Autoimmune Encephalitis

How autoimmune encephalitis works

Antibodies target proteins on the surface of brain cells, such as receptors that pass signals between neurons. This disrupts brain signaling and causes inflammation, a form of encephalitis that is not caused by infection. Because surface proteins can recover when the antibodies are removed, these forms often respond well to treatment.

A second group involves immune attacks on proteins inside cells, often triggered by a cancer (paraneoplastic encephalitis). These are driven by T cells, cause more permanent damage and respond less well.

Triggers include:

• Tumors: for example ovarian teratomas in anti-NMDA receptor encephalitis, and small cell lung cancer in some paraneoplastic forms.
• Infections: herpes simplex viral encephalitis can trigger anti-NMDA receptor encephalitis weeks later.
• Cancer immunotherapy drugs (checkpoint inhibitors).
• Unknown: in many cases no trigger is found.

Main types

Symptoms

Symptoms usually develop over days to a few weeks (subacute onset) and may follow a flu-like illness:

• Psychiatric: anxiety, agitation, paranoia, hallucinations, mania or catatonia. People are sometimes first admitted to psychiatric units with suspected psychosis.
• Memory and thinking: short-term memory loss, confusion, disorientation.
• Seizures: focal or generalized, sometimes very frequent and hard to control.
• Movements: repetitive mouth and face movements, writhing limbs, rigid postures.
• Speech: reduced speech or mutism.
• Sleep: severe insomnia or excessive sleep.
• Autonomic problems: swings in heart rate, blood pressure and temperature, and breathing problems needing intensive care.

Diagnosis

There is no single test, and treatment often starts before antibody results return. Doctors use:

• MRI of the brain: may show inflammation in the temporal lobes (limbic encephalitis), but is normal in many anti-NMDA receptor cases.
• EEG: slowing or seizure activity. An "extreme delta brush" pattern suggests anti-NMDA receptor encephalitis.
• Lumbar puncture: spinal fluid may show raised white cells or protein, and is tested for infection, including meningitis, and antibodies.
• Antibody panels in blood and spinal fluid. Spinal fluid testing is more sensitive for NMDA receptor antibodies.
• Tumor search: pelvic ultrasound or MRI for ovarian teratoma, and CT or PET scans for other cancers.
• Tests to exclude infection, especially herpes simplex virus, which is treated with acyclovir until ruled out.

Treatment

First-line immunotherapy

• high-dose intravenous steroids
• intravenous immunoglobulin (IVIG)
• plasma exchange, which filters antibodies out of the blood

Second-line immunotherapy

If there is no clear improvement within about 2 weeks, doctors use rituximab or cyclophosphamide. Long-term steroid-sparing drugs such as mycophenolate or azathioprine may help prevent relapse.

Tumor treatment

Removing an ovarian teratoma or treating the underlying cancer is essential and speeds recovery.

Supportive care

Anti-seizure medicines (some people are left with epilepsy), management of agitation and abnormal movements, intensive care for breathing or heart rhythm problems, and later rehabilitation for memory, speech and mood.

Outlook

With early treatment, about 8 in 10 people with anti-NMDA receptor encephalitis make a good or full recovery, although it may take 18 months or more, and some memory or behavioral problems can persist. Relapses occur in around 1 in 10 people, more often without a tumor or if treatment was limited. Paraneoplastic types with intracellular antibodies have a poorer outlook. Delayed diagnosis is a major cause of worse outcomes.

Frequently asked questions

What are the first symptoms of autoimmune encephalitis?

Early symptoms often include anxiety, insomnia, behavioral changes, paranoia or hallucinations, short-term memory problems and confusion. Some people have a headache or flu-like illness first. Seizures and abnormal movements often follow over days to weeks.

What causes autoimmune encephalitis?

The immune system makes antibodies or immune cells that attack brain proteins. This can be triggered by a tumor such as an ovarian teratoma, by a prior infection such as herpes encephalitis, or by cancer immunotherapy. In many people no trigger is found.

Can autoimmune encephalitis be cured?

Many people recover fully or nearly fully with early immunotherapy and removal of any tumor. Recovery can take many months. Some people have lasting memory or mood problems, and relapses can occur, so long-term follow-up is needed.

How is autoimmune encephalitis different from viral encephalitis?

Viral encephalitis is caused by direct infection of the brain, typically with fever, and is treated with antiviral drugs. Autoimmune encephalitis is caused by the immune system and is treated with immunotherapy. Herpes encephalitis can trigger autoimmune encephalitis weeks later.

Can autoimmune encephalitis be mistaken for mental illness?

Yes. Sudden psychosis, agitation or catatonia in a young person may first be treated as a psychiatric illness. Seizures, abnormal movements, reduced speech, confusion or reduced consciousness are clues that a neurological cause needs urgent testing.