Overview: Anti-NMDAR encephalitis, a rare autoimmune disease, can cause extreme psychiatric symptoms such as hallucinations, paranoia, and memory loss, often mimicking bipolar disorder and schizophrenia. The condition, more common in women in their 20s and 30s, is caused by antibodies that attack receptors in the brain that are essential for cognition and memory.
New research reveals that antibodies have different binding patterns to these receptors, which may account for differences in symptoms between patients. This finding highlights the potential for personalized treatments to enable more targeted and effective treatments in the management of this underdiagnosed disease.
Important facts:
Anti-NMDAR encephalitis often causes psychotic symptoms similar to schizophrenia. Antibody binding patterns on brain receptors vary and influence the development of symptoms. The findings highlight the need for personalized treatment for this rare autoimmune disease.
Source: CSHL
Imagine waking up in the hospital with no memory of the last month. Doctors say you have had a series of violent episodes and paranoid delusions. You have become convinced that you are suffering from bipolar disorder. Then, after special tests, a neurologist diagnoses a rare autoimmune disease called anti-NMDAR encephalitis.
This is what happened to Susannah Cahalan, a New York Post reporter who went on to write the best-selling memoir, Brain on Fire: My Month of Madness.
Anti-NMDAR encephalitis can cause hallucinations, syncope and psychosis, says Hiro Furukawa, a professor at Cold Spring Harbor Laboratory.
It primarily occurs in women between the ages of 25 and 35, which is the same age at which schizophrenia often develops. But what is happening in anti-NMDAR encephalitis is something else.
Dr. Furukawa specializes in NMDARs, brain receptors that play important roles in cognition and memory.
“In anti-NMDAR encephalitis, antibodies bind to these receptors and prevent them from working,” he explains. The brain becomes inflamed as an autoimmune reaction, resulting in a state of “brain burning.”
Several treatments are available, but their effectiveness depends on the severity of the symptoms. A new study from Furukawa’s lab may explain why. In a recent study, Furukawa et al. mapped how antibodies from three patients bound to NMDARs.
They found that each of the three antibodies binds to NMDAR differently. This discovery is an important step toward a better understanding of anti-NMDAR encephalitis, a disease first diagnosed in 2008. Furthermore, it suggests that personalized medicine may be important in treating this disease.
“For NMDARs, different binding patterns appear at different levels of functional regulation,” Furukawa explains.
“This affects neural activity, so differences in binding sites may correspond to changes in patients’ symptoms.”
Elucidating these correlations may lead to more accurate treatment strategies. For example, imagine that scientists have identified several binding sites that are common to encephalitis patients.
Pharmacologists could then design new drugs that target these sites. But that’s not all. Personalized medicine could also mean more accurate diagnosis, Furukawa said.
“Although this is still a rare disease, it can be misdiagnosed or underdiagnosed. So we need to spread awareness. For example, do some people with schizophrenia also have this disease? Is it because of antibodies?”
Currently, anti-NMDAR encephalitis is said to affect 1 in 1.5 million people. But in time, it may prove to be more common than previously assumed. That’s a scary thought.
But it may explain why existing psychiatry doesn’t work for some people diagnosed with bipolar disorder and other mental health conditions, and this could help explain not only the patients but also the care they receive. This is a huge revelation for families and therapists alike.
About this neurological research news
Author: Sara Giarnieri
Source: CSHL
Contact: Sara Giarnieri – CSHL
Image: Image credited to Neuroscience News
Original research: Closed access.
“Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis” Hiroshi Furukawa et al. Structural biology and molecular biology of nature
abstract
Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis
Autoantibodies against nerve membrane proteins can cause autoimmune encephalitis, leading to seizures, cognitive dysfunction, and psychosis.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most prevalent autoimmune encephalitis. However, insight into how autoantibodies recognize and alter receptor function remains limited.
Here we used single-particle cryo-electron microscopy to determine the structures of human and rat NMDARs bound to antibodies from three different patients.
These antibodies bind to different regions within the amino-terminal domain of the GluN1 subunit.
We showed through electrophysiology that all three autoantibodies acutely and directly reduce NMDAR channel function in primary neurons.
The antibodies exhibit different stoichiometry of binding and antibody-receptor complex formation, with antibody 003-102 also resulting in decreased synaptic localization of NMDARs.
These studies demonstrate the mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies that underlie autoimmune encephalitis.
