Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.

Acompanhamento do comportamento do HIV através de exames laboratoriais em portadora do vírus: relato de caso / Monitoring of HIV behavior through laboratory tests in a virus carrier: case report

O vírus da imunodeficiência humana é o agente etiológico da AIDS, doença crônica que destrói o sistema imunológico e é caracterizada pela baixa contagem de células TCD4, alta contagem de partículas virais no sangue e manifestações clínicas da doença. O diagnóstico se dá com o aparecimento de infecções oportunistas, que levam a contagem de TCD4 a níveis menores que 200 céls/mm³. Os exames laboratoriais para o diagnóstico do HIV foram os principais avanços para o início do tratamento, reduzindo a transmissão. Detecção de anticorpos, detecção de antígenos e amplificação do genoma do vírus são alguns dos exames laboratoriais utilizados para diagnóstico. Os dois principais biomarcadores são os exames de contagem de células TCD4, que verifica o sistema imune, e a quantificação de carga viral, que informa a quantidade de partículas virais, mostrando a progressão da infecção. Quanto maior a carga viral, maior o dano ao sistema imune. Uma carga viral indetectável é inferior a 50 cópias/mL, mas valores menores ou iguais a 200 cópias/mL também impedem a transmissão. Uma declaração de consenso afirma que Indetectável é igual a Intransmissível. Portanto, quando indetectável, a transmissão inexiste. O presente estudo relata e discute o caso clínico de uma paciente diagnosticada com HIV/AIDS aos 28 anos, que sobreviveu, apesar do diagnóstico tardio, e sob presença de doença oportunista com um grave grau de diminuição de células TCD4 (22 cél/mm³). Por meio do diagnóstico, introdução e adesão correta da terapia antirretroviral e monitorização de exames laboratoriais, conseguiu evitar a morte e ter uma vida semelhante à de um HIV negativo. Ultrapassou a expectativa de vida que na descoberta era de 10 anos, com uma qualidade de vida considerável, não sendo transmissora do vírus, diminuindo assim o estigma e preconceito. O biomédico é peça fundamental nesse contexto, considerando que deve fornecer informações precisas e fidedignas, tão necessárias ao acompanhamento de pessoas vivendo com HIV, para que autoridades e profissionais de saúde adotem medidas adequadas, tanto na prevenção, quanto no diagnóstico e monitoramento da doença.

The human immunodeficiency virus is the etiological agent of AIDS, a chronic disease that destroys the immune system and is characterized by low TCD4 cell count, high viral particle count in blood and clinical manifestations of the disease. The diagnosis is due to the appearance of opportunistic infections, which lead to TCD4 counts below 200 cells / mm³. Laboratory tests for the diagnosis of HIV were the main advances in starting treatment, reducing transmission. Antibody detection, antigen detection and virus genome amplification are some of the laboratory tests used for diagnosis. The two main biomarkers are the TCD4 cell count tests, which checks the immune system, and viral load quantification, which reports the number of viral particles, showing the progression of infection. The higher the viral load, the greater the damage to the immune system. An undetectable viral load is less than 50 copies / mL, but values less than or equal to 200 copies / mL also prevent transmission. A consensus statement states that Undetectable equals Non-Transmissible. Therefore, when undetectable, transmission does not exist. The present study reports and discusses the clinical case of a patient diagnosed with HIV / AIDS at age 28, who survived despite late diagnosis and under the presence of opportunistic disease with a severe degree of TCD4 cell reduction (22 cells / mm³). Through the diagnosis, introduction and correct adherence of antiretroviral therapy and monitoring of laboratory tests, she was able to avoid death and have a life similar to that of an HIV negative. Exceeded the life expectancy that in the discovery was 10 years, with a considerable quality of life, not transmitting the virus, thus reducing the stigma and prejudice. The biomedical is a key player in this context, considering that he must provide accurate and reliable information, which is so necessary for the monitoring of people living with HIV, so that authorities and health professionals adopt appropriate measures, both in prevention, diagnosis and monitoring of the disease.

Hypertrophic chronic pachymeningitis associated with Epstein-Barr virus reactivation: a case report.

Hypertrophic pachymeningitis is a rare inflammatory condition characterized by the thickening of the dura mater. We describe a patient who presented with intractable headache and complex cranial nerve palsy. Hypertrophy of the frontal dura was accompanied by pleocytosis and detection of Epstein-Barr virus (EBV) by PCR in cerebrospinal fluid. Clinical symptoms gradually improved after acyclovir and corticosteroid treatment, whereas dural pathology remained unchanged on neuroimaging. This case points at an expansion of the spectrum of neurological manifestations for EBV.

Transient and asymptomatic meningitis in human immunodeficiency virus-1 subtype C: a case study of genetic compartmentalization and biomarker dynamics.

Human immunodeficiency virus (HIV) genetic compartmentalization is defined as genetic differences in HIV in different tissue compartments or subcompartments that characterize viral quasispecies. This descriptive, longitudinal study assessed the dynamics of inflammation, humoral immune response, blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury biomarkers in serially obtained CSF and serum samples from an antiretroviral (ARV) therapy-naïve patient with HIV-1 subtype C with CSF HIV genetic compartmentalization that resolved spontaneously without ARV treatment. The first CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm3) and a marked increase in the levels of inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)α, interleukin (IL)-10, IP-10, and regulated on activation, normal T cell expressed and secreted (RANTES), which raise the suspicion of dual infection. Serum sample analysis showed all cytokine levels to be normal, with only IP-10 slightly increased. These results corroborate the hypothesis that the CNS immunologic response in a patient with HIV infection was independent of the systemic immunologic response. The patient also had persistently elevated levels of sCD14, neopterin, and ß2M, which were strongly suggestive of persistent CNS immunologic stimulation. This report describes a patient with HIV subtype C who developed a transient episode of asymptomatic HIV meningitis with compartmentalization of HIV in the CSF that resolved independently of ARV therapy. Extensive CSF studies were performed as part of an ongoing longitudinal study, which revealed CNS immune abnormalities. This case presents evidence of HIV-1 subtype C neurotropism and compartmentalization.

Crimean-Congo Hemorrhagic Fever in Humanized Mice Reveals Glial Cells as Primary Targets of Neurological Infection.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. In the current study, we inoculated NSG-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low-passage CCHF virus strains isolated from human patients. In humanized mice, lethal disease develops, characterized by histopathological change in the liver and brain. To date, targets of neurological infection and disease have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis, and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggest a role for astrocyte dysfunction in neurological disease and identify key regions of infection in the CNS for future investigations of CCHF.

The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.

A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx.

Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.

BACKGROUND: Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice. OBJECTIVE: Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis. DESIGN AND METHODS: A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture (n = 26); (b) bacterial meningitis with negative culture or not performed (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed (n = 42); and (e) controls (n = 44). RESULTS: Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group (P < 0.001). As a diagnostic tool for bacterial meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis. CONCLUSION: Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory.

Epidemiology of meningitis in an HIV-infected Ugandan cohort.

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains needed, and implementation of cryptococcal diagnostics is critical.

Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica na região metropolitana de Salvador, Bahia / Impact of pneumococcal conjugate vaccine 10-valent pneumococcal meningitis in the metropolitan region of Salvador, Bahia

INTRODUÇÃO: Em 2010, a vacina conjugada 10-valente (PCV10) foi incorporada ao programa nacional de imunizações (PNI) brasileiro. Este imunobiológico confere imunização contra os dez principais tipos capsulares de Streptococcus pneumoniae, patógeno responsável por diversas manifestações clínicas e com elevada contribuição nas taxas de incidência e mortalidade por meningite, que é a condição clínica mais grave. OBJETIVO: O presente estudo teve como objetivo avaliar o impacto da PCV10 na epidemiologia da meningite pneumocócica na região metropolitana de Salvador (RMS) Bahia, comparando o período anterior (2008-2010) e posterior (2011-2013) a sua utilização, bem como realizar uma caracterização molecular minuciosa a partir de uma série histórica (1996-2012) entre os isolados resistentes a enicilina (PNSSP com CIM≥ 0,125 μg/mL) e para os sorotipos não-vacinais (2008-2012). MATERIAL E MÉTODOS: Foram incluídos todos casos de meningite pneumocócica confirmados laboratorialmente no período entre 1996 a 2013. Taxas de incidência para a Salvador e RMS foram calculadas com base nos dados populacionais do IBGE/2010. A determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a nove antimicrobianos foi testada através das técnicas disco-difusão,microdiluição e E-test. Para caracterizar o perfil molecular foram aplicadas as técnicas de genotipagem de PFGE e MLST. RESULTADOS: Um total de 939 casos de meningite pneumocócica foram identificados no período de 1996-2013, sendo que 70 casos ocorrem entre 2011 a 2013 (período pós-vacinal). A incidência de meningite pneumocócica em todas as faixas etárias na RMS reduziu de 0,70 casos/100.000 habitantes para 0,59 casos/100.000 habitantes considerando o período de três anos antes e após a vacinação com PCV10 [p<0,05; RR IC 95%: 1,46 (1,03-2,05)]. Esta redução foi significativa na faixa etária de 0-2 anos e nos casos por sorotipos relacionados à PCV10. Não houve aumento significativo de casos por sorotipos não vacinais nesta casuística,apesar do surgimento de casos por sorotipos não-vacinais não detectados anteriormente na série histórica de MP (10F, 21, 22F, 15A e 24F). Os isolados resistentes à penicilina analisados na série histórica se restringiram a 13 sorotipos, entre os quais: 14 (45,1 %; 78/173), 23F (19,1%; 33/173), 6B (14,4 %; 25/173), 19F (9,2 %; 16/173) e 19A (5,2 %; 9/173). 94% dos casos nãosusceptíveis à penicilina (PNSSP) foram de sorotipos vacinais. Os grupos clonais caracterizados pelo PFGE/MLST predominantes ao longo dos anos foram representados pelo sorotipo 14, denominado grupo A/ST 66 [35,3 %(61/173)] e grupo GK/ST 156 [4.6 % (8/173)], este último associado com níveis elevados de resistência a penicilina e ceftriaxona. Não foram detectados grupos clonais emergentes associados a tipos capsulares não-vacinais.CONCLUSÕES: Estes achados sugerem que a introdução da PCV10 modificou a epidemiologia da meningite pneumocócica na população estudada.

INTRODUCTION: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Brazilian national immunization program (NIP). This immunobiological provides immunization against the main ten capsular types of Streptococcus pneumoniae, the pathogen responsible for different clinical manifestations and high contribution in the incidence and mortality from meningitis, which is the most severe clinical condition. OBJECTIVE: This study aimed to evaluate the impact of PCV10 in the epidemiology of pneumococcal meningitis in the metropolitan area of Salvador (RMS) Bahia, comparing the previous (2008-2010) and after (2011-2013) periods its use, as well as conduct a thorough molecular characterization from a historical series (1996-2012) among isolates resistant to penicillin (PNSSP with CIM≥ 0.125 g / ml) and nonvaccine serotypes (2008-2012). MATERIAL AND METHODS: We included all cases of pneumococcal meningitis laboratory confirmed for the period 1996 to 2013. Incidence rates for Salvador and RMS were calculated based on population data from IBGE/2010. The capsular type determination was performed by multiplex PCR and/or Quellung reaction. Isolates Nine antibiotics were tested by disk-diffusion test, broth micro-dilution and E-test. To characterize the molecular profiling techniques were applied genotyping PFGE and MLST...

Molecular detection and identification of enteroviruses in children admitted to a university hospital in Greece.

Although enteroviral infections occur frequently during childhood, the circulation of particular serotypes has never been studied in Greece. The objectives of the present report were molecular detection and identification of human enteroviruses in children admitted with nonspecific febrile illness or meningitis to a university hospital during a 22-month period. A one-step Real-Time RT-PCR protocol was used for rapid enterovirus detection in genetic material extracted directly from clinical samples, and a sensitive reverse transcription-semi-nested PCR targeting part of the VP1-coding region was used for genotypic identification of the different serotypes. Twenty-one enterovirus strains were detected and identified in 20 stool samples, one cerebrospinal fluid (CSF) sample, one whole blood sample and one throat swab from 21 out of 134 febrile patients (15.7%). Ten strains belonged to Human Enterovirus Species B (HEV-B) (six serotypes) and eleven to HEV-A (four serotypes). Most of the strains were closely associated with virulent strains circulating in Europe and elsewhere. Detection of the emerging pathogen enterovirus 71 for a first time in Greece was particularly important.

Incidencia del virus herpes simplex en pacientes con infecciones agudas del sistema nervioso central / Incidence of herpes simplex virus infection in patients with acute central nervous system infections

Los Virus Herpes Simple son responsables de una variedad de infecciones a nivel de mucosas bucal y genital, son neurotrópicos, capaces de alojarse en células nerviosas y permanecer latentes con subsecuentes reactivaciones, en algunos casos pueden provocar meningitis y encefalitis. tienen una morbilidad significativa y una mortalidad elevada. El presente estudio tiene como objetivo determinar la incidencia de VHS en la etiología de los síndromes agudos del SNC mediante la detección en suero y LCR de anticuerpos específicos. Se estudiaron 93 muestras pareadas de pacientes con afecciones neurológicas que mostraron resultados negativos en el estudio bacteriológico de LCR y cuya relación Alb-LCR/Alb-suero fue <0,0075. Los anticuerpos fueron detectados por el método de inmunoensayo enzimático Elisa: Enzygnost® anti virus VHS/IgM-IgG (Behring, 1994), donde 1,2% (1/93) de las muestras de suero resultaron positivas para IgM; 89,24% (83/93)de los sueros resultaron positivos para IgG; y 27,39% (20/93) de las muestras de LCR presentaron anti-IgG positivo. La presencia de IgG en LCR sugiere la producción intratecal de estos anticuerpos en el SNC, lo que muestra una participación importante de este agente viral en las infecciones y enfermedades asociadas al SNC

Herpes simplex viruses are agents responsible for a variety of infections on buccal and genital mucosa; they are neurotropic, capable of lodging in the nerve cells and remaining latent with subsequent reactivations; in some cases, they can provoke meningitis and encephalitis; and they have a significant morbidity and are associated with a high mortality. The present project aims to determine HSV’s effect on the etiology of acute central nervous system (CNS) syndromes using the detection of specific antibodies in serum and cerebrospinal fluid. The 93 paired samples from patients with neurological affectations studied demonstrated negative results in the LCR bacteriological study and their Alb-LCR/Alb-serum relation was < 0.0075. Antibodies were detected by the enzymatic immunoassay ELISA method, where 1.2% (1/93) of the serum samples turned out positive for IgM; 89.24% (83/93) of the serum samples resulted positive for IgG; and 27.39% (20/93) of LCR samples were positive for anti-IgG. IgG presence in LCR suggested the intrathecal production of these antibodies inside the CNS, which demonstrates a significant participation by this viral agent in infections and diseases associated with the CNS

Dengue infection in patients presenting with neurological manifestations in a dengue endemic population / Infección de dengue en pacientes que se presentan con manifestaciones neurológicas en una población con dengue endémico

The evaluation of the contribution of neurological dengue in suspected central nervous system (CNS) viral infections is essential to better understand the impact of neurological dengue on morbidity and mortality in dengue endemic regions such as Jamaica. For this study, 401 cases of suspected viral CNS infections were investigated for evidence of dengue infection. The frequency of neurological dengue among these CNS cases was found to be 13.5% (54/401). Fifty-three cases were confirmed serologically by haemagglutination inhibition assay (HI) and IgM antibody (ELISA) and the virus was isolated in one case only. Clinical manifestations among dengue positive CNS cases included encephalitis in 51.8% (28/54), meningitis in 33.3% (18/54), seizures in 11.1% (6/54) and acute flaccid paralysis/Guillain-Barré syndrome in 3.7% (2/54). The clinical diagnosis of dengue neurological infection corresponded with laboratory confirmation in 22.2% (12/54) of cases only. Deaths occurred in 3.7% (2/54) of cases and were associated with patients with dengue neurological infection. The high risk of dengue among patients with suspected viral CNS infections in this study supports the need for an increased index of suspicion of dengue in patients presenting with neurological manifestations in dengue endemic countries.

La evaluación de la contribución del dengue neurológico en las infecciones virales sospechadas del sistema nervioso central (SNC) resulta esencial para un mejor entendimiento del impacto del dengue neurológico en la morbilidad y mortalidad en regiones donde el dengue es endémico tales como Jamaica. Para este estudio 401 casos de infecciones virales sospechadas del SNC fueron investigados en busca de evidencia de infección por dengue. Se haló entonces que la frecuencia del dengue neurológico entre estos casos de SNC, fue de 13.5% (54/401). Cincuenta y tres casos fueron confirmados por serología mediante ensayos de inhibición de hemaglutinación (IH) y ELISA para la detección de anticuerpos IgM, siendo el virus aislado sólo en un caso. Las manifestaciones clínicas entre los casos que resultaron positivos al dengue, incluyeron encefalitis en 51.8 % (28/54), meningitis en 33.3% (18/54), convulsiones en 11.1% (6/54) y parálisis facial aguda/síndrome Barré Guillain en 3.7% (2/54). El diagnóstico clínico de infección neurológica por dengue estuvo en correspondencia con la confirmación del laboratorio sólo en el 22.2% (12/ 54) de los casos. Se produjeron muertes en el 3.7% (2/54) de los casos, las cuales estuvieron asociadas con pacientes con infección neurológica por dengue. El alto riesgo de dengue entre los pacientes con sospecha de infecciones virales de SNC en este estudio, apunta a la necesidad de aumentar el índice de sospecha de dengue en pacientes que se presentan con manifestaciones neurológicas en países donde el dengue es endémico.

[Case of recurrent transverse myelitis and diplopia after meningomyeloradiculitis caused by Epstein-Barr virus].

A 60-year-old woman was admitted to our hospital because of pyrexia, headache, gait disturbance, and sensory disturbance in the lower part of the body four days after she received an epidural block for postherpetic neuralgia. Neurological tests revealed neck stiffness, flaccid paraparesis in the legs with absent deep tendon reflexes, and hyperesthesia below Th7. According to a cerebrospinal fluid examination, the protein concentration was 245 mg/dl and the cell count was 176/mm3. PCR analysis of the cerebrospinal fluid was positive for Epstein-Barr virus (EBV). Serological tests for EBV yielded mild increases of serum IgG antibodies against EBV nuclear antigen (EBNA) and IgG antibodies against EBV viral capsid antigen (VCA). In a spinal MRI, the inferior lumbar meninges showed gadolinium enhancement. Nerve conduction studies revealed a decreased F wave ratio in the bilateral tibial nerves. The patient was diagnosed with meningomyeloradiculitis caused by EBV. The symptoms improved after steroid pulse therapy, but relapses of transverse myelitis and diplopia due to disturbance of the bilateral abducent nerves and left trochlear nerve occurred 7, 12, 16, and 26 months after treatment. The relapses were sometimes accompanied by small fluctuations in cerebrospinal fluid protein concentration, cell count, or serum anti-EBV antibody titer. These findings suggest that the myelopathy and diplopia were induced by a secondary immune reaction after inflammation caused by EBV infection.

A case of hypertrophic pachymeningitis with prolonged headache, attributable to Epstein-Barr virus.

Hypertrophic pachymeningitis is a condition characterized by significant chronic inflammatory thickening of the cranial dura mater, frequently presenting with symptoms such as headache and cranial neuropathy. In this report, we describe a very rare case of hypertrophic pachymeningitis, considered to be attributable to Epstein-Barr virus (EBV), which was diagnosed in a patient who visited our hospital with a complaint of ongoing severe headaches. The diagnosis was based on positive specific serum EBV antibody titers, with VCA-IgM levels of less than 1:10, VCA-IgG levels of 1:160, and EBNA levels of 1:40, as well as on the results of magnetic resonance imaging of the head with contrast media.

Primary and opportunistic pathogens associated with meningitis in adults in Bangui, Central African Republic, in relation to human immunodeficiency virus serostatus.

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with meningitis in Bangui in order to provide guidance to physicians for case management. METHODS: Adults with proven or suspected meningitis were enrolled in this prospective study. LABORATORY TESTS: Full blood count, blood chemistry, and HIV tests were performed. Cerebrospinal fluid (CSF) was submitted for routine microbiology, chemistry (glucose, protein), and hematology testing. When classical microbiology analyses were negative, a broad-range bacterial polymerase chain reaction (BRBPCR) was used. RESULTS AND CONCLUSIONS: Of the 276 patients enrolled, 215 (77.9%) were HIV positive. In HIV-positive patients cryptococcal meningitis (CM) was the most common cause of meningitis (39.1%) followed by pyogenic meningitis (PM) (30.7%), mononuclear meningitis (MM) (28.8%), and tuberculous meningitis (TM) (1.4%). In HIV-negative patients, PM was the most common cause (60.7%) followed by MM (37.7%) and CM (1.6%, one case). In-hospital mortality was higher in HIV-positive patients (73/128 = 57%) compared to those HIV negative (3/18 = 16.7%) (p = 0.001). Streptococcus pneumoniae (n = 26) was the most common bacterial diagnosis, mainly in HIV-positive patients (n = 22, 10.2%). Meningococcal meningitis (14 Neisseria meningitidis of group A and one W135) was diagnosed in nine (4.2%) HIV-positive and six (9.8%) HIV-negative patients. Gram-negative rods were isolated from five HIV-positive and two HIV-negative patients, respectively. The bacteria and fungi involved in meningitis did not display high levels of in vitro resistance. Conventional microbiology techniques failed to detect the causative agent in 55 (53.4%) PM cases. Broad-range bacterial PCR detected DNA from S. pneumoniae in three samples, N. meningitidis in two, Escherichia coli in one, Listeria monocytogenes in two and Staphylococcus aureus in one sample. In the CSF of five (three HIV negative and two HIV positive), PCR products were not identified with the oligonucleotide probes specific for the usual species of bacteria found in CSF, or genera commonly considered potential contaminants of clinical samples. Among the MM cases, 77 (90.5%) probable viral meningitis (54 HIV positive and 23 HIV negative) and eight TM (HIV positive) were suspected.

Mollaret's meningitis: cytopathologic analysis of fourteen cases.

Mollaret's meningitis (MM) is a rare disease of benign nature characterized by recurrent episodes of aseptic meningitis. Cerebrospinal fluid (CSF) examination remains the sole diagnostic modality. Eighteen CSF samples from 14 patients were studied along with the clinical data. Specimens were prepared by cytocentrifugation and Millipore filtration and were stained with Diff-Quik and Papanicolaou stains. Eight patients were men and six were women, with an age range of 17-74 yr (mean age 37 yr). Most common clinical presentation was recurrent episodes of headaches and photophobia followed by a sustained mild fever lasting 5-7 days. The CSF showed markedly increased cellularity with pleocytosis. The differential count showed predominant monocytosis ranging from 84% to 100% (mean 96). In our series, two patients had herpes simplex virus type 2 (HSV-2) DNA detected by polymerase chain reaction (PCR) in the CSF. The monocytes were seen predominantly singly, but three cases showed a strong tendency to aggregate in small groups. Phenotypically, these cells had bean-shaped bilobed nuclei as well as multiple deep nuclear clefts depicting the so-called "footprint" appearance. In four cases, multiple blunt-tipped cytoplasmic pseudopods were noted. Degenerated monocytes with the appearance of the so-called "ghost cells" were noted in one-half of the cases. Background cells were mostly small mature lymphocytes; however, one-half of cases showed a significant amount of plasma cells and/or polymorphonuclear leukocytes (PMNs). Lysed blood with hemosiderin-laden macrophages and numerous leptomeningeal cells were seen in two cases. CSF examination of MM presents a spectrum of cytomorphologic features. When interpreted in light of the appropriate clinical setting. the latter, although nonspecific, provides an accurate diagnosis. The differential diagnosis includes various degenerative, inflammatory/infectious, and lymphoproliferative disorders of the central nervous system.

Infections of the central nervous system of suspected viral origin: a collaborative study from Finland.

We studied 3231 patients with acute central nervous system (CNS) symptoms of suspected viral origin to elucidate the current etiologic spectrum. In 46% of the cases, a viral finding was observed. Varicella-zoster virus (VZV) was the main agent associated with encephalitis, as well as meningitis and myelitis. VZV comprised 29% of all confirmed or probable etiologic agents. Herpes simplex virus (HSV) and enteroviruses accounted 11% each, and influenza A virus 7%. VZV seems to have achieved a major role in viral infections of CNS. In encephalitis in our population, VZV is clearly more commonly associated with these neurological diseases than HSV. The increase in VZV findings may in part be a pseudophenomenon due to improved diagnostic methods, however, a true increase may have occurred and the pathogenetic mechanisms behind this should be elucidated.