The circumstances of the death of Knut, the famous polar bear born in the Zoo Berlin, have finally been unraveled four years later. The answer presents a little scientific sensation which was published in “Scientific Reports” on August 27th. Knut fell sick with a so-called anti-NMDA receptor encephalitis, a brain inflammation caused by autoantibodies against the receptor protein NMDA. The autoimmune disease was described in 2007 for the first time, and since then, has been diagnosed in humans exclusively.
Knut was born in the Zoo Berlin in 2006 and was raised by his keeper Thomas Dörflein. The polar bear cub was beloved by the visitors and turned into one of the best known zoo animals, internationally. In 2011, the bear drowned after suffering epileptic seizures and falling into the enclosure’s pool. Substantial analyses were conducted to identify the trigger of the epileptic seizures. However, results did not provide a satisfying explanation (e. g. a bacterial or viral infection). Final diagnosis: encephalitis of unknown etiology.
Prior to identification of anti-NMDA receptor antibodies, this diagnosis had also been established in many human patients with this particular disease – this analogy to Knut’s case prompted the neurologist Dr. Harald Prüß (Charité, Berlin) and Prof. Alexander Greenwood (head of department Wildlife Diseases at the Leibniz Institute for Zoo and Wildlife Research) to examine the bear’s brain once more.
Autopsy and histological analysis of the tissue confirmed the diagnosed encephalitis. Additionally, the researchers detected a very high concentration of anti-NMDA receptor antibodies in CSF (cerebrospinal fluid). Immunofluorescence assays applying neuronal tissue sections and transfected cell lines, which are regarded as gold standard for detection of these autoantibodies, revealed an extraordinarily high antibody titer of more than 1:1,000 in the course of Knut’s CSF examination. The results were verified with the help of the EUROIMMUN IFA Autoimmune Encephalitis Mosaic 1. The presence of further autoantibodies associated with autoimmune encephalitis (e. g. autoantibodies against AMPA receptors Caspr2, LGl1, GABAb) could be excluded within the same test incubation.
Therewith, the clinical and serological image of Knut’s disease fulfilled all criteria which have to be met for a definite diagnosis of anti-NMDA receptor encephalitis in humans: 1) clinical symptoms of encephalitis (e. g. epileptic seizures, reduced level of consciousness, cognitive changes), 2) evidence for brain inflammation, 3) exclusion of other causes for encephalitis, e. g. bacterial or viral infection, 4) presence of autoantibodies against NMDA receptor.
Based on these data, the researchers assume that autoimmune encephalitis might occur much more frequently in mammals (not just humans) than supposed previously. If this is true, animals suffering from symptoms of encephalitis could be well treated with immunosuppressive therapy, as it is possible in human patients.