This paper has been compiled by the Encephalitis Society in conjunction with Dr Sarosh Irani, Dr Angela Vincent and Dr Camilla Buckley from Oxford NHS Trust.
The brain could be regarded as being in three parts. The brain stem is the most
primitive part and sits above the spinal cord at the base of the rest of the brain.
The brain stem plays a vital role in basic attention, arousal, and consciousness.
All information to and from our body passes through the brain stem on the way to
or from the brain. The brain stem is responsible for many of the functions that
give us life such as breathing, heart function, sleep wake cycle, temperature control.
Wrapped around this basic brain is the “limbic brain” or intermediate
brain. It includes the hippocampus, thalamus, hypothalamus and amygdala which are
involved in memory and much of the behaviour related to sex, hormones, food, fight
or flight responses, the perception of pleasure and competition with others. The
limbic brain is the seat of higher emotions including the protection of the young
and feelings such as love, sadness and jealousy.
The third and major part of the brain is the neocortex, the rational brain. The
neocortical brain provides logic and thought, it is the seat of processes such as
speaking, planning and writing.
Limbic encephalitis, implies inflammation in the limbic system. It is therefore
an anatomical diagnosis and not all cases share the same cause.
Causes of Limbic Encephalitis
All types of encephalitis fall into 2 main categories:
Infectious encephalitis – caused by direct invasion of the brain by an infectious
agent, usually a virus.
Auto-immune encephalitis – caused by the persons own immune system reacting
against itself.
Infectious causes
Any infection of the brain can potentially cause an inflammation of the limbic area
of the brain. A number of viruses appear to target this area and can, but not always,
include the herpes simplex virus. Some people may therefore be given the diagnosis
of “limbic encephalitis” whilst others may be given the diagnosis “herpes
simplex encephalitis” for the same condition. It would be clearer for people
affected by encephalitis affecting the limbic system if both terms were used –
“herpes simplex encephalitis affecting mainly the limbic area of the brain”
– but that is rather long winded!
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.
Voltage-gated potassium channel (VGKC) antibody-associated
encephalitis
This syndrome has been called voltage-gated potassium channel (VGKC) 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.
This article has been compiled by the Encephalitis Society in conjunction with Dr
Sarosh Irani, Prof. Angela Vincent and Dr Camilla Buckley from Oxford NHS Trust.
Last modified: March 2008