Acute infections of the central nervous system (CNS) can be caused by a range of pathogenic agents. Although rare, they can present as life-threatening emergencies, requiring rapid diagnosis. Clinical manifestations include meningitis, meningoencephalitis or encephalitis.

Diagnosis can be challenging, as patients may present with non-specific symptoms such as fever, headache and altered mental state. Alongside direct pathogen detection by PCR and other cerebrospinal fluid (CSF) analyses, investigation of intrathecally produced antibodies plays an important diagnostic role.

Viral meningitis is the most frequent clinical presentation of CNS infection. Among the major causative pathogens are herpes viruses, such as herpes simplex viruses (HSV-1/2), varicella zoster virus (VZV) and Epstein-Barr virus (EBV). Mumps virus is one of the main causes in unvaccinated populations. Further neurotropic viruses include cytomegalovirus (CMV), rubella virus, tickborne encephalitis (TBEV) and measles virus. The bacterial pathogens Borrelia and Treponema pallidum and the protozoan Toxoplasma gondii can also cause neurological disease. Neurosyphilis and neurotoxoplasmosis are a particular concern in immunocompromised patients such as HIV-infected individuals.

Some non-infectious chronic inflammatory diseases such as multiple sclerosis (MS) trigger a polyspecific humoral immune response, leading to intrathecal production of antibodies against various non-causative agents. The detection of intrathecal antibodies against measles virus, rubella virus and/or VZV (MRZ reaction) is a specific indicator of MS and can help to differentiated MS from clinically similar diseases.

Antibody indices

In CNS infection diagnostics, it is important to distinguish intrathecally produced antibodies from antibodies that have diffused from the blood into the CSF. This is done by comparing the concentration of pathogen-specific antibodies to total immunoglobulin in CSF and serum. The calculated quotient is known as the antibody index (AI). An AI value or more than 1.5 indicates pathogen-specific antibody production in the CSF. In cases of elevated total IgG in CSF, the limes quotient, which is derived from the CSF/serum quotient for albumin, is additionally used in the calculation of the AI.

Ease of evaluation

EUROIMMUN offers a broad range of CE-marked ELISAs for quantitative measurement of antibodies in CSF/serum pairs. Tests for different parameters can be performed in parallel due to identical incubation schemes and exchangeable reagents. Results are quantified by means of four to six-point calibration curves or using a single recalibrator with reference to a stored master curve generated by EUROLabCSF software. Use of a single calibrator increases the cost-effectiveness since fewer ELISAs wells are needed per analysis.

The EUROIMMUN CSF product range encompasses the parameters HSV-1/2, EBV-CA, TBE virus, CMV, measles virus, mumps virus, rubella virus. VZV, Borrelia, Treponema pallidum and Toxoplasma gondii. A further ELISA is available for determination of the chemokine CXCL13 in CSF. CXCL13 serves as an early marker of acute neuroborreliosis and is also useful for therapy monitoring.

To facilitate the result evaluation, EUROIMMUN has developed EUROLabSCF software, which automatically calculates the quotients for pathogen-specific antibodies, total immunoglobulin and albumin, as well as the limes quotient and AI. The software communicates bidirectionally with the processing instruments and the LIS, so that time-consuming and error-prone manual data transfer is no longer required.

The CSF antibody analysis is thus fully automatable from start to finish, providing a high level of efficiency and standardisation.