Old doc, new disease: Anti-NMDA receptor encephalitis

Casey Parker

15/04/2019 12:34:14 PM

Dr Casey Parker reflects on an intriguing presentation that made him ask: What else do I not know?

Solving a maze
‘You cannot diagnose what you do not know.’ Dr Casey Parker has asked himself, what else do I not know?

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

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Shafiq mamon   16/04/2019 6:59:48 AM

No one is expected to know exactly the types of encephalitis.However,any patient with emerging neuropsychiatric sypmtoms and negative neuri deficit presenting to rural GP merits urgent action including CT ,bloods and a phone call to nearby base hospital to discuss with ED consultant and possible referral to neurologist.

Sinnappu Sivacolundhu   16/04/2019 8:26:15 PM

This, even for a GP in Metro region, is for an urgent referral to a Neurologist: If not in private hospital cover, to one of the more senior Public Hospital Emergency Department will be my opinion --- even if they do object!!!

Paul   16/04/2019 11:03:34 PM

Ex ICU doing GP. Saw a few of these in my ICU time, the last one was horrific. So so bad, constant fevers, constant tachycardias, and other abnormal stuff, the consultants had no clue, each one would re organise what the last one would do, and then after 2 weeks or so someone would come back from leave to find that yet another was re inventing the wheel by trying the same things as when they had gone on holiday.
Her father was amazing, got to know the other parents of other patients, actually help them out when he saw them struggling, took them to the hospital cafe and such, all while watching his daughter chew her own tongue off.
He was epically strong.
I fear this diagnosis to put it mildly.

Chris Hogan   17/04/2019 8:58:44 PM

This is an example of how our knowledge is still in its infancy, There is always something new or something unknown to all of us out there- if we keep our eyes open. Sometimes there will be another doctor out there who might know something about it - sometimes.
Book learning is not enough to answer all the questions we encounter, sometimes we have to point out to our colleagues that there is something unknown & provide them with the clues we have discovered
There will always be a place for GP research, observation & clinical acumen

Stephanie   18/04/2019 11:20:27 AM

Not a GP, but a patient who was admitted via Emergency due to this disease. Initial symptoms were quite general and it wasn't until I could not void that my GP told me to go to ER. Luckily I was in hospital when the psychiatric symptoms started. It wasn't until a full blood panel test was done with Immunology that they found the cause. Also had a lumbar puncture test and full gamut of scans.

Penny   21/04/2019 10:29:35 PM

Mother’s instincts are so important!! It does not matter the age of the child or the mother. My adult son has AE, unknown cause. I knew, as a mom and a nurse that he had a brain issue. He started with symptoms late summer following a virus, saw a multitude of doctors and health practitioners in our state, no one listened. It took me several months to convince my son and others to go to a specialist in Boston. All the time I watched brain damage happen! He, luckily, did not have psychosis symptoms or seizures. It is so heart breaking and I empathize with all families and patients.
I wrote to the Medical Ass. in our state encouraging education on AE, got no response. I also informed his primary practice, and others he saw, one was a neurologist. I have confidence in his current care.