Autoimmune encephalitis (AE) is a serious, potentially treatable neurological disorder in which the body’s own immune system mistakenly attacks the brain. This misdirected immune response leads to inflammation of the brain tissue, or encephalitis. The condition can cause rapid and complex changes in a person’s mental status, behavior, and physical health. Recognizing AE as a non-infectious cause of brain inflammation has been a significant development in modern neurology. Early and accurate diagnosis, followed by prompt treatment, is important for minimizing long-term complications and improving recovery.
How the Immune System Attacks the Brain
Autoimmune encephalitis occurs when the immune system, which normally produces protective antibodies against foreign invaders, turns against healthy brain cells. This self-directed attack is the “autoimmune” component of the disease. The core mechanism involves the production of specific autoantibodies that target crucial proteins and receptors located on the surface of neurons in the central nervous system (CNS).
These autoantibodies interfere with the normal signaling between brain cells, leading to neurological dysfunction. For instance, antibodies targeting the N-methyl-D-aspartate receptor (NMDAR) can cause the receptor to be internalized, reducing its presence on the cell surface and disrupting synaptic transmission. Other common targets include the voltage-gated potassium channel (VGKC) complex proteins, such as Leucine-rich glioma-inactivated 1 (LGI1) and Contactin-associated protein-like 2 (CASPR2).
The development of AE is distinct from infectious encephalitis, which is caused by a virus, bacterium, or other pathogen directly invading the brain. In autoimmune forms, the inflammation is mediated by the immune system itself. While some cases of AE may be triggered by a preceding infection or an underlying tumor, the resulting brain damage is a consequence of the body’s immune attack, not the pathogen itself.
Identifying the Clinical Signs
The clinical presentation of autoimmune encephalitis is broad and often confusing, frequently overlapping with symptoms of primary psychiatric disorders. Symptoms typically develop over a period of weeks to a few months, a subacute onset that helps distinguish it from long-standing mental illnesses. The initial changes can be subtle, sometimes beginning with flu-like symptoms such as headache or fever.
Psychiatric changes are common and can include new-onset psychosis, involving hallucinations, delusions, or paranoia. Patients may also exhibit severe mood disturbances, agitation, catatonia, or rapid personality changes. These behavioral shifts can be so pronounced that the condition is initially misdiagnosed as a primary mental health crisis.
Neurological deficits also form a major part of the clinical picture, often presenting alongside or shortly after the psychiatric symptoms. Seizures are one of the most common features and can sometimes be refractory to standard anti-seizure medications. Patients may also experience memory loss or significant cognitive decline.
Movement disorders, such as involuntary facial or limb movements or dystonia, are another frequent characteristic. Autonomic dysfunction can occur, involving issues with involuntary bodily functions. This may manifest as changes in heart rate, blood pressure instability, or problems with sleep.
Confirming the Diagnosis
Diagnosing autoimmune encephalitis requires a comprehensive approach that combines clinical observation with specialized laboratory and imaging tests. A primary step is the exclusion of infectious causes, which can present with similar symptoms and require immediate, different treatment. The diagnosis is based on criteria that assess the pattern of subacute symptoms alongside objective evidence of brain inflammation.
Neuroimaging, typically an MRI, is a standard part of the workup. The MRI may show signs of inflammation, particularly in the medial temporal lobes, which are associated with memory and emotion. However, a normal MRI does not rule out the diagnosis, underscoring the need for other tests.
Electroencephalography (EEG), which measures the electrical activity of the brain, is used to detect seizure activity and characteristic patterns of brain wave slowing. This test can help identify abnormal electrical discharges even if the patient is not having visible seizures.
The most specific diagnostic step is the analysis of cerebrospinal fluid (CSF), obtained through a lumbar puncture or spinal tap. The CSF is tested for inflammatory markers, such as an elevated white blood cell count. Critically, the CSF and blood are tested for the presence of specific neural autoantibodies. Testing the CSF is often more sensitive for certain antibodies and can better reflect the active disease process.
Acute and Long-Term Management
Treatment for autoimmune encephalitis is divided into two tiers, focusing on halting the acute immune attack and preventing future relapses. Prompt initiation of therapy is important for achieving a favorable long-term outcome. The first-line, or Tier 1, treatment aims to rapidly suppress the misdirected immune response.
Acute therapies include high-dose corticosteroids, which reduce brain inflammation. Intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are also used as first-line options. IVIG provides the body with healthy antibodies to interfere with the pathogenic ones, while PLEX involves filtering blood to remove the harmful autoantibodies. These treatments may be used sequentially or in combination, depending on the severity of the condition.
If the patient does not respond adequately to the initial Tier 1 treatments, or for severe or recurring cases, Tier 2 therapies are introduced. These treatments use stronger, more targeted immunosuppressive agents for long-term control. Rituximab, a monoclonal antibody that targets and depletes B-cells, is a common long-term agent, particularly for cases involving cell-surface antibodies.
Another Tier 2 option is cyclophosphamide, a chemotherapy agent used for its potent immunosuppressive effects. Following the acute phase, patients often require rehabilitation services, such as physical, occupational, and speech therapy, to manage lingering neurological effects. Long-term management may also involve addressing potential neurological sequelae like persistent seizures or cognitive impairment.