Review article
Molecular diagnosis of viral infections of the central nervous system

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Epidemiology of EVs as neuropathogens

The EVs (polioviruses [PVs], coxsackieviruses group A and B [CVA and CVB, respectively], echoviruses [ECVs], and the numbered EVs) are common neuropathogens of humans (Table 1) [1], [2]. Enteroviral infections of the CNS occur predominantly in children and are seasonally associated. In temperate climates, EV infections occur predominantly during the summer and fall, whereas in tropical regions of the world, infections occur year-round, with a higher incidence during the rainy season.

With the

RT-PCR for detection of EV CNS infections

A detailed discussion of the methodology for RT-PCR detection of the EVs is beyond the scope of this review. The reader is directed to several reviews of the material [12], [18], [19] if more in-depth information is desired.

“Real-time” RT-PCT

Reports have begun to appear of “real-time” RT-PCR for EV detection [35], [40]. The reported approaches have exploited the 5′-3′ exonuclease activity of Taq polymerase in conjunction with sequence-specific probes labeled with reporter and quencher dyes at the 5′ and 3′ ends, respectively, to permit fluorometric detection of the amplicon simultaneous with amplification. The RT and amplification reactions are performed in a single-sealed glass capillary tube. The thermal conduction

Herpes simplex virus infections of the CNS

The spectrum of herpes simplex virus (HSV) infections is vast, and includes oropharyngeal disease, genital infections, encephalitis, neonatal disease, ocular disease, and cutaneous infections. Of these, the most devastating are herpes simplex encephalitis (HSE), which can occur in children and adults, and neonatal HSV disease, which by definition manifests during the neonatal period and can include CNS involvement. In keeping within the scope of this review, the following discussion of HSV

Neonatal HSV disease

The diagnosis of neonatal HSV infections has been revolutionized by the application of PCR technology to clinical specimens, including CSF [66], [71], [77], [78], [79], [80], [81]. Direct comparisons of results of these studies are complicated by differences in laboratory methodology. In the largest series [66], CSF specimens from 77 neonates with culture-proven HSV disease were evaluated retrospectively by PCR. These 77 infants had been enrolled previously in a comparative study of vidarabine

Interpretation of diagnostic results

Tremendous advances have occurred over the past 3 decades in the knowledge of the natural history of CNS HSV. Even with diagnostic advances such as PCR, prompt diagnosis of neonatal HSV disease and HSE will continue to rely primarily on a high index of clinical suspicion. PCR now is considered by most experts to be the test of choice for the diagnosis of HSV CNS infections [83], [98], [99]. The reported sensitivity of PCR in the diagnosis of CNS disease has ranged from 75% to 100% [66], [71],

JCV infections of the CNS

JCV is a member of the polyomavirus group and the causal agent of a rapidly progressive and universally fatal CNS disease known as progressive multifocal leukoencephalopathy (PML). Seroepidemiologic studies [101] indicate that 70% to 90% of adults have been infected with JCV. Primary infection results in persistent infection of the kidney. JCV is neurotropic and most likely gains entry to the CNS via infected mononuclear cells. Cytolytic infection is restricted to oligodendrocytes and occurs in

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      Due to commonly low numbers of infectious particles in patients specimen (CSF) and problematic cultivation of several coxsackievirus A serotypes (CVA) (Schmidt et al., 1965), a RT-PCR is advantageous as demonstrated in comparative studies (Abzug et al., 1995; Ahmed et al., 1997; Furione et al., 1998; Tanel et al., 1996; Yerly et al., 1996). Diagnosis by RT-PCR can increase the yield of detection of enteroviruses from CSF by approximately 20% over tissue culture (Romero and Kimberlin, 2003; Stellrecht et al., 2002; van Vliet et al., 1998). However, these RT-PCR assays were often in a (semi-) nested format or required amplicon detection by hybridization, which possesses contamination hazards.

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    This work was supported under contract with the Virology Branch, Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID), NO1-AI-15113 and NO1-AI-62554; and by grants from the General Clinical Research Center Program (RR-032) and the State of Alabama.

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