More than four years after Knut the celebrity polar bear's death, scientists have finally uncovered the cause of his premature demise.
In a study published Thursday in the journal Scientific Reports, researchers say that Knut died from inflammation of the brain caused by an autoimmune disease known as anti-NMDA receptor encephalitis.
The disease has previously only been seen in humans, and symptoms include headaches, psychotic episodes, epileptic seizures and hyperventilation.
Although the disease can be devastating in humans, it is responsive to medical treatment, the authors write, and it is possible that it might be treatable in bears too.
"We are relieved to have finally solved the mystery of Knut's disease, especially as these insights could have practical applications," Alex Greenwood of the Leibniz Institute for Zoo and Wildlife Research in Berlin said in a statement. "If the current therapy for human patients is also suitable to wild animals, many cases of fatal encephalitis in zoos may be prevented in the future."
Knut's death in 2011 stunned the world. The polar bear was born in the Berlin Zoological Garden in December 2006 and was hand-raised by a devoted zookeeper after being rejected by his mother as an infant. Because of his sad origin story and adorable looks, the young polar bear quickly became an international superstar, gracing the cover of Vanity Fair in 2007 as well as a German stamp.
But then tragedy struck. In March 2011, Knut suffered an epileptic seizure that ultimately led to his drowning in a pool in his enclosure while hundreds of people watched in horror. At the time of his death, he was just 4 years old, a teenager in bear years.
An autopsy revealed that the epileptic seizure was due to encephalitis, or inflammation of the brain, but the root cause of the swelling proved elusive. Bacterial, viral and parasitic infections were all ruled out. And so, for most of the last four years, the agent of Knut's death was described as "encephalitis from unknown causes."
The breakthrough to this medical mystery came after Dr. Harald Preuss, a neuroscientist at the German Center for Neurodegenerative Diseases, read Knut's autopsy report. Preuss reached out to Greenwood, who led the primary study on Knut's death, and asked whether he had considered that the polar bear may have suffered from an auto-immune disease of the brain. The two researchers soon became collaborators.
In the last five years doctors have discovered that most patients who suffer from encephalitis not caused by a virus, bacteria or parasite have anti-NMDA receptor encephalitis. The recently named illness occurs when the body's immune system starts to produce antibodies that attack nerve cells rather than pathogens.
At a news conference, Preuss said the disease affects roughly 200,000 people a year--80% of them young women. Early symptoms include headache and fever, but 100% of the cases progress to psychotic episodes including mood disorders and hallucinations, he said. Eventually patients suffer epileptic seizures and hyperventilation, and require intensive care treatment.
In humans, a diagnosis of anti-NMDA encephalitis is made if a person has evidence of encephalitis with no viral or bacterial causes and antibodies against the NMDA receptor are found in the cerebrospinal fluid -- the clear fluid around the brain and spine.
Tests on frozen pieces of Knut's brain revealed the polar bear had an abundance of the telltale antibodies, while the brain of a polar bear that died of bloat did not.
The researchers say that people who suffer from the disease that probably killed Knut generally recover if immunosuppressive therapy is started early and is aggressive.
This knowledge may not have been able to save Knut, but it might save other animals in the future.