Encephalitis means inflammation (swelling) of the brain, often caused by a virus. In the UK Herpes simplex virus (HSV) is the most prominent cause, affecting 1 per 250,000-500,000 people. Although classed as a very rare disease, it has a significant impact because survivors are incapacitated with severe disability, with estimated costs of £3-5 million per severe case.

Inflammation and swelling occurs as part of the body’s defence against infection. However in the brain it can cause damage, because the brain is in a fixed space (the skull) with no room for swelling. In herpes encephalitis (HSV encephalitis) the temporal lobes of the brain are especially affected. These lobes are very important for memory. Thus verbal memory is especially badly affected in HSV encephalitis. Verbal memory is the ability to remember the names of objects and people, and to listen to and recall spoken information Brain magnetic resonance imaging (MRI) scans can be used to assess brain swelling. Doctors sometimes give anti-inflammatory corticosteroid drugs (e.g. dexamethasone) to reduce the swelling. However, these drugs can also impair the immune defence system, potentially allowing uncontrolled virus replication. Thus we don’t know whether or not giving corticosteroids is a good thing.

Does the corticosteroid drug dexamethasone improve verbal memory in HSVencephalitis by reducing brain temporal lobe swelling (as seen on brain scans)? The DexEnceph study will be conducted in 90 adults with HSV encephalitis across hospitals which are part of the Brain Infections UK Network. Half the patients with HSV encephalitis will receive corticosteroid, and the other half will not. When patients have blood tests, lumbar punctures, and brain scans we will collect images and samples for our study. Dexamethasone is given intravenously once a day for four days. It is a generally safe drug, given in several brain infections, with few short-term side effects. For the main outcome we will assess verbal memory at 6 months through neuropsychological testing. We will also examine swelling of the brain by MRI scanning. We will see if virus is detectable in the spinal fluid two weeks after admission. We will also examine the drug’s effect on host immune proteins, and will examine neuropsychological and imaging outcomes at 18 months.

For those with non-HSV encephalitis, we will aim to identify & understand the mechanisms causing encephalitis from the various etiologies.