What is Autoimmune Encephalitis (AE)?AE is a serious medical condition in which the immune system attacks the brain, impairing function. While AE may be triggered by an infection, many cases have an unknown cause. Depending on what part of the brain is affected, and which part of the immune system is activated, the symptoms can vary broadly. AE is a severe condition, with an approximately 6% mortality rate. While rapid diagnosis and appropriate treatment allows many patients to recover most or all functions, a significant percentage of patients have persistent symptoms that negatively impact their ability to function. What are the most common symptoms of AE?Autoimmune encephalitis can produce a wide range of neuro-psychiatric symptoms. Click here for a full discussion of symptoms. Is AE considered a “new” disease? Is it rare? While the term “autoimmune encephalitis” appears in the medical literature in the 1970’s and 1980’s, the first specific antibody mediated AE, was identified in 2005 when Dr. Josep Dalmua described the anti-NMDA-receptor antibody encephalitis type. The field of AE has expanded rapidly since then. As of early 2017, there have been ~22 antibodies discovered, including auto-antibodies directed against NMDA, LGI1, CASPR2, VGKC-complex antibodies, AMPA, and GABA. According to one prominent researcher, a new antibody is being discovered roughly every six month. Initially considered very rare, the disease is now increasingly recognized as a significant diagnosis in the spectrum of brain illnesses related to malfunctions of the immune system. These types of disorders may be much more common than previously thought, but the true frequency is not yet known. Are you more likely to be diagnosed with AE due to age or gender? The disease occurs in men, women and children of all ages, but it has historically been diagnosed most frequently in young women. This is similar to other autoimmune diseases, where women are more commonly affected. An older study suggests that out of 100-plus known autoimmune diseases, 75% of people affected are female. However, it is important to recognize males also get autoimmune diseases and not overlook their presentations. What kind of doctors treat AE? Because AE can affect different part of the brain, people with AE can have poor memory or cognition, develop seizures or movement abnormalities, or have changes in their mood or behavior with hallucinations or personality changes. AE is a multi-disciplinary disease. Diagnosis and treatment often requires the combined efforts of multiple specialists including: psychiatrists, neurologists, rheumatologists, and immunologists. Psychiatrists specialize in the diagnosis and treatment of mental disorders and are key to “ruling out” neurological causes of psychiatric symptoms and treating the psychiatric symptoms of AE along with other treatments targeting the immune system and neurologic deficits. Neurologists specialize in the diagnosis and treatment of diseases involving the nervous system, which includes the brain, spinal cord, and body’s network of nerves. Immunologists specialize in the diagnosis and treatment of problems with the immune system, including immunodeficiency, when the immune system is compromised or impaired, and autoimmunity, when the immune system attacks its own body. Rheumatologists specialize in the diagnosis and treatment of certain conditions where the immune system attacks the joints, blood vessels, muscles or organs. Rheumatologists are trained in using medications that suppress or slow down the overactive immune system. Rheumatologists and immunologists have some similar areas of practice around autoimmune disease. Immunologists specialize in the diagnosis and treatment of problems with the immune system, including immunodeficiency, when the immune system is compromised or impaired, and autoimmunity, when the immune system attacks its own body. How do clinicians currently recognize and establish a diagnosis of AE? Until recently, no broadly accepted criteria existed for diagnosing AE. This lead many doctors to rely on testing for the presence of antibodies (i.e. anti-NMDA receptor antibodies) or diagnosing by process of elimination and diagnosis-through-treatment. For example, if the person had a clinical picture consistent with AE, and test results for all other diseases are negative and the disease symptoms improve with immune-modulation therapy. In 2016, a Lancet Neurology article by Dalmau et al provides the first broadly accepted diagnostic criteria for autoimmune encephalitis. The article was followed by a precis that provides a series of panels for use in diagnosing AE. Among the key findings of the new criteria:
Read the AE Alliance blog post on precis for more information. Consider sharing both the article and the precis with your medical team if they have not read these articles. What are the known causes of AE? The direct cause of most cases of AE remain unknown. However the following have been shown to trigger AE:
A teratoma or cancer is found only in a small minority of AE patients. Active infection is also uncommon in patients presenting with AE. Unfortunately, the immediate trigger of many episodes of AE remains unknown. Are family members at greater risk of contracting AE? No research to date shows increased risk of contracting AE among family members of those with the disease. What kind of outcomes can we expect from this disease? How long does it take to get better? More research is needed on recovery and outcomes associated with AE. One study from 2013 provides the best data. The 2013 Lancet Neurology article reviewed the study of 577 patients with AE reported that 53% of patients who received immunomodulation therapy showed improvement within 4 weeks. 81% of patients showed substantial or complete recovery. On average, patients continued to improve for 14 months after onset of acute AE. 12% of patients who recovered from a first acute episode had at least one relapse in the next two years. Overall mortality associated with the disease was approximately 6%. [Note that this study is limited to one type of AE – anti-NMDA-receptor antibody encephalitis]. How can I determine whether someone I’m caring for has AE or not? If you suspect that you or a family member may have AE, you should consult your primary care physician in addition to specialists in neurology, psychiatry, immunology, or rheumatology. Workup should include a thorough history and physical exam to determine if the clinical course could be consistent with AE. If presentation is consistent, then tests including MRI, EEG, spinal tap and blood tests for known antibodies, and in some cases scans for teratomas or other cancers should be strongly considered. At least fifteen different types of autoimmune encephalitis have been identified in the laboratory. Several commercial labs provide diagnostic tests for AE including Mayo Labs, Euroimmun and Athena Diagnostics. See “How do clinicians currently recognize and establish a diagnosis of AE?” above for links to diagnostic criteria for AE. What are the most common treatments for AE? As soon as a patient is diagnosed with AE, they should receive one or more of the four (4) first-line treatments.
“Second line” treatments—immunosuppressant drugs—should be started promptly if first-line treatments fail to improve symptoms. These medications work by decreasing the number and function of the immune cells that cause inflammation and autoimmunity. The three most commonly used drugs are:
What other medications are commonly prescribed to patients with AE? Are there any medications that specifically should not be taken by someone suffering from AE? For treatment of symptoms – in particular agitation and sleeplessness – benzodiazepines are commonly prescribed. High-dose Lorazepam (trademark: Ativan) can be highly effective for AE patients. Note that because of the completely different disease mechanism, use of anti-psychotic drugs commonly used to treat bipolar disorder and schizophrenia such as Clozapine (Clozaril) and Risperidone (Risperidal) may not be effective, and according to some clinicians may actually increase the severity of AE symptoms. This varies depending on the type of AE and where patients are in the treatment course. Prior to initiating immunotherapy, these medications are less likely to be helpful and more side effects may be seen. Once the inflammatory process is being treated, these medicaitons may be essential to reduce suffering from the symptoms of AE and maximizing funcationing as patients recover. Failure to respond to anti-psychotics may be a diagnostic clue that the actual cause of psychosis may be autoimmune encephalitis. However, given not all patients with psychiatric disease respond to the first anti-psychotic tried, it is important to have psychiatrists involved in these cases to help guide diagnostic and treatment considerations, as well as looking for other symptoms which would also suggest AE (cognitive decline, seizures, abnormal movements, sleep disruption etc.). What is the frequency of relapse after having an acute episode of AE? The Lancet Neurology article reported that 12% of patients with NMDAR AE had at least one relapse within two years. While there is less data for the other forms of AE, some types seem to have higher and lower rates of relapses and refractory disease. What social services are available for children (in the U.S.) who have AE? School age children are entitled to accommodations under U.S. law, and may qualify for an Individualized Education Program (IEP) for acquired cognitive problems and/or ADD. Both the National Center for Learning Disabilities and the National Dissemination Center for Children with Disabilities provide useful information on IEPs and other resources. My doctor says my family member does not have AE. Should I get a second opinion? It is critical that you feel that your medical provider is addressing all of your medical concerns. If you feel you aren’t being heard, we highly recommend getting a second opinion. You are your best advocate. It is important to recognize there are many conditions that can have overlapping symptoms with AE and not all patients with new onset neuropsychiatric symptoms have an autoimmune condition or require an evaluation for AE. If you are looking for a second opinion, you can access the AE Clinicians Network here. The network is a list of self-identified AE experts. Is AE related to PANDAS, and if so, how? PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) is a disease that results in psychiatric symptoms, including obsessive-compulsive behaviors, that is triggered by a strep infection. PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) is the broader category of infection induced . Small clinical trials have not shown consistent response to immunotherapy for PANDAS, but ongoing studies are underway. How PANDAS/PANs relates to AE is an area of ongoing exploration. While some feel PANDAS/PANS is on a continuum with AE, others feel they are distinct entities. Currently, there are different diagnostic criteria and treatment recommendations for PANS/PANDAS and AE. What is the mission of the AE Alliance? How can I help? The Autoimmune Encephalitis Alliance seeks to improve the lives of autoimmune encephalitis patients and their families through :
Please visit our contact page to connect with the AE Alliance and join our mailing list. A family member has recovered from AE, and we would like to reach out to help others coping with this illness. How can we help? There are many ways that you can assist the AE Alliance and other families going through the disease. Share your story with us. In the near future, we plan to establish a patient/family peer-to-peer network. But also you can host an event in your area or share this information broadly to your network. Keep in touch on facebook, twitter or other social media. We want to spread the word and help educate a community on this disease. Please visit our volunteer signup. AUDIO VIDEO |
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来自： Janegyj > 《神经感染免疫与脑脊液》
