Diagnostics in infectious encephalitis

 

What is infectious encephalitis?

Infectious encephalitis is an inflammation of the brain caused by an infection invading the brain.  Viruses are the most common cause of infectious encephalitis. Some of the viruses that can cause encephalitis include herpes viruses, enteroviruses, insect-borne viruses (e.g., Japanese encephalitis virus, West Nile virus) and tick-borne viruses. Bacteria, fungus and parasites can cause infectious encephalitis more rarely. Encephalitis can also be caused by the body’s immune system attacking itself, which is known as autoimmune encephalitis.

Why is a diagnosis of infectious encephalitis important?

Encephalitis is a neurological emergency which needs to be diagnosed promptly to avoid severe after-effects (acquired brain injury) or death. If a doctor suspects that a patient may have encephalitis, they need to act quickly. At the same time, they need to make sure the patient is stable (assure breathing, circulation), look for a cause of the inflammation and may start treatment even before a cause is found.

Firstly, diagnosis of infectious encephalitis aims to establish that there is inflammation within the brain, and secondly to find the cause of the inflammation. Finding the exact cause of inflammation is important as various types of encephalitis have different treatments. Although the identification of the pathogens causing encephalitis remains challenging, and in many cases the cause is still unknown, there have been many advances in the encephalitis diagnostics in the last years. Now, tests take much shorter time to get results (an hour in some instances), they are more reliable, and they look for much larger number of pathogens than before.

Overview of diagnostics in infectious encephalitis

Not one test/symptom is enough for making a diagnosis of encephalitis, but rather a combination of tests and assessments. Initially, the doctor will try to:

• Get a thorough history of the illness (e.g., when did it start, what symptoms were experienced).
• Assess the current symptoms and patient state (physical observation).
• Get any travel history (if there was travel any contact with animals, mosquito, ticks, fresh water).

Based on the answers at the above assessments, the doctor will perform various diagnostics tests to confirm the diagnosis and find the cause of encephalitis. They will also try to eliminate other illnesses with similar symptoms such as: bacterial meningitis, strokes, brain tumours, and encephalopathy of various causes.

Following initial testing and any treatment given, the doctor will assess the test results and the patient’s response to treatment. The initial testing is aimed at the most common or possible causes for that patient. If the cause is not found, it may be necessary to do further testing and consult with specialist doctors. Patients can be transferred to a more specialised centre.

Diagnostics tests

Diagnostics tests, which can help to confirm a diagnosis of encephalitis include laboratory tests which analyse cerebrospinal fluid, blood, urine and other body fluids and radiological tests (computed tomography – CT, magnetic resonance imaging – MRI, electroencephalogram – EEG). For an overview of neuroimaging in encephalitis please see our Neuroimaging webpage.

Cerebrospinal fluid (CSF) analysis

This is the vital test to establish a diagnosis of encephalitis. The CSF is produced within the brain and flows out at the base of the brain to surround and cushion the brain and spinal cord. Cerebrospinal fluid is collected from the patients via a lumbar puncture (LP) (spinal tap). All patients suspected of encephalitis should have a lumbar puncture as soon as possible unless there is a clear contraindication.

The procedure involves passing a needle, under local anaesthetic, between two of the backbones at the base of the spine. Approximately 10% of adult patients suffer a headache after this procedure. This headache is typically mild and worse upon being upright and better lying flat. It usually improves with simple painkillers and good hydration. Some doctors advocate caffeine, from tea or coffee.

Sufficient sample of CSF should be tested. There is a window in which the sample can give accurate results, even if the treatment has started.

Various laboratory tests are performed on CSF. Some tests give results within hours whereas others can take days. Immediate tests performed on CSF include analysis under the microscope to assess the number and type of white blood cells present. A raised number of white blood cells in CSF is indicative of inflammation within the brain, spinal cord or lining of the brain (meninges). Other parameters including the opening pressure of CSF, its appearance, CSF protein content and ratio of CSF to blood glucose level can also be helpful in distinguishing between different types of brain infections.

Other CSF tests are more complicated and include

• Culture for microbes.
• Antibody and auto-antibody studies.
• Conventional microbiological tests to detect viruses or bacteria such as polymerase chain reaction – PCR or high-throughput sequencing (HTS) of CSF.
• Metagenomic next generation sequencing (mNGS) (not available as a routine test) aimed at identifying a broad range of pathogens in a single test.

Some of these tests may be negative in the first few days after the onset of the illness. In this case, an LP may have to be repeated during an individual’s illness.

Other laboratory screening

Blood, urine, as well as other body fluids can help detect and identify brain and/or spinal cord infection especially when CSF analysis is not possible, or it is negative. These tests can also exclude other causes of encephalitis’ mimics.

Brain biopsy

A brain biopsy can be considered when the cause of encephalitis remains unknown despite extensive investigations and the patient condition does not improve.  However, often in cases where the cause of encephalitis is unknown, a brain biopsy is not performed as it is so invasive. It is very rare these days when a biopsy is performed.

The journey of the sample

After the sample (CSF, blood) is collected from the patient, it is transported to the laboratory. There, it is stored and analysed by laboratory professionals using various machines and equipment. The results are logged into computer and/or sent to the doctor who treats the patient.

Please see our animation on the Journey of a Sample for more information.

Diagnostics tests results

The doctor will analyse the laboratory results as well as considering the results of other tests (imaging, EEG), the patient’s condition and the response to treatment. Even negative results are important as the doctor can eliminate some of the possible causes which means they can stop the treatment they have initiated, and they can look somewhere else.

The diagnostics test can help to confirm a diagnosis when a direct cause is found (there is evidence the pathogen has caused the inflammation), can make a probable diagnosis (when all tests and clinical features suggest a cause and treatment seems to be efficient) or a diagnosis of encephalitis with an unknow cause. In some cases, the encephalitis is not confirmed, and an alternative diagnosis is made.

The results of the tests may depend on the time they were performed and are correlated with the evolution of the illness. It is not unusual for the results of some tests to be ‘normal’ at the beginning of the illness, but then change during the illness. In some cases where the CSF is obtained very early in the disease course, the tests can be falsely negative. So, if the doctor still suspects encephalitis, tests will need to be repeated.

The challenges of diagnostics in encephalitis

There are many challenging when trying to establish an encephalitis diagnosis, some of the challenges are associated with the nature of the condition or the patient and others with diagnostics tests and methods.

• Patient’s symptoms and signs can be non-specific, which means that are common for various other conditions.
• The variety and multitude of possible causes. There are over 100 pathogens that can cause infectious encephalitis.
• Encephalitis is a condition that can start suddenly and rapidly worsens; patients often require intensive supportive management as they can be severely ill.
• Lack of encephalitis specialists. Patients with encephalitis are not usually looked after by specialist teams such as it happens with stroke patients.
• Establishing that a specific pathogen found in the brain/spinal fluid has caused that encephalitis.
• Not having access to specific diagnostics testing in the local hospital. Sample will need to be sent to other hospitals which requires time.
• Reluctance of professionals to perform certain diagnostics tests such as an LP.
• Costs of diagnostics testing not covered by patient’s insurance.

 

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By Alina Ellerington, Encephalitis International and reviewed by Dr Yun Huang, University of Liverpool

This information resource was supported by an educational grant from bioMerieux!

FS035V1 Diagnostics in infectious encephalitis

Date created: January 2022; Review date: January 2025

Disclaimer: We try to ensure that the information is easy to understand, accurate and up-to-date as possible. If you would like more information on the source material and references the author used to write this document please contact the Encephalitis International. None of the authors of the above document has declared any conflict of interest, which may arise from being named as an author of this document.