Autoimmune Encephalitis
Autoimmune encephalitis is a group of conditions where the body’s immune system mistakenly attacks healthy brain cells, causing inflammation that can lead to memory loss, seizures, psychiatric symptoms, and other serious neurological problems.
Table of contents
- What is Autoimmune Encephalitis?
- What Causes Autoimmune Encephalitis?
- Risk Factors
- Types of Autoimmune Encephalitis
- Signs and Symptoms
- Possible Complications
- How is Autoimmune Encephalitis Diagnosed?
- Treatment Options
- Recovery and Living with Autoimmune Encephalitis
What is Autoimmune Encephalitis?
Autoimmune encephalitis, also known as AE, is a group of conditions that cause swelling and inflammation in the brain[1]. This happens when the immune system, which normally protects the body from harmful invaders like viruses and bacteria, makes a serious mistake. Instead of attacking only dangerous substances, it produces antibodies (protective proteins) that attack healthy nerve cells and their proteins in the brain[2].
Autoimmune encephalitis is different from encephalitis caused by viral or bacterial infections, known as infectious encephalitis. While infectious encephalitis results directly from germs invading the brain, autoimmune encephalitis is caused by the body’s own immune response, and therefore requires different types of treatment[1].
Research has found that the number of people with autoimmune encephalitis is about the same as the number of people with infectious encephalitis. A study from 2018 found about 13.7 cases per 100,000 people[1][5]. While autoimmune encephalitis was once considered rare, doctors are finding more cases as their ability to diagnose it improves[5].
What Causes Autoimmune Encephalitis?
Experts don’t fully know what causes autoimmune encephalitis[1]. Like many other autoimmune conditions, researchers don’t understand why the immune system attacks healthy cells[2]. Current research suggests that autoimmune antibodies target specific proteins on the surface of nerve cells or within nerve cells. When these antibodies attach to these proteins, they block their normal function and cause widespread inflammation in the brain[4].
In some cases, autoimmune encephalitis happens alongside certain cancers. Healthcare providers call this paraneoplastic AE. Sometimes a tumor, which can be either benign (not cancerous) or cancerous, may trigger the production of these harmful antibodies[2][3].
For some people, autoimmune encephalitis is triggered by infections. Exposure to certain bacteria and viruses, including streptococcus and herpes simplex virus, may cause the condition[5]. In these cases, the term “post-infectious encephalitis” may be used[3].
However, many people develop autoimmune encephalitis with no known trigger or cause. The condition can also be triggered by certain medicines[1].
Risk Factors
You’re more likely to develop autoimmune encephalitis if you[2][7]:
- Have had or develop cancer, especially small cell lung cancer, thymoma (a type of tumor in the chest), or ovarian cancer
- Have had treatment with immune checkpoint inhibitors (a type of cancer treatment)
- Have had infectious encephalitis
- Have an autoimmune disease or a family history of autoimmune disease
Certain personal characteristics also affect risk. Like many autoimmune diseases, this illness affects women more often than men. It can happen at any age but is diagnosed most often in young women. Some research suggests it may be much more common among Black people, but more research is needed[5].
It’s important to know that it’s also possible to develop autoimmune encephalitis without any of these risk factors[2].
Types of Autoimmune Encephalitis
Autoimmune encephalitis includes several different types, which are identified by the specific antibodies found in blood or cerebrospinal fluid (the liquid that surrounds the brain and spinal cord). Other forms are associated with finding specific antibodies such as VGKC complex (anti-LGI1 and Caspr2), NMDA receptor, GAD, AMPAR and GABA antibodies[3].
Types of autoimmune encephalitis include[5]:
- Acute disseminated encephalomyelitis (ADEM)
- Anti-NMDAR receptor encephalitis (the most commonly studied type)
- Hashimoto’s encephalopathy
- LGI1/CASPR2-antibody encephalitis
- Limbic encephalitis
- Rasmussen’s encephalitis
The most commonly studied subtype of autoimmune encephalitis is anti-N-methyl-D-aspartate receptor encephalitis, so the management approach is primarily based on that type[4].
Signs and Symptoms
Autoimmune encephalitis symptoms can vary widely from person to person. The signs and symptoms depend on the individual and the specific type of the condition[3]. Symptoms typically develop and progress over a period of days or weeks, though some sources report symptoms can take weeks to three months to develop[2][4].
Many people start with symptoms that feel like an infection, such as headache, fever, and other flu-like symptoms. These early-phase symptoms may also include nausea and muscle pain[1][5].
Common symptoms that follow include[1][2][3]:
- Memory problems and confusion: Trouble with memory loss and difficulty with concentration are common
- Cognitive impairment: Progressive decline in thinking abilities and trouble organizing thoughts
- Seizures: These can be focal (affecting one part of the brain) or generalized (affecting the whole brain), and often don’t respond to standard antiseizure medication
- Psychiatric symptoms: These can include anxiety, panic attacks, changes in behavior, agitation, hallucinations (seeing or hearing things that aren’t there), delusions (false beliefs), paranoia, psychosis, depression, mania, and catatonia (a state of unresponsiveness)
- Language problems: Difficulty with language, including trouble speaking (called aphasia)
- Abnormal movements: Involuntary movements such as tremors, muscle twitches, repetitive movements of the mouth and face, rigidity, an exaggerated startle response, and involuntary movements of the face (called facial dyskinesia)
- Problems with balance or coordination: Difficulty with balance, speech, or vision (called ataxia)
- Altered behaviors: Altered sexual behaviors, compulsive behaviors, loss of inhibition, behavior changes such as fear or euphoria
- Autonomic dysfunction: Changes in heart rate and blood pressure, labile blood pressure, and tachycardia (rapid heartbeat)
- Sleep disturbances: Insomnia and excessive sleepiness are frequent
- Physical symptoms: Weakness or numbness, urinary incontinence
Later symptoms may be more severe, such as a lower level of consciousness, loss of consciousness, or coma[5]. Psychiatric symptoms may appear, disappear, and reappear[5].
It’s important to get medical help right away if you or someone you know develops these symptoms[2].
Possible Complications
Without treatment, autoimmune encephalitis can cause serious complications[1]. Possible complications include[2][11]:
- Cognitive impairment (lasting problems with thinking and memory)
- Prolonged seizures (called status epilepticus)
- Progressive neurologic decline
- Permanent brain injury
- Coma
- Death
Starting treatment early seems to decrease long-term complications and the risk of relapse, as well as lead to faster recovery[11].
How is Autoimmune Encephalitis Diagnosed?
Autoimmune encephalitis diagnosis involves a review of your symptoms, a physical exam, and several tests. It’s important to get an accurate diagnosis because autoimmune encephalitis can be mistaken for other diseases, including mental health disorders or drug abuse[5][8].
Diagnosing autoimmune encephalitis can be challenging, as the symptoms can be non-specific and may resemble those of other conditions, such as infectious encephalitis or psychiatric disorders[3]. Sometimes people are incorrectly diagnosed with autoimmune encephalitis[8].
Healthcare providers diagnose autoimmune encephalitis based on the presence of symptoms in a certain timeframe. They also rely on test results that show inflammation in your brain[2]. Experts have created autoimmune encephalitis criteria to help healthcare professionals look for patterns of symptoms that signal the condition[8].
Given the large number of conditions that can look like autoimmune encephalitis, you may need several tests. Diagnosis can sometimes take many weeks[2]. Tests and exams providers use to diagnose autoimmune encephalitis include[2][8]:
- Physical exam and detailed medical history
- Neurological exam: To check nerve function and brain activity
- Cognitive tests: To assess thinking and memory abilities
- Blood tests: To check for antibodies that attack brain cells and to rule out other causes
- Cerebrospinal fluid (CSF) analysis: CSF is removed using a procedure known as a lumbar puncture (also called a spinal tap). During the procedure, a healthcare professional numbs the lower back and uses a hollow needle to remove cerebrospinal fluid for testing. This test helps detect the presence of autoantibodies
- Brain imaging: An MRI (magnetic resonance imaging) of your brain can look for signs of autoimmune encephalitis or rule out other causes of your symptoms. Other imaging tests may look for signs of cancer that may have triggered the condition
- Electroencephalogram (EEG): This test measures the electrical activity in your brain and may show seizure activity or abnormal brain wave patterns
To get the best results from antibody testing, both blood and cerebrospinal fluid samples need to be analyzed in patients with suspected autoimmune encephalitis. Both false positive and false negative test results can occur, so it is important to send testing to a reference laboratory[7].
Your provider may also recommend other tests to rule out metabolic, infectious, and nutritional causes of brain problems[7]. Once the diagnosis is established, patients should undergo cancer screening due to a high degree of association with underlying cancer, particularly small-cell lung cancer[4][7].
Treatment Options
Autoimmune encephalitis is usually treatment-responsive with immunotherapy, and treatments can lead to recovery. Many people with autoimmune encephalitis make a full recovery, but some can have lasting symptoms[1].
If the combination of symptoms and test results suggest that a person has “possible AE,” current recommendations are to start treatment early in the course, even before all test results are back. Although these tests can be time-consuming, clinicians should consider initiating treatment early if their clinical suspicion is high, as the condition is often treatment-responsive and has significantly improved outcomes when treatment is started early[4][11].
First-Line Treatments
The main treatment goals for autoimmune encephalitis include reducing inflammation in the brain and removing tumors if they are present[2]. First-line medications that treat inflammation in the brain include[2][11]:
- Corticosteroids (also called steroids): Anti-inflammatory medications
- IV immunoglobulins (IVIG): Antibodies given through a vein
- Plasma exchange (plasmapheresis): A procedure that removes harmful antibodies from the blood
Right now, there are no research studies that tell healthcare providers which of these medications, or which combination, should be used first. As a result, treatment may differ in patients based on their ages, how severe their symptoms are, and where they are being treated[11].
Second-Line Treatments
If first-line therapy isn’t effective, the next treatment options include[2][11]:
- Rituximab: A monoclonal antibody injection
- Cyclophosphamide: A chemotherapy medication
- Other medications such as mycophenolate mofetil or azathioprine
These medications may be started early (within weeks of diagnosis) in patients who are not improving with first-line treatments. Or, these medications may be started later if there are signs of ongoing inflammation or if the doses of first-line treatments cannot be decreased without symptoms coming back[11].
Tumor Treatment
If you have a tumor, your healthcare team will recommend surgically removing it and/or chemotherapy. This helps speed up the improvement of autoimmune encephalitis[2].
Symptom Management
In addition to the medications that act on the immune system to decrease brain inflammation, many people with autoimmune encephalitis will need supportive medications to treat the symptoms that cause suffering and disability[11]. You may need additional medications to manage the symptoms, including[2][11]:
- Antiseizure medications: To reduce or prevent seizures
- Medications for abnormal movements: To decrease uncontrolled movements
- Medications for anxiety or depression
- Antipsychotic medications: For patients who hallucinate
- Medications that improve attention
- Medications that help with sleep
Sometimes, medications that treat the symptoms of autoimmune encephalitis don’t work well when a person is first diagnosed, but doctors may recommend trying them again later after the brain inflammation has decreased because they may work better[11].
Rehabilitation
Physical therapy, occupational therapy, and speech therapy may be very helpful to improve recovery and may be started in the hospital and sometimes continued in rehabilitation centers[11].
Treatment Response
Some people with autoimmune encephalitis improve within days of receiving their first-line treatments and don’t need additional medications that act on the immune system. Steroids and/or IVIG may be continued for several weeks to months, slowly decreasing the dose, to ensure that the brain inflammation stops[11].
Other people with autoimmune encephalitis will need more medications that act on the immune system in order to stop the brain inflammation. Some will need intense medication regimes and a long duration of treatment. Right now, there are no symptoms, signs, or test results that tell the doctors in advance how a patient will respond to treatment[11].
Recovery and Living with Autoimmune Encephalitis
The long-term outlook for people affected by autoimmune encephalitis varies considerably. In some instances, people come through the illness with little or no lasting effects. In others, people have different degrees of life-long difficulties[14].
Recovery Timeline
Recovery from autoimmune encephalitis may take time, sometimes months to a year. Initial recovery may be rapid but usually falls short of complete. Further recovery takes place more slowly over a period of months, even years[14][18]. People are different, and no two cases of encephalitis will have an identical outcome. People recover at different paces[14].
It is not uncommon for problems to present more at home as you try to get back to normal life. Some of these features may be subtle when in hospital and maybe ignored or not noticed at that time by family and/or professionals[14].
Tips for Living Well
Living with autoimmune encephalitis can be challenging. Those affected experience various neurological issues that can impact daily life[13]. Here are some tips that can help[13][14]:
- Educate yourself about the disease: The more you know about your condition, the better you can handle it. Understand the different causes, symptoms, and types of the disease
- Establish a support system: Having family and friends who understand your condition can make a world of difference. They can help by encouraging you during difficult times, offering emotional support, and helping with daily tasks. You can also find support through support groups and online forums
- Prioritize self-care: Stay hydrated, eat a balanced diet rich in fruits, vegetables, whole grains, and lean proteins, and engage in light to moderate physical activity
- Rest and pace yourself: Recovery can be helped by a structured timetable where short period activities (physical and mental) are followed by rest. Initially rest periods should be long and activity periods short. As recovery takes place, activities can become longer and breaks become shorter
- Track changes in symptoms: Keep a diary to help you monitor your activities and symptoms
- Stay positive and resilient: Coming to terms with the problems can be very distressing and challenging for everyone concerned
- Communicate with your healthcare team: Take an active role in your care. If you have any questions or concerns, talk with your doctor
Impact on Life
Autoimmune encephalitis can affect the whole family. The person you knew, or who you were, may have changed and the person they have become, or you have become, may present with a number of problems. The impact will be different for each individual depending on the part of the brain affected, their personality, their emotional and physical health state prior to their illness, and their social support network[14].
Autoimmune encephalitis can be life changing. The symptoms may be hard to cope with[18]. Some people are discharged to rehabilitation units, some are discharged at home having been referred to community-based services, and others are discharged at home with no follow-up plan or pending referrals[14].
Follow-up care is important because autoimmune encephalitis may relapse[12].
