Structural and Immunological Alterations at the Human Cribriform Plate in Streptococcus pyogenes Meningitis: A Case Study

Streptococcus pyogenes or group A Streptococcus (GAS) meningitis is a rare but deadly infection with a high mortality. Its mechanisms of invasion are unknown, but it has been proposed to enter either through the cribriform plate olfactory nerve bundles or the blood brain barrier. Knowledge of how GAS impacts the cribriform plate olfactory nerves can help us better understand GAS pathogenesis and invasion, as well as how it impacts the olfactory nerve bundles. Here we present the case of a 39-year-old otherwise healthy man who presented to the local emergency department with altered mental status and expired the following day. Neuropathologic examination revealed bacterial leptomeningitis; blood and cerebrospinal fluid cultures both grew Streptococcus pyogenes. Examination of the cribriform plate was notable for perineural accumulation of GAS around certain olfactory nerve bundles. The accumulation around nerves seems to be random and not correlated to size. Nerves that are impacted by GAS as well as nerves that are not impacted display similar levels of gliosis markers GFAP and podoplanin. Neuropeptide Y, a neuropeptide that implicated in neuro-proliferation and hunger was found to colocalize with CD68 positive immune cells within the nasal epithelium, leading to speculations of its involvement in the inflammatory profile during this case of GAS meningitis. Cribriform plate skull channels had undergone width expansion within the patient, pointing towards local bone marrows involvement during infections. These findings are essential to better understanding the human cribriform plates role in CNS immune response and drainage.