Autoimmune encephalitis: symptoms, causes, treatment and recovery

Encephalitis is inflammation of the brain. The NHS describes it as an uncommon but serious condition that can be life threatening, requires urgent treatment in hospital, and can affect anyone, although the very young and very old are most at risk. Sometimes the cause is an infection, and sometimes, the NHS explains, something goes wrong with the immune system and it mistakenly attacks the brain, causing it to become inflamed.

Encephalitis International, the UK-based charity that supports people affected, uses the term autoimmune encephalitis for the forms in which the immune system is attacking the brain. Some of these are linked to antibodies found in the blood or spinal fluid, such as antibodies against the NMDA receptor, LGI1, CASPR2, GAD, AMPA receptor or GABA receptors. Others, such as acute disseminated encephalomyelitis (ADEM), follow an infection, in which case the term post-infectious encephalitis is used.

Antibodies are normally proteins that help remove bacteria and viruses. In autoimmune encephalitis they react in error with proteins on or in brain cells. The charity says the reason these antibodies are produced is not known in most cases, although sometimes a tumour, benign or cancerous, generates the antibody.

Encephalitis International says the signs vary widely from person to person and with the underlying cause. The NHS notes that encephalitis in general often starts with flu-like symptoms such as a high temperature and headache, with more serious symptoms coming on over hours, days or weeks.

• Psychiatric symptoms: these can range from psychosis and depression to anxiety.

• Seizures: focal or generalised.

• Abnormal movements: tremors, rigidity and chorea.

• Cognitive impairment: memory loss and difficulty concentrating.

• Autonomic dysfunction: changes in heart rate and blood pressure.

• Sleep disturbances: insomnia and excessive sleepiness.

• Confusion, disorientation, changes in personality and behaviour, difficulty speaking, weakness or loss of movement in parts of the body, and loss of consciousness (NHS).

Two of the best known forms are described below using the Encephalitis International factsheets. Many other types exist, so this is not a complete list, and an individual diagnosis always comes from the specialist team.

In NMDAR-antibody encephalitis the first features are typically prominent and mixed psychiatric symptoms, seizures, confusion and memory loss. The charity says that 10 to 20 days later people often develop a movement disorder, variations in blood pressure, heart rate and temperature, and loss of awareness. Patients are often initially looked after in mental health hospitals.

In LGI1 or CASPR2-antibody encephalitis, family members typically first notice seizures and that the person becomes forgetful, confused, drowsy and withdrawn. Brief jerks of the face and arm, called faciobrachial seizures, are described as a diagnostic sign highly suggestive of LGI1 antibodies.

Because the immune system is the problem, treatment aims to reduce inflammation and prevent further damage to the brain. Encephalitis International lists corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange (plasmapheresis) and rituximab as common approaches, along with anticonvulsants for seizures and psychiatric medicines for psychiatric symptoms. The NHS adds that encephalitis needs to be treated in hospital and that the earlier treatment is started, the more successful it is likely to be.

IVIG is a blood product given into a vein. The charity says an infusion can take a few hours, a full dose may be divided over two to five days, and it can be repeated. Plasma exchange removes harmful antibodies by filtering the plasma and replacing it, takes about a couple of hours per session, and a course often involves several sessions over a week or two. Possible side effects of both include fever, shivering, muscle aches, sickness and headaches.

For NMDAR-antibody encephalitis the charity says treatment consists of immune therapies and removal of a tumour if present. Rituximab is recommended by NHS guidelines for people who have not improved enough with first-line therapies, and cyclophosphamide can sometimes be used with or instead of it. For LGI1 and CASPR2 encephalitis it says no single set of medicines is proven to be better than others, that steroid tablets or other immune therapies may continue for 1 to 2 years, and that anti-seizure medicines may also be given.

Some people are treated on the basis of their symptoms and signs while the antibody result is awaited, to speed recovery. All of these medicines have known side effects, and their benefits are weighed against them for each person.

In most cases the cause is not known. Encephalitis International says the reason the antibodies are produced is unknown in most people. Known triggers include a tumour that generates the antibody, which is why a search for a tumour is part of the work-up, and, for NMDAR-antibody encephalitis, herpes simplex virus encephalitis, after which some people develop the autoimmune form.

Post-infectious forms such as ADEM follow an infection. The NHS reminds readers that encephalitis from the immune system is different from encephalitis caused by viral, bacterial or fungal infections, and that some infectious types are spread by mosquitoes, ticks or animals. Autoimmune encephalitis itself is not passed from person to person.

Encephalitis International says diagnosis can be challenging because the symptoms are non-specific and may resemble infectious encephalitis or psychiatric disorders. A definitive diagnosis typically needs clinical evaluation, imaging and laboratory tests.

• Cerebrospinal fluid (CSF) analysis by lumbar puncture, which helps detect autoantibodies and exclude infection.

• MRI or CT scans of the brain to rule out other causes and look for changes of inflammation.

• An electroencephalogram (EEG) to look for seizures or abnormal brain activity.

• Blood tests, including antibody tests (best done in both blood and spinal fluid for NMDAR antibodies), and to check for infections or other autoimmune disorders. In LGI1 encephalitis blood tests often show a low salt (sodium) level.

• A search for a tumour with pelvic or body imaging once an antibody such as NMDAR is found.

Recovery varies a great deal. The NHS says how long someone with encephalitis needs to stay in hospital can range from a few days to several weeks or even months, that some people eventually make a full recovery although it can be a long and frustrating process, and that many never make a full recovery and are left with long-term problems.

For NMDAR-antibody encephalitis the charity says recovery is usually slow, with many people spending a few months in hospital including time on intensive care, and those who return to work typically doing so after a year or two. For LGI1 and CASPR2 encephalitis, improvements may be seen within days or only after several months, and the time to treatment with immunosuppressive drugs is the main observed factor in determining outcome.

Common lasting effects of encephalitis listed by the NHS include memory loss, frequent seizures, personality and behavioural changes, problems with attention, concentration, planning and problem solving, and persistent tiredness. Rehabilitation, including a neuropsychological assessment, can help people rebuild independence, and Encephalitis International offers support to patients and families.

The NHS says to dial 999 for an ambulance immediately if you or someone else has serious symptoms of encephalitis. Do not wait to see whether they settle.

• Confusion or disorientation.

• Seizures or fits.

• Changes in personality and behaviour.

• Difficulty speaking.

• Weakness or loss of movement in some parts of the body.

• Loss of consciousness.

Autoimmune encephalitis is diagnosed and treated in hospital, usually under neurology teams, often with input from intensive care, psychiatry, oncology and rehabilitation depending on the person. Most people reach care through emergency admission or an urgent referral from a GP. The antibody tests and treatments described above are delivered by NHS specialist services.

Some people seek a private neurological opinion or private rehabilitation after the acute illness. Wherever follow-up is arranged, ask that results and plans are shared with your GP and hospital neurology team, and ask about relapse warning signs and who to contact if symptoms return.