Autoimmune encephalitis

[Cleo Bagchus]

[cleo.bagchus@hotmail.com]

[4386736]

Seminar 1:

Speaker:      Josep Dalmau

Department: neuroscience                                                                                                                              

Subject: Autoimmune encephalitis                 

Location: Rotterdam            

Date: 07-09-2015   

Autoimmune encephalitis is a disease in which the immune system attacks the brain. Antibodies often bind to the synapses of the patients, leading to impaired brain function. The earliest symptoms are agitation and problems with information processing. But as the disease progresses this leads to inability to control movement and eventually some patients even fall into a coma. Next to these symptoms the disease is often accompanied by tumours. In the US 20 000 patients were hospitalized in 2010 because of encephalitis. In 50% of these cases the cause of the disease was unknown. A recovery can be (almost) complete, but often takes years, which makes it a very costly disease. In many cases the patient has no recollection of the disease or the recovery.

The disease is divided into three categories: intracellular, synaptic intracellular and synaptic surface. Dr. Dalmau’s research focuses on anti-NMDAR encephalitis. which falls under synaptic surface encephalitis. Anti-NMDAR encephalitis most often occurs in young females. In young, male cases the disease is often not accompanied by tumours.

In anti-NMDAR disease antibodies attack proteins on the surface of synapses. The NMDAR receptor and the ephrin B2 receptor are attacked. Antibodies of patients decrease the number of NMDAR clusters. These clusters become internalized. The clusters can recover if you remove the antibody. Antibodies disrupt the cell surface interaction between NMDAR and Ephrin-B2 receptors. This leads to a lower current running through the synapses. Patient’s antibodies cause a homeostatic decrease of inhibitory synapse density. Because of this the synapses start to dysfunction.

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image 1: the amount of  NMDAR-receptors related to the progress of the disease (from: Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis written by Prof Josep Dalmau, MD Eric Lancaster, MD, Eugenia Martinez-Hernandez, MD, Prof Myrna R Rosenfeld, MD, Prof Rita Balice-Gordon, PhD, http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70253-2/fulltext?rss=yes)

As you can see in image 1 the clinical worsening of the disease is directly linked to the amount of NMDAR-receptors still present on the synaptic surface.

Josep Dalmau wants to answer two questions with his research. Why is the recovery of anti-NMDAR encephalitis so slow? What can we learn from the pathology of this disease to help speed up its recovery?

To answer these questions he made a mouse-model of the effects of NMDAR antibodies. They injected mice with cerebrospinal fluid from patients that contained NMDAR antibodies. After eighteen days a dramatic drop in memory was seen. Also the infected mice showed signs of depression. There was a progressive detection of brain-bound antibodies that cause the synapses to dysfunction. Some of these symptoms are prevented by ephrin B2. Ephrin B2 protects synapses from the antibody. When the antibodies were removed the symptoms slowly disappeared. Possible medicines can also be tested on these mice.

I had never heard of encephalitis, so the entire subject of the lecture was new for me. I learned about the disease, the symptoms and the way researchers try to find out more about this disease. The fact that patients could recover almost fully after brain function was impaired so drastically, made this subject very exciting to me.

I believe it is important that the reason patients get encephalitis is discovered. Now in 50 % of the cases the cause of the disease is unknown. I believe you can treat a disease much better if you know what causes it and this might also prevent relapses. So I believe research should focus on discovering the cause of encephalitis. For this will lead to a better understanding of the disease and eventually a better treatment of the disease.

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