Mycoplasma pneumoniae: manifestaciones neurológicas y controversias diagnósticas. A propósito de un caso / Mycoplasma pneumoniae: neurologic manifestations and diagnostic controversies. A case report

Mycoplasma pneumoniae (Mp) es el agente causal de un 30% de las manifestaciones respiratorias de la población general. La neumonía ocupa el primer lugar dentro de este grupo. Las manifestaciones neurológicas representan las formas más frecuentes de presentación clínica extrapulmonar (40%). Las encefalitis y meningoencefalitis son las formas más habituales de sintomatología neurológica asociada a infección por Mp. La presentación de más de una variante clínica en un mismo paciente asociada a primoinfección por Mp es posible. El diagnóstico serológico plantea, habitualmente, controversias en su interpretación. A partir del caso de una niña de 7 años con inyección conjuntival, adenopatía cervical, rash descamativo y fotofobia con "pseudoedema de papila bilateral", que desarrolla durante su evolución parálisis facial periférica y meningitis aséptica, se analizarán las controversias que se plantean en relación con la interpretación diagnóstica asociada al compromiso neurológico por Mp.

Mycoplasma pneumoniae (Mp) is responsible for 30% of the respiratory manifestations of the general population. Pneumonia occupies the first place within this group. Among the extra-respiratory forms (40%), the neurological ones are the most frequent. Meningoencephalitis and aseptic meningitis are the most common. The presentation of more than one clinical variant in the same patient associated with primoinfection by Mp is possible. In relation to the serological diagnosis, controversies in interpretation sometimes occur. This is a 7-year-old girl with conjunctival injection, cervical adenopathy, photophobia with bilateral papilla pseudoedema, and scaly rash that develops peripheral facial paralysis and aseptic meningitis. We will discuss diagnostic controversies.

[Mycoplasma pneumoniae: neurologic manifestations and diagnostic controversies. A case report]. / Mycoplasma pneumoniae: manifestaciones neurológicas y controversias diagnósticas. A propósito de un caso.

Mycoplasma pneumoniae (Mp) is responsible for 30% of the respiratory manifestations of the general population. Pneumonia occupies the first place within this group. Among the extra-respiratory forms (40%), the neurological ones are the most frequent. Meningoencephalitis and aseptic meningitis are the most common. The presentation of more than one clinical variant in the same patient associated with primoinfection by Mp is possible. In relation to the serological diagnosis, controversies in interpretation sometimes occur. This is a 7-year-old girl with conjunctival injection, cervical adenopathy, photophobia with bilateral papilla pseudoedema, and scaly rash that develops peripheral facial paralysis and aseptic meningitis. We will discuss diagnostic controversies.

Mycoplasma pneumoniae (Mp) es el agente causal de un 30% de las manifestaciones respiratorias de la población general. La neumonía ocupa el primer lugar dentro de este grupo. Las manifestaciones neurológicas representan las formas más frecuentes de presentación clínica extrapulmonar (40%). Las encefalitis y meningoencefalitis son las formas más habituales de sintomatología neurológica asociada a infección por Mp. La presentación de más de una variante clínica en un mismo paciente asociada a primoinfección por Mp es posible. El diagnóstico serológico plantea, habitualmente, controversias en su interpretación. A partir del caso de una niña de 7 años con inyección conjuntival, adenopatía cervical, rash descamativo y fotofobia con "pseudoedema de papila bilateral", que desarrolla durante su evolución parálisis facial periférica y meningitis aséptica, se analizarán las controversias que se plantean en relación con la interpretación diagnóstica asociada al compromiso neurológico por Mp.

Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention.

The etiologies of meningitis range in severity from benign and self-limited to life-threatening with potentially severe morbidity. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Most cases of aseptic meningitis are viral and require supportive care. Viral meningitis is generally self-limited with a good prognosis. Examination maneuvers such as Kernig sign or Brudzinski sign may not be useful to differentiate bacterial from aseptic meningitis because of variable sensitivity and specificity. Because clinical findings are also unreliable, the diagnosis relies on the examination of cerebrospinal fluid obtained from lumbar puncture. Delayed initiation of antibiotics can worsen mortality. Treatment should be started promptly in cases where transfer, imaging, or lumbar puncture may slow a definitive diagnosis. Empiric antibiotics should be directed toward the most likely pathogens and should be adjusted by patient age and risk factors. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Vaccination against the most common pathogens that cause bacterial meningitis is recommended. Chemoprophylaxis of close contacts is helpful in preventing additional infections.

Central nervous system manifestations of Mycoplasma pneumoniae infections.

Mycoplasma pneumoniae infection is associated with several manifestations from the central nervous system (CNS) such as encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy. In the current paper epidemiologic, clinical, laboratory and treatment data on these manifestations are reviewed. The M. pneumoniae induced immune dysregulation and its contributing role in the pathogenesis of neurological insult is discussed. The recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between M. pneumoniae infection and CNS disease especially encephalitis. Clinicians should be aware of the potential association between M. pneumoniae infection and several CNS manifestations. The role of various anti-microbial or immunomodulating therapies in treating such manifestations should be further explored.

Cytokines involved in CNS manifestations caused by Mycoplasma pneumoniae.

Mycoplasma pneumoniae sometimes causes central nervous system manifestations, which may involve the host immune response, as the organism does not directly damage neural cells, or release toxins. Therefore we measured the levels of interleukin-6, interleukin-8, interleukin-18, interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta1 in serum and cerebrospinal fluid samples from patients who manifested central nervous system manifestations during acute M. pneumoniae infection. The subjects were nine patients with early-onset encephalitis (central nervous system disease onset within 7 days from the onset of fever), four with late-onset encephalitis (onset at 8 days or later), three with encephalitis but without fever, and three with aseptic meningitis. Intrathecal elevations of interleukin-6 and interleukin-8 in all four types of central nervous system manifestations, and of interleukin-18 in late-onset encephalitis were observed. None of the cerebrospinal fluid samples contained detectable levels of interferon-gamma, tumor necrosis factor-alpha, or transforming growth factor-beta1. In conclusion, interleukin-6, interleukin-8, and interleukin-18 might be involved in the inflammatory process leading to the central nervous system manifestations caused by M. pneumoniae.

Síndrome da meningite asséptica por enterovírus e Leptospira sp em crianças de Salvador, Bahia / Aseptic meningitis syndrome due to enterovirus and Leptospira sp in children of Salvador, Bahia

Objetivando verificar a freqüência de enterovírus (EV), leptospiras e arbovírus como agentes causais da síndrome da meningite asséptica (SMA), em períodos näo-epidêmicos, e comparar os pacientes com e sem diagnóstico etiológico determinado, foram selecionados 112 pacientes de idade entre 3 meses e 15 anos, com suspeita clínica de SMA, referenciados para Hospital Couto Maia, especializado em Doenças Infecciosas e Parasitárias (Salvador, Bahia), Em 44,6 por cento (n=50) a etiologia foi determinada: enterovírus em 37,7 por cento (n=42) dos casos, pelo teste de PCR Amplicor, por cultura do líquor e/ou de fezes; a Leptospira sp. em 7,1 por cento (n=8), pelo método da micro-aglutinaçäo, e nenhum caso de arbovírus foi detectado (inibiçäo da hemaglutinaçäo passiva). Entre os 14 enterovírus dos 22 isolados, foram identificados seis diferentes sorotipos, sendo o Echovirus-4 predominante (27,2 por cento; 6/22) entre outros (Coxsackie B2, B3, B6 e B9; EV 71). Conclui-se que, os enterovírus foram os agentes mais freqüentes, e que a leptospirose deve ser lembrada no diagnóstico diferencial da SMA. Uma vez que as características clínicas e liquóricas dos pacientes dos grupos com e sem determinaçäo do agente etiológico foram semelhantes, pode-se supor que o diagnóstico presuntivo de SMA é de provável etiologia viral ou pela leptospira

Mycobacterium tuberculosis meningitis and other etiologies of the aseptic meningitis syndrome.

Mycobacterium tuberculosis is one of the most common infectious agents in the world. It causes an insidious form of meningitis characterized by headache, low-grade fever, stiff neck and cranial nerve palsies, and an acute meningoencephalitis characterized by coma, raised intracranial pressure, seizures, and focal neurological deficits. This review focuses on the diagnosis and therapy of the insidious form of tuberculous meningitis and discusses the differential diagnosis of infectious and noninfectious etiologies of the aseptic meningitis syndrome.

Study of the aetiologic agents of meningitis in Kumasi, Ghana, with special reference to Cryptococcal neoformans.

OBJECTIVE: To evaluate the importance of Cryptococcus neoformans, an opportunistic in meningitis, in healthy and HIV infected patients in Kumasi, Ghana. DESIGN: A prospective study; isolating the aetiologic agents of meningitis from cerebrospinal fluid (CSF) using standard methods. SETTING: Kumasi city, Ashanti region of central Ghana. SUBJECTS: One thousand five hundred and seventy patients suspected of meningitis, including 28 HIV infected and AIDS patients. MAIN OUTCOME MEASURE: The pattern and distribution of the main etiologic agents of meningitis in Kumasi, Ghana shown. RESULTS: Of the 1570 CSF samples examined, 1256 (80%) showed no abnormality. Of the 314 (20%) with abnormalities, 147 were bacterial, and 167 diagnosed aseptic. No cryptococcal cells were found. CONCLUSION: There is a paucity of cryptococcal meningitis in Kumasi, Ghana, and it is not recommended to screen routinely for the fungus in meningitis investigations.

Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella (Rochalimaea) henselae infection in immunocompetent patients and patients infected with human immunodeficiency virus type 1.

Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.

Nested PCR for specific detection and rapid identification of human picornaviruses.

A nested PCR for the detection and rapid identification of human picornaviruses is described. Enteroviruses and rhinoviruses were amplified with the same set of four primers from the 5'-noncoding region. The nested primers allowed the detection of far less than 1 PFU in diluted virus stocks without Southern blot hybridization. In patients with neurological disorders (mainly aseptic meningitis), 43% of 37 specimens (11 of 21 cerebrospinal fluid specimens, 2 of 10 serum specimens, and 3 of 6 stool specimens) were positive by PCR. A total of 21% (10 of 47 specimens) of heart biopsy specimens from patients with dilative cardiomyopathy were PCR positive, whereas 3% (2 of 70 specimens) of control biopsy specimens from patients with coronary artery disease were PCR positive. PCR-amplified fragments from 27 of 29 clinical isolates and 14 of 28 patient samples were successfully serotyped by restriction enzyme digestion. Two specimens were further investigated by direct sequencing of PCR products, leading to the identification of a poliovirus type 3 isolate with a sequence that was highly divergent from previously published sequences.

Brote epidémico de meningitis aséptica: experiencias en un hospital infantil privado / Epidemic of aseptic meningitis experience of private hospital

Se informa acerca de las experiencias obtenidas en 193 niños con meningitis aséptica, estudiados durante un brote epidémico registrado entre febrero y julio de 1992. Los cultivos de líquido cefalorraquídeo hechos en el Instituto de Referencia Epidemiológica permitieron identificar al virus Echo 30 como un agente a la meningitis en 48 niños

Estudios de líquido cefalorraquídeo en meningitis: evaluación d la confiabilidad / Tests of cerebrospinal fluid in meningitis

MARCO TEORICO: Las meningitis representan un problema grave y frecuente en nuestro medio particularmente edades pediátricas. En vista de que su etiología es diversa resulta indispensable contar con estudios confiables y oportunos del LCR para dar un tratamiento específico. OBJETIVO: Determinar la frecuencia con la que se establecen los diagnósticos de meningitis aséptica y purulenta en nuestro Hospital, conocer el tipo de paciente en el que se realiza este diagnóstico y finalmente cuantificar el valor predictivo positivo (VVP) de los diversos componentes del estudio del LCR incluyendo los estudios citoquímicos, inmunológicos y microbiológicos. TIPO DE ESTUDIO: Clínico, epidemiológico, retrospectivo, observacional, comparativo, corte transversal de un período comprendido entre 1991 y 1992. Laspruebas de coaglutinación incluidad fueron: E. coli, H influenzae, S. pneumoniae, S. agalactiae, N. meniningitidis A,B, y C. (Sanofi Diagnostics. Pasteur, France). RESULTADOS: Se estudiaron 247 LCR de los cuales 25 por ciento procedieronn a pediatría, 19 por ciento de Medicina Interna y 15 por ciento del Servicio de Urgencias. En base a los estudios citoquímicos se consideró que 13 por ciento de los casos tenían características compatibles con meningitis aséptica y 7 por ciento con aspecto piógeno. Hubo desarrollo en 17 cultivos (7 por ciento), hubo Gram negativos en el 51 por ciento, neumococo fue el microrganismo más frecuente (30 por ciento). Solo se aisló Cándida en dos casos (1 por ciento). En la predicción de desarrollo las tinciones de Gram mostraron un VPP del 99 por ciento mientras que en la identificación del microrganismo las aglutinaciones tuvieron un VPP de 97 por ciento. En conjunto ambas determinaciones alcanzaron un VPP acumulativo del 100 por ciento. Los estudios citoquímicos tuvieron VPP bajos: Glucosa 86 por ciento, Proteínas 65 por ciento, leucocitos 59 por ciento, Eritrocitos 56 por ciento. CONCLUSION: Consideramos que las coaglutinaciones representan un significativo avance en microbiología por su confiabilidad y rapidez diagnóstica. Representan el complemento ideal de la tinción de Gram del cultivo y del antibiograma.

Isolation of parainfluenza virus type 3 from cerebrospinal fluid associated with aseptic meningitis.

Parainfluenza virus type 3 has been isolated from the cerebral spinal fluid (CSF) from six individuals--four children and two adults--over a 10-year period. All had fever, and four had signs of meningitis. All recovered uneventfully, including one child undergoing chemotherapy for medulloblastoma. The clinical presentation of this child who developed parainfluenza virus type 3 meningitis is described, and the cases of five other individuals with parainfluenza virus type 3 isolated from the CSF are briefly reviewed. The paramyxovirus parainfluenza type 3, in addition to mumps virus, may be considered capable of infecting the central nervous system.

Neuropathology of human immunodeficiency virus infection.

Neuropathology has defined novel HIV-specific diseases at tissue level: HIV encephalitis and HIV leukoencephalopathy. Both occur usually in the later stages of the AIDS infection and consistently demonstrate large amounts of HIV products. In contrast to this HIV-specific neuropathology, HIV-associated neuropathology features unspecific syndromes with disputed relation to HIV infection: myelin pallor, vacuolar myelopathy, vacuolar leukoencephalopathy, lymphocytic meningitis, and diffuse poliodystrophy. All types of neuropathology may contribute to clinical manifestation according to severity, extent, and distribution of lesions, but clinico-pathologic correlation may be poor in the individual case. Neuropathologic and other data suggest two major pathogenetic pathways of HIV-associated CNS damage: First, systemic and local increase of the virus load leads to HIV encephalitis or HIV leukoencephalopathy; this is corroborated by prominent HIV production within such lesions. Second, neuronotoxicity by HIV proteins or factors secreted from infected cells is supported by histological changes of diffuse poliodystrophy and by morphometric loss of frontocortical neurons.

Immunopathogenesis of HIV encephalitis.

HIV infection leads to severe immunosuppression and in a sub-population of patients, encephalitis. Whether systemic immunosuppression is required for CNS infection is still unclear. However, latent infection of monocytes/macrophages is an important mechanism by which HIV escapes immune surveillance and enters the CNS. Unlike other viral encephalitides, HIV predominantly infects macrophages/microglia and not neurons and glia. These cells produce retroviral proteins and cytokines which may be neurotoxic. Despite significant MHC expression within the CNS, there is a limited infiltration of immune cells, possibly due to a defect in systemic immunity. Anti-retroviral therapy by decreasing viral replication and reversing immunosuppression, may arrest nervous system damage.

Clinical observations and virological study of aseptic meningitis in the Kaohsiung area.

During 1988, an endemic outbreak of aseptic meningitis was noted in the Kaohsiung area. Throughout the year, a total of 89 cases were identified by cerebrospinal fluid (CSF) examination at the Pediatric Department of Kaohsiung Medical College. The peak incidence was from June to October. Scattered cases still occurred during November and December. The male to female ratio was 1.7:1 and the age distribution ranged from 1 month to 15 years old. Two peaks of age distribution were observed; one in infancy and the other in the 4-7 year old age group. Most of them exhibited fever (94.4%), headache (68.9%), and vomiting (68.5%). Other associated symptoms and signs included neck stiffness, sore throat, cough, Brudzinski's sign, abdominal pain, seizure, dizziness, rhinorrhea, diarrhea, Kernig's sign, skin rash, hyperemic conjunctiva, apnea, and oral ulcers. Most of them had CSF white blood cell (WBC) counts less than 1000/mm3, normal or mild elevated protein, and normal CSF/plasma sugar ratio. Three patients were found to have a virus in their CSF without pleocytosis. Virus isolations from CSF throat swabs and/or rectal swabs were performed in 65 patients, half of them (35/65, 53.8%) had positive results including echovirus type 9 (sixteen), echovirus type 30 (eighteen), and adenovirus type 3 (one). Echovirus type 9 was predominant during July and August whereas echovirus type 30 became predominant after September. All patients recovered spontaneously without any sequelae.

Preliminar characterization of a new virus isolated from the spinal fluid of patients with meningitis in Säo Paulo, Brazil

De dezembro de 1982 a março de 1983 um total de 138 pacientes com idade de 4 meses a 57 anos foram atendidos em diferentes hosptais de Säo Paulo com sintomas de meningite asséptica. Um agente transmissível foi isolado de 35 das 53 amostras de líquor. A replicaçäo desse novo vírus ou de um grupo de vírus relacioandos antigenicamente com características semelhantes foi detectada através do efeito citopático produzido em cultura de células de MDCK. O agente isolado demonstrou ter um diâmtro em torno de 40 nm quando examinado ao microscópio eletrônico através da coloraçäo negativa. Nenhuma atividade hemaglutinante foi detectada em pH 7,2 com hemácias humanas de cobaias ou de galinha e em pH 6,0 - 7,2 com hemácias de ganso. Esse agente näo se mostrou patogênico ao camundongo recém-nascido e adulto, era sensível ao clorofórmio e näo foi inibido pelo BuDR, o que indica conter o genoma RNA

Increased reactivity to HTLV-I in inflammatory nervous system diseases.

The presence of IgG antibodies reacting with purified and disrupted human T-lymphotropic virus type I (HTLV-I) was examined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain-Barré syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV-I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV-I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV-I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti-HTLV-I-IgG antibodies by the 24-hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV-I antigen-coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV-I-related human retrovirus in the etiology of MS.

Echovirus type 7 meningitis in young children.

Clinical and virological features are presented of an epidemic of aseptic meningitis in children caused by echovirus type 7. The majority of patients were younger than 1 year of age. Symptoms varied according to age. The degree of CSF pleocytosis was inversely related to age and was significantly greater in infants 7 months of age and younger than in those older than 7 months. A CSF polymorphonuclear pleocytosis was documented in 66% of the cases. Human placental fibroblast provided a more rapid detection of cytopathic effect and improved final recovery rates when compared with rhesus monkey kidney cells, Vero cells, and human epidermoid (Hep-2) cells. Several possible explanations for the sudden appearance of echovirus type 7 activity are discussed.