Encephalitis

Encephalitis refers to the inflammation of the brain. In some cases, it can cause swelling and damage to the brain and its surrounding membranes. Encephalitis can affect anyone at any age, and the severity can vary between patients.

Symptoms of encephalitis include:

• Headaches
• Seizures
• Drowsiness
• Confusion
• Memory loss
• Behavioural changes
• Abnormal movements
• Disrupted sleep

What are the complications of encephalitis?

Some patients may develop serious complications of encephalitis such as:

• Persistent seizures, with no recovery of consciousness between seizures
• Respiratory failure
• Issues with the autonomic system, which controls functions such as heart rate and blood pressure

What causes encephalitis?

There are two main causes of encephalitis:

1.      Infections, causing Infectious Encephalitis

2.      Autoimmune responses, which cause Autoimmune Encephalitis (AIE)

Infections

Infections from the head or neck area can travel to the brain due to close proximity. Other infections elsewhere in the body can also reach the brain via the bloodstream and cause encephalitis.

Viruses are the most common cause of infectious encephalitis, particularly:

• Herpes simplex type I, a virus that can cause cold sores and fluid blisters around the mouth and face, and is spread through skin-to-skin contact or saliva.
• Herpes simplex type II, a virus that causes genital herpes and is spread through sexual or skin-to-skin contact.
• Varicella-zoster, a virus that can cause chickenpox (varicella) and shingles (herpes zoster). It is spread through airborne droplets, direct contact or contaminated surfaces.
• Enteroviruses, a category of viruses that can cause respiratory diseases such as hand, foot, and mouth disease. It is spread through airborne droplets, direct contact, and contaminated water.

Other types of infections from bacteria, parasites and certain fungi can also cause encephalitis.

Autoimmune Responses

Autoimmune Encephalitis (AIE) occurs when the immune system attacks the brain cells and causes inflammation. However, the specific cause of why AIE develops is not known.

Antibodies are proteins produced by our immune system, and function to identify and remove foreign antigens such as viruses, bacteria and other substances that can cause illnesses. In AIE, patients develop antibodies that target and attack receptors on brain cells instead.

Encephalitis may arise due to a combination of infections and autoimmune responses. For example, Acute Disseminated Encephalomyelitis (ADEM), a type of AIE, may have been triggered by infections. As such, the term ‘Post-Infectious Encephalitis’ is used.

What are the possible risk factors for encephalitis?

• Weakened immune systems, such as in those living with HIV or taking immunosuppressant medications
• Previous infection, particularly recent viral infections
• Tumours (non-cancerous or cancerous growths) in the body
• Certain cancer therapies, such as the use of immune checkpoint inhibitors (ICIs). ICIs are a class of cancer immunotherapy drugs that work by releasing the "brakes" on the immune system, allowing it to more effectively recognise and attack cancer cells.
• Vaccinations (however this is very rare and the benefits of vaccinations outweigh risk of encephalitis)

When doctors suspect encephalitis, a combination of tests is required to form the diagnosis:

1. Magnetic Resonance Imaging (MRI) of the brain, to look for features of AIE and to rule out other causes of brain inflammation
2. Lumbar puncture for cerebrospinal fluid (CSF) examination, to test for infections and inflammation
3. Electroencephalogram (EEG) to look for abnormal brain activity or seizures
4. Blood tests to evaluate for auto-antibodies and rule out underlying infections
5. CT scans of the body and ultrasound scans to check for any tumours or cancer

In infectious encephalitis, antibiotics and/or antiviral medications may be prescribed for up to a few weeks. In cases with severe brain swelling, surgery may be required.

Treatment of AIE may involve multiple stages. The initial stage includes steroids, intravenous immunoglobulin, and plasma exchange. Following that, immunotherapy, which refers to treatment using immunomodulatory agents, may be required.

Types of immunomodulatory agents involved may include:

• Rituximab

In certain types of autoimmune diseases, the body’s B cells (a type of immune cell) may be producing harmful antibodies that attack the body’s tissue. Rituximab is a medicine that destroys these B cells.

It is given via a drip into the vein (intravenously) every six months. There is a slight risk of infection, which can be reduced by blood monitoring.

• Tocilizumab

This medicine blocks the effect of a specific protein (Interleukin-6), which may be causing harmful inflammation.

Tocilizumab may be injected under the skin at the abdomen or thigh (a subcutaneous injection). This can be done independently at home.

Alternatively, it is injected into the vein via infusion (intravenous infusion). This has to be done in the hospital or clinic for typically one hour.

• Cyclophosphamide

This medication damages DNA found inside cells, to stop them from multiplying and growing.

Cyclophosphamide is injected into the vein (intravenous infusion). The infusion duration ranges from ten minutes to a few hours, and delivered into the bloodstream slowly and consistently.

• Mycophenolate Mofetil

This medicine suppresses a specific white blood cell (lymphocytes), preventing it from attacking new cells or a new organ in the body.

Mycophenolate mofetil is taken orally thirty minutes to one hour before food.

• Azathioprine

This medication stops lymphocytes from making new DNA and multiplying, suppressing the body’s immune system.

Azathioprine is an oral medication to be taken with or after food, to reduce stomach upset.

Some patients may also require other interventions such as anti-seizure medications and psychiatric medications to help with complications of encephalitis.

Encephalitis is a treatable condition in most cases. Recovery takes time, and many people continue to see improvements with the right treatment, care, and support.

Recovery looks different for everyone, and some may experience:

• Tiredness or fatigue
• Changes in balance and the manner in which a person walks (gait)
• Loss of sensation
• Changes in memory, focus and concentration
• Changes in mood, personality or behaviour
• Seizures or epilepsy
• Speech, language and communication difficulties

Many people benefit from rehabilitation therapies, which can help them adapt, regain independence and continue making progress throughout their recovery journey.