Epstein-Barr virus infections of the central nervous system

OBJECTIVE: Epstein-Barr virus (EBV), a lymphotropic herpes virus causing infectious mononucleosis (IM), also causes various central nervous system (CNS) infections. In the present study, EBV CNS infections were investigated. PATIENTS AND METHODS: For adult inpatients in our hospital and related hospitals between 1984-2002, CNS syndromes with IM symptoms were examined, and serologic positives were assessed according to established criteria. Polymerase chain reaction (PCR) was performed for cerebrospinal fluid (CSF) from seven patients. RESULTS: Ten patients with EBV-related CNS infections were found; their mean age was 36 years (20-79 years). The neurologic forms were as follows: acute encephalitis (4 patients), acute cerebellar ataxia (1), acute disseminated encephalomyelitis (ADEM) (2), myelitis (1), and meningitis (2). The PCR from CSF was positive in two patients with meningitis, one patient with ADEM, and one patient with encephalitis-associated chronic EVB infection. One case of encephalitis and another of relapsing ADEM were attributed to chronic EBV infection. CONCLUSION: Our study identified a variety of EBV-related CNS infections. EBV CNS infections are divided into two groups: 1) CNS syndromes associated with primary EBV or reactivated infection, and 2) those associated with chronic EBV infection; it is notable that in the former, diverse CNS syndromes including ADEM can occur, whereas in the latter, chronic or recurrent CNS syndromes are produced.     

HIV-related Hodgkin's disease with central nervous system involvement and association with Epstein-Barr virus

Central nervous system (CNS) involvement is a rare occurrence in the course of human immunodeficiency virus (HIV)-related Hodgkin's disease (HD). We report the clinical course of a patient with HIV infection who developed systemic HD, mixed cellularity subtype, later complicated by leptomeningeal involvement. The patient died from his illness, and autopsy was performed. Examining the brain lesion, Epstein-Barr virus (EBV) presence was demonstrated in Reed-Sternberg cells by immunohistochemistry using an EBER probe for EBV RNA. This is the second case report in the English literature of HD involving the CNS in an HIV-positive individual, and the first demonstrating EBV presence. Extranodal presence of Hodgkin's disease in patients with HIV infection is probably related to immunosuppression, and physicians treating this illness should be alert to the potential of unusual sites of involvement.     

Herpesvirus infections of the central nervous system

In recent years, advances in the diagnosis and treatment of herpes simplex encephalitis (HSE) have been achieved due to the prevalence of antiviral drugs and the introduction of the polymerase chain reaction (PCR) to test the cerebrospinal fluid. The several clinical forms of herpes simplex virus type 1 (HSV-1) infections of the central nervous system (CNS), including acute disseminated encephalomyelitis and brainstem encephalitis, have been clarified. However, fatal, prolonged, or relapsed cases are still observed, and early detection and appropriate treatment is necessary to lead to a good prognosis for these intractable HSE cases. In adult HSV-2 infections, meningitis and myelitis associated with genital herpes are common. In the past, HSV-2 myelitis has been reported as a form of fatal necrotizing myelopathy; however, using PCR and magnetic resonance imaging studies, mild surviving cases are increasingly likely to be identified. Meanwhile, various CNS syndromes resulting from the herpes group viruses, including varicella-zoster virus and Epstein-Barr virus have also been reported. These herpesviruses have several characteristics in common, e.g., they exist in the latent state and they occur in both mucocutaneous and CNS infections. Adult HSV-1 and -2 infections of the CNS are discussed together with other herpes group virus infections of the CNS.     

Neurocritical care of patients with central nervous system infections

Bacterial meningitis and viral encephalitis are life-threatening infections with high mortality rates. Patients who survive these infections often remain permanently disabled. Potential neurologic complications requiring careful attention include impaired consciousness, elevated intracranial pressure, hydrocephalus, stroke, and seizures. Systemic complications are also common and are frequently the immediate cause of death. Critical care of these patients should focus not only on treatment of the underlying infection and its immediate complications but also on minimizing secondary brain injury. Given the increasing complexity of the diagnostic and therapeutic modalities available in managing central nervous system infections, the involvement of neurocritical care units and neurointensivists may be particularly helpful in improving outcomes.     

Antibacterial agents in infections of the central nervous system

Experimental animal models have provided information applicable to antimicrobial therapy of infections of the central nervous system. The efficacy of an antimicrobial agent in the therapy of bacterial meningitis depends on its ability to penetrate the blood-brain barrier, its activity in purulent cerebrospinal fluid, and a demonstration of rapid bactericidal activity against the offending pathogen. The recent emergence of resistant pathogens is challenging the therapy for bacterial meningitis. Various strategies for treating resistant pathogens have been evaluated in experimental animal models. Encouraging results have led to clinical trials to evaluate the efficacy of newer agents, alone or in combination with standard regimens.     

Phlebotomus-transmitted toscana virus infections of the central nervous system: a seven-year experience in Tuscany

Toscana virus (TOSv) is a recently discovered Phlebotomus-transmitted human pathogen involved in acute infections of the central nervous system (CNS) occurring during the summer in natural foci in Italy. The purpose of this prospective study was to investigate the role of this virus in 170 patients with meningitis-meningoencephalitis of suspected viral origin, admitted to the Departments of Infectious Diseases at the Siena Hospital from 1990 to 1996. Infections caused by tick-borne encephalitis virus (TBEv) and TOSv or other neurotropic viruses were routinely diagnosed by means of conventional virological methods. 89 cases were attributed to TOSv, about 10% of which were Europeans on vacation in Tuscany. All of the TOSv-positive cases were observed during the summer and were residents of hilly areas in Siena and its province at an altitude not above 500 m. An increase in the number of cases was observed over the years, with a higher incidence among younger people. The clinical picture was similar to that observed in other viral infections of the CNS. Evolution was benign in all cases; in 2 subjects symptoms and signs of encephalitis were present.     

Laboratory diagnosis of central nervous system infections.

The laboratory diagnosis of CNS infection is essential for optimal therapy. Acute infection requires rapid turn-around testing with high predictive values, that is, the ability of a test to accurately identify those patients who do or do not have disease caused by a specific etiology. The Gram's stain, fungal stains of direct smears, antigen testing for C. neoformans, and culture of bacteria, fungi, mycobacteria, and some viruses are important tests for the diagnosis of acute infection. The laboratory diagnosis of chronic infection necessitates discussion between the clinician and laboratory technician to allow triaging of testing. Antigen tests for bacteria, fungi, and viruses; antibody tests for multiple microorganisms; and PCR testing for bacteria, M. tuberculosis, and many viruses are all important in limited clinical situations. All testing for acute or chronic disease depends on sufficient specimen that is transported to the laboratory in a manner that will not compromise viability or chemical integrity. Sterile containers that maintain moisture content, exclude oxygen for anaerobic requests, and are stored at proper temperatures (22 degrees C room, 4 degrees C refrigeration, or -20 degrees C freezer depending on pathogen and test) are mandatory. Many laboratory issues addressing the diagnosis of CNS infection are changing or evolving. Most important is the recognition that bacterial antigen testing for the diagnosis of acute bacterial meningitis rarely impacts patient management and is not routinely needed, CSF shunt infections differ from usual meningeal infections and require rapid diagnosis, and TB meningitis remains a difficult disease to diagnosis but may be confirmed first by PCR testing of CSF. In addition, Whipple's disease of the CNS can be confirmed using PCR with CSF; CJD has a marker protein, referred to as 14-3-3 antigen, that can be detected in CSF, and the diagnosis of fungal CNS disease requires careful interpretation of direct smears, antigen and antibody testing, and culture. Most difficult to diagnose among the CNS infections are viral meningitis and encephalitis. The appearance of new etiologies, such as West Nile virus, and the common use of PCR for the herpes viruses and enteroviruses represent important advances. Evolving methods for the laboratory diagnosis of CNS infection represent significant improvements over previous testing; however, the array of tests available demands more attention for appropriate selection, is significantly more expensive, and requires new skills for performance and interpretation. The responsibility for proper use of laboratory testing lies both with the clinician and laboratory technician.     

HIV/AIDS合并中枢神经系统机会性感染73例临床分析

目的 探讨HIV感染及AIDS患者群(HIV/AIDS)的各种中枢神经系统机会性感染(opportunistic infections,OIs)情况,以提高诊断水平及临床治愈率,改善预后.方法 统计73例HIV/AIDS中枢神经系统OIs的临床数据,分析其临床表现、实验室检查结果和头颅影像学表现,评价其疗效及预后.结果...     

Epstein-Barr virus-targeted therapy for AIDS-related primary lymphoma of the central nervous system

Epstein-Barr virus (EBV) targeted therapeutic strategies for viral associated malignant diseases have received only perfunctory consideration, first, because latent herpesviruses have been intractable to antiviral chemotherapy and, second, because the role EBV has in maintenance of the malignant cell phenotype has been uncertain. Two patients with EBV related primary central nervous system lymphoma (PCNSL) in the setting of advanced AIDS, were treated with low dose hydroxyurea based on in vitro anti-EBV activity. The responses obtained here suggest the promise of antiviral approaches in select cancers.     

Rapid diagnosis of viral infections in the central nervous system

Rapid diagnosis of viral infections in the central nervous system has become increasingly important. Antiviral treatment, prevention of spread of disease and differentiation from infections caused by agents sensitive to antibiotics may be the important consequences of a virus specific diagnosis gained early in the disease. The diagnosis can be obtained by detection of virus or viral antigen in the human specimen: herpes simplex virus by electron microscopy, immunofluorescence or immunosorbent assays in brain biopsies; rabies virus by immunofluorescence in corneal cells or skin and mucous membranes. The presence of measles or influenza antigens in nasopharyngeal secretions, shown by immunofluorescence or enzyme immunoassays, may diagnose an encephalitis caused by either of these viruses. Where suitable material is not available the detection of virus-specific IgM in a single serum specimen may be used for diagnosis. Mumps specific IgM activity is detected by enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence techniques; tick-borne encephalitis (TBE) specific IgM by immunosorbent assays or by reduction of hemagglutination-inhibition (HI) titer by 2-mercaptoethanol treatment of serum. Reports have been given on the detection of IgM activity by ELISA also in other arboviral infections such as Japanese and LaCrosse encephalitis. The demonstration of an intrathecal production of virus-specific immunoglobulins may reveal the type of virus causing the infection in the central nervous system.