CNS Fungal Infections in Immuno-competent patients; diagnostic dilemma and therapeutic challenges. Dr Mahmoud Taha, Dr. Hatim S. AlKhanjaf, Dr Tarek Jallul, Dr Reem Bunyan, Dr Baha Abdelhameed Department of Neurosurgery, Department of Neurology, Department of Microbiology King Fahad Specialist Hospital-Dammam, Saudi Arabia Introduction Fungal infections of the central nervous system (CNS) are rare clinical entities. It presents with different clinical manifestations and causes high morbidity and mortality.  Methods This is a retrospective case series study on patients with CNS fungal infections who were immune-competent in a tertiary care hospital. The study covers a 5 years period 2012-2016. We reviewed clinical presentations, radiological imaging, laboratory diagnosis, treatment, and clinical progress. Results We found 4 patients, all male, age range (21-65). Two had a direct invasion from the nasal sinuses (Aspergillus infection) with a very aggressive clinical and radiological behavior. The other two were blood-borne with multiple lesions resembling infective emboli and stoke (Dematiaceous infection; one Bipolaris subtype and one Chaetomium subtype). All patients failed to respond to medical and surgical treatment and died within few months from diagnosis. Discussion CNS fungal infection in immuno-competent patients is a catastrophic disease with a very poor outcome. Despite aggressive surgical and medical therapy the mortality can be between 60-100%. There are two main sources of infections and types. 1- Local invasion from the paranasal sinuses, usually the pathogens are Aspergilosus, and they behave like aggresive, invasive, mass lesions. 2- Blood-born source, caused by different types of fungus (usually mould) and it present by stroke (embolic or hemorrhagic), then progress into multiple mass lesions and necrosis.. Both types can invade brain vessels and cause ischemia which contribute to the poor prognosis. Aggressive surgery is not always possible in CNS fungal infections due to location of the lesions and proximity to eloquent areas of the brain. Failure of medical therapy might be due to the poor diffusion through the blood brain barrier and/or the presence of resistance in certain regions or places (like in our cases) Conclusion CNS fungal infections in immuno-competent can present in different syndromes (skull base invasion or vascular) and can be quite challenging to diagnose and to treat. More studies are needed to study the resistance of some fungal pathogens to medical therapy. References Jose Gavito-Higuera, Carola Birgit Mullins, Luis Ramos-Duran, et al. Fungal Infections of the Central Nervous System: A Pictorial Review, J Clin Imaging Sci. 2016; 6: 24 J.M.K Murthy. Fungal infections of the central nervous system: The clinical syndromes. Neurology India, 2007; 55: 3; 221-225.