Enceph-IG

Intravenous Immunoglobulin in Autoimmune Encephalitis in Adults –A Randomised Double-Blind Placebo-Controlled Trial.

Background

The ENCEPH-IG trial is a study led by investigators from the University of Liverpool looking at whether or not early treatment with Intravenous Immunoglobulin improves recovery in autoimmune encephalitis.

Autoimmune encephalitis is inflammation and swelling of the brain caused by the body’s own immune defence system. It affects about 1 in 100,000 people per year in the UK. The symptoms can include abnormal behaviour, memory problems and seizures. Some patients recover completely, but in others it can cause death or severe disability.

Autoimmune encephalitis is treated with steroids, which reduce inflammation and swelling. If patients are not improving, intravenous immunoglobulin (IVIG) is often also given, usually after a couple of weeks. IVIG is a protein product extracted from the blood of healthy donors. It is given through a drip into a vein each day for five days and is used for other diseases that affect the nervous system.

Some doctors think that if IVIG is used from the start of treatment, patients may recover more quickly and have less side effects from the illness. While IVIG may help patients it can have side effects, including blood clots or allergic reactions, is expensive and may not help recovery. Currently it is used in about 50% of patients with autoimmune encephalitis. The ENCEPH-IG trial (Intravenous immunoglobulin in autoimmune encephalitis in adults) is a study looking at whether or not early treatment with IVIG improves recovery.

Aims

The aims of the trial are:

To work out whether, in adults with autoimmune encephalitis, early treatment with IVIG leads to a different time to recovery and improves the outcome.
To carry out scientific studies to better understand the disease processes in autoimmune encephalitis and see how IVIG affects them.

Design and methods

ENCEPH-IG is an individually randomised controlled trial of 356 adults: half will receive IVIG, and the other half will receive a placebo. The study will be carried out at approximately 50 hospitals in the Brain Infections UK network.

Participants who meet the entry criteria will be randomised in a ratio of 1:1. It is double blinded, meaning neither the patients nor their medical staff will know what treatment they have received. In addition, all patients will receive the standard steroid treatment.

Inclusion criteria

Adults (16 years or older) with altered consciousness level and/or behavioural change and/or working memory deficit and/or psychiatric symptoms
This episode persisting for more then 24 hours and less then 3 months
In whom clinician thinks autoimmune encephalitis is the most likely diagnosis
CSF polymerase chain reaction (PCR) negative for HSV 1 and 2, and varicella zoster virus
CSF microscopy and culture negative at 48 hours for organisms

Plus 2 or more of:

Seizures (not explained by previously known seizure disorder) OR new movement disorder
Cerebrospinal fluid (CSF) white blood cell count 6-1000/mm3
Electroencephalogram consistent with encephalitis
Brain magnetic resonance imaging (MRI) or computer tomography (CT) changes consistent with encephalitis (including normal scan)

Exclusion criteria

Another likely diagnosis
Current or recent (within last 6 months) treatment with IVIG
Contraindication to IVIG
Intolerance of corticosteroids
Recent history of gastric ulcers
CSF analysis not performed
CSF polymerase chain reaction (PCR) positive for any viruses
Brain imaging not performed
Alternative diagnosis on brain imaging (CT or MRI)
Known HIV infection
On long term steroids or other disease modifying anti-inflammatory therapies for other conditions
Not able to live independently prior to onset of condition