Cryptococcosis is an infection of global importance with significant mortality. Typically, in Immunosuppressed, however seen also in immunocompetent hosts. It can present as meningitis, meningoencephalitis and CNS Cryptococcomas. We report a unique presentation of CNS cryptococcosis.

48 year old lady with a history of Diabetes mellitus and hypothyroidism presented with apathy of 1 week duration with decreased speech output of 1 day duration.On Examination, she was conscious but apathetic. Routine blood investigations were unremarkable. MRI Brain revealed T2 FLAIR hyperintensities with post contrast enhancement and diffusion restriction seen in cortical and deep white matter. CSF study revealed mild pleocytosis and all the infective markers and NMO/MS panel were negative. Considering the possibility of demyelination, she was pulsed with steroids during the course of which she worsened clinicoradiologically. Brain biopsy was suggestive of demyelination. However Cryptococcus PCR in CSF and biopsy specimen were positive. But Indian Ink and fungal cultures persisted to be negative. She improved with amphotericin and flucytosine.

The immunopathogenesis in cryptococcal infection is complex and it is the fungus host interaction that determine the outcome. Our case had extensive demyelination due to excess inflammation mounted by the host,but the process was ineffective to clear the fungus as well as evidenced by PCR positivity on CSF and biopsy specimens. Worsening on steroids and response to anticryptococcal regime gives the evidence of fungus mediated disease.

This case shows that any demyelination should be extensively investigated for secondary causes before labelling it resistant.