Autoimmune Epilepsy
What Is Autoimmune-Associated Epilepsy?
Autoimmune-associated epilepsy (AAE) is caused by damage to the brain from inflammation. AAE seizures continue to occur even after the initial inflammation goes away.
The immune system normally protects the body from infections. In some people, the immune system mistakenly attacks healthy tissue (this is called an "autoimmune" response). When an autoimmune attack happens in the brain, it causes inflammation that can lead to acute seizures. In many cases, the seizures stop once the inflammation in the brain is over. However, in some people, inflammation can cause long-term damage to the brain that results in epilepsy. This ongoing seizure condition is called autoimmune-associated epilepsy (AAE).
Autoimmune-associated epilepsy can occur at any age, although it is often diagnosed in adulthood. Autoimmune associated epilepsies are becoming increasingly recognized and are highly treatable forms of seizures. Rapid testing for immune causes and referral to centers with expertise in autoimmune epilepsy is extremely helpful, since early detection is generally associated with better long-term outcomes.
How Can Brain Inflammation Lead to Epilepsy?
Autoimmune-associated epilepsy usually develops after a person has autoimmune encephalitis, a condition in which the person's immune system mistakes cells in the brain for an infectious agent. The autoimmune response causes inflammation in the brain that by itself can lead to seizures. For some people, seizures stop once the inflammation is treated. Others continue to have seizures because the inflammation caused damage that leaves lasting changes in the brain; this is AAE.
Not everyone with autoimmune encephalitis develops autoimmune-associated epilepsy. Autoimmune encephalitis has been associated with identifiable antibodies, which are proteins the immune system creates to identify and attack specific targets. The chances of developing AAE in autoimmune encephalitis depend on the type of antibodies. Testing for certain antibodies can help healthcare providers better understand the cause of seizures and choose the most appropriate treatment.
Autoimmune encephalitis may also cause:
- Problems with memory or thinking
- Changes in mood, behavior, or personality
- New psychiatric symptoms
- Weakness or unusual movements
Autoimmune Conditions Associated with Epilepsy
Several autoimmune conditions can cause seizures or epilepsy. These conditions affect the brain in different ways and may vary in their symptoms, treatment, and long-term outlook.
- Autoimmune encephalitis: A group of conditions in which the immune system causes inflammation in the brain that can lead to seizures and other neurological symptoms.
- Anti-NMDA receptor encephalitis: A form of autoimmune encephalitis that can cause seizures.
- Anti-LGI1 encephalitis: An antibody associated autoimmune condition where symptoms may progress gradually over months.
- Anti-GAD65 disease: An antibody associated condition where patients may also have chronic epilepsy without an initial autoimmune encephalitis, often causing a delay in diagnosis. The temporal lobe epilepsy in this disease is typically drug-resistant.
- Rasmussen encephalitis: A rare condition that causes ongoing inflammation in one side of the brain and can lead to seizures. Seizures may be involuntary movements affecting one side of the body.
What Are the Signs That Seizures May Have an Autoimmune Cause?
Your healthcare provider may consider an autoimmune cause if you have:
- New seizures along with recent changes in memory, thinking, mood, behavior, or personality
- Specific types of seizure, such as those triggered by hearing music or having goosebumps
- Seizures that continue despite treatment with two anti-seizure medications
- Seizures that began after a recent illness or infection
- New epilepsy that starts in adulthood without a clear cause
- Seizures that occur with symptoms such as a rising feeling in the stomach, a racing heartbeat, flushing, goosebumps, or changes in hearing
These signs do not always mean seizures are autoimmune, but they may prompt additional testing.
How Is Autoimmune-Associated Epilepsy Diagnosed?
There is no single test that can confirm autoimmune-associated epilepsy. Healthcare providers typically use a combination of medical history, symptoms, examination findings, and test results to determine whether seizures may have an autoimmune cause. Symptoms of autoimmune-associated epilepsy can be like those of other seizure disorders, which can make diagnosis challenging.
Healthcare providers may use several tests to help make a diagnosis. This may include:
Blood, Spinal Fluid, and Antibody Tests
Blood tests and spinal fluid tests may look for antibodies linked to autoimmune conditions that affect the brain.
Antibodies are proteins made by the immune system to help fight infections. In some autoimmune conditions, antibodies mistakenly target healthy brain tissue and contribute to inflammation.
Identifying certain antibodies can help healthcare providers diagnose autoimmune conditions, better understand the cause of seizures, and guide treatment decisions. However, not everyone with autoimmune-associated epilepsy has detectable antibodies.
MRI
Magnetic resonance imaging (MRI) uses detailed images to look for signs of inflammation or changes in the brain that may be related to seizures.
EEG
An electroencephalogram (EEG) records the brain's electrical activity. It can help identify seizure types and changes from treatment.
Cancer Screening
In some cases, autoimmune conditions that affect the brain can be linked to certain types of cancer. If healthcare providers suspect this connection, they may recommend additional tests to look for underlying cancer.
Additional Testing
Depending on a person's symptoms and medical history, healthcare providers may recommend additional tests to look for underlying autoimmune conditions, infections, or other possible causes of seizures.
Why Early Diagnosis Matters
Early diagnosis and treatment may improve the chances of controlling seizures and reducing long-term effects from brain inflammation.
If healthcare providers suspect an autoimmune cause, identifying and treating the inflammation as early as possible may help improve outcomes.
Learn More:
Find a DoctorHow Is Autoimmune-Associated Epilepsy Treated?
Treatment focuses on controlling seizures and reducing inflammation in the brain. Patients that continue to experience seizures despite prolonged treatment with immunotherapy and antiseizure medications may benefit from undergoing workup for epilepsy surgery, or neuromodulation such as vagal nerve stimulation (VNS), responsive neurostimulation (RNS), or deep brain stimulation (DBS). Autoimmune causes of epilepsy do not preclude patients from undergoing epilepsy surgery and neuromodulation.
Anti-Seizure Medications
Anti-seizure medications help prevent seizures and are an important part of treatment for many people.
Immunotherapy
Immunotherapy helps reduce inflammation in the brain by changing how the immune system responds. Treatment may include pills or injected medications. The type and length of treatment vary based on the type of autoimmune condition.
Many people respond well to treatment when autoimmune-related seizures are identified early.
Epilepsy Surgery and Neuromodulation
Some people continue to have seizures despite treatment with anti-seizure medications and immunotherapy. In these situations, epilepsy surgery or neuromodulation may be considered.
Neuromodulation uses an implanted device to send electrical signals to specific nerves or areas of the brain to help reduce seizures over time.
Learn More:
Treating SeizuresFrequently Asked Questions About Autoimmune-Associated Epilepsy
What is the difference between autoimmune encephalitis and autoimmune-associated epilepsy?
Autoimmune encephalitis and autoimmune-associated epilepsy are closely related, but they are not the same condition. Autoimmune encephalitis is inflammation in the brain caused by the immune system. Autoimmune-associated epilepsy is ongoing epilepsy that continues after the inflammation has improved or resolved.
In simple terms:
- Autoimmune encephalitis = active brain inflammation.
- Autoimmune-associated epilepsy = ongoing seizures that continue after the inflammation has improved.
What are antibodies?
Antibodies are proteins made by the immune system that help protect the body from infection. In some autoimmune conditions, antibodies mistakenly target healthy brain tissue instead. This can cause inflammation that may lead to seizures. Testing for certain antibodies can help healthcare providers better understand the cause of seizures and choose the most appropriate treatment.
Can seizures be the only symptom of an autoimmune condition?
Yes. Some people experience seizures as their main symptom. Others may also have memory problems, mood changes, personality changes, or other neurologic symptoms.
Why might my healthcare provider recommend a spinal tap?
A spinal tap, also called a lumbar puncture, allows healthcare providers to collect cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord. Testing this fluid can help identify inflammation, check for antibodies, and rule out infections that may cause similar symptoms.
What autoimmune conditions can cause seizures?
Several autoimmune conditions can cause seizures or autoimmune-associated epilepsy. Conditions that infrequently develop long-term epilepsy:
- Anti-NMDA receptor
- Anti-LGI1
- Anti-CASPR2
- Anti-GABAB
Conditions that typically develop long-term epilepsy:
- Anti-GAD65 encephalitis
- Anti-Hu
- Anti-Ma2
Seronegative autoimmune encephalitis causes seizures but does not have identifiable antibodies. However, healthcare providers use other criteria to diagnose this condition.
Can autoimmune-associated epilepsy be cured?
Outcomes depend on the cause of the inflammation, how quickly treatment begins, and how well seizures respond to treatment.
References
View References
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- Liu X, Guo K, Lin J, et al.. Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update. Epilepsia. 2022;63(7):1812-1821. doi:10.1111/epi.17245
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- Rocamora R, Becerra JL, Fossas P, Gomez M, Vivanco-Hidalgo RM, Mauri JA, Molins A. Pilomotor seizures: an autonomic semiology of limbic encephalitis? Seizure. 2014 Sep;23(8):670-3. doi: 10.1016/j.seizure.2014.04.013. Epub 2014 May 2. PMID: 24890932.
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Resources
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