Sequelae Of Bacterial Meningitis Research Articles

Improved Activities of Daily Living With Adjunctive Intravenous Steroids in Bacterial Meningitis: A Nationwide, Population-Based Medical Database Study.

The benefit of using adjunctive intravenous steroids (IVS) to reduce the neurological sequelae in bacterial meningitis remains inconclusive. This study evaluated the effect of IVS on improving the subsequent Activities of Daily Living (ADL) in bacterial meningitis by analyzing data from a large nationwide administrative medical database in Japan. Data from 1,132 hospitals, covered by the administrative Diagnosis Procedure Combination (DPC) payment system from 2016 to 2022, were evaluated. The ADL levels at admission and discharge were measured using the Barthel Index (BI). Out of the cumulative 47,366,222 patients hospitalized, 8,736 were diagnosed with acute bacterial meningitis and had BI data available. The BI at discharge, adjusted for sex, age, and BI at admission, was significantly better among those treated with IVS (p<0.0001). Exploratory subgroup analyses suggested that this benefit is expected across a broad spectrum of bacterial species. In summary, the use of IVS for improving the subsequent ADL level in bacterial meningitis was suggested.

Pediatric Hearing Thresholds Post-bacterial Meningitis.

Introduction: Disabling hearing loss as a sequela of bacterial meningitis results from damage to the auditory system. This study was designed to ascertain the hearing thresholds in survivors of bacterial meningitis and the risk factors of hearing loss in childhood bacterial meningitis.Methodology: One hundred and two children admitted and treated for bacterial meningitis were recruited prospectively along with 102 age- and sex-matched controls who had auditory evaluation using otoacoustic emission and auditory brain stem response tests 48 h prior to hospital discharge. This was also repeated at the follow-up clinic at 1 month after hospital discharge, irrespective of the initial hearing assessment results.Result: There were 57 (55.9%) males and 45 (44.1%) females among the cases (mean age, 5.34 ± 4.40 years) and 55 (53.9%) males and 47 (46.1%) females among the controls (mean age, 5.31 ± 3.15 years). The prevalence of hearing loss was 30.4% among the cases, while it was 6.9% among the controls. The risk factors of hearing impairment in this study were the presence of anemia, leukocytosis, and hypoglycorrhachia.Conclusion: Hearing impairment with varying degrees of severity is a frequent complication of bacterial meningitis in children.

Adjunctive Daptomycin Attenuates Brain Damage and Hearing Loss More Efficiently than Rifampin in Infant Rat Pneumococcal Meningitis

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis

It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1–3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels ( p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels ( p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels ( p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone ( p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.

Reply: neuropsychological sequelae of bacterial meningitis: the influence of alcoholism and adjunctive dexamethasone therapy

Van de Beek et al. present new important data concerning the clinical outcome of patients with alcoholism and pneumococcal meningitis. The data was derived from a subgroup analysis of the patient population of their comparative key study on neuropsychological sequelae after pneumococcal versus meningococcal meningitis (van de Beek et al., 2002). With respect to our paper, they raised three issues: (i) Absence of statistically significant differences between patients after Streptococcus pneumoniae and Neisseria meningitidis meningitis in our study. Van de Beek et al. reported that only 2 of 26 patients of the pneumococcal meningitis group who were actually examined neuropsychologically suffered from alcoholism. In contrast to our findings (Schmidt et al., 2006), van de Beek et al. found significant neuropsychological differences between patients who survived pneumococcal and meningococcal meningitis. Before we received the information from van de Beek et al. by this communication, we presumed that one of several possible reasons for this discrepancy was the different proportion of patients with alcoholism in our study versus those in van de Beek’s study. This now can be ruled out. Searching for further explanations, van de Beek et al. suggest that different Glasgow Outcome Scores (GOS) or differing intervals between hospital stay and re-examination of the respective meningitis group might have led to this discrepancy. Patients examined after pneumococcal meningitis in our study had a significantly lower mean GOS value than patients examined after meningococcal meningitis. Therefore, the differences should have been even more pronounced. The interval between hospital admission and neuropsychological testing was not significantly different in our pneumococcal and meningococcal patient groups. Van de Beek et al. pointed out that a group size of 16 patients per group might not yield enough statistical power to discriminate differences. This is true, especially for domains with only limited inter-group differences. We think that the reported difference between meningococcal and pneumococcal meningitis patients in van de Beek’s study (or in other terms the non-existing difference in our study) might be a result of different statistical approaches: In contrast to our colleagues’ work we compared the groups using two-sided tests (not assuming a priori one group to be more severely affected than the other). This approach results in an alpha error twice as high as with one-sided testing. If one-tailed tests are used, it is recommended to calculate with half the alpha error that would have been used with a twotailed study [according to the ICH topic E9 (EMEA, 1998)]. Applying a P-value of 0.025, only 3 out of 14 neuropsychological examinations for which van de Beek et al. gave mean T-values with standard deviations were significantly different (Visuospatial reasoning, WMS-R immediate memory, Trailmaking B) after their univariate analysis of covariance. Comparing the T-values of van de Beek’s groups in our way with two-sided t-tests for independent samples, only the items Visuospatioal reasoning and Trailmaking B yielded statistically significant differences in van de Beek’s study groups. Contrary to our analysis of alertness functions (performed after age-related transformation into z-values), reaction speed (dominant/non-dominant hand) and a two-choice paradigm in van de Beek’s paper were significantly slower for the pneumococcal than for the meningococcal meningitis group. In contrast to all other domains, for the comparison of the reaction speed, a transfer of the raw data into age-adapted zor T-values (derived from age-matched controls or with the standard values from the respective test manuals) was not

Review: adjuvant corticosteroid therapy reduces death, hearing loss, and neurological sequelae in bacterial meningitis

van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2003;(3):CD004305. Q In children and adults with acute bacterial meningitis...

Dexamethasone Beneficial for Bacterial Meningitis in Adults

The significant sequelae of bacterial meningitis are thought to be caused by inflammation related to bacterial lysis, and studies have shown a clear

Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis.

Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) converting enzyme (TACE) contribute synergistically to the pathophysiology of bacterial meningitis. TACE proteolytically releases several cell-surface proteins, including the proinflammatory cytokine TNF-alpha and its receptors. TNF-alpha in turn stimulates cells to produce active MMPs, which facilitate leucocyte extravasation and brain oedema by degradation of extracellular matrix components. In the present time-course studies of pneumococcal meningitis in infant rats, MMP-8 and -9 were 100- to 1000-fold transcriptionally upregulated, both in CSF cells and in brain tissue. Concentrations of TNF-alpha and MMP-9 in CSF peaked 12 h after infection and were closely correlated. Treatment with BB-1101 (15 mg/kg subcutaneously, twice daily), a hydroxamic acid-based inhibitor of MMP and TACE, downregulated the CSF concentration of TNF-alpha and decreased the incidences of seizures and mortality. Therapy with BB-1101, together with antibiotics, attenuated neuronal necrosis in the cortex and apoptosis in the hippocampus when given as a pretreatment at the time of infection and also when administration was started 18 h after infection. Functionally, the neuroprotective effect of BB-1101 preserved learning performance of rats assessed 3 weeks after the disease had been cured. Thus, combined inhibition of MMP and TACE offers a novel therapeutic strategy to prevent brain injury and neurological sequelae in bacterial meningitis.

Nitric oxide production during bacterial and viral meningitis in children.

Nitric oxide is very likely to play a role in physiopathological mechanisms of bacterial meningitis. As shown by in vitro studies, nitric oxide is toxic to endothelial cells, as well as to neurones, and thus may be responsible for neurological sequelae in bacterial meningitis. Increased level of nitric oxide can also inhibit mitochondrial respiration, enhancing anaerobic glycolysis. Twenty-seven children with documented bacterial meningitis, 73 with viral (mumps and enteroviral) meningitis, and 51 controls were studied. All children with bacterial meningitis were given cefotaxime (200 mg/kg per day). Glucose and protein concentrations and cerebrospinal fluid cell counts were determined routinely, as well as nitrite and nitrate levels. The levels of nitrite and nitrate in cerebrospinal fluid on admission were higher in patients with bacterial meningitis than in controls or in children with viral meningitis. In 10 patients, dexamethasone therapy (0.4 mg/kg every 12 h for 2 days) was started about 10 min before the first antibiotic dose. A significantly lower nitrite concentration was observed after 24-48 h of treatment compared with non-steroid-treated patients. Significant positive correlations between the nitrite and granulocyte counts and the protein concentration in cerebrospinal fluid were found in all patients with meningitis. Increased nitric oxide production in cerebrospinal fluid during the acute phase of bacterial meningitis may result from the inflammatory process and tissue injury. Dexamethasone administered before the first parenteral antibiotic dose seems to reduce nitric oxide production in the cerebrospinal fluid during bacterial meningitis.

Possible Involvement of Nitric Oxide in the Sensorineural Hearing Loss of Bacterial Meningitis

Amaee FR, Comis SD, Osborne MP, Drew S, Tarlow MJ. Possible involvement of nitric oxide in the sensorineural hearing loss of bacteria! meningitis. Acta Otolaryngol (Stockh) 1997; 117: 329-336.Microperfusion of scala tympani with the NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), produced marked depression of the compound action potential (CAP) and cochlear microphonic (CM) together with severe and widespread morphological damage to hair cells and supporting cells in the organ of Corti. In addition, direct perfusion of N-methyl-D-aspartate (NMDA) into scala tympani, which probably induces excess stimulation of NMDA receptors within the cochlea and which is known to lead to the release of NO, was found to elicit similar electrophysiological and structural lesions in the cochlea. Pre-perfusion of scala tympani with L-methyl arginine (L-MA), which inhibits the release of NO, or superoxide dismutase (SOD), an O2-scavenger, conferred marked protection upon the cochlea from the lesions caused by NO donors. These observations indicate that enhanced NO production is likely to be an important factor responsible for pathological insult of the cochlea. The possibility is discussed that this factor is involved in the chain of events leading to hearing loss caused by bacterial meningitis. Such hearing loss is a major sequela of bacterial meningitis in children.

Impairment of respiratory rhythmogenesis and sequelae of bacterial meningitis

A 9-year-old boy with respiratory disturbance associated with medullary lesions after pneumococcal meningitis is reported. Although he lives a normal daily life, he cannot cough or sneeze. A polysomnographic study revealed a low respiration rate and an irregular respiratory rhythm not only during REM sleep but also during slow wave sleep, and marked desaturation during sleep. Respiratory function tests including CO 2 response revealed normal values. Magnetic resonance imaging demonstrated bilateral small lesions in the medulla. This patient is unusual because respiratory rhythm is impaired, without decreased ventilatory capacity or CO 2 response, supporting the possibility that rhythmogenetic respiratory neurons are located in a limited area of the human medulla.

The use of adjunctive therapy to alter the pathophysiology of bacterial meningitis.

The inflammation in the subarachnoid space (SAS) that develops in the course of bacterial meningitis may have a role in eradicating the infection, but also, ultimately, is the cause of the neurological sequelae associated with this infection. The presence of an inflammatory exudate in the SAS leads to alterations in the blood-brain barrier, altered cerebrospinal fluid dynamics, cerebral edema and increased intracranial pressure, and loss of cerebral auto-regulation. Our increasing understanding of the pathophysiology of meningeal inflammation has led to therapeutic interventions to limit the degree of meningeal inflammation and neurologic sequelae. The inflammatory cascade that leads to alterations in central nervous system physiology will be reviewed as well as the experimental evidence and clinical trials demonstrating the efficacy of adjunctive therapy in reducing meningeal inflammation and decreasing the incidence and severity of neurological sequelae in bacterial meningitis.

Auditory sequelae in bacterial meningitis treated with dexamethasone

Auditory sequelae in bacterial meningitis treated with dexamethasone

Pathology associated with meningoencephalitis during bacterial kidney disease of salmonids

The neural pathology associated with spontaneous cases of bacterial kidney disease (BKD), in five species of commercially reared salmonids, was investigated histopathologically and with immunofluorescence. Patterns of localisation of the causative organism of BKD within the central nervous system suggest that haematogenous spread to the meninges, particularly the tela choroidea posterior, the tela choroidea and vascularised capsule of the saccus dorsalis and epiphysis of the epithalamus, and the saccus vasculosus of the hypophysis, appears to be a frequent route by which the central nervous system becomes infected. Retrograde extension from the posterior uvea to the floor of the diencephalon along the epineurium and perineurium of the optic nerve also may be a mechanism of neural invasion. Extension appeared to occur from these sites into adjacent areas of the meninges, the neural parenchyma and ventricles. Demonstration of bacteria within sahnonid ependymal cells, as well as the apparent ability of salmonid ependymal cells to respond metaplastically suggest a similarity to mammalian type III ependymal cells (tanycytes). Based on this study, it is apparent that teleosts can survive protracted severe brain damage. This, combined with the apparent similarities of neural response to infection between the salmonids used in this study and higher vertebrates, suggests that teleosts may be a useful lower vertebrate model for studying the pathogenesis and sequelae of bacterial meningitis.

Neurologic Sequelae of Bacterial Meningitis

The occurrence of chronic neurologic sequelae including late seizures or epilepsy was determined in a nine year follow-up study of 185 infants and children with bacterial meningitis at the Departments of Pediatrics and Neurology, Washington University School of Medicine, St. Louis, MO and the Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Long Term Sequelae of Bacterial Meningitis in Children

Long Term Sequelae of Bacterial Meningitis in Children

A Comparative Study on CT and Neurological Sequelae in Bacterial Meningitis in Children

A Comparative Study on CT and Neurological Sequelae in Bacterial Meningitis in Children