We fight to improve the lives
of everyone affected by epilepsy

Epilepsy and limbic encephalitis (LE)

Limbic encephalitis (LE) is a very rare but important cause of seizures and epilepsy.

LE is more common in adults. It is not known exactly how common LE is. It probably affects 1 in 150,000 to 1 in 300,000 children each year in the UK.

Limbic refers to the ‘limbic system’. This system is a network in the brain which includes the temporal lobes and other important structures, usually the ‘hypothalamus’, ‘frontal lobes’ and ‘basal ganglia’.

LE is thought to be an auto-immune condition. This means that the body’s own antibodies start to attack parts of the body and in LE this is the brain. This is also what happens in Rasmussen syndrome.

It is not known why these antibodies do this. A common trigger to this happening in children seems to be viral infections or, very rarely following a vaccination. Other triggers include another auto-immune disease, such as diabetes mellitus type I, thyroiditis (inflammation of the thyroid gland) or a condition called systemic lupus erythematosus (SLE).

Limbic encephalitis can also occur with some tumours and cancers, particularly of the ovary and breast in women, testes in men and the lung in men and women. When this happens, it is called ‘paraneoplastic limbic encephalitis’. Neoplastic refers to the tumour or cancer.

In children, the most common cause seems to be a simple viral infection and paraneoplastic LE is very rare. However, sometimes no trigger is found.

LE can occur at any age in children but the two most common peaks are between 1 and 6 years of age and between 12 and 16 years of age. Girls are affected slightly more frequently than boys. In adults, females are also more affected than males.

Many different antibodies may be found in LE. The most common ones in children are:

  • Anti-VGKC antibodies (VGKC stands for voltage-gated potassium [K is the chemical symbol for potassium] channels)
  • Anti-NMDA receptor antibodies (NMDA stands for N-methyl-D-aspartate, which are types of receptors in the brain)
  • Anti-GAD (GAD stands for glutamic acid decarboxylase)
  • Anti-MOG antibodies (MOG stands for myelin oligodendrocyte glycoprotein)


Symptoms

Seizures, behavioural difficulties and short-term memory problems are the most common symptoms in children. Movement disorders, called ‘chorea’ or ‘dystonia’ and psychiatric difficulties may also occur. Seizures and short-term memory problems are the usual presentation in children and adults with anti-VGKC antibodies. Movement disorders and psychiatric difficulties are the usual presentations of someone with ant-NMDA receptor antibodies, but seizures may also occur.

The onset or beginning of LE is usually quite sudden, over a few days. However, it can also develop much more slowly over weeks or even months. The more gradual onset usually occurs in adults and the cause is often an underlying tumour.

Seizures in LE are usually very frequent and occur every day and usually many times a day. Seizures can be generalised or focal, or both. The generalised seizures are myoclonic (‘jerks’), clonic (which means repeated and rhythmic myoclonic or ‘jerks’) and tonic-clonic. The focal seizures happen in many different ways. This includes clonic movements that affect just one side of the body and periods of being un-responsive and not speaking, often with the head or eyes deviated to one side. Focal seizures can be brief or prolonged and last many minutes or even hours.


Diagnosis

The most important part of the diagnosis is made by the doctor taking a careful history. The history is the account that parents and older children give the doctor which describes when and how the seizures started. This includes asking about any infection or vaccination that might have happened in the days or couple of weeks before the seizures or other symptoms such as weight loss, skin rashes, being generally unwell or having difficulties in school.

LE is sometimes called a ‘diagnosis of exclusion’. This means that other more common diagnoses and conditions should be looked for first. If the tests for these more common conditions are negative and therefore ‘excluded’, then LE becomes the most likely diagnosis. The common conditions that need to be considered are very low levels of calcium (‘hypocalcaemia’) or glucose (‘hypoglycaemia’), herpes simplex encephalitis, bacterial meningitis and a brain tumour.

All children will need blood tests, an electroencephalogram (EEG) and a magnetic resonance imaging (MRI) brain scan. Most children will also need a lumbar puncture to look at the cerebrospinal fluid (CSF). The CSF is the fluid that covers the surface of and circulates inside the cavities of the brain, called the ‘ventricles’. CSF analysis is important in the diagnosis of bacterial and viral meningitis or encephalitis. The CSF often shows milder abnormalities that may help to diagnose LE.

The EEG and MRI brain scan often show abnormalities that help to diagnose LE but this is not always the case. The most important test is the measurement of the auto-antibodies that cause LE. In children, this will usually be the anti-VGKC, anti-NMDA receptor and anti-MOG antibodies. However, auto-antibodies are only found in about 50-60% of all children that have LE.

The EEG and MRI brain scan often show abnormalities that help to diagnose LE but this is not always the case. The most important test is the measurement of the auto-antibodies that cause LE. In children, this will usually be the anti-VGKC, anti-NMDA receptor and anti-MOG antibodies. However, auto-antibodies are only found in about 50-60% of all children that have LE.


Treatment

Although epilepsy medicines may be used to treat the seizures, these are not always helpful. Even if they do reduce the number of seizures, it is unlikely they will ever stop them completely.

The most important treatment for LE is to find the cause, particularly if the cause is a tumour. This is very rare in children but removal of any tumour is the first and most important step in treatment.

If the cause is thought to be a viral infection, then the child should receive a medicine that is effective against viruses. Herpes simplex encephalitis is the most common treatable viral encephalitis in children and must be treated with medicine called aciclovir.

Children with LE should then be treated with a medicine called an ‘immunotherapy’ medicine. The most common ones are corticosteroids, called prednisolone which can be given intravenously (through a ‘drip’) or orally (by mouth) and intravenous immunoglobulins. Other immunotherapy medicines include cyclophosphamide or rituximab (rituximab is a medicine called a ‘mono-clonal antibody). All of these are given intravenously.

Many children will need treatment for many weeks or months to prevent the LE coming back (called a ‘relapse’). Because of this, children will usually be given a few weeks of prednisolone which is then followed by courses of rituximab or cyclophosphamide over many months.

There is another treatment, called ‘plasma exchange’ also called ‘plasmapheresis’. This treatment filters the blood and removes the auto-antibodies that cause the seizures and other symptoms in LE. Plasma exchange is always followed by at least one immunotherapy medicine to prevent more auto-antibodies from being made and therefore prevent a relapse.

More information about medicines can be found on the Medicines for Children website


Outcome

The earlier LE is diagnosed and treatment started, the better the outcome. All the symptoms that occur in LE, including seizures, respond well to immunotherapy medicines. This means that the seizures may stop completely and the short-term memory and behaviour difficulties also recover. However, if the diagnosis and treatment is given late after the symptoms have been present for many months, the outcome is not always as good. This is because the auto-antibodies may have caused scarring (‘damage’) to one or both of the temporal lobes and other parts of the limbic system.

Unfortunately, even if the diagnosis is made early, some children will still not respond very well to treatment. Fortunately, this is uncommon.

Immunotherapy medicines are usually given for many months to prevent a relapse in LE. However, relapses can occur months or even years after the first episode.

 

Support

Encephalitis Society
32 Castlegate
Malton, North Yorkshire YO17 7DT
United Kingdom
Telephone: +44 (0)1653 699599
Website: https://www.encephalitis.info/
E-mail: support@encephalitis.info

Contact
Charity for families of disabled children.
Freephone helpline: 0808 808 3555
Website: contact.org.uk
Email: helpline@contact.org.uk


What is a syndrome?

A syndrome is a group of signs and symptoms that, added together, suggest a particular medical condition. In epilepsy, examples of these signs and symptoms would be things like the age at which seizures begin, the type of seizures, whether the child is male or female and whether they have physical or learning disabilities, or both. The results of an EEG are also used to help identify epilepsy syndromes.
If you would like to know more about an epilepsy syndrome, please speak to your doctor. If you would like to know more about epilepsy in general, please contact the Epilepsy Action Helpline.

Code: 
S035.01
Event Date: 
Wednesday 26 February 2020

Epilepsy Action would like to thank Dr Richard Appleton, consultant paediatric neurologist and honorary professor in paediatric neurology at Alder Hey Children’s Hospital, Liverpool, for preparing this information.

This information is exempt under the terms of Epilepsy Action's information quality standards.

  • Updated February 2020
    To be reviewed February 2023

There are no comments yet. Be the first to comment...

Subscribe to the e-action newsletter

Stay up to date with the latest news on coronavirus, epilepsy news and events, and how you can get involved.

Epilepsy Action will never swap, share or sell your details. For more information, read our privacy policy.
By clicking subscribe you agree to our privacy policy.