111\u2005Delayed neurological worsening in an immunocompetent adult with Cryptococcus gattii meningoencephalitis

Abstract

Objective While typically considered a condition of immunocompromised patients, Cryptococcus gattiimeningoencephalitis is increasingly observed in immunocompetent individuals, where the clinical outcomes are generally worse.1 2 Methods Case report. Results 24year old male represented with a three-week history of progressively worsening headache, lethargy, generalised weakness, binocular diplopia, hearing loss and unintentional weight loss. Two weeks prior, he had presented with coryzal symptoms and received outpatient treatment for community acquired pneumonia. A lumbar puncture was performed with an opening pressure greater than 34cmH2O, pleocytosis and positive India ink stain. Cryptococcus gattii was cultured at a titre of 1:2048. MRI brain demonstrated bilateral basal ganglia change and leptomeningeal enhancement consistent with Cryptococcal meningitis. Serum HIV was negative. Induction treatment with ambisome-flucytosine was initiated. Lumbar drain and subsequent VP shunt were required for management of persistent symptomatic increased intracranial pressure. After 6weeks of therapy he was transitioned to consolidation fluconazole. Repeat CSF demonstrated improved Cryptococcal Ag titre of 1:512. Two months into rehabilitation he suffered a seizure and rapid progressive neurological decline. EEG demonstrated a moderately severe diffuse encephalopathy. Repeat CSF cryptococcal Ag was stable. CSF limbic encephalitis and NMDA antibodies were negative. Repeat MRI brain demonstrated worsening supratentorial leptomeningeal enhancement and parenchymal vasogenic oedema, consistent with paradoxical upgrading reaction (PUR). Prednisolone 1mg/kg was initiated and the patient improved in days. Conclusions PUR is an immune-reconstitution like event that can occur in immunocompetent patients. It represents an important cause of neurological deterioration in Cryptococcus gattii meningoencephalitis, requiring differentiation from relapse on consolidation therapy. References Franco-Paredes, et al. Management of cryptococcus gattii meningoencephalitis. Lancet Infect Dis 2014;15(3):348–355. Chen, et al. Cryptococcus gattii infections. Clin Microbiol Rev 2014;27(4):980–1024.