Transmissible spongiform encephalopathies (TSE) are characterized by very long incubation periods before irreversible brain and nerve damage occurs, resulting in progressive dementia and death. There are no signs or symptoms in the early course of the diseases and the first signs or symptoms may not appear for years or even decades after the infection first occurred. After symptoms do appear, the diseases tend to progress very quickly, often leading to death within a year.

Most TSEs have similar symptoms, although the severity of certain symptoms may be greater in one form than in another. The first symptoms of many TSEs are psychiatric problems (e.g., depression, anxiety, insomnia). Personality changes may also occur. Eventually, neurological signs develop. Patients may experience unpleasant sensations, problems walking and a lack of muscle coordination. They may have involuntary jerking motions (myoclonus). Vision problems, which may lead to blindness, are also common. They may feel confused, forgetful, or have difficulty thinking and speaking.

Most TSEs do not cause disturbances in the endocrine system or autonomic nervous system (the part of the nervous system that controls body functions). Fatal familial insomnia (FFI) is the exception. Patients with FFI may experience excessive sweating, high body temperatures, increased heart rate and high blood pressure.

In later courses of the diseases, patients become unable to speak or move muscles as the brain degenerates. They eventually may enter a coma. Infections (e.g., pneumonia) are common and may be the cause of death for many patients. The presence of tiny holes in the brain (giving it a spongy appearance) at autopsy indicates TSE.