Chapter 50 : Molecular Approaches to the Diagnosis of Meningitis and Encephalitis

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This chapter reviews various diagnostic tests available for central nervous system (CNS) infections and provides a detailed discussion of specific molecular approaches to the most common organisms causing meningitis and encephalitis in the United States. A vast array of organisms have been associated with encephalitis, including bacteria, fungi, viruses, and protozoa. Just as meningitis and encephalitis localize to distinct compartments of the CNS, the pathogens causing these two syndromes differ, and the respective microbiologies of meningitis and encephalitis are discussed separately. While the chapter focuses on the use of molecular assays for diagnosis of CNS infection, traditional microbiological diagnostic approaches continue to play an important role in pathogen identification and are complementary to nucleic acid amplification techniques. A DNA probe array has been developed for the simultaneous identification of herpesviruses, enteroviruses, and flaviviruses after several PCR amplifications. Nucleic acid amplification techniques have markedly improved the identification of CNS infections caused by viral and fastidious bacterial pathogens. Molecular techniques such as PCR allow rapid diagnosis, with consequent improvement of outcomes and cost savings. Results of molecular diagnostic testing for CNS infections must be interpreted in the context of the individual patient presentation and clinical illness, and close cooperation between the laboratory and the clinician is required for optimal use of these technologies.

Citation: Bloch K, Tang Y. 2011. Molecular Approaches to the Diagnosis of Meningitis and Encephalitis, p 767-784. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch50
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1. Aberle, S. W.,, J. H. Aberle,, C. Steininger, and, E. Puchhammer-Stockl. 2005. Quantitative real time PCR detection of varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological disease. Med. Microbiol. Immunol. 194: 712.
2. Ahmed, A.,, F. Brito,, C. Goto,, S. M. Hickey,, K. D. Olsen,, M. Trujillo, and, G. H. McCracken, Jr. 1997. Clinical utility of the polymerase chain reaction for diagnosis of enteroviral meningitis in infancy. J. Pediatr. 131: 393397.
3. Allawi, H. T.,, H. Li,, T. Sander,, A. Aslanukov,, V. I. Lyamichev,, A. Blackman,, S. Elagin, and, Y. W. Tang. 2006. Invader plus method detects herpes simplex virus in cerebrospinal fluid and simultaneously differentiates types 1 and 2. J. Clin. Microbiol. 44: 34433447.
4. al-Shahi, R.,, M. Bower,, M. R. Nelson, and, B. G. Gazzard. 2000. Cerebrospinal fluid Epstein-Barr virus detection preceding HIV-associated primary central nervous system lymphoma by 17 months. J. Neurol. 247: 471472.
5. Amsler, L.,, P. Bauernfeind,, C. Nigg,, R. C. Maibach,, R. Steffen, and, M. Altwegg. 2003. Prevalence of Tropheryma whipplei DNA in patients with various gastrointestinal diseases and in healthy controls. Infection 31: 8185.
6. Antinori, S.,, A. Radice,, L. Galimberti,, C. Magni,, M. Fasan, and, C. Parravicini. 2005. The role of cryptococcal antigen assay in diagnosis and monitoring of cryptococcal meningitis. J. Clin. Microbiol. 43: 58285829.
7. Aronin, S. I.,, P. Peduzzi, and, V. J. Quagliarello. 1998. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann. Intern. Med. 129: 862869.
8. Arosio, M.,, F. Nozza,, M. Rizzi,, M. Ruggeri,, P. Casella,, G. Beretta,, A. Raglio, and, A. Goglio. 2008. Evaluation of the MicroSeq 500 16S rDNA-based gene sequencing for the diagnosis of culture-negative bacterial meningitis. New Microbiol. 31: 343349.
9. Auyeung, P.,, and A. Dunn. 2008. Atypical case of herpes simplex encephalitis. Intern. Med. J. 38: 294295.
10. Avery, R. A.,, G. Frank, and, S. C. Eppes. 2005. Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis. Pediatr. Infect. Dis. J. 24: 705708.
11. Bakardjiev, A.,, P. H. Azimi,, N. Ashouri,, D. P. Ascher,, D. Janner,, F. L. Schuster,, G. S. Visvesvara, and, C. Glaser. 2003. Amebic encephalitis caused by Balamuthia mandrillaris: report of four cases. Pediatr. Infect. Dis. J. 22: 447453.
12. Barah, F.,, P. J. Vallely,, M. L. Chiswick,, G. M. Cleator, and, J. R. Kerr. 2001. Association of human parvovirus B19 infection with acute meningoencephalitis. Lancet 358: 729730.
13. Baran, J., Jr.,, K. M. Riederer, and, R. Khatib. 2000. Limits of detection of Mycobacterium tuberculosis in spiked cerebrospinal fluid using the polymerase chain reaction in tuberculous meningitis. Eur. J. Clin. Microbiol. Infect. Dis. 19: 4750.
14. Beersma, M. F.,, K. Dirven,, A. P. van Dam,, K. E. Templeton,, E. C. Claas, and, H. Goossens. 2005. Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as the “gold standard.” J. Clin. Microbiol. 43: 22772285.
15. Beghi, E.,, A. Nicolosi,, L. T. Kurland,, D. W. Mulder,, W. A. Hauser, and, L. Shuster. 1984. Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950–1981. I. Epidemiology. Ann. Neurol. 16: 283294.
16. Bergstrom, T.,, A. Vahlne,, K. Alestig,, S. Jeansson,, M. Forsgren, and, E. Lycke. 1990. Primary and recurrent herpes simplex virus type 2-induced meningitis. J. Infect. Dis. 162: 322330.
17. Bidstrup, C.,, P. H. Andersen,, P. Skinhoj, and, A. B. Andersen. 2002. Tuberculous meningitis in a country with a low incidence of tuberculosis: still a serious disease and a diagnostic challenge. Scand. J. Infect. Dis. 34: 811814.
18. Bitnun, A.,, E. L. Ford-Jones,, M. Petric,, D. MacGregor,, H. Heurter,, S. Nelson,, G. Johnson, and, S. Richardson. 2001. Acute childhood encephalitis and Mycoplasma pneumoniae. Clin. Infect. Dis. 32: 16741684.
19. Blazer, S.,, M. Berant, and, U. Alon. 1983. Bacterial meningitis. Effect of antibiotic treatment on cerebrospinal fluid. Am. J. Clin. Pathol. 80: 386387.
20. Bloch, K. C.,, and C. Glaser. 2007. Diagnostic approaches for patients with suspected encephalitis. Curr. Infect. Dis. Rep. 9: 315322.
21. Bohr, V.,, N. Rasmussen,, B. Hansen,, H. Kjersem,, O. Jessen,, N. Johnsen, and, H. S. Kristensen. 1983. 875 cases of bacterial meningitis: diagnostic procedures and the impact of preadmission antibiotic therapy. Part III of a three-part series. J. Infect. 7: 193202.
22. Boom, R.,, C. J. Sol,, M. M. Salimans,, C. L. Jansen,, P. M. Wertheim-van Dillen, and, J. van der Noordaa. 1990. Rapid and simple method for purification of nucleic acids. J. Clin. Microbiol. 28: 495503.
23. Briese, T.,, W. G. Glass, and, W. I. Lipkin. 2000. Detection of West Nile virus sequences in cerebrospinal fluid. Lancet 355: 16141615.
24. Burke, D. G.,, R. C. Kalayjian,, V. R. Vann,, S. A. Madreperla,, H. E. Shick, and, D. G. Leonard. 1997. Polymerase chain reaction detection and clinical significance of varicella-zoster virus in cerebrospinal fluid from human immunodeficiency virus-infected patients. J. Infect. Dis. 176: 10801084.
25. Busch, M. P.,, S. Caglioti,, E. F. Robertson,, J. D. McAuley,, L. H. Tobler,, H. Kamel,, J. M. Linnen,, V. Shyamala,, P. Tomasulo, and, S. H. Kleinman. 2005. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. N. Engl. J. Med. 353: 460467.
26. Caws, M.,, S. M. Wilson,, C. Clough, and, F. Drobniewski. 2000. Role of IS 6110-targeted PCR, culture, biochemical, clinical, and immunological criteria for diagnosis of tuberculous meningitis. J. Clin. Microbiol. 38: 31503155.
27. Centers for Disease Control and Prevention. 2003. Outbreaks of aseptic meningitis associated with echoviruses 9 and 30 and preliminary surveillance reports on enterovirus activity—United States, 2003. MMWR Morb. Mortal. Wkly. Rep. 52: 761764.
28. Cerar, T.,, K. Ogrinc,, J. Cimperman,, S. Lotric-Furlan,, F. Strle, and, E. Ruzic-Sabljic. 2008. Validation of cultivation and PCR methods for diagnosis of Lyme neuroborreliosis. J. Clin. Microbiol. 46: 33753379.
29. Chang, L. Y.,, L. M. Huang,, S. S. Gau,, Y. Y. Wu,, S. H. Hsia,, T. Y. Fan,, K. L. Lin,, Y. C. Huang,, C. Y. Lu, and, T. Y. Lin. 2007. Neurodevelopment and cognition in children after enterovirus 71 infection. N. Engl. J. Med. 356: 12261234.
30. Chapman, A. S.,, J. S. Bakken,, S. M. Folk,, C. D. Paddock,, K. C. Bloch,, A. Krusell,, D. J. Sexton,, S. C. Buckingham,, G. S. Marshall,, G. A. Storch,, G. A. Dasch,, J. H. McQuiston,, D. L. Swerdlow,, S. J. Dumler,, W. L. Nicholson,, D. H. Walker,, M. E. Eremeeva, and, C. A. Ohl. 2006. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis—United States: a practical guide for physicians and other health-care and public health professionals. MMWR Morb. Mortal. Recommend. Rep. 55: 127.
31. Childs, J. E.,, J. W. Sumner,, W. L. Nicholson,, R. F. Massung,, S. M. Standaert, and, C. D. Paddock. 1999. Outcome of diagnostic tests using samples from patients with culture-proven human monocytic ehrlichiosis: implications for surveillance. J. Clin. Microbiol. 37: 29973000.
32. Christen, H. J.,, H. Eiffert,, A. Ohlenbusch, and, F. Hanefeld. 1995. Evaluation of the polymerase chain reaction for the detection of Borrelia burgdorferi in cerebrospinal fluid of children with acute peripheral facial palsy. Eur. J. Pediatr. 154: 374377.
33. Christie, L. J.,, S. Honarmand,, D. F. Talkington,, S. S. Gavali,, C. Preas,, C. Y. Pan,, S. Yagi, and, C. A. Glaser. 2007. Pediatric encephalitis: what is the role of Mycoplasma pneumoniae? Pediatrics 120: 305313.
34. Chuck, S. L.,, and M. A. Sande. 1989. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N. Engl. J. Med. 321: 794799.
35. Chung, P. W.,, Y. C. Huang,, L. Y. Chang,, T. Y. Lin, and, H. C. Ning. 2001. Duration of enterovirus shedding in stool. J. Microbiol. Immunol. Infect. 34: 167170.
36. Cinque, P.,, S. Bossolasco,, L. Vago,, C. Fornara,, S. Lipari,, S. Racca,, A. Lazzarin, and, A. Linde. 1997. Varicella-zoster virus (VZV) DNA in cerebrospinal fluid of patients infected with human immunodeficiency virus: VZV disease of the central nervous system or subclinical reactivation of VZV infection? Clin. Infect. Dis. 25: 634639.
37. Cinque, P.,, M. Brytting,, L. Vago,, A. Castagna,, C. Parravicini,, N. Zanchetta,, A. D’Arminio Monforte,, B. Wahren,, A. Lazzarin, and, A. Linde. 1993. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 342: 398401.
38. Cinque, P.,, G. M. Cleator,, T. Weber,, P. Monteyne,, C. J. Sindic, and, A. M. van Loon. 1996. The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis. J. Neurol. Neurosurg. Psychiatry 61: 339345.
39. Cinque, P.,, L. Vago,, H. Dahl,, M. Brytting,, M. R. Terreni,, C. Fornara,, S. Racca,, A. Castagna,, A. D. Monforte,, B. Wahren,, A. Lazzarin, and, A. Linde. 1996. Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients. AIDS 10: 951958.
40. Connolly, A. M.,, W. E. Dodson,, A. L. Prensky, and, R. S. Rust. 1994. Course and outcome of acute cerebellar ataxia. Ann. Neurol. 35: 673679.
41. Corcoran, C.,, K. Rebe,, H. van der Plas,, L. Myer, and, D. R. Hardie. 2008. The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons. J. Clin. Virol. 42: 433436.
42. Corey, L.,, and P. G. Spear. 1986. Infections with herpes simplex viruses (1). N. Engl. J. Med. 314: 686691.
43. Corey, L.,, and P. G. Spear. 1986. Infections with herpes simplex viruses (2). N. Engl. J. Med. 314: 749757.
44. Corless, C. E.,, M. Guiver,, R. Borrow,, V. Edwards-Jones,, A. J. Fox, and, E. B. Kaczmarski. 2001. Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J. Clin. Microbiol. 39: 15531558.
45. Crawford, D. H.,, K. F. Macsween,, C. D. Higgins,, R. Thomas,, K. McAulay,, H. Williams,, N. Harrison,, S. Reid,, M. Conacher,, J. Douglas, and, A. J. Swerdlow. 2006. A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis. Clin. Infect. Dis. 43: 276282.
46. Crepin, P.,, L. Audry,, Y. Rotivel,, A. Gacoin,, C. Caroff, and, H. Bourhy. 1998. Intravitam diagnosis of human rabies by PCR using saliva and cerebrospinal fluid. J. Clin. Microbiol. 36: 11171121.
47. Dagan, R. 1996. Nonpolio enteroviruses and the febrile young infant: epidemiologic, clinical and diagnostic aspects. Pediatr. Infect. Dis. J. 15: 6771.
48. Dauphin, G.,, and S. Zientara. 2007. West Nile virus: recent trends in diagnosis and vaccine development. Vaccine 25: 55635576.
49. Davis, L. E.,, and R. T. Johnson. 1979. An explanation for the localization of herpes simplex encephalitis? Ann. Neurol. 5: 25.
50. Davison, K. L.,, N. S. Crowcroft,, M. E. Ramsay,, D. W. Brown, and, N. J. Andrews. 2003. Viral encephalitis in England, 1989–1998: what did we miss? Emerg. Infect. Dis. 9: 234240.
51. Debiasi, R. L.,, and K. L. Tyler. 2004. Molecular methods for diagnosis of viral encephalitis. Clin. Microbiol. Rev. 17: 903925.
52. De La Blanchardiere, A.,, F. Rozenberg,, E. Caumes,, O. Picard,, F. Lionnet,, J. Livartowski,, J. Coste,, D. Sicard,, P. Lebon, and, D. Salmon-Ceron. 2000. Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection. Scand. J. Infect. Dis. 32: 263269.
53. Demaerel, P.,, G. Wilms,, W. Robberecht,, K. Johannik,, P. Van Hecke,, H. Carton, and, A. L. Baert. 1992. MRI of herpes simplex encephalitis. Neuroradiology 34: 490493.
54. Denning, D. W.,, J. Anderson,, P. Rudge, and, H. Smith. 1987. Acute myelopathy associated with primary infection with human immunodeficiency virus. Br. Med. J. (Clin. Res. Ed.) 294: 143144.
55. Deutch, S.,, L. N. Pedersen,, L. Podenphant,, R. Olesen,, M. B. Schmidt,, J. K. Moller, and, L. Ostergaard. 2006. Broad-range real time PCR and DNA sequencing for the diagnosis of bacterial meningitis. Scand. J. Infect. Dis. 38: 2735.
56. Domingues, R. B.,, F. D. Lakeman,, M. S. Mayo, and, R. J. Whitley. 1998. Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis. J. Clin. Microbiol. 36: 22292234.
57. Doong, H.,, J. Xu,, M. McCormac,, H. J. Li,, M. J. Espy,, K. Liu,, T. F. Smith,, J. X. Wang, and, Y. W. Tang. 2008. Duplex eQ-PCR for simultaneous detection and differentiation of herpes simplex viruses and enteroviruses in cerebrospinal fluid. Abstr. no. C-239. Abstr. 108th Gen. Meet. Am. Soc. Microbiol. American Society for Microbiology, Washington, DC.
58. Dumler, J. S.,, J. E. Madigan,, N. Pusterla, and, J. S. Bakken. 2007. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin. Infect. Dis. 45 (Suppl. 1): S45S51.
59. Dunbar, S. A.,, R. A. Eason,, D. M. Musher, and, J. E. Clarridge. 1998. Microscopic examination and broth culture of cerebrospinal fluid in diagnosis of meningitis. J. Clin. Microbiol. 36: 16171620.
60. Dunn, B. E.,, T. P. Monson,, J. S. Dumler,, C. C. Morris,, A. B. Westbrook,, J. L. Duncan,, J. E. Dawson,, K. G. Sims, and, B. E. Anderson. 1992. Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells. J. Clin. Microbiol. 30: 22072210.
61. Durand, M. L.,, S. B. Calderwood,, D. J. Weber,, S. I. Miller,, F. S. Southwick,, V. S. Caviness, Jr., and, M. N. Swartz. 1993. Acute bacterial meningitis in adults. A review of 493 episodes. N. Engl. J. Med. 328: 2128.
62. Enzinger, F.,, and E. Helwig. 1963. Whipple’s disease; a review of the literature and report of fifteen patients. Virchows Arch. Pathol. Anat. Physiol. Klin. Med. 336: 238269.
63. Espy, M. J.,, J. R. Uhl,, L. M. Sloan,, S. P. Buckwalter,, M. F. Jones,, E. A. Vetter,, J. D. Yao,, N. L. Wengenack,, J. E. Rosenblatt,, F. R. Cockerill III, and, T. F. Smith. 2006. Real-time PCR in clinical microbiology: applications for routine laboratory testing. Clin. Microbiol. Rev. 19: 165256.
64. Fenollar, F.,, P. E. Fournier,, C. Robert, and, D. Raoult. 2004. Use of genome selected repeated sequences increases the sensitivity of PCR detection of Tropheryma whipplei. J. Clin. Microbiol. 42: 401403.
65. Fenollar, F.,, S. Laouira,, H. Lepidi,, J. M. Rolain, and, D. Raoult. 2008. Value of Tropheryma whipplei quantitative polymerase chain reaction assay for the diagnosis of Whipple disease: usefulness of saliva and stool specimens for first-line screening. Clin. Infect. Dis. 47: 659667.
66. Fenollar, F.,, X. Puechal, and, D. Raoult. 2007. Whipple’s disease. N. Engl. J. Med. 356: 5566.
67. Fenollar, F.,, M. Trani,, B. Davoust,, B. Salle,, M. L. Birg,, J. M. Rolain, and, D. Raoult. 2008. Prevalence of asymptomatic Tropheryma whipplei carriage among humans and nonhuman primates. J. Infect. Dis. 197: 880887.
68. Fishbein, D. B.,, and L. E. Robinson. 1993. Rabies. N. Engl. J. Med. 329: 16321638.
69. Fodor, P. A.,, M. J. Levin,, A. Weinberg,, E. Sandberg,, J. Sylman, and, K. L. Tyler. 1998. Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology 51: 554559.
70. Fox, J. D.,, S. Han,, A. Samuelson,, Y. Zhang,, M. L. Neale, and, D. Westmoreland. 2002. Development and evaluation of nucleic acid sequence based amplification (NASBA) for diagnosis of enterovirus infections using the NucliSens Basic Kit. J. Clin. Virol. 24: 117130.
71. Gautheret-Dejean, A.,, C. Manichanh,, F. Thien-Ah-Koon,, A. M. Fillet,, N. Mangeney,, M. Vidaud,, N. Dhedin,, J. P. Vernant, and, H. Agut. 2002. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J. Virol. Methods 100: 2735.
72. Gerard, A.,, F. Sarrot-Reynauld,, E. Liozon,, P. Cathebras,, G. Besson,, C. Robin,, A. Vighetto,, J. F. Mosnier,, I. Durieu,, D. Vital Durand, and, H. Rousset. 2002. Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore) 81: 443457.
73. Gilden, D. 2004. Varicella zoster virus and central nervous system syndromes. Herpes 11 (Suppl. 2): 89A94A.
74. Gilden, D. H.,, B. K. Kleinschmidt-DeMasters,, J. J. LaGuardia,, R. Mahalingam, and, R. J. Cohrs. 2000. Neurologic complications of the reactivation of varicella-zoster virus. N. Engl. J. Med. 342: 635645.
75. Gilden, D. H.,, R. Mahalingam,, R. J. Cohrs, and, K. L. Tyler. 2007. Herpesvirus infections of the nervous system. Nat. Clin. Pract. Neurol. 3: 8294.
76. Glaser, C. A.,, S. Gilliam,, D. Schnurr,, B. Forghani,, S. Honarmand,, N. Khetsuriani,, M. Fischer,, C. K. Cossen, and, L. J. Anderson. 2003. In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998–2000. Clin. Infect. Dis. 36: 731742.
77. Glaser, C. A.,, S. Honarmand,, L. J. Anderson,, D. P. Schnurr,, B. Forghani,, C. K. Cossen,, F. L. Schuster,, L. J. Christie, and, J. H. Tureen. 2006. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin. Infect. Dis. 43: 15651577.
78. Goh, K. J.,, C. T. Tan,, N. K. Chew,, P. S. Tan,, A. Kamarulzaman,, S. A. Sarji,, K. T. Wong,, B. J. Abdullah,, K. B. Chua, and, S. K. Lam. 2000. Clinical features of Nipah virus encephalitis among pig farmers in Malaysia. N. Engl. J. Med. 342: 12291235.
79. Gooskens, J.,, K. E. Templeton,, E. C. Claas, and, A. P. van Dam. 2006. Evaluation of an internally controlled real-time PCR targeting the ospA gene for detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid. Clin. Microbiol. Infect. 12: 894900.
80. Gregoire, S. M.,, V. van Pesch,, S. Goffette,, A. Peeters, and, C. J. Sindic. 2006. Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system. J. Neurol. Neurosurg. Psychiatry 77: 938942.
81. Gubler, D. J. 2007. The continuing spread of West Nile virus in the western hemisphere. Clin. Infect. Dis. 45: 10391046.
82. [Reference deleted.]
83. Hamilton, M. S.,, M. A. Jackson, and, D. Abel. 1999. Clinical utility of polymerase chain reaction testing for enteroviral meningitis. Pediatr. Infect. Dis. J. 18: 533537.
84. Hankins, D. G.,, and J. A. Rosekrans. 2004. Overview, prevention, and treatment of rabies. Mayo Clin. Proc. 79: 671676.
85. Hanson, K. E.,, B. D. Alexander,, C. Woods,, C. Petti, and, L. B. Reller. 2007. Validation of laboratory screening criteria for herpes simplex virus testing of cerebrospinal fluid. J. Clin. Microbiol. 45: 721724.
86. Hasbun, R.,, J. Abrahams,, J. Jekel, and, V. J. Quagliarello. 2001. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N. Engl. J. Med. 345: 17271733.
87. Hayden, R. T.,, and L. D. Frenkel. 2000. More laboratory testing: greater cost but not necessarily better. Pediatr. Infect. Dis. J. 19: 290292.
88. Hayward, R. A.,, M. F. Shapiro, and, R. K. Oye. 1987. Laboratory testing on cerebrospinal fluid. A reappraisal. Lancet i: 14.
89. Hemachudha, T.,, J. Laothamatas, and, C. E. Rupprecht. 2002. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol. 1: 101109.
90. Hiatt, B.,, L. DesJardin,, T. Carter,, R. Gingrich,, C. Thompson, and, M. de Magalhaes-Silverman. 2003. A fatal case of West Nile virus infection in a bone marrow transplant recipient. Clin. Infect. Dis. 37: e129e131.
91. Hilt, D. C.,, D. Buchholz,, A. Krumholz,, H. Weiss, and, J. S. Wolinsky. 1983. Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused by cerebral angiitis: diagnosis and management approaches. Ann. Neurol. 14: 543553.
92. Hindiyeh, M.,, L. M. Shulman,, E. Mendelson,, L. Weiss,, Z. Grossman, and, H. Bin. 2001. Isolation and characterization of West Nile virus from the blood of viremic patients during the 2000 outbreak in Israel. Emerg. Infect. Dis. 7: 748750.
93. Ho, M.,, E.-R. Chen,, K.-H. Hsu,, S.-J. Twu,, K.-T. Chen,, S.-F. Tsai,, J.-R. Wang, and S.-R. Shih for the Taiwan Enterovirus Epidemic Working Group. 1999. An epidemic of enterovirus 71 infection in Taiwan. N. Engl. J. Med. 341: 929935.
94. Hochberg, F. H.,, G. Miller,, R. T. Schooley,, M. S. Hirsch,, P. Feorino, and, W. Henle. 1983. Centralnervous-system lymphoma related to Epstein-Barr virus. N. Engl. J. Med. 309: 745748.
95. Hongo, I.,, and K. C. Bloch. 2006. Ehrlichia infection of the central nervous system. Curr. Treat. Options Neurol. 8: 179184.
96. Huang, C.,, D. Morse,, B. Slater,, M. Anand,, E. Tobin,, P. Smith,, M. Dupuis,, R. Hull,, R. Ferrera,, B. Rosen, and, L. Grady. 2004. Multiple-year experience in the diagnosis of viral central nervous system infections with a panel of polymerase chain reaction assays for detection of 11 viruses. Clin. Infect. Dis. 39: 630635.
97. Huang, C.,, B. Slater,, R. Rudd,, N. Parchuri,, R. Hull,, M. Dupuis, and, A. Hindenburg. 2002. First isolation of West Nile virus from a patient with encephalitis in the United States. Emerg. Infect. Dis. 8: 13671371.
98. Huang, C. C.,, C. C. Liu,, Y. C. Chang,, C. Y. Chen,, S. T. Wang, and, T. F. Yeh. 1999. Neurologic complications in children with enterovirus 71 infection. N. Engl. J. Med. 341: 936942.
99. Ihekwaba, U. K.,, G. Kudesia, and, M. W. McKendrick. 2008. Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin. Infect. Dis. 47: 783789.
100. Isaacson, E.,, C. A. Glaser,, B. Forghani,, Z. Amad,, M. Wallace,, R. W. Armstrong,, M. M. Exner, and, S. Schmid. 2005. Evidence of human herpesvirus 6 infection in 4 immunocompetent patients with encephalitis. Clin. Infect. Dis. 40: 890893.
101. Iten, A.,, P. Chatelard,, P. Vuadens,, J. Miklossy,, R. Meuli,, R. Sahli, and, P. R. Meylan. 1999. Impact of cerebrospinal fluid PCR on the management of HIV-infected patients with varicella-zoster virus infection of the central nervous system. J. Neurovirol. 5: 172180.
102. Ivers, L. C.,, A. Y. Kim, and, P. E. Sax. 2004. Predictive value of polymerase chain reaction of cerebrospinal fluid for detection of Epstein-Barr virus to establish the diagnosis of HIV-related primary central nervous system lymphoma. Clin. Infect. Dis. 38: 16291632.
103. Iwamoto, M.,, D. B. Jernigan,, A. Guasch,, M. J. Trepka,, C. G. Blackmore,, W. C. Hellinger,, S. M. Pham,, S. Zaki,, R. S. Lanciotti,, S. E. Lance-Parker,, C. A. DiazGranados,, A. G. Winquist,, C. A. Perlino,, S. Wiersma,, K. L. Hillyer,, J. L. Goodman,, A. A. Marfin,, M. E. Chamberland, and, L. R. Petersen. 2003. Transmission of West Nile virus from an organ donor to four transplant recipients. N. Engl. J. Med. 348: 21962203.
104. Jeffery, K. J.,, S. J. Read,, T. E. Peto,, R. T. MayonWhite, and, C. R. Bangham. 1997. Diagnosis of viral infections of the central nervous system: clinical interpretation of PCR results. Lancet 349: 313317.
105. Johnson, R. T.,, and C. A. Mims. 1968. Pathogenesis of viral infections of the nervous system. N. Engl. J. Med. 278: 2330, cont’d.
106. Johnson, R. T.,, and G. A. Mims. 1968. Pathogenesis for viral infections of the nervous system. N. Engl. J. Med. 278: 8492, concl.
107. Kaiser, R.,, and S. Rauer. 1999. Serodiagnosis of neuroborreliosis: comparison of reliability of three confirmatory assays. Infection 27: 177182.
108. Kanegaye, J. T.,, P. Soliemanzadeh, and, J. S. Bradley. 2001. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 108: 11691174.
109. Keinath, R. D.,, D. E. Merrell,, R. Vlietstra, and, W. O. Dobbins III. 1985. Antibiotic treatment and relapse in Whipple’s disease. Long-term follow-up of 88 patients. Gastroenterology 88: 18671873.
110. Khetsuriani, N.,, R. C. Holman, and, L. J. Anderson. 2002. Burden of encephalitis-associated hospitalizations in the United States, 1988–1997. Clin. Infect. Dis. 35: 175182.
111. Khetsuriani, N.,, A. Lamonte-Fowlkes,, S. Oberst, and, M. A. Pallansch. 2006. Enterovirus surveillance—United States, 1970–2005. MMWR Surveill. Summ. 55: 120.
112. Kimberlin, D. W.,, F. D. Lakeman,, A. M. Arvin,, C. G. Prober,, L. Corey,, D. A. Powell,, S. K. Burchett,, R. F. Jacobs,, S. E. Starr, and, R. J. Whitley for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 1996. Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. J. Infect. Dis. 174: 11621167.
113. King, R. L.,, S. A. Lorch,, D. M. Cohen,, R. L. Hodinka,, K. A. Cohn, and, S. S. Shah. 2007. Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics 120: 489496.
114. Kleinschmidt-DeMasters, B. K.,, and D. H. Gilden. 2001. The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol. 11: 440451.
115. Kleinschmidt-DeMasters, B. K.,, B. A. Marder,, M. E. Levi,, S. P. Laird,, J. T. McNutt,, E. J. Escott,, G. T. Everson, and, K. L. Tyler. 2004. Naturally acquired West Nile virus encephalomyelitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features. Arch. Neurol. 61: 12101220.
116. Korimbocus, J.,, N. Scaramozzino,, B. Lacroix,, J. M. Crance,, D. Garin, and, G. Vernet. 2005. DNA probe array for the simultaneous identification of herpesviruses, enteroviruses, and flaviviruses. J. Clin. Microbiol. 43: 37793787.
117. Koskiniemi, M.,, M. Korppi,, K. Mustonen,, H. Rantala,, M. Muttilainen,, E. Herrgard,, P. Ukkonen, and, A. Vaheri. 1997. Epidemiology of encephalitis in children. A prospective multicentre study. Eur. J. Pediatr. 156: 541545.
118. Koskiniemi, M.,, H. Piiparinen,, T. Rantalaiho,, P. Eranko,, M. Farkkila,, K. Raiha,, E. M. Salonen,, P. Ukkonen, and, A. Vaheri. 2002. Acute central nervous system complications in varicella zoster virus infections. J. Clin. Virol. 25: 293301.
119. Kost, C. B.,, B. Rogers,, M. S. Oberste,, C. Robinson,, B. L. Eaves,, K. Leos,, S. Danielson,, M. Satya,, F. Weir, and, F. S. Nolte. 2007. Multicenter beta trial of the GeneXpert Enterovirus assay. J. Clin. Microbiol. 45: 10811086.
120. Kupila, L.,, T. Vuorinen,, R. Vainionpaa,, V. Hukkanen,, R. J. Marttila, and, P. Kotilainen. 2006. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology 66: 7580.
121. Kupila, L.,, T. Vuorinen,, R. Vainionpaa,, R. J. Marttila, and, P. Kotilainen. 2005. Diagnosis of enteroviral meningitis by use of polymerase chain reaction of cerebrospinal fluid, stool, and serum specimens. Clin. Infect. Dis. 40: 982987.
122. Lakeman, F. D.,, and R. J. Whitley for the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 1995. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J. Infect. Dis. 171: 857863.
123. Lanciotti, R. S.,, A. J. Kerst,, R. S. Nasci,, M. S. Godsey,, C. J. Mitchell,, H. M. Savage,, N. Komar,, N. A. Panella,, B. C. Allen,, K. E. Volpe,, B. S. Davis, and, J. T. Roehrig. 2000. Rapid detection of West Nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. J. Clin. Microbiol. 38: 40664071.
124. Landry, M. L.,, R. Garner, and, D. Ferguson. 2005. Real-time nucleic acid sequence-based amplification using molecular beacons for detection of enterovirus RNA in clinical specimens. J. Clin. Microbiol. 43: 31363139.
125. Lebech, A. M.,, K. Hansen,, F. Brandrup,, O. Clemmensen, and, L. Halkier-Sorensen. 2000. Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis. Mol. Diagn. 5: 139150.
126. Lebech, A. M.,, K. Hansen,, B. J. Rutledge,, C. P. Kolbert,, P. N. Rys, and, D. H. Persing. 1998. Diagnostic detection and direct genotyping of Borrelia burgdorferi by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. Mol. Diagn. 3: 131141.
127. Louis, E. D.,, T. Lynch,, P. Kaufmann,, S. Fahn, and, J. Odel. 1996. Diagnostic guidelines in central nervous system Whipple’s disease. Ann. Neurol. 40: 561568.
128. Lu, C. H.,, W. N. Chang, and, H. W. Chang. 2001. The prognostic factors of adult tuberculous meningitis. Infection 29: 299304.
129. Lu, H.,, Y. Zhou,, Y. Yin,, X. Pan, and, X. Weng. 2005. Cryptococcal antigen test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J. Clin. Microbiol. 43: 29892990.
130. Lynch, M.,, B. Lee,, P. Azimi,, J. Gentsch,, C. Glaser,, S. Gilliam,, H. G. Chang,, R. Ward, and, R. I. Glass. 2001. Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review. Clin. Infect. Dis. 33: 932938.
131. Lynch, T.,, J. Odel,, D. N. Fredericks,, E. D. Louis,, S. Forman,, H. Rotterdam,, S. Fahn, and, D. A. Relman. 1997. Polymerase chain reaction-based detection of Tropheryma whippelii in central nervous system Whipple’s disease. Ann. Neurol. 42: 120124.
132. Machetti, M.,, M. Zotti,, L. Veroni,, N. Mordini,, M. T. Van Lint,, A. Bacigalupo,, D. Paola, and, C. Viscoli. 2000. Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole. Transpl. Infect. Dis. 2: 140144.
133. Malm, G.,, and M. Forsgren. 1999. Neonatal herpes simplex virus infections: HSV DNA in cerebrospinal fluid and serum. Arch. Dis. Child. Fetal Neonatal Ed. 81: F24F29.
134. Mantero, G.,, A. Zonaro,, A. Albertini,, P. Bertolo, and, D. Primi. 1991. DNA enzyme immunoassay: general method for detecting products of polymerase chain reaction. Clin. Chem. 37: 422429.
135. Marcos, M. A.,, E. Martinez,, M. Almela,, J. Mensa, and, M. T. Jimenez de Anta. 2001. New rapid antigen test for diagnosis of pneumococcal meningitis. Lancet 357: 14991500.
136. Marshall, G. S.,, M. A. Hauck,, G. Buck, and, G. P. Rabalais. 1997. Potential cost savings through rapid diagnosis of enteroviral meningitis. Pediatr. Infect. Dis. J. 16: 10861087.
137. McMillan, D. A.,, C. Y. Lin,, S. I. Aronin, and, V. J. Quagliarello. 2001. Community-acquired bacterial meningitis in adults: categorization of causes and timing of death. Clin. Infect. Dis. 33: 969975.
138. Morishima, T.,, T. Togashi,, S. Yokota,, Y. Okuno,, C. Miyazaki,, M. Tashiro, and, N. Okabe. 2002. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin. Infect. Dis. 35: 512517.
139. Muir, P.,, and A. M. van Loon. 1997. Enterovirus infections of the central nervous system. Intervirology 40: 153166.
140. Musher, D. M.,, and R. F. Schell. 1973. False-positive Gram stains of cerebrospinal fluid. Ann. Intern. Med. 79: 603604. (Letter.)
141. Nagaraj, T.,, J. P. Vasanth,, A. Desai,, A. Kamat,, S. N. Madhusudana, and, V. Ravi. 2006. Ante mortem diagnosis of human rabies using saliva samples: comparison of real time and conventional RT-PCR techniques. J. Clin. Virol. 36: 1723.
142. Nagel, M. A.,, R. J. Cohrs,, R. Mahalingam,, M. C. Wellish,, B. Forghani,, A. Schiller,, J. E. Safdieh,, E. Kamenkovich,, L. W. Ostrow,, M. Levy,, B. Greenberg,, A. N. Russman,, I. Katzan,, C. J. Gardner,, M. Hausler,, R. Nau,, T. Saraya,, H. Wada,, H. Goto,, M. de Martino,, M. Ueno,, W. D. Brown,, C. Terborg, and, D. H. Gilden. 2008. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 70: 853860.
143. Nagel, M. A.,, B. Forghani,, R. Mahalingam,, M. C. Wellish,, R. J. Cohrs,, A. N. Russman,, I. Katzan,, R. Lin,, C. J. Gardner, and, D. H. Gilden. 2007. The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 68: 10691073.
144. Nahmias, A. J.,, R. J. Whitley,, A. N. Visintine,, Y. Takei, and, C. A. Alford, Jr. 1982. Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J. Infect. Dis. 145: 829836.
145. Neuman, M. I.,, S. Tolford, and, M. B. Harper. 2008. Test characteristics and interpretation of cerebrospinal fluid Gram stain in children. Pediatr. Infect. Dis. J. 27: 309313.
146. Nigrovic, L. E.,, N. Kuppermann, and, R. Malley. 2002. Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post- Haemophilus influenzae era. Pediatrics 110: 712719.
147. Nix, W. A.,, M. S. Oberste, and, M. A. Pallansch. 2006. Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J. Clin. Microbiol. 44: 26982704.
148. Nocton, J. J.,, B. J. Bloom,, B. J. Rutledge,, D. H. Persing,, E. L. Logigian,, C. H. Schmid, and, A. C. Steere. 1996. Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis. J. Infect. Dis. 174: 623627.
149. Noordhoek, G. T.,, A. H. Kolk,, G. Bjune,, D. Catty,, J. W. Dale,, P. E. Fine,, P. Godfrey-Faussett,, S. N. Cho,, T. Shinnick, and, S. B. Svenson. 1994. Sensitivity and specificity of PCR for detection of Mycobacterium tuberculosis: a blind comparison study among seven laboratories. J. Clin. Microbiol. 32: 277284.
150. Noordhoek, G. T.,, S. Mulder,, P. Wallace, and, A. M. van Loon. 2004. Multicentre quality control study for detection of Mycobacterium tuberculosis in clinical samples by nucleic amplification methods. Clin. Microbiol. Infect. 10: 295301.
151. Nowak, D. A.,, R. Boehmer, and, H. H. Fuchs. 2003. A retrospective clinical, laboratory and outcome analysis in 43 cases of acute aseptic meningitis. Eur. J. Neurol. 10: 271280.
152. Olano, J. P.,, E. Masters,, W. Hogrefe, and, D. H. Walker. 2003. Human monocytotropic ehrlichiosis, Missouri. Emerg. Infect. Dis. 9: 15791586.
153. Paddock, C. D.,, P. W. Greer,, T. L. Ferebee,, J. Singleton, Jr.,, D. B. McKechnie,, T. A. Treadwell,, J. W. Krebs,, M. J. Clarke,, R. C. Holman,, J. G. Olson,, J. E. Childs, and, S. R. Zaki. 1999. Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease. J. Infect. Dis. 179: 14691476.
154. Pai, M.,, L. L. Flores,, N. Pai,, A. Hubbard,, L. W. Riley, and, J. M. Colford, Jr. 2003. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect. Dis. 3: 633643.
155. Pallansch, M. A.,, and R. P. Roos. 2001. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses, p. 723–775. In D. M. Knipe,, P. M. Howley,, D. E. Griffin,, R. A. Lamb,, M. A. Martin,, B. Roizman, and, S. E. Straus (ed.), Fields Virology, 4th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
156. Pandit, L.,, S. Kumar,, I. Karunasagar, and, I. Karunasagar. 2005. Diagnosis of partially treated culture-negative bacterial meningitis using 16S rRNA universal primers and restriction endonuclease digestion. J. Med. Microbiol. 54: 539542.
157. Panegyres, P. K.,, R. Edis,, M. Beaman, and, M. Fallon. 2006. Primary Whipple’s disease of the brain: characterization of the clinical syndrome and molecular diagnosis. QJM 99: 609623.
158. Perkins, M. D.,, S. Mirrett, and, L. B. Reller. 1995. Rapid bacterial antigen detection is not clinically useful. J. Clin. Microbiol. 33: 14861491.
159. Peters, G.,, D. G. du Plessis, and, P. R. Humphrey. 2002. Cerebral Whipple’s disease with a stroke-like presentation and cerebrovascular pathology. J. Neurol. Neurosurg. Psychiatry 73: 336339.
160. Petry, F.,, M. Torzewski,, J. Bohl,, T. Wilhelm-Schwenkmezger,, P. Scheid,, J. Walochnik,, R. Michel,, L. Zoller,, K. J. Werhahn,, S. Bhakdi, and, K. J. Lackner. 2006. Early diagnosis of Acanthamoeba infection during routine cytological examination of cerebrospinal fluid. J. Clin. Microbiol. 44: 19031904.
161. Polage, C. R.,, and C. A. Petti. 2006. Assessment of the utility of viral culture of cerebrospinal fluid. Clin. Infect. Dis. 43: 15781579.
162. Potasman, I.,, L. Resnick,, B. J. Luft, and, J. S. Remington. 1988. Intrathecal production of antibodies against Toxoplasma gondii in patients with toxoplasmic encephalitis and the acquired immunodeficiency syndrome (AIDS). Ann. Intern. Med. 108: 4951.
163. Powell, K. F.,, N. E. Anderson,, R. W. Frith, and, M. C. Croxson. 1990. Non-invasive diagnosis of herpes simplex encephalitis. Lancet 335: 357358.
164. Priem, S.,, M. G. Rittig,, T. Kamradt,, G. R. Burmester, and, A. Krause. 1997. An optimized PCR leads to rapid and highly sensitive detection of Borrelia burgdorferi in patients with Lyme borreliosis. J. Clin. Microbiol. 35: 685690.
165. Puchhammer-Stockl, E.,, T. Popow-Kraupp,, F. X. Heinz,, C. W. Mandl, and, C. Kunz. 1991. Detection of varicella-zoster virus DNA by polymerase chain reaction in the cerebrospinal fluid of patients suffering from neurological complications associated with chicken pox or herpes zoster. J. Clin. Microbiol. 29: 15131516.
166. Rabenau, H. F.,, A. Clarici,, G. Mühlbauer,, A. Berger,, A. Vince,, S. Muller,, E. Daghofer,, B. I. Santner,, E. Marth, and, H. H. Kessler. 2002. Rapid detection of enterovirus infection by automated RNA extraction and real-time fluorescence PCR. J. Clin. Virol. 25: 155164.
167. Rafi, W.,, M. M. Venkataswamy,, V. Ravi, and, A. Chandramuki. 2007. Rapid diagnosis of tuberculous meningitis: a comparative evaluation of in-house PCR assays involving three mycobacterial DNA sequences, IS6110, MPB-64 and 65 kDa antigen. J. Neurol. Sci. 252: 163168.
168. Ramers, C.,, G. Billman,, M. Hartin,, S. Ho, and, M. H. Sawyer. 2000. Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management. JAMA 283: 26802685.
169. Rantala, H.,, and M. Uhari. 1989. Occurrence of childhood encephalitis: a population-based study. Pediatr. Infect. Dis. J. 8: 426430.
170. Rolain, J. M.,, F. Fenollar, and, D. Raoult. 2007. False positive PCR detection of Tropheryma whipplei in the saliva of healthy people. BMC Microbiol. 7: 48.
171. Romero, J. R.,, and J. G. Newland. 2003. Viral meningitis and encephalitis: traditional and emerging viral agents. Semin. Pediatr. Infect. Dis. 14: 7282.
172. Rotbart, H. A.,, M. H. Sawyer,, S. Fast,, C. Lewinski,, N. Murphy,, E. F. Keyser,, J. Spadoro,, S. Y. Kao, and, M. Loeffelholz. 1994. Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay. J. Clin. Microbiol. 32: 25902592.
173. Rouah, E.,, B. B. Rogers,, D. R. Wilson,, J. B. Kirkpatrick, and, G. J. Buffone. 1990. Demonstration of Epstein-Barr virus in primary central nervous system lymphomas by the polymerase chain reaction and in situ hybridization. Hum. Pathol. 21: 545550.
174. Rowley, A. H.,, R. J. Whitley,, F. D. Lakeman, and, S. M. Wolinsky. 1990. Rapid detection of herpes-simplex-virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet 335: 440441.
175. Saha, S. K.,, G. L. Darmstadt,, N. Yamanaka,, D. S. Billal,, T. Nasreen,, M. Islam, and, D. H. Hamer. 2005. Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden. Pediatr. Infect. Dis. J. 24: 10931098.
176. Scheld, W. M.,, U. Koedel,, B. Nathan, and, H. W. Pfister. 2002. Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J. Infect. Dis. 186 (Suppl. 2): S225S233.
177. Schlesinger, Y.,, M. H. Sawyer, and, G. A. Storch. 1994. Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management. Pediatrics 94: 157162.
178. Schloss, L.,, A. M. van Loon,, P. Cinque,, G. Cleator,, J. M. Echevarria,, K. I. Falk,, P. Klapper,, J. Schirm,, B. F. Vestergaard,, H. Niesters,, T. Popow-Kraupp,, W. Quint, and, A. Linde. 2003. An international external quality assessment of nucleic acid amplification of herpes simplex virus. J. Clin. Virol. 28: 175185.
179. Schuurman, T.,, R. F. de Boer,, A. M. Kooistra-Smid, and, A. A. van Zwet. 2004. Prospective study of use of PCR amplification and sequencing of 16S ribosomal DNA from cerebrospinal fluid for diagnosis of bacterial meningitis in a clinical setting. J. Clin. Microbiol. 42: 734740.
180. Sejvar, J. J.,, A. V. Bode,, A. A. Marfin,, G. L. Campbell,, D. Ewing,, M. Mazowiecki,, P. V. Pavot,, J. Schmitt,, J. Pape,, B. J. Biggerstaff, and, L. R. Petersen. 2005. West Nile virus-associated flaccid paralysis. Emerg. Infect. Dis. 11: 10211027.
181. Sexton, D. J.,, S. S. Kanj,, K. Wilson,, G. R. Corey,, B. C. Hegarty,, M. G. Levy, and, E. B. Breitschwerdt. 1994. The use of a polymerase chain reaction as a diagnostic test for Rocky Mountain spotted fever. Am. J. Trop. Med. Hyg. 50: 5963.
182. Simko, J. P.,, A. M. Caliendo,, K. Hogle, and, J. Versalovic. 2002. Differences in laboratory findings for cerebrospinal fluid specimens obtained from patients with meningitis or encephalitis due to herpes simplex virus (HSV) documented by detection of HSV DNA. Clin. Infect. Dis. 35: 414419.
183. Solomon, T. 2003. Exotic and emerging viral encephalitides. Curr. Opin. Neurol. 16: 411418.
184. Standaert, S. M.,, T. Yu,, M. A. Scott,, J. E. Childs,, C. D. Paddock,, W. L. Nicholson,, J. Singleton, Jr., and, M. J. Blaser. 2000. Primary isolation of Ehrlichia chaffeensis from patients with febrile illnesses: clinical and molecular characteristics. J. Infect. Dis. 181: 10821088.
185. Steiner, I.,, P. G. Kennedy, and, A. R. Pachner. 2007. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol. 6: 10151028.
186. Stellrecht, K. A.,, I. Harding,, A. M. Woron,, M. L. Lepow, and, R. A. Venezia. 2002. The impact of an enteroviral RT-PCR assay on the diagnosis of aseptic meningitis and patient management. J. Clin. Virol. 25 (Suppl. 1): S19S26.
187. Storch, G. A. 2000. Diagnostic virology. Clin. Infect. Dis. 31: 739751.
188. Straus, S. E.,, J. I. Cohen,, G. Tosato, and, J. Meier. 1993. NIH conference. Epstein-Barr virus infections: biology, pathogenesis, and management. Ann. Intern. Med. 118: 4558.
189. Sutlas, P. N.,, A. Unal,, H. Forta,, S. Senol, and, D. Kirbas. 2003. Tuberculous meningitis in adults: review of 61 cases. Infection 31: 387391.
190. Takahashi, T.,, and T. Nakayama. 2006. Novel technique of quantitative nested real-time PCR assay for Mycobacterium tuberculosis DNA. J. Clin. Microbiol. 44: 10291039.
191. Takahashi, T.,, M. Tamura,, S. N. Takahashi,, K. Matsumoto,, S. Sawada,, E. Yokoyama,, T. Nakayama,, T. Mizutani,, T. Takasu, and, H. Nagase. 2007. Quantitative nested real-time PCR assay for assessing the clinical course of tuberculous meningitis. J. Neurol. Sci. 255: 6976.
192. Tandale, B. V.,, S. S. Tikute,, V. A. Arankalle,, P. S. Sathe,, M. V. Joshi,, S. N. Ranadive,, P. C. Kanojia,, D. Eshwarachary,, M. Kumarswamy, and, A. C. Mishra. 2008. Chandipura virus: a major cause of acute encephalitis in children in North Telangana, Andhra Pradesh, India. J. Med. Virol. 80: 118124.
193. Tang, Y. W. 2007. Laboratory diagnosis of CNS infections by molecular amplification techniques. Expert Opin. Med. Diagn. 1: 489509.
194. Tang, Y. W.,, J. R. Hibbs,, K. R. Tau,, Q. Qian,, H. A. Skarhus,, T. F. Smith, and, D. H. Persing. 1999. Effective use of polymerase chain reaction for diagnosis of central nervous system infections. Clin. Infect. Dis. 29: 803806.
195. Tang, Y. W.,, P. S. Mitchell,, M. J. Espy,, T. F. Smith, and, D. H. Persing. 1999. Molecular diagnosis of herpes simplex virus infections in the central nervous system. J. Clin. Microbiol. 37: 21272136.
196. Tang, Y. W.,, P. N. Rys,, B. J. Rutledge,, P. S. Mitchell,, T. F. Smith, and, D. H. Persing. 1998. Comparative evaluation of colorimetric microtiter plate systems for detection of herpes simplex virus in cerebrospinal fluid. J. Clin. Microbiol. 36: 27142717.
197. Tang, Y. W.,, S. E. Sefers,, H. Li,, D. J. Kohn, and, G. W. Procop. 2005. Comparative evaluation of three commercial systems for nucleic acid extraction from urine specimens. J. Clin. Microbiol. 43: 48304833.
198. Tarafdar, K.,, S. Rao,, R. A. Recco, and, M. M. Zaman. 2001. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clin. Infect. Dis. 33: 406408.
199. Tavakoli, N. P.,, H. Wang,, S. Nattanmai,, M. Dupuis,, H. Fusco, and, R. Hull. 2008. Detection and typing of enteroviruses from CSF specimens from patients diagnosed with meningitis/encephalitis. J. Clin. Virol. 43: 207211.
200. Tilley, P. A.,, J. D. Fox,, G. C. Jayaraman, and, J. K. Preiksaitis. 2006. Nucleic acid testing for West Nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients. J. Infect. Dis. 193: 13611364.
201. Tunkel, A. R.,, C. A. Glaser,, K. C. Bloch,, J. J. Sejvar,, C. M. Marra,, K. L. Roos,, B. J. Hartman,, S. L. Kaplan,, W. M. Scheld, and, R. J. Whitley. 2008. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 47: 303327.
202. Tunkel, A. R.,, and W. M. Scheld. 1993. Pathogenesis and pathophysiology of bacterial meningitis. Clin. Microbiol. Rev. 6: 118136.
203. Tyler, K. L. 2004. Update on herpes simplex encephalitis. Rev. Neurol. Dis. 1: 169178.
204. Tyler, K. L. 2004. West Nile virus infection in the United States. Arch. Neurol. 61: 11901195.
205. Tzanakaki, G.,, M. Tsopanomichalou,, K. Kesanopoulos,, R. Matzourani,, M. Sioumala,, A. Tabaki, and, J. Kremastinou. 2005. Simultaneous single-tube PCR assay for the detection of Neisseria meningitidis, Haemophilus influenzae type b and Streptococcus pneumoniae. Clin. Microbiol. Infect. 11: 386390.
206. Tzianabos, T.,, B. E. Anderson, and, J. E. McDade. 1989. Detection of Rickettsia rickettsii DNA in clinical specimens by using polymerase chain reaction technology. J. Clin. Microbiol. 27: 28662868.
207. van der Meer, J. T.,, W. L. Drew,, R. A. Bowden,, G. J. Galasso,, P. D. Griffiths,, D. A. Jabs,, C. Katlama,, S. A. Spector, and, R. J. Whitley. 1996. Summary of the International Consensus Symposium on advances in the diagnosis, treatment and prophylaxis of cytomegalovirus infection. Antivir. Res. 32: 119140.
208. Van Vliet, K. E.,, P. Muir,, J. M. Echevarria,, P. E. Klapper,, G. M. Cleator, and, A. M. Van Loon. 2001. Multicenter proficiency testing of nucleic acid amplification methods for the detection of enteroviruses. J. Clin. Microbiol. 39: 33903392.
209. Verdon, R.,, S. Chevret,, J. P. Laissy, and, M. Wolff. 1996. Tuberculous meningitis in adults: review of 48 cases. Clin. Infect. Dis. 22: 982988.
210. Verweij, P. E.,, K. Brinkman,, H. P. Kremer,, B. J. Kullberg, and, J. F. Meis. 1999. Aspergillus meningitis: diagnosis by non-culture-based microbiological methods and management. J. Clin. Microbiol. 37: 11861189.
211. Viscoli, C.,, M. Machetti,, P. Gazzola,, A. De Maria,, D. Paola,, M. T. Van Lint,, F. Gualandi,, M. Truini, and, A. Bacigalupo. 2002. Aspergillus galactomannan antigen in the cerebrospinal fluid of bone marrow transplant recipients with probable cerebral aspergillosis. J. Clin. Microbiol. 40: 14961499.
212. Visvesvara, G. S.,, H. Moura, and, F. L. Schuster. 2007. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol. Med. Microbiol. 50: 126.
213. von Herbay, A.,, H. J. Ditton,, F. Schuhmacher, and, M. Maiwald. 1997. Whipple’s disease: staging and monitoring by cytology and polymerase chain reaction analysis of cerebrospinal fluid. Gastroenterology 113: 434441.
214. von Herbay, A.,, H. F. Otto,, M. Stolte,, F. Borchard,, T. Kirchner,, H. J. Ditton, and, M. Maiwald. 1997. Epidemiology of Whipple’s disease in Germany. Analysis of 110 patients diagnosed in 1965–95. Scand. J. Gastroenterol. 32: 5257.
215. Weil, A. A.,, C. A. Glaser,, Z. Amad, and, B. Forghani. 2002. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin. Infect. Dis. 34: 11541157.
216. Weinberg, A.,, K. C. Bloch,, S. Li,, Y. W. Tang,, M. Palmer, and, K. L. Tyler. 2005. Dual infections of the central nervous system with Epstein-Barr virus. J. Infect. Dis. 191: 234237.
217. Weinberg, A.,, S. Li,, M. Palmer, and, K. L. Tyler. 2002. Quantitative CSF PCR in Epstein-Barr virus infections of the central nervous system. Ann. Neurol. 52: 543548.
218. Welinder-Olsson, C.,, L. Dotevall,, H. Hogevik,, R. Jungnelius,, B. Trollfors,, M. Wahl, and, P. Larsson. 2007. Comparison of broad-range bacterial PCR and culture of cerebrospinal fluid for diagnosis of community-acquired bacterial meningitis. Clin. Microbiol. Infect. 13: 879886.
219. Wheat, L. J.,, C. E. Musial, and, E. Jenny-Avital. 2005. Diagnosis and management of central nervous system histoplasmosis. Clin. Infect. Dis. 40: 844852.
220. Whitley, R. J. 2006. Herpes simplex encephalitis: adolescents and adults. Antivir. Res. 71: 141148.
221. Whitley, R. J.,, C. A. Alford,, M. S. Hirsch,, R. T. Schooley,, J. P. Luby,, F. Y. Aoki,, D. Hanley,, A. J. Nahmias, and, S. J. Soong. 1986. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N. Engl. J. Med. 314: 144149.
222. Wolthers, K. C.,, K. S. Benschop,, J. Schinkel,, R. Molenkamp,, R. M. Bergevoet,, I. J. Spijkerman,, H. C. Kraakman, and, D. Pajkrt. 2008. Human parechoviruses as an important viral cause of sepsislike illness and meningitis in young children. Clin. Infect. Dis. 47: 358363.
223. Wormser, G. P.,, R. J. Dattwyler,, E. D. Shapiro,, J. J. Halperin,, A. C. Steere,, M. S. Klempner,, P. J. Krause,, J. S. Bakken,, F. Strle,, G. Stanek,, L. Bockenstedt,, D. Fish,, J. S. Dumler, and, R. B. Nadelman. 2006. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin. Infect. Dis. 43: 10891134.
224. Young, N. P.,, and C. J. Klein. 2007. Encephalopathy with seizures having PCR-positive Anaplasma phagocytophilum and Ehrlichia chaffeensis. Eur. J. Neurol. 14: e3e4.
225. Zerr, D. M. 2006. Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation. J. Clin. Virol. 37 (Suppl. 1): S52S56.


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Relatively common causes of meningoencephalitis in immunocompetent patients

Citation: Bloch K, Tang Y. 2011. Molecular Approaches to the Diagnosis of Meningitis and Encephalitis, p 767-784. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch50
Generic image for table

Less common causes of meningoencephalitis in immunocompetent patients

Citation: Bloch K, Tang Y. 2011. Molecular Approaches to the Diagnosis of Meningitis and Encephalitis, p 767-784. In Persing D, Tenover F, Tang Y, Nolte F, Hayden R, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555816834.ch50

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