Question:

What is Autoimmune Epilepsy?

Answer:

Autoimmune epilepsy (AE) is caused by a change in the body’s immune function. Seizures are the main features of AE. This type of epilepsy was recently included in the new way of classifying epilepsy by the International League Against Epilepsy (ILAE). The ILAE has proposed that seizures that occur during the active phase of immune-mediated encephalitis should be defined as acute symptomatic seizures secondary to autoimmune encephalitis. In contrast, the term autoimmune-associated epilepsy should be restricted to chronic seizures that persist beyond the active phase of autoimmune encephalitis.

 Although seizures are common in the acute phase of autoimmune encephalitis associated with antibodies against surface antigens, only a minority of patients develop seizures that persist after the encephalitis has resolved.  However, most patients with autoimmune encephalitis do not develop autoimmune-associated epilepsy. In contrast, patients with GAD antibodies may have isolated pharmaco-resistant temporal lobe epilepsy, and GAD autoimmunity represents the main cause of autoimmune epilepsy.

Our immune system protects the body from foreign substances or things that could harm the body. Certain types of cells are important in the body’s immune response, such as macrophages, lymphocytes (B cells and T cells), and antibodies.

• Antibodies are large proteins found in the blood or other body fluids that protect the body.
• An antigen is something that invades the body, like a virus, infection, or something else. An antibody can see when an invader enters the body and acts to stop it.
• Antibodies that target the brain may be the cause of autoimmune epilepsy.
• The most common antibodies target specific receptors in the brain, such as N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), and glutamic acid decarboxylase 65 (GAD65).
• If these antibodies are associated with a tumor, they are called paraneoplastic. If an infection of the brain is present, it may be called autoimmune encephalitis.
• While the paraneoplastic syndromes are usually cancer-related, autoimmune encephalitis may occur with or without cancer.

Finding an autoimmune cause of seizures is very important and will affect its treatment.

What Are The Common Features Of Autoimmune Epilepsy?

AE often begins with seizures developing over days to weeks. A person may have had an illness with fever too.

• Seizures often happen several times a day right from the beginning.
• Focal seizures are the most common seizure type.
• Seizures that affect one side of the face and arm on the same side of the body (called facial brachial dystonic seizures (FBDS)) strongly suggest autoimmune epilepsy.
• Seizure medicines usually don’t control these seizures well.
• People may also have problems with memory, personality changes, and changes in mood or behavior (e.g., paranoia, depression, or hallucinations).

Who Is At Risk For Autoimmune Epilepsy?

We don’t know exactly how often autoimmune epilepsy happens. It is estimated that 1 to 7 out of 20 (5-35%) people with new onset seizures may have an autoimmune cause. These include people with:

• A history of another autoimmune disease (such as rheumatoid arthritis, Graves’ disease, Hashimoto’s thyroiditis, Crohn’s disease, ulcerative colitis, and systemic lupus erythematosus)
• A history of cancer
• A first-degree relative (parent, sibling or child) with an autoimmune disease

A sudden and severe onset of seizures is also a red flag that epilepsy could have an autoimmune cause.

How is Autoimmune Epilepsy Diagnosed?

Routine tests for people thought to have AE include basic blood tests, an EEG (electroencephalogram), and an MRI (magnetic resonance imaging) of the brain. Other tests that may be done include

• PET (positron emission tomography) scan
• Lumbar puncture (spinal tap) to look for certain antibodies in the cerebrospinal fluid (CSF) surrounding the brain.

Results of tests show that some people with AE do not have a known autoantibody. Brain MRI is often normal, especially when it’s done early after seizures start. Signs of inflammation may be seen in the temporal lobes. EEG may not help much. Often video-EEG to record a person’s typical seizures is needed.

Since autoimmune epilepsy can be due to cancer somewhere in the body or a history of cancer, the workup should also look for a tumor or cancer.

What Is The Importance Of Diagnosing Autoimmune Epilepsy Early?

When autoimmune epilepsy is diagnosed early, starting treatment quickly may lead to seizure freedom. Proper treatment can also slow or stop inflammation of the brain. Tumors, if present, can be found early and treated too.

What Is The Typical Treatment For Autoimmune Epilepsy?

Studies suggest that immunotherapy may be very effective in AE. Immunotherapy is a way of treating the inflammation in the brain. The treatment is typically steroids (such as methylprednisolone or prednisone) given by mouth or into the blood stream (intravenous, IV). Immunoglobulin (IVIg) may also be given into the bloodstream.

How well this works depends on the type of antibody the person has.

• Generally, those with cancer-related autoimmune epilepsy may not do as well as people with antibodies that target the surface of brain cells (e.g., NMDA receptor antibody or LGI-1 antibody encephalitis).
• In paraneoplastic AE, treating the underlying tumor is also critical where feasible.
• Starting immunotherapy early in non-paraneoplastic AE is important to quickly stop seizures and prevent injury to brain cells.

Types Of Autoimmune Epilepsies

• • Rasmussen’s syndrome
  • antiNMDA receptor encephalitis
  • Limbic encephalitis (LG1, CASPR2, other)
  • GAD65 antibody related epilepsy

References

1. Scheffer IE, Berkovic S, Capovilla G et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512-521.
2. Dubey D, Alqallaf A, Hays R, Freeman M, Chen K, Ding K, Agostini M, Vernino S. Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology. JAMA Neurol. 2017;74:397-402.
3. Toledano M, Britton JW, McKeon A, et al. Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy. Neurology. 2014; 82:1578-1586.
4. Feyissa AM, López Chiriboga AS, Britton JW. Antiepileptic drug therapy in patients with autoimmune epilepsy. Neurol Neuroimmunol Neuroinflamm. 2017 May 10;4(4):e353.