Abstract
A 64-year-old man with idiopathic CD4+ lymphocytopenia developed cognitive impairment and gait ataxia with isolated obstructive hydrocephalus, which was fatal. Cerebrospinal fluid showed mild pleocytosis, but the etiology was not revealed by extensive analysis. At autopsy, inflammatory cells, CD8+ lymphocytes and abundant macrophages but not CD4+ lymphocytes were infiltrating the meninges at the base of the brain. Electron microscopy demonstrated that inflammation was caused by Cryptococcus neoformans, which was localized exclusively within macrophages, where it grew with budding. Our study suggests that, in idiopathic CD4+ lymphocytopenia, macrophages can efficiently phagocytize but inefficiently digest C. neoformans, thus representing a vehicle of chronic intracellular infection.
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Acknowledgments
We acknowledge the following physicians for referring their patient: Alfredo Colucci and Marco Sarà (Casa di Cura San Raffaele, Cassino). Finally, we thank Mr. Alfredo Colantoni and Mr. Antonio Volpe for expert assistance with immune-histochemistry and electron microscopy studies.
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Appendix
Appendix
Tests used to detect Cryptococcus in CSF
Indian ink preparation. A small amount of India ink (Becton–Dickinson) was added to the CSF sample and observed at 400×.
Gram stain. The pellet of CSF was also used to prepare Gram slides. Particularly, 10 μl of the pellet were placed on a clean slide, air-dried, stained using a Gram stain machine (Delcon) and then observed at 1,000× with mineral oil.
Latex agglutination. The latex agglutination was performed on CSF using the CALAS kit (Meridian Diagnostics, Cincinnati, OH, USA); the assay was performed as described by the manufacturer on serial dilution of the CSF (1:2, 1:4, 1:8, 1:16).
Culture. Shortly after collection, the CSF was centrifuged at 1,800×g for 15 min at room temperature. The supernatant was transferred in a clean sterile tube, while the pellet was suspended in 200 μl of the supernatant and used for culture procedures. Particularly, using a 10 μl calibrate loop, the sample were cultured onto blood and chocolate agar as well as on Sabouraud dextrose agar (Oxoid), without adding cycloheximide to the media. The culture was incubated at 37°C either in ordinary atmosphere as well as in CO2-enriched conditions, and maintained for 5 days. Plates were observed every 24 h until the end of the culture.
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Sancesario, G., Palmieri, G., Viola, G. et al. Difficulty diagnosing chronic cryptococcal meningitis in idiopathic CD4+ lymphocytopenia. Neurol Sci 32, 519–524 (2011). https://doi.org/10.1007/s10072-011-0496-5
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DOI: https://doi.org/10.1007/s10072-011-0496-5