Many viral pathogens possess the ability to invade the CNS. Some viruses, such as HSV, VZV and rabies are truly neurotropic, whereas others may reach and affect the CNS during the course of general viraemia, such as is the case for mumps and measles. 

Although most infections with neurotropic viruses are asymptomatic or give mild symptoms, aseptic meningitis, and viral meningoencephalitis are the two major clinical presentations, the latter being particularly important, since it may cause death or permanent neurological sequel. Overall, the enteroviruses cause most acute viral CNS infections worldwide (35 to 80 per cent), with mumps a distant second (one to 40 per cent).

All herpes group, measles, rubella and vector borne viruses can all cause CNS disease. More recently HIV has been identified as a cause of human CNS disease. Immuno-compromised hosts are more susceptible to viral involvement of the CNS. Some virus infections such as influenza, HSV and CMV are associated with post-infectious CNS reactions such as Guillain-Barré, ataxia and transverse myelitis.
The diagnosis of viral CNS infections is notoriously difficult; the virologist is often involved at a late stage of disease when the pathogen might have disappeared, but neurological symptomatology remains. The recent introduction of PCR analysis of CSF specimens has made the diagnosis of viral CNS infections faster and easier. Some guidelines are listed below.

Laboratory diagnosis - viral CNS infections. 

• Where facilities for brain scans and MRI are available, they will be the first line of laboratory investigations. A CSF sample may, in the general chemistry lab, give a hint of whether there is likely viral involvement. For specific viral diagnosis, the microbiologist should be consulted.
• Appropriate initial specimens when viral CNS disease is suspected include: NPW or throat swab, stool sample (do not forget enteroviruses), paired CSF and serum samples, fluid from vesicular rash, and urine (if mumps is suspected).
• PCR analysis of CSF is the most rapid and sensitive diagnostic method. We offer PCR testing for HSV, CMV, EBV, VZV, HHV6 and enterovirus.
• If a brain biopsy is performed, consult the microbiologist to extract the maximum amount of information from the specimen.
• Virus culture of CSF is only helpful in the detection of mumps virus and some enteroviruses in cases of aseptic meningitis. Occasionally, HSV 2 can be cultured from adolescents with meningitis. Herpes simplex virus does not grow from CSF from patients with herpes simplex encephalitis (HSE)!
• The late diagnosis of the etiologic viral agent in meningoencephalitis and encephalitis commonly may require a multi-pronged approach using antigen and antibody detection in CSF. Rapid viral CSF antigen detection assays for CSF analysis and PCR analysis are first-line tests. However, in late diagnosis, the determination of antiviral antibody synthesis, including the detection of intrathecal antibody production, still plays an important role in the diagnosis of acute and chronic viral CNS disease. The demonstration of intrathecal production of virus-specific antibodies requires the concomitant analysis of CSF and serum for the determination of the virus-specific IgG antibody ratio. Normally, IgG diffuses passively across the blood-brain barrier (BBB) to render a CSF concentration 250- to 600-fold lower than in serum. When virus specific IgG is synthesised intrathecally, the serum CSF ratio of the anti virus IgG in question is less than 250. If, on the other hand, such a ratio is noted for several specific antiviral IgG antibodies, this is more consistent with a damage of the BBB with subsequent diffusion of all serum IgG to CSF. Occasionally intrathecal synthesis of virus specific IgM antibodies may be found, which is diagnostic of viral CNS invasion. Interpretational help from the virologist is recommended when virus serology of the CSF is performed.
• One clear disadvantage with CSF serology is that intrathecal antibody production does not usually occur until well into the patient's illness. With the availability of effective antiviral agents such as acyclovir, such late diagnosis is unacceptable, and the development of a laboratory test is currently heavily focused on rapid tests of the CSF of which PCR assays appear the most successful and should be attempted if available.
• Postinfectious encephalopathies pose another diagnostic dilemma. New techniques must be developed to appropriately service this patient population.