Bacterial Infections Of Central Nervous System Research Articles

Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

BackgroundMeningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D.MethodsIn vivo, we studied the effects of vitamin D3 on survival and the host’s immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured.ResultsMice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation.ConclusionOur observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions.

Incidence and mortality of bacterial meningitis are strongly increased in aged compared to younger adults demanding new strategies to improve prevention and therapy of bacterial central nervous system (CNS) infections the elderly. Here, we established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients: After intracerebral challenge with E. coli K1, aged mice showed a higher mortality, a faster development of clinical symptoms, and a more pronounced weight loss. Elimination of bacteria and systemic inflammatory response were impaired in aged mice, however, the number of infiltrating leukocytes and microglial cells in the CNS of aged and young mice did not differ substantially. In vitro, primary microglial cells and peritoneal macrophages from aged mice phagocytosed less E. coli and released less NO and cyto-/chemokines compared to cells from young mice both without activation and after stimulation by agonists of TLR 2, 4, and 9. Our results suggest that the age-related decline of microglia and macrophage functions plays an essential role for the higher susceptibility of aged mice to intracerebral infections. Strategies to improve the phagocytic potential of aged microglial cells and macrophages appear promising for prevention and treatment of CNS infections in elderly patients.

Improved Detection of Bacterial Central Nervous System Infections by Use of a Broad-Range PCR Assay

A universal PCR assay for bacteria and fungi detected meningitis pathogens in 65% of 20 cerebrospinal fluid (CSF) samples from patients with suspected central nervous system (CNS) infections compared to a 35% detection rate by culture and/or microscopy methods. Thus, the PCR assay can improve the diagnosis rate of infective meningitis when standard methods provide a negative result.

Pathophysiology of Bacterial Infection of the Central Nervous System and its Putative Role in the Pathogenesis of Behavioral Changes

Invasion of the central nervous system (CNS) by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

Although IL-17A (commonly referred to as IL-17) has been implicated in the pathogenesis of central nervous system (CNS) autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R) knockout (KO) mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25). In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT) cell and gamma-delta (γδ) T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT) animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

Safety of intraventricular hemorrhage (IVH) thrombolysis based on CT localization of external ventricular drain (EVD) fenestrations and analysis of EVD tract hemorrhage.

The purpose of the study is to review the CT findings associated with ventriculostomy placement in regards to the safety of an EVD plus recombinant tissue plasminogen activator (rt-PA) for IVH. A retrospective review was conducted for patients receiving intraventricular rt-PA for IVH from January 2004 to September 2009. Safety was assessed by the presence of EVD tract hemorrhage by CT at baseline after EVD placement, worsening hemorrhage after rt-PA, and CSF infection. IVH volumetrics were assessed by the Le Roux score and outcomes by Glasgow Outcome Scale and modified Rankin Scale. Twenty-seven patients received rt-PA for IVH. Median dose was 2 mg (range 0.3-8) and a median of two doses (range 1-17) were given. Worsening EVD catheter tract hemorrhage after rt-PA was 46.7 %, with a significantly higher incidence of worsening tract hemorrhage seen with incorrectly placed EVDs (p = 0.04). IVH hematoma burden decreased by a median Le Roux score of 10 (range 3-16) prior to rt-PA to 4 (range 0-16) after rt-PA. There were no central nervous system bacterial infections. Intraventricular rt-PA appears to be relatively safe especially when all EVD fenestrations are within the ventricle and reduces IVH burden similar to other studies. We describe a CT-based EVD tract hemorrhage grading scale to evaluate EVD tract hemorrhage before and after thrombolysis, and a bone-window technique to evaluate EVD fenestrations prior to IVH thrombolysis. Further research is needed evaluating these imaging techniques in regard to intraventricular thrombolytic safety and EVD tract hemorrhage.

Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review

IntroductionLyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV) -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth caseCase presentationsWe present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis.ConclusionGiven the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with oral doxycycline with a good outcome, further proving the efficacy of this regime.

16S rDNA-PCR and Sequencing Improves Diagnosis of Bacterial Infection of the Central Nervous System

Rapid initiation of antibiotic treatment and fast diagnosis are essential in bacterial infection of the central nervous system (CNS). Culture as common method for detecting bacteria is time consuming and unreliable once antibiotic treatment has been initiated. Eubacterial 16S rDNA-PCR with species differentiation by sequencing appears to be a promising tool. Our experiences with this method performed on specimens from patients with neurological disorders between 2004 and 2006 are presented. The follow-up of 26 patients revealed bacterial infection in 12 cases (ten on effective antibiotics). The pathogen was identified in seven cases (one by culture and PCR, six by PCR alone). Additionally, two positive PCR-results failed to be sequenced, yet suggest bacterial infection. Contamination was revealed in two cases without infection, one by PCR and one by PCR and culture. In conclusion, 16S rDNA-PCR may be useful for diagnosis bacterial infection of CNS, especially after onset of antibiotic therapy.

Fusobacterium Septicemia Complicated by Cerebral Subdural and Epidural Empyemas: A Rare Case of Lemierre Syndrome

BackgroundLemierre syndrome is characterized by postanginal septicemia and internal jugular vein thrombophlebitis with secondary septic emboli, typically to the lungs. The central nervous system (CNS) is rarely involved. ObjectiveTo present a case of Lemierre syndrome featuring cerebral subdural and epidural empyemas. Case ReportThis case report describes the case of a 17-year-old youth with cerebral subdural and epidural empyemas. The findings of chest computed tomography of the neck and the blood cultures were compatible with Lemierre syndrome. The patient recovered well after antibiotic treatment and surgical debridement. ConclusionLemierre syndrome can result in infection spreading to the CNS, including cerebral subdural and epidural empyemas. This disease entity should be included in the differential diagnoses of CNS bacterial infections.

Role of Glial Cells in the Functional Expression of LL-37/Rat Cathelin-Related Antimicrobial Peptide in Meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.

Minocycline Modulates Neuroinflammation Independently of Its Antimicrobial Activity in Staphylococcus aureus-Induced Brain Abscess

Minocycline exerts beneficial immune modulatory effects in several noninfectious neurodegenerative disease models; however, its potential to influence the host immune response during central nervous system bacterial infections, such as brain abscess, has not yet been investigated. Using a minocycline-resistant strain of Staphylococcus aureus to dissect the antibiotic's bacteriostatic versus immune modulatory effects in a mouse experimental brain abscess model, we found that minocycline significantly reduced mortality rates within the first 24 hours following bacterial exposure. This protection was associated with a transient decrease in the expression of several proinflammatory mediators, including interleukin-1beta and CCL2 (MCP-1). Minocycline was also capable of protecting the brain parenchyma from necrotic damage as evident by significantly smaller abscesses in minocycline-treated mice. In addition, minocycline exerted anti-inflammatory effects when administered as late as 3 days following S. aureus infection, which correlated with a significant decrease in brain abscess size. Finally, minocycline was capable of partially attenuating S. aureus-dependent microglial and astrocyte activation. Therefore, minocycline may afford additional therapeutic benefits extending beyond its antimicrobial activity for the treatment of central nervous system infectious diseases typified by a pathogenic inflammatory component through its ability to balance beneficial versus detrimental inflammation.

Clinical features, prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram's stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients.

Toxocara Infection is not Associated with Viral or Bacterial Central Nervous System Infection in Children

Helminth infections with larvae that migrate through the tissues have been considered risk factors for CNS infections. The present work was designed to investigate the prevalence of anti- TOXOCARA antibodies in the serum and/or in the cerebrospinal fluid (CSF) of children with infectious meningitis or meningoencephalitis and of a control group, without meningitis, admitted at the Children's Hospital NS Glória, Vitória, ES, Brazil. After adsorption with ASCARIS LUMBRICOIDES antigen, serum and/or cerebrospinal fluid of 381 inpatients (201 with meningitis and 180 without meningitis) were submitted to an ELISA IgG, for anti- TOXOCARA antibodies using secretion/excretion antigens of third stage larvae of T. CANIS. No significant differences between the meningitis and the control groups were observed in the frequencies of positive tests for anti- TOXOCARA antibodies in the serum or CSF (respectively for the meningitis and control group: 33/103 or 32 % and 52/152 or 34.2 % for the serum, p = 0.821; 48/184 or 26.1 % and 23/121 or 19.0 % for the CSF; p = 0.196. The results demonstrated that TOXOCARA infection, evaluated by detection of anti- TOXOCARA antibodies in serum or CSF, is not associated with viral or bacterial meningitis or meningoencephalitis in children in our country.

Defining bacterial meningitis and other infections of the central nervous system

To define central nervous system infections of infants and children that occur as co-morbid or predisposing conditions of sepsis. Standard pediatric infectious disease references and the pertinent literature in English were reviewed from 1960 to 2002 to ascertain the previous methods and definitions utilized in clinical studies of the epidemiology and treatment of bacterial infections of the central nervous system. An accepted definition of bacterial meningitis defined by the Infectious Disease Society of America was reviewed and adapted to the previous clinical definitions. The information was formulated into a proposed standard for definite, probable, and possible bacterial infections of the central nervous system. The diagnosis of definite bacterial infection of the central nervous system, including bacterial meningitis, requires the isolation of the pathogen from the cerebrospinal fluid or other significant clinical site such as surgical tissue, an implanted device, or blood. Probable bacterial infection is defined by the association of a compatible clinical syndrome or cerebrospinal fluid changes associated with bacterial meningitis or other central nervous system infection, and confirmed as an anatomically defined infection by imaging or surgery, in association with positive blood cultures or bacterial antigen from cerebrospinal fluid. Possible bacterial meningitis may be defined as a compatible clinical syndrome with predefined cerebrospinal fluid changes in the absence of a confirmatory culture or antigen test from any site. Bacterial meningitis and other central nervous system bacterial infections can be defined as definite, probable, and possible with a combination of a defining compatible clinical syndrome and an anatomic definition by surgery or imaging, coupled with isolation of the organism, bacterial antigen, or other defining molecular component of the organism.

Molecular genetic methods in diagnosis and direct characterization of acute bacterial central nervous system infections

Acute bacterial infection of the central nervous system requires rapid and adequate management. Etiological diagnosis is hence crucial. Moreover, the epidemic threat of certain bacteria necessitates a reliable characterization of the involved bacterial strains to follow the spread of epidemic strains. Conventional identification and characterization of etiological agents are basically based on culture and identification of bacterial markers most frequently by serological assays. Molecular identification and characterization of bacteria have been employed. They provide more reliable analysis of bacterial isolates. Molecular methods for non-culture diagnosis of bacterial infections have recently been developed. In many cases, the molecular assays have decreased the identification time of positive cultures and rescued detection of pathogens in culture-negative clinical samples.

Does Lumbar Cerebrospinal Fluid Reflect Ventricular Cerebrospinal Fluid? A Prospective Study in Patients with External Ventricular Drainage

Ventriculitis may sometimes occur after an external ventricular drain has been removed, and diagnosis has to be made by lumbar puncture. But are the lumbar findings comparable to previously obtained ventricular results? In a prospective study, sample pairs of ventricular and lumbar cerebrospinal fluid (CSF) were obtained at an interval of <30 min in 25 patients with increased intracranial pressure suffering from cerebral hemorrhage (n = 15), meningitis/encephalitis (n = 6), cerebral infarction (n = 3), and meningeosis carcinomatosa (n = 1). CSF was analyzed for protein, albumin, IgG, IgA, IgM, glucose, lactate, and leukocytes including cytological differentiation. A significant ventriculo-lumbar increase was observed for protein, albumin, and the immunoglobulins. Lactate was distributed equally in ventricular and lumbar CSF, as well as glucose in the cerebral hemorrhage subgroup (n = 15). Cell count failed to show a clear ventriculo-lumbar ratio. Cytological distribution was comparable in lumbar and ventricular CSF, except for macrophages showing a significant rostrocaudal decrease. In conclusion, in cases of clinically suspected bacterial central nervous system infection after removal of an external ventricular drain, lumbar CSF lactate, glucose, and cytology are comparable to previously determined ventricular values, and thus may help physicians to choose the best treatment.

Predictive value of serum and cerebrospinal fluid procalcitonin levels for the diagnosis of bacterial meningitis.

The value of serum and cerebrospinaL fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis was assessed and compared to other parameters which are usually used in clinical practice. 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study. The median serum procalcitonin Level in patients with bacterial meningitis was 6.45 ng/ml (range 0.25-43.76 ng/ml) and in the group with viral meningitis 0.27 ng/ml (range 0.05-0.44 ng/ml). 11 patients with bacterial meningitis had an elevated procalcitonin concentration not only in serum, but also in CSF. A serum procalcitonin Level > 0.5 ng/ml had a positive predictive value for bacterial meningitis of 100% and a negative predictive value of 93%, while corresponding values for CSF procalcitonin were 100% and 74%, respectively. Serum and CSF procalcitonin concentrations > 0.5 ng/ml appear to be a reliable indicator of bacterial central nervous system (CNS) infection, with maximal positive predictive values and high negative predictive values.

Neuropathology and general autopsy findings in AIDS during the last 15 years

A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53 females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999 compares the central nervous system (CNS) findings in three cohorts: 1984-1992 (190 cases), 1993-1995 (162 cases) and 1996-1999 (98 cases, after introduction of triple antiretroviral therapy) and the relationship of CNS findings to systemic AIDS pathology in the latter two cohorts. In these two groups, following involvement of the lung (85% and 75%, respectively), the brain continued to be the second most frequently involved organ (decrease from 80% to 60%, respectively). Extracerebral protozoal (Pneumocystis carinii, toxoplasmosis), Mycobacterium avium complex, viral [e.g., cytomegalovirus (CMV)], multiple opportunistic organ and CNS infections, and Kaposi sarcoma significantly decreased over time. There was less decrease in fungal infections, while bacterial organ and CNS infections (except for mycobacteriosis), lymphomas, HIV-associated CNS lesions (around 30%), non HIV-associated changes (vascular, metabolic, etc.) and negative CNS findings (10-11%) remained unchanged. Nonspecific CNS changes (e.g., meningeal fibrosis) increased. Extracerebral pathology in subjects with advanced HIV-related CNS lesions showed more frequent but decreasing systemic bacterial and CMV infections than those with negative or nonspecific neuropathology, while other opportunistic and multiple organ infections and lymphomas showed no differences between both groups. In a cohort of drug abusers, HIV encephalitis, progressive multifocal leukoencephalopathy, bacterial infections, hepatic encephalopathy, and negative CNS findings were more frequent than in non-users who showed increased incidence of CMV, toxoplasmosis, or other opportunistic CNS infections, and nonspecific CNS findings; the frequency of lymphomas was similar in both drug abusers and non-users. Similar to a recent autopsy study from San Diego, these data suggest that despite the beneficial effects of modern antiretroviral combination therapy, involvement of the brain in AIDS subjects continues to be a frequent autopsy finding, while the increased incidence of HIV encephalitis in our small cohort of drug users was less than observed in other recent autopsy studies.

Bacterial and fungal brain infections in AIDS.

Many bacterial and fungal pathogens can infect the central nervous system (CNS) in patients also infected with human immunodeficiency virus (HIV). Most of these organisms cause meningitis, and this is sometimes accompanied by focal parenchymal infection. More virulent pathogens, such as Mycobacterium tuberculosis hominis, can cause disease in individuals with mild degrees of HIV-associated immunosuppression. Less virulent pathogens, such as Cryptococcus neoformans, tend to affect individuals with more advanced immunosuppression. This review focuses on the clinical manifestations, diagnosis, and treatment of the more common bacterial and fungal CNS infections.

Association between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: a 28-year follow-up.

Maternal exposure to influenza epidemics during pregnancy may increase the risk of schizophrenia in the offspring. We investigated the association between central nervous system (CNS) infections defined prospectively up to the age of 14, and later onset of schizophrenia and other psychoses in the 1966 birth cohort in Northern Finland, which covers 96% of all births in the area during that year. Data regarding CNS infections were collected 1966-1980. Registered diagnoses of psychoses in 1982-1993 were validated on DSM-III-R criteria. Out of 11,017 subjects, 145 had suffered a CNS infection during childhood, 102 of them a viral infection, 76 had DSM-III-R schizophrenia and 53 some other psychosis. Four cases of schizophrenia had suffered viral CNS infection and two cases of other psychosis bacterial infection. When neurological abnormalities and father's social class were adjusted odds ratio (OR) of schizophrenia after viral CNS infection was 4.8 (95% confidence intervals [CI] : 1.6-14.0); the other significant risk factors being intelligence quotient (IQ) < 85, perinatal brain damage and male sex but not epilepsy. Similarly adjusted OR of other psychoses was 6.9 (95% CI: 1.4-32.8) after bacterial CNS infection; the other significant risk factors being IQ < 85 and severe hearing defect. Two of the live viral infections were caused by Coxsackie B5 during an epidemic in which 16 neonates were infected together. Central nervous system infections during childhood clearly carried an increased risk of adult onset schizophrenia or other psychoses, viral infections being important for schizophrenia, particularly Coxsackie B5 during the newborn period.