Rare Disease Report
Physicians
Physicians
Patients & Caregivers

Anti-NMDA Receptor Encephalitis: A Rare Disease Story

AUGUST 16, 2016
James Radke and Levent Efe

This story was originally published in 2014. Due to popular demand we are bringing it back for your entertainment and education. Enjoy.


Sheila was loud, excitable, erratic, and messy. Really messy.

More importantly, her wild behavior was starting to affect the whole neighborhood.

And they all used to get along so well. They dreamed together. They created great art together. They did math homework together. They had wonderful planning sessions together.They were a well organized group of high functioning neurons committed to helping the brain function efficiently and effortlessly. But not anymore.

Now their area was filled with excess metabolites floating around a group of tired and overworked neurons.


“This is all Sheila’s fault. Her crazy behavior is ruining the whole neighborhood,” whispered Irene to the nearby cells.
 

Another neuron – Cleo - did not like what Irene said. “Be nice. Crazy is a mean word. Sheila can’t help what is happening. She’s just responding to these new antibodies,” said Cleo as she pointed to the antibodies floating around the extracellular space. Cleo added “I feel sorry for Sheila. She is not looking well.”
 

Irene had to agree that Sheila did look unhealthy and tired. In contrast, Cleo and Irene were still beautiful neurons with wide dendritic trees and well myelinated axons. But they were looking tired too. And being tired meant they were susceptible to getting excited at inappropriate times.
 

Irene thought the problem began when the antibodies arrived and starting picking on Shelia.
 

Irene asked, “Do you think these antibodies will leave Sheila alone soon?”
 

Cleo shrugged her cell body. “I hope so.  Rumor has it that the doctors are giving us some medicine to get rid of the antibodies but it could take awhile.”
 

“Who started that rumor?” asked Irene.
 

“Neurons in the auditory cortex,” answered Cleo.
 

Irene nodded. They were a reliable source.
 

“Did the Auds say anything else?”
 

Cleo smiled. She knew Irene liked rumors. “According to the Auds, the doctors said that we have something called Anti-NMDA receptor encephalitis.”
 

“What’s that mean?”
 

“That means all those antibodies floating around are attaching to the NMDA receptors. Since Sheila has NMDA receptors, she is having a hard time trying to control her neural activity….or something like that,” answered Cleo, adding, “Nobody quite understands what is going on but they all agree that it is really messed up.”
 

“All this because Sheila has NMDA receptors on her membrane?” questioned Irene.
 

“If it was just Sheila, it would be a pretty easy to control. But the antibodies are attaching to a lot of neurons with NMDA receptors. That is the real problem. There are so many of them.”
 

“Where’d the antibodies come from?” wondered Irene.
 

Cleo was about to answer when she saw a wave of electrical activity coming towards her.  Suddenly, all her postsynaptic membranes were being bombarded with neurotransmitters and she spent the next 2 minutes firing non-stop to keep up with all the chemical and electric activity.
 

Irene was overly excited too. Action potentials were running all long her dendritic and axonal membranes. All the cells in the region were firing in strange new patterns they had never seen before. It was complete chaos.
 

Then it suddenly stopped.
 

After taking a couple seconds to catch her breath, Irene looked over at Cleo.
 

“Are you okay?”
 

“Yeah. But I am getting really tired of these seizures,” replied Cleo.
 

“What were we talking about before?” asked Irene.
 

 “I don’t remember,” answered Cleo, adding, “These seizures make me forget things.”
 

Cleo and Irene stopped communicating and just focused on cleaning up the mess from the seizure. Their cytoplasms and extracellular spaces were filled with excess metabolites that needed to be reorganized.
 

And while cleaning up, Cleo remembered what they were talking about. “The antibodies come from us.”
 

Irene stopped cleaning and asked, “What?”
 

Cleo spoke quickly – just in case another round of seizure activity came through – “The doctor said that we have an autoimmune disease which means we made the antibodies ourselves.”
 

“Why’d we do that?”
 

“The doctors aren’t sure. Sometimes the condition is associated with a tumor and sometimes it is not,” answered Cleo, adding, “but they are working hard to figure it out.”
 

Irene was still confused. “What’s the treatment?”
 

“The doctor is giving us lots of medicine to get rid of the antibodies but it is tricky and takes time,” replied Cleo.
 

Irene silently went back to cleaning up her cytoplasm. Cleo could tell she was upset.
 

“Don’t worry Irene, it will be over one of these days,” said Cleo, “The doctors said it is a temporary condition and once these antibodies are gone, we will all be back to normal – including Sheila.”
 

Irene smiled at Cleo and thanked her for the explanation. Then the two of them went back to cleaning up the area before another seizure came through.
 

When Irene finally had her intracellular and extracellular spaces looking somewhat normal again, she looked over and saw Sheila staring at her. Sheila looked scared and alone. Now that Irene had a better understanding of why Sheila was behaving so erratically, Irene was more sympathetic.  Irene smiled and gave Sheila a ‘two dendrites up’ signal.
 

“We’re going to get through this,” yelled Irene to Sheila, adding, “We just have to wait for the treatment to work.”
 

Sheila weakly held up two dendrites in return. It was nice to have supportive neighbors. 
 

About anti-NMDA receptor encephalitis

Anti-NMDA (N-methyl D-aspartate) receptor encephalitis is an autoimmune reaction towards subunits of NMDA receptors located in the brain. Most patients are young female adults [mean age 23 years (5-76 range)]. The exact pathophysiology is not fully understood but many patients with anti-NMDA receptor encephalitis have tumors in their ovaries.  How anti-NMDA antibodies get into the brain to target NMDA receptors is also not fully understand.

Symptoms of anti NMDA receptor encephalitis vary but patients often present with acute central (psychosis, catatonia, seizures, memory deficit, dyskinesias, speech problems) and peripheral (breathing dysregulation) problems.  Treatment often involves tumor removal, anti-inflammatory drugs, plasmapheresis, and/or IV immunoglobulin. While this is a very serious -and sometimes lethal - condition, most patients make a full recover from the episode.

Recommended readings

Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurol. 2013;2(2):57–65. doi: 10.1016/S1474-4422(12)70310-1.

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10(1):63-74. doi: 10.1016/S1474-4422(10)70253-2.


 

Story by James Radke. Copyright Rare Disease Report  www.raredr.com

Image by Levent Efe. Copyright Dr. Levent Efe CMI   www.leventefe.com.au/



Copyright © RareDR 2013-2017 Rare Disease Communications. All Rights Reserved.