LGI1-antibody encephalitis

What is it?

LGI1 (Leucine-rich glioma-inactivated 1) antibody encephalitis is an autoantibody mediated form of limbic encephalitis. It is the most common antibody-mediated encephalopathy in those over 50 years of age. It was accurately first described in 2010. However, the clinical syndrome was also observed in association with voltage gated potassium channel antibodies in 2004 – it later became apparent the actual target of these antibodies was LGI1.

LGI1 is a secreted neuronal protein which helps regulate the communication between neurons. Researchers have determined that LGI1 binds to receptor proteins on the surface of neurons, which help LGI1 signal to the neurons. Together, these, and other, proteins help control the release of certain brain chemicals called neurotransmitters which allow neighboring neurons to communicate and relay signals throughout the brain. LGI1 is found primarily in neurons in the brain, including a part of the brain called the temporal lobe. The temporal lobe of the brain is involved in memory and emotion and its disruption is especially vulnerable to causing seizures.

Who is affected?

LGI1-antibody encephalitis is the second most common form of autoimmune encephalitis overall and the most common in those over 50 years. Men are affected more frequently than women (2:1) and it is extremely rare in children.


Faciobrachial dystonic seizures (FBDS) are the most common seizure type associated with this type of encephalitis and are seen in around 60% of cases. A person with FBDS typically appears awake during the episodes. Initially, they will experience occasional involuntary muscle jerk of their arm and their face, on that same side. FBDS may begin as only a rare episode, lasting 1 to 30 seconds, but their progressively increase to become very frequent, often hundreds of time per day. Also, patients develop other types of seizures including those which involve shivering feelings and twitching of their mouth and fingers.

FBDS, and the other seizures in patients with LGI1-antibody encephalitis, typically appear earlier than other symptoms. As early treatment is thought to improve outcomes, therefore, they are important to recognize. Other symptoms associated with LGI1-antibody encephalitis are: cognitive impairment, which often present as memory deficits, seizures (including FBDS), sleep disturbance, psychiatric and behavioral disorders.


Diagnosis of LGI1-antbody encephalitis can be difficult; patients may present to psychiatrists or movement disorder specialists prior to autoimmune neurologists. LGI1-antibodies can be detected in spinal fluid and blood although with a higher rate of detection in blood.

Around 50% of MRI scans show changes in the affected parts of the brain (especially the temporal lobe). The spinal fluid can show increased white blood cell count and protein levels but is often completely normal. Hence, both MRI and spinal fluid tests can be normal in these patients. Brainwave examination (“EEG”) often shows abnormal activity in the affected areas.
Some patients have reduced blood sodium levels as a clue to the illness, although this can be found in many conditions.

Is there a tumor associated with this disease?

A tumor is rarely seen, when found, it is often tumor of the thymus gland in the upper chest.


Patients with LGI1 autoantibodies respond very well to immunotherapy, with improvements in >95% of patients. Treatment is classically described as first line immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange), with early combinatorial treatments providing better efficacy. It may sometimes be necessary to add second-line immunotherapy (cyclophosphamide or rituximab). FBDS are largely resistant to antiseizure medications but respond well to immunotherapies – and so immunotherapies should be prioritized over antiseizure medications.


The forecast is considered good. Most patients recover to recapture many of their previous functions. However, there is often persistent memory and cognitive difficulties and a range of side effects from the immunotherapies. Also, there is a risk that the disease may flare up again in approximately 25% of patients. This is usually seen within the first few months, often with treatment withdrawal. LGI1-antibody encephalitis has a very low mortality rate, in the order of <1%.

Reviewed by

Sarosh Irani, Associate Professor and Consultant Neurologist, University of Oxford and John Radcliffe Hospital, Oxford, UK


Lisa shares her journey with Autoimmune Encephalitis

I was diagnosed with LGI1 Autoimmune Encephalitis (AE) in February 2018. Encephalitis is a devastating brain disease that affects about 500,000 people worldwide. The type that I have is called LGI1 Autoimmune Encephalitis – it is extremely rare and known to affect about 0.83 people in a million. With Autoimmune Encephalitis the body starts to produce an antibody that attacks the brain. In my case, this led to seizures, problems with cognitive function such as short term memory loss and aphasia which makes it difficult for you to find the right word when speaking or trying to write something down. It also affected my mobility, and I was dependent on a walker for 3 months and then a cane for a further 3 months after that. Sometimes Autoimmune Encephalitis causes psychiatric symptoms too but I was fortunate to not experience those.

Lisa shares her journey with Autoimmune Encephalitis

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