Studies on the incidence and spectrum of complications and prognostic factors in adults with pneumococcal meningitis are scarce. Therefore, we analysed 87 consecutive cases who were treated in our department between 1984 and 2002. Meningitis-associated intracranial complications developed in 74.7% and systemic complications in 37.9% of cases. Diffuse brain oedema (28.7%) and hydrocephalus (16.1%) developed more frequently than previously reported. The incidences of arterial (21.8%) and venous (9.2%) cerebrovascular complications were also very high. Furthermore, 9.2% of cases developed spontaneous intracranial haemorrhages (two patients with subarachnoid and two with subarachnoid and intracerebral bleedings, all in association with vasculitis; one subject with intracerebral haemorrhage due to sinus thrombosis; and three cases with intracerebral bleedings of unknown aetiology). Other new findings were the incidence of acute spinal cord dysfunction due to myelitis (2.3%) and that of hearing loss (19.5% of all patients and 25.8% of survivors). The in-hospital mortality was 24.1%. Only 48.3% of the patients had a good outcome at discharge [Glasgow Outcome Scale Score (GOS) = 5]. Outcome did not change during the study period, as mortality and GOS were similar for patients treated between 1984 and 1992 and for those treated between 1993 and 2002. Factors associated with a bad outcome (GOS or =60 years was associated with a higher mortality (36.7 versus 17.5%), but the GOS of the survivors was comparable to that of the surviving younger patients. The causes of death were mostly systemic complications in the elderly and cerebral complications in the younger patients. A haematogenous pathogenesis seemed likely in asplenic patients, while contiguous spread from sinusitis or otitis was the major cause of meningitis in non-asplenic individuals. Furthermore, asplenic patients had a raised incidence of meningitis-associated intracranial complications, but their outcome was similar to that of non-asplenic subjects. The morbidity and mortality of pneumococcal meningitis in adults are still devastating. We report higher incidences (diffuse brain swelling, hydrocephalus, cerebrovascular complications) or new incidences (myelitis, hearing loss, subarachnoid bleeding) of intracranial complications. Our detailed analysis of prognostic factors may help clinicians to identify patients at risk and may also be helpful in the design of clinical trials.

BackgroundThe chemokine CXCL13 is known to dictate homing and motility of B cells in lymphoid tissue and has been implicated in the formation of ectopic lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking during acute infection, is largely unclear. In previous studies, we showed that (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is released by monocytes upon recognition of borrelial outer surface proteins by Toll-like receptor 2. Here, we assessed the role of CXCL13 - in comparison to other chemokines - in the recruitment of B cells to the CSF of patients with acute LNB.MethodsMeasurement of chemokines was done by ELISA. B cells were isolated from whole blood using magnetic cell separation (MACS). For migration experiments, a modified Boyden chamber assay was used and the migrated B cells were further analysed by FACS. The migration was inhibited either by preincubation of the CSF samples with neutralizing antibodies, heating to 60°C, removal of proteins >3 kDa, or by pre-treatment of the B cells with pertussis toxin. The principal statistical tests used were one-way analysis of variance and Bonferroni test (chemokine measurements) as well as paired Student's t-test (migration experiments).ResultsMeasurements of chemokine levels revealed an increase in three of the four known major B cell chemoattractants CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12. Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after preincubation with a neutralizing CXCL13 antibody, while combined preincubation with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further reduction. Since treatment with pertussis toxin, heating to 60°C, and removal of proteins >3 kDa abrogated the chemotactic activity, further not yet identified chemokines seem to be involved in B cell recruitment to LNB CSF.ConclusionCombined, our study suggests a key role of CXCL13 in B cell migration to sites of infection as shown here for the CSF of LNB patients.

Using protein expression profiling, the authors identified an upregulation of the chemokine B lymphocyte chemoattractant (BLC) in the CSF of patients with neuroborreliosis but not in patients with noninflammatory and various other inflammatory neurologic diseases. This upregulation was confirmed by ELISA, showing increased BLC levels in every neuroborreliosis patient while being undetectable in patients with noninflammatory neurologic diseases. These results point to BLC as a putative additional diagnostic marker for neuroborreliosis.

for the guideline group* T he scientists and physicians involved in research on Lyme neuroborreliosis agree that this disease can be reliably diagnosed and permanently stopped with a two-to three-week course of antibiotic treatment. There nonetheless exists a widespread fear that Lyme disease (as it is also called) can lead to a wide variety of nonspecific symptoms, such as chronic pain, fatigue, and difficulty concentrating, despite antibiotic treatment. This view often leads to repeated courses of antibiotic treatment being given for several months at a time, sometimes with serious adverse effects; there have even been a few deaths (e1-e3). The objective of the S3 guideline on Lyme neuroborreliosis issued by the German Society of Neurology (Deutsche Gesellschaft für Neurologie) is, therefore, to provide clear recommendations on the diagnosis and treatment of this disease which are based on a structured evidence and consensus process. Epidemiology Lyme borreliosis is an infectious disease that manifests itself primarily on the skin, in the nervous system, and in the joints. Five species of Borrelia burgdorferi that are pathogenic for human beings have been identified as the responsible organisms in Europe; they are transmitted by the bite of Ixodes ricinus, a species of hard tick. The number of new cases in Germany each year is variably estimated from 60 000 to over 200 000 (e4, e5), in the absence of precise figures. The seroprevalence of Borrelia-specific antibodies in healthy persons ranges from 5% to 20%, depending on their age and place of residence (e6-e8). According to German surveys, tick bites lead to seroconversion in 2.6%-5.6% of cases, and to overt disease in 0.3-1.4% (e9-e11). Method The first step in the creation of the guideline was a search for, and an assessment of, already existing guidelines on the subject, of which eight were found. Structured evaluation revealed that all of them had low quality scores, with the result that none of their recommendations could be adopted without further investigation (1). To assess the various proposed modes of antibiotic treatment, systematic literature searches were carried out in three databases: • Medline (via Ovid), • Embase (via Scopus), • and the Cochrane Central Register of Controlled Trials. Each included study was assessed in structured fashion (2, 3). The results for all of the included Summary Background: The new German S3 guideline on Lyme neuroborreliosis is intended to provide physicians with scientifically based information and recommendations on the diagnosis and treatment of this disease. Methods: The scientific literature was systematically searched and the retrieved publications were assessed at the German Cochrane Center (Deutsches Cochrane Zentrum) in Freiburg in the 12 months beginning in March 2014. In addition to the main search terms "Lyme disease," "neuroborreliosis," "Borrelia," and "Bannwarth," 28 further terms relating to neurological manifestations of the disease were used for the search in the Medline and Embase databases and in...

Recent studies have suggested an important role for the B-cell-attracting chemokine CXCL13 in the B-cell-dominated cerebrospinal fluid (CSF) infiltrate in patients with neuroborreliosis (NB). High levels of CXCL13 were present in the CSF of NB patients. It has not been clear, however, whether high CSF CXCL13 titers are specific for NB or are a characteristic of other spirochetal diseases as well. Furthermore, the mechanisms leading to the observed CXCL13 expression have not been identified yet. Here we describe similarly elevated CSF CXCL13 levels in patients with neurosyphilis, while pneumococcal meningitis patient CSF do not have high CXCL13 levels. In parallel, challenge of human monocytes in vitro with two of the spirochetal causative organisms, Borrelia garinii (the Borrelia species most frequently found in NB patients) and Treponema pallidum, but not challenge with pneumococci, induced CXCL13 release. This finding implies that a common spirochetal motif is a CXCL13 inducer. Accordingly, we found that the lipid moiety N-palmitoyl-S-(bis[palmitoyloxy]propyl)cystein (Pam 3 C) (three palmitoyl residues bound to N-terminal cysteine) of the spirochetal lipoproteins is critical for the CXCL13 induction in monocytes. As the Pam 3 C motif is known to signal via Toll-like receptor 2 (TLR2) and an anti-TLR2 monoclonal antibody blocked CXCL13 production of human monocytes incubated with B. garinii, this suggests that TLR2 is a major mediator of Borrelia-induced secretion of CXCL13 from human monocytes.Spirochetes are a group of bacteria that can be distinguished morphologically from other bacteria based on the fact that they are thin, long, and helical or corkscrew shaped. While in the northern hemisphere Borrelia burgdorferi is the predominant spirochete responsible for neuroinfectious diseases, infections of the central nervous system (CNS) with Treponema pallidum are endemic in regions all over the world. Moreover, a dramatic increase in the incidence of syphilis has been noted in several countries (9). In contrast to their high prevalence, the pathogenesis of neuroborreliosis (NB) and neurosyphilis (NS) is not yet well understood. After crossing the blood-brain barrier, both spirochetes elicit an inflammatory response in the cerebrospinal fluid (CSF), predominantly mediated by mononuclear cells. This contrasts with the massive invasion of polymorphonuclear cells into the CSF of patients with pneumococcal meningitis (PM), the most frequent bacterial infection of the adult CNS.It is assumed that the infiltration and the composition of the immunocompetent cells in the CSF are mainly the result of the intrathecal production of chemokines. Besides being grouped according to common motifs in their amino acid sequences, chemokines can be subdivided according to the cell populations that they predominantly attract. B lymphocytes, in contrast to other leukocytes, show substantial migration in response to only a very few chemokines, namely, CCL19, CCL21, CXCL12, and CXCL13 (3). Since the proportion of B lymphocytes in the C...