Autoimmune Encephalitis (Encephalopathy) is a rare treatable group of CNS disorders that can be progressive or relapse-remitting. It is caused when the immune system makes auto-antibodies that are not supposed to be there. These auto-antibodies (aka antibodies) begin to attack healthy brain cells wrongly identifying them as foreign. An autoimmune response is now occurring as the body’s immune system mistakes its own healthy brain cells for invaders causing inflammation of the brain.
The antibody attacks by targeting special receptors in the brain. The antibodies can target the attack to receptors on the cell surface of healthy nerve cells in the brain or target the attack to synaptic receptors that are exposed to the attacking antibody or ion channels. These antibodies bind to the healthy brain cell on the outside of the cell. These antibodies are called extracellular because they bind or attach themselves to the healthy brain cells outside surface. The healthy brain cells are now destroyed or no longer function properly. Severe brain inflammation occurs. The brain now malfunctions. All brain functions can be compromised: emotions, psychosis, memory, cognition, problem solving, speech, movement, seizures, balance, visual processing planning, sensory, hunger, thirst, behavior and personality traits, often followed by suppressed levels of consciousness and coma may occur.
These diseases are not always cancer-related which makes them different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, the intracellular antibodies. (See: Paraneoplastic Autoimmune Encephalitis)
Most importantly, Autoimmune Encephalitis IS TREATABLE and almost invariably responds to immunotherapies with considerable potential to reverse the impairments caused by these attacking antibodies. Immunotherapies can slow down the progression of the disease, stop the antibodies from attacking and with some treatments kill the attacking antibody which may sometimes leads to complete recovery.
A unique feature of the autoimmune encephalitis is that they can affect patients of all ages including infants and the elderly, some types more often occurring in children and young adults. Autoimmune Encephalitis occurs more frequently in women than in men and they can develop with or without an underlying tumor. The incidence of autoimmune encephalitis has been reported to be higher among African Americans than Caucasians. Autoimmune Encephalitis prevalence~1.2 per 100,000 VS. Infectious Encephalitis ~1.0 per 100,000 ~14 per 100,000 had autoimmune encephalitis in their lifetime ~12 per 100,000 who had infectious encephalitis. This study allows us to estimate that approximately 1 million people worldwide had autoimmune encephalitis in their lifetime. It has also been estimated that, currently, about 90,000 people around the world develop autoimmune encephalitis each year.
Most autoimmune encephalitides occur in patients with no apparent immunologic triggers, leading some investigators to postulate a genetic predisposition to these disorders. One study suggested a genetic predisposition to anti-NMDAr encephalitis in Maori and Pacific Island populations. Four studies showed an association of anti-LGI1 encephalitis with HLA class II genes, including HLA-DRB1*07 (DR7) and HLA-DRB4 in a 2017 Dutch population study and DRB1*07:01–DQB1*02:02 in a 2017 Korean population study. A 2018 German study also showed a link with anti-LGI1 and HLA class II genes encompassing DRB1*07:01, DQA1*02:01 and DQB1*02:02 as well as a genetic component in anti-NMDAr encephalitis with HLA-I allele B*07:02. Recently a 2020 study in the Chinese Han population found a HLA subtype had strong susceptibility of LGI1 autoimmune encephalitis and a May 2018 study by the Oxford group showed a non-heritable but consistent genetic predisposition to LGI1 and CASPR2. Research just published out of China shows genetic link to anti-NMDAR encephalitis. This study for the first time, demonstrates an association between specific HLA class II alleles, DRB1*16:02 in anti-NMDAR encephalitis, providing novel insights into the mechanism by which the disease occurs. This adds to LGI1 and CASPR2 HLA-DRB associations.
Dr. Maarten Titulaer Webinar 1 hour
Autoimmune Encephalitis – anti-NMDAr encephalitis and Beyond 2017
Dr. Josep Dalmau
2016 AAN Autoimmune Encephalitis
Gregory Day, MD, MSc, FRCPC
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From Witchcraft to Neurologic Wizardry
Eric Lancaster, MD, PhD
Autoimmune Synaptic Encephalitis
Dr. Sarosh Irani
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Andrew McKeon, M.B., B.CH.,M.D
Co-Director of the Neuroimmunology