Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases are called prion diseases. Prion proteins enter cells and cause normal cellular proteins to adopt abnormal three-dimensional structures, which in turn leads to disease called prion. Common features of all prion diseases include progressive neurologic impairment, the absence of inflammatory CSF findings and presence of spongiform changes on neuropathologic examination. Invasive neurosurgical procedures for patient with suspected prion disease are discouraged because of the potential for contamination of surgical instruments and exposure of healthcare workers to infectious tissues. Once infection occurs, there is a long incubation period that typically lasts several years. When prions reach a critical level in the brain, symptoms such as depression, difficulty walking and dementia occur and progress rapidly. Definite diagnosis of sporadic CJD in living patients remains a challenge. A test that detects the specific marker for CJD, the prion protein (PrPCJD), by means of real-time quaking-induced conversion (RT-QuIC) testing of CSF has a sensitivity of 80–90% for the diagnosis of sporadic CJD. There are currently no treatments available for these conditions, which are invariably fatal.