Total Brain Death is a tier 4 symptom exclusive to the Simian Flu DLC. It allows the virus to completely replace human brain's cells DNA, resulting in a massive autoimmune response that results in a total, irreversible loss of brain function that quickly leads to death. This is one of the most lethal symptoms in Plague Inc.
This symptom is very lethal, but is not recommended when playing on Brutal or Mega Brutal difficulties because the previous symptoms required to unlock it increase research speed. However, if these symptoms (i.e. Neuro-enhancement 1, etc.) evolve by themselves (most likely due to the fact that Creationist and other similar genes are unavailable in Simian Flu), it is fine to evolve Total Brain Death. Total Brain Death can be safely evolved when a sizable portion of the world is infected.
- In the movie, Will's father, Charles, is given the ALZ-112 virus to cure his Alzheimer's. The cure works for several years until his immune system rejects it, resulting in his death.