Autoimmune encephalitis

Autoimmune causes

Autoimmune encephalitis presents with many of the same symptoms (e.g. memory loss, seizures and confusion) as infectious encephalitis but a causative virus, such as herpes simplex, is not present. In fact, the cause is an antibody - made by the immune system.

Antibodies are made by all healthy individuals in response to infections or after vaccination. The antibodies attack the infectious agent (such as a virus) and help the body’s immune system get rid of the infection. The immune system has to make literally millions of different antibodies in order to combat effectively different infections. It also makes antibodies to damaged or abnormal tissue, such as cancer tissue. Unfortunately, a few of these antibodies may “cross-react” with the patient’s healthy tissue proteins, attacking the tissue and causing an autoimmune disease.

There are two forms of autoimmune limbic encephalitis, paraneoplastic limbic encephalitis (PLE) and non-paraneoplastic limbic encephalitis (NPLE).

Paraneoplastic limbic encephalitis (PLE)
Paraneoplastic limbic encephalitis (PLE) occurs in a small proportion of people with particular cancers. Most individuals with PLE will turn out to have a cancer of the lung, thymus gland, the breast or the testis. In many cases, PLE can be diagnosed by testing for one of a group of paraneoplastic autoantibodies in the patient’s blood. These antibodies are made by the patient in their attempt to attack the cancerous tissue. The condition may improve or at least stabilise if the cancer is detected and treated effectively, but unfortunately in many cases the tumour proves difficult to identify or the treatment does not cure the patient’s neurological symptoms.

Non-paraneoplastic limbic encephalitis (NPLE).
NPLE has only been clearly recognised in the last five years. Doctors began to identify patients who had the symptoms of paraneoplastic limbic encephalitis but who did not have any of the marker paraneoplastic antibodies in their blood and never developed a tumour. Moreover, some of these patients got better if they were treated with drugs that suppress the immune system It is becoming increasingly clear that NPLE is caused, at least in part, by specific antibodies in the patient’s blood that target the patient’s brain tissue, particularly the hippocampus and other limbic areas. The antibody binds to a protein, present in all brain tissue: the potassium channel. This causes a reduction in the number of potassium channels, decreasing the control over electrical signals operating in the brain. Potassium channels are proteins that lie in the surrounding membrane of nerve cells in the brain and in the nerves that lead to the muscles of the skeleton, the gut and the heart. They are particularly common in the hippocampus and other limbic areas of the brain.

Potassium Channel Complex Antibody Associated Encephalitis
It is thought that this type of Autoimmune Encephalitis is currently under-diagnosed and, hence, under-treated. The main reason for this under-diagnosis is the current lack of awareness of the condition. Also, it does show marked similarities to Infectious Encephalitis, in its symptoms and brain imaging features, making differentiation difficult.

The diagnosis of Autoimmune Encephalitis is particularly important because the disease is potentially treatable, using immunosuppressive drugs such as steroids. As this syndrome was only described in 2001, there is still much to be done to raise awareness amongst clinicians. Future research aims to understand the biological mechanisms by which this antibody affects the potassium channels, and hence causes disease. Researchers also hope to discover further antibodies which may allow other autoimmune encephalitides to be diagnosed.