Old doc, new disease: Anti-NMDA receptor encephalitis

It turns out Paul’s mother was right.
 
The first time I saw him, Paul seemed to have a post-viral malaise. A head cold that lingered, a low mood and lethargy.
 
His second visit two weeks later, however, left me confused. Paul seemed odd. Mumbling, disorganised and suspicious. I was concerned. This looked like an emerging psychosis, but there was nothing firm enough upon which to act.
 
Paul’s mum was also worried. She could sense that something was seriously awry in her son’s mind. So I did another examination, which also proved fruitless.
 
Paul seemed completely normal in many ways, but not in others. He had been doing his engineering exams a just month ago, but he was now struggling to do simple maths.
 
I ordered a batch of bloods and a brain scan in desperation, and resolved to see Paul in a few days. If the investigations were not illuminating then he would need to go in for assessment by the mental health team.
 
The CT scan, as it turned out, was pristine. When I phoned Paul’s mother to deliver the ‘good news’, she did not seem reassured. She then mentioned that Paul was displaying increasingly paranoid behaviour; she suspected he was hearing voices. I agreed to see him in the morning.
 
The bloods were all normal, besides a C-reactive protein (CRP) creep. When I told her about my concerns regarding Paul’s mental health, his mother was disbelieving. ‘No, he isn’t mad. There is something wrong with his brain,’ she insisted.
 
She was right.
 
Paul never returned for his appointment that week. He suffered a seizure in the night and an ambulance took him to the emergency department. After a long barrage of sedation, testing and imaging, he was eventually seen by the neurologist, who made the diagnosis. The answer was hiding in Paul’s cerebrospinal fluid – a rare condition first described in 2007.
 
Anti-NMDA receptor encephalitis is an autoimmune process, in which antibodies against the NMDA (N-methyl-D-aspartate) receptors are produced. About 80% of female patients with the condition have an ovarian teratoma that is thought to be the site of the extra-cerebral tissue that triggers the immune system to attack the brain.
 
The inflammation occurs in the limbic system, particularly the mesolimbus, hippocampus and dorsolateral prefrontal cortex. The autonomic system is involved later in the disease, resulting in unstable cardiovascular and respiratory function.
 
While lesser known, anti-NMDA encephalitis is more common than viral encephalitis in young people, and women are four times more likely to develop the syndrome. Those that have coexisting teratomas have a good prognosis if diagnosed early.
 
Initial treatment involves immunosuppressive therapy with steroids. Screening for and surgical removal of any teratomas should be a priority. Second line therapies include intravenous immunoglobulin or immunotherapy with agents such as rituximab.
 
One curious aspect about this syndrome is that it is palindromic – that is, the symptoms reappear in reverse order as the treatment is maintained.
 
As such, patients may paradoxically redevelop psychotic symptoms after initiating steroids due to unopposed dopaminergic activity. Resolution generally occurs over a period of months. Some patients will not make a full recovery – approximately 10–15% will experience a recurrence.
 
Paul’s case was an important one for me. You cannot diagnose what you do not know. My ignorance of this condition made me question my practice.
 
What else do I not know?
 
Although anti-NMDA encephalitis is a rare diagnosis, it is commonly misdiagnosed. A missed case has potentially tragic outcomes for a healthy young person. If he has been undiagnosed, Paul would have been exposed to harmful antipsychotic medications. He may have spiraled into a coma with loss of precious function.
 
So next time you see a young person with emerging psychotic symptoms ask yourself: could it be?

disease encephalitis NMDA receptor