Autoimmune encephalitis / encephalitis is a group of diseases in which the immune system attacks the brain. Symptoms increasing over days-weeks. The diagnosis is complicated and is usually made after extensive investigation by a neurologist. There are several types of autoimmune encephalitis that are distinguished on the basis of symptoms, antibody in blood and spinal fluid and other examination findings. Some cases are related to other autoimmune diseases, incl Systemic lupus erythematosus (SLE) or autoimmune metabolic disease (Hashimoto's thyroiditis). Others may have an underlying cancer. If concurrent rheumatic disease is suspected, the investigation is carried out in collaboration with a rheumatologist.
Autoimmune encephalitis is very rare. The most common form of autoimmune encephalitis is anti-NMDAR encephalitis. The number of new cases annually (incidence) is calculated at one per 1,5 million people annually (Dalmau J, 2019).
The symptoms can be acute or come on more gradually. Usually the symptoms over days-weeks, so that the signs of the disease are evident within six weeks. The symptoms vary according to the type of autoimmune encephalitis involved. These are partly antibody-related (see investigations below). Symptoms include psychiatric signs such as altered behaviour/personality, movement disorders and seizures. Other signs are headache, confusion, hallucinations, aggressiveness and memory impairment (reference: Graus F, 2016). Some people get symptoms from the autonomic nervous system with abnormally heavy sweating, high blood pressure, fast pulse and reduced breathing rate (Dutra LA, 2018).
Medical history in the case of autoimmune encephalitis, includes whether a similar condition has been detected in a close relative, as well as current symptoms (see above).
Clinical a neurological examination is carried out, but also an assessment of other concurrent conditions such as Systemic lupus (SLE), other autoimmune diseases, metabolic diseases, infections and cancer.
Blood tests may show signs of mild inflammation with elevated CRP and SR, but not in all cases. Antibodies in blood (serum) include ANA with subgroups and ANCA (PR3 and MPO) but are usually normal.
- Antibody in blood (serum) and spinal fluid. In a large part of the cases, more or less typical neuro-antibody tests can turn out. However, low titer results must be interpreted with caution because insignificant "false positive" results occur. The antibodies are directed against proteins in the central nervous system (CNS). These can be membrane receptors and ion channel associated proteins on the surface of neurons. Thyroid antibody (anti-TPO) in Hashimoto thyroiditis and Hashimoto encephalitis (SREAT). The antibodies include Anti-N-methyl-D-aspartate receptor (NMDAR), Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (anti-AMPAR), Anti-gamma-aminobutyric acid A receptor (anti- GABA-AR), Anti-gamma-aminobutyric acid B receptor (anti-GABA-BR), Anti-LGI1 and anti-CASPR2, Glutamic acid decarboxylase (GAD), Anti-Glycine receptor (anti-GlyR), Anti-Dipeptidyl peptidase-like protein 6 (DPPX), Anti-IgLON5, Anti-Metabotropic glutamate receptor 1 (anti-mGluR1) and anti-metabotrophic glutamate receptor 5 (anti-mGluR5).
Diagnostic criteria have been proposed (reference: Dutra LA, 2018). These are based on symptom development (medical history), findings in the spinal fluid, EEG and MRI examinations, as well as the exclusion of infections and other causes.
Similar conditions, differential diagnoses
There are many differential diagnoses. Acute disseminated encephalopathy, neuromyelitis optica diseases, CNS vasculitis, whether primary (PACNS) or secondary, neuropsychiatric lupus (SLE), angiocentric lymphoma, Rasmussen's encephalitis, and febrile infection-related epilepsy. It is also important to rule out infections such as HIV, syphilis, herpes virus-6-associated encephalitis in immunosuppressed patients, as well as Creutzfeld-Jacob disease (reference: Granerød J, 2010). Some concrete conditions are listed below:
Virus encephalitis: Herpes simplex, enterovirus, West Nile Virus, Ebstein-Barr Virus (EBV).
Fungal infection (in the case of a weakened immune system due to drugs or HIV): Cryptococcus, Aspergillus. More comprehensive list of infections that can attack the brain here (Wikipedia).
- Carcinomatic meningitis (in case of cancer)
- CNS vasculitis (in the blood vessels of the brain)
- Systemic lupus erythematosus (SLE) with involvement of the brain
- Wernicke encephalitis
Immunosuppressive drugs are applicable. The choice of treatment regimen depends on the degree of severity and which subtype is present. Among drugs are corticosteroids such as prednisolone, intravenous immunoglobulin, rituximab and cyclophosphamide. In addition, plasma replacement/plasmapheresis is used (reference: Titles MJ, 2016). Best prognosis is associated with early treatment, no need for intensive treatment (Höftberger R, 2013).