Pediatric autoimmune encephalitis (AE)
Autoimmune encephalitis (au·to·im·mune - en·ceph·a·li·tis) or AE refers to a group of disorders in which the body's immune system makes antibodies that target brain cells called neurons. In particular, components of the outer surface of neurons may be affected, disrupting the normal functioning of neurons and leading to neurological and psychiatric symptoms.
What are the different types of pediatric autoimmune encephalitis (AE)?
Types of AE have been named and classified in multiple ways. Some of the earliest identified forms of AE involved the immune system fighting a tumor or cancer that leads to production of antibodies that cross react to parts of the nervous system (paraneoplastic autoimmune encephalitis). These antibodies are often directed to proteins inside of the cells, and often did not respond favorably to immunotherapies and require treating the underlying tumor or cancer itself. When the target of the antibodies was a part of the brain important in memory and emotion called the limbic system, the term limbic encephalitis was also used.
More recently, forms of AE in which the immune system makes antibodies targeting the outer surface of neurons have been discovered, including anti-NMDA receptor encephalitis, LGI1 encephalitis, and Caspr2 encephalitis, among others.
These forms of AE have been named based on the target of the antibodies and are typically more responsive to immunotherapies as the antibodies may lead to reversible changes in neuronal function. In some cases, these are also triggered by tumors, but much of the time, no known cause is found and it is thought that an infection may have triggered this abnormal immune response.
What are the signs and symptoms of pediatric autoimmune encephalitis (AE)?
Depending on the part of the nervous system affected, the signs and symptoms of AE may vary.
When the target of the inflammation is parts of the brain involved in memory formation and emotional processing (the limbic system), common symptoms include changes in thinking, mood and behavior. This may outwardly appear as confusion, agitation, seeing or hearing things that are not there (visual or auditory hallucinations) and/or unusual or irrational thoughts (delusions).
When parts of the brain involved in movement are affected, symptoms can be involuntary writhing or jerking movements, muscle stiffness or loss of voluntary movement. Seizures commonly emerge due to dysfunction of neurons leading to abnormal patterns of electrical activity. Seizures related to AE may not respond as expected to antiseizure medications, but rather, require treating the underling autoimmune process.
How is pediatric autoimmune encephalitis (AE) diagnosed?
AE is diagnosed based on identification of specific antibodies targeting neurons such as anti-NMDA, anti-LGI1, and/or Caspr2 antibodies in the blood and/or cerebrospinal fluid.
Sometimes, a specific antibody is not identified but neuroimaging or spinal fluid studies identify signs of inflammation (such as IV contrast escaping into parts of the brain where the blood-brain barrier is disrupted or finding the presence of too many immune cells in the spinal fluid). It is important to rule out infection, as this can lead to similar findings but requires treatment with antibiotics and antiviral medications.
An electroencephalogram (EEG), a study to look at the electrical activity of the brain, can be used to look for abnormal electrical patterns related to seizures or impaired thinking. In rare cases in which the diagnosis is uncertain, a brain biopsy to look for evidence of inflammation may be required.
How is pediatric autoimmune encephalitis (AE) treated?
Like other autoimmune and inflammatory disorders of the central nervous system, AE is both treated during the acute time period as well as with long-term treatments, if needed to suppress ongoing inflammation or prevent future inflammation.
Steroids work by reducing the ability of inflammatory cells to enter the brain, interrupting their communication or interfering with their ability to make chemicals involved in inflammation. They can be administered orally or intravenously (IV). Most children do not have side effects, but some may experience mood changes, appetite changes, difficulty sleeping or irritability. Rarely, patients can experience infection or bone abnormalities.
Plasmapheresis (PLEX) - PLEX is used to clean the blood of inflammatory components. It requires special IV access and a portable machine to clean the blood. A patient’s blood is circulated through the machine and proteins such as antibodies are removed. A therapy session takes about 90 minutes and is usually well tolerated. A patient usually receives five to seven treatments to complete a PLEX course.
Intravenous immunoglobulin (IVIG) - IVIG is made up of antibodies collected and pooled from blood donors that is thought to reduce the patient’s own abnormal immune response.
Long-term immunosuppressive medications - When symptoms do not fully respond to these treatments or a person has had more than one episode of AE, long-term immunosuppressive medications can be used to prevent further inflammation. Commonly used medications include Rituximab® (which targets B cells involved in making antibodies), CellCept® or mycophenolate mofetil (a drug that reduces the proliferation of immune cells) and IVIG (to prevent or interfere with the body’s ability to make disease-causing antibodies). Most current guidelines are based on expert opinion and case reports. Natural history studies and clinical trials are needed to determine how to optimally monitor these conditions over time and what the best treatments are for the different forms of autoimmune encephalitis.
Psychosocial support and/or therapy - In addition to evaluation by a neuropsychologist for cognitive, emotional and/or behavioral problems, patients may also require psychosocial support or other therapies to manage the impacts of AE.