BRIEF COMMUNICATION Difficulty diagnosing chronic cryptococcal meningitis in idiopathic CD4 + lymphocytopenia Giuseppe Sancesario • Giampiero Palmieri • Gemma Viola • Carla Fontana • Alessandra Perfetti • Lucia Anemona • Roberto Floris • Simone Marziali • Giorgio Bernardi • Luigi Giusto Spagnoli Received: 30 April 2010 / Accepted: 16 February 2011 / Published online: 8 March 2011 Ó Springer-Verlag 2011 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. Keywords Cryptococcosis Á Cryptococcus neoformans Á Idiopathic CD4 lymphocytopenia Á Macrophages Á Electron microscopy Introduction Cryptococcus neoformans is an encapsulated yeast that is responsible for the most common fungal infection of the central nervous system (CNS), which usually manifests with acute meningitis and meningoencephalitis [1]. The diagnosis of cryptococcal meningitis is rarely a problem in patients with AIDS and other forms of immunosuppression, since Cryptococcus can be detected microscopically in cerebrospinal fluid (CSF) preparations, in standard culture systems, and by highly sensitive and specific cryptococcal antigen testing [2]. However, the conventional diagnostic approaches may sometimes fail to identify the pathogen and its antigens in the CSF, especially in immunocompe- tent patients, and then a false-negative diagnosis eventually ensues [2–5]. Undiagnosed and untreated cryptococcosis may have a poor prognosis also in immunocompetent patients. In the present report, we illustrate the occurrence of a chronic infection around the brain stem caused by C. neoformans, and clarify the pathogenesis and difficulty in diagnosis of such an insidious form of focal chronic cryptococcal meningitis, as opposed to acute disseminated meningitis. Patient and methods Patient A 64-year-old male engineer presented with a history of progressive cognitive impairment of 5 months duration, followed by gait ataxia and spastic tetraparesis. He was admitted to the local hospital with suspicion of Creutz- feldt–Jacob disease, but 14-3-3 protein immunoassay of G. Sancesario (&) Á C. Fontana Á G. Bernardi Dipartimento di Neuroscienze, Universita ` di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy e-mail: sancesario@med.uniroma2.it G. Palmieri Á C. Fontana Á A. Perfetti Á L. Anemona Á R. Floris Á S. Marziali Á L. G. Spagnoli Department of Biopathology, University of Rome Tor Vergata, Rome, Italy G. Viola Á C. Fontana Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy G. Sancesario Á C. Fontana Á G. Bernardi Santa Lucia Foundation, Rome, Italy 123 Neurol Sci (2011) 32:519–524 DOI 10.1007/s10072-011-0496-5