microglial activation, astrocytosis and axonal injury in the white matter without additional demyelination as characteristic features of this infectious disease. An increased rate of hippocampal neuronal apoptosis was detected in fungal encephalitis, while the number of recently generated TUC-4 and calretinin-expressing neurons in the dentate gyrus did not differ between patients and controls.
Unlike in other infectious diseases of the nervous system where a co-existence of damage and repair was observed, fungal encephalitis is characterized by strong damage and minimal neuronal regeneration.