Course Of Meningitis Research Articles

Long-term sequelae after viral meningitis and meningoencephalitis are frequent, even in mildly affected patients, a prospective observational study.

An increasing number of studies demonstrate that viral meningitis and meningoencephalitis, even those with a mild course of meningitis, can result in residual sequelae. We aimed to investigate the long-term outcome in both viral meningitis and meningoencephalitis/encephalitis patients and impact of long-term sequelae on patients' social and professional daily lives in a prospective observational study with a follow-up period of 20 months. A total of 50 patients (12% encephalitis, 58% meningoencephalitis and 30% meningitis) and 21 control persons participated in the study. The most common cause was the tick-borne encephalitis (TBE) virus. The most important persistent signs and symptoms after 2 years were subjective cognitive impairment (36%), fatigue and/or excessive daytime sleepiness (31%), disturbed nighttime sleep (31%) and headaches (13%), as well as feeling more rapidly exhausted after cognitive effort (53%). Independent of disease severity in the acute phase, almost one third of patients still reported mildly impaired social and/or professional life due to the long-term sequelae, with scores in the health status assessment still significantly lower compared to healthy controls. Regardless of the severity of the acute illness and despite constant improvement within 2 years, 67% of patients still had persistent signs and symptoms, but these were only relevant to everyday social or professional life in about 30% of these patients.

Analysis of fatal outcomes of meningococcal infection in adults

Clinical characteristics and pathomorphological manifestations in 69 patients aged 18 to 86 years with a fatal outcome of the disease were examined in order to analyze the causes of severe course and high mortality of generalized forms meningococcal infection. It was found that the main clinical form was meningococcemia (90%), in the majority in combination with meningitis (52%). The fulminant course in 77% of patients with meningococcal sepsis manifested itself as a sudden onset, rapid development of typical symptoms. Hemorrhagic exanthema was detected on the first day of meningococcemia. The leading complications and critical conditions were infectious-toxic shock, disseminated intravascular coagulation and acute adrenal insufficiency (Waterhouse-Friederiksen syndrome). The severe course of meningitis (in 10%) led to the development of cerebral coma, the morphological substrate of which was edema - swelling of the brain.

Severe courses of meningitis and encephalitis in children and adolescents

Die bakterielle Meningitis und die virale Enzephalitis sind die infektiösen Erkrankungen des Zentralnervensystems (ZNS), die meist mit schwerwiegenden Folgeerscheinungen bis hin zum Tod einhergehen. Trotz Fortschritten in der Prävention durch Impfungen ist die globale Krankheitslast der bakteriellen Meningitis enorm. Die Inzidenz der viralen Enzephalitis im Kindesalter war vor der durch die „coronavirus disease 2019“ (COVID-19) ausgelösten Pandemie zunehmend. Dies hängt mit der wachsenden Verbreitung von „emerging pathogens“ wie dem Enterovirus-A71 und dem West-Nil-Virus in den hiesigen Breitengraden zusammen, aber auch mit der häufigeren Anwendung von Immunsuppressiva und der häufigeren Durchführung von Stammzelltransplantationen im Kindesalter.In der vorliegenden Übersichtsarbeit werden Häufigkeit und klinische Zeichen von infektiösen ZNS-Erkrankungen zusammengefasst und die aktuellen Therapieempfehlungen dargestellt.

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion.

Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood–brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood–cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.

Human Parvoviruses May Affect the Development and Clinical Course of Meningitis and Meningoencephalitis

Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1–4 (HBoV1–4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1–4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1–4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology.

Cerebrospinal fluid inflammatory markers in children with aseptic meningitis

Abstract Aseptic meningitis is one of the most common inflammatory disorders of the meninges of the central nervous system (CNS). The aim of our study was to investigate the cytokine profiles in the CSF and in the serum of children with aseptic meningitis to determine their role in CNS inflammation. Sixty-eight (68) children were kept under observation. Cytokine profile of CSF and blood (based on the results of determining of IL-1β, IL-4, IL-10, TNF-α levels) and procalcitonin in children were revealed, meningitis severity were estimated by AMSS score. It was found that in the majority of patients with aseptic meningitis, the levels of IL-1β, TNF-α, IL-10 in CSF were increased and exceeded the serum cytokines levels. The severe course of meningitis was characterized by significantly higher concentrations of IL-1β and TNF-α in CSF, which was confirmed by positive correlation between AMSS score and IL-1β concentration (r=0.46, p<0.01), IL-10 (r=0.32, p<0.01), TNF-α (r=0.62, p<0.05). The IL-10/TNF-α ratio was – 17.8. PCT level in CSF was within normal limits in the majority of patients with meningitis. Increasing of anti-inflammatory cytokine levels in aseptic meningitis contributes to preventing of excessive inflammatory/immune responses in the brain. This can cause a longer diseases course and a longer recovery period. This can an indicate active production of cytokines in the central nervous system due to intrathecal inflammation and activation of immune responses caused by viral infection, but not due to penetration across the blood-brain barrier.

Meningococcal meningitis complicated by subdural empyema and epiduritis in an infant

Subdural empyema is a rare but terrible complication of meningococcal meningitis in children, which can be fatal. The article describes a clinical case of meningococcal meningitis, complicated by subdural empyema and epiduritis, in a three-year-old child. The development of complications was manifested by a new wave of fever, bulging of a bregmatic fontanelle and an increase in the inflammatory markers in the blood, as well as the development of neutrophilic pleocytosis after normalization of the cellular composition of the cerebrospinal fluid. The child was diagnosed on the basis of magnetic resonance imaging of the brain and spinal cord. A longterm antibiotic therapy was effective, and the surgery was not required. The development of such complications should be assumed in all cases of a prolonged course of meningitis, accompanied by an increase in the level of inflammatory markers in the blood, even in the absence of the classic symptoms of subdural empyema.

Клиническое течение менингитов, вызванных Streptococcus Pneumoniae у ВИЧ-позитивных пациентов

Клиническое течение менингитов, вызванных Streptococcus Pneumoniae у ВИЧ-позитивных пациентов

Sequential transmigration of polymorphonuclear cells and naive CD3+ T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30

Viral meningitis by non-polio enteroviruses (NPEV) is a major public health burden causing fatal outcomes especially in the younger population. Strong evidence exists that the blood-cerebrospinal-fluid (CSF) barrier (BCSFB) serves as an entry point for enterovirus and leucocytes into the central nervous system (CNS). Moreover, analysis of clinical CSF specimens of patients with a NPEV infection revealed a predominance of polymorphonuclear granulocytes (PMN) in the early phase and mononuclear cells in the later course of meningitis. By applying a functional in vitro model of the BCSFB consisting of human choroid plexus papilloma (HIBCPP) cells, we aimed to analyse the mechanisms of sequential migration of PMN and naive CD3+ T lymphocytes following infection with Echovirus 30 (EV30). EV30 infection led to increased transmigration of PMN and naive CD3+ T lymphocytes. Transmigration of PMN was significantly enhanced in the presence of naive CD3+ T lymphocytes, but not vice versa. The barrier function was not differentially altered under the respective conditions. Infection with EV30 led to an upregulation of CXCL3 and CXCL11 on the RNA-level. Additional analysis of cytokine secretion revealed relatively high concentrations of IL-8, CCL20, CXCL3, CXCL10 and M-CSF. Overall, there was a predominantly polar direction of cytokine secretion to the basolateral side. IL-7 was the only cytokine which was strongly secreted to the apical side and that was enhanced following EV30 infection in our model. In conclusion, this study highlights the role of the choroid plexus and cytokines in regulating leucocyte entry into the CNS in the context of EV30 infection.

The markers of damage of neurons and glia in cerebrospinal liquor under meningitis in children.

The actuality of analysis of cerebrospinal fluid under meningitis in children is conditioned by severity of course of disease with development of residual aftermaths in part of patients. The appearance of proteins specific for neurons, astro- and oligodendroglia in liquor and blood serum can serve as a marker of severity of damage of cerebral parenchyma and as a predictor of development of neurological deficiency. The analysis was applied to samples of liquor obtained during diagnostic lumbar puncture in 44 children (33 with viral serous meningitis, 11 with bacterial purulent meningitis). The detection of protein S-100, glial fibrillar acid protein and and neuron-specific enolase was implemented using solid-phase immune enzyme technique. The maximal increasing of concentrations of protein S-100 and glial fibrillar acid protein was detected at initial stage of bacterial purulent meningitis with consequent decreasing of at the stage of re-convalescence. Under serous meningitis at acute stage maximal high proved to be average value of concentration of neuron-specific enolase with tendency to its increasing at the stage of re-convalescence. The multi-directional correlation relationships are established concerning levels of of neuron-specific enolase, glial fibrillar acid protein and protein S-100 with standard liquorologic indices and their direct mutual relationships. The variability of levels of neuron-specific proteins in liquor is established associated with clinical characteristics of course of meningitis in children that testifies possibility of their application for specifying involvement into pathological process of different brain structures and necessity of further studying of relationship of infection affection of brain with development of neurological aftermaths at the residual period.

Inhibition of matrix metalloproteinases attenuates brain damage in experimental meningococcal meningitis

BackgroundApproximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage.MethodsThe model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge.ResultsMice that received BB-94 presented significantly diminished MMP-9 levels (p < 0.01), intracerebral bleeding (p < 0.01), and blood-brain barrier (BBB) breakdown (p < 0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p < 0.01) and BBB disruption (p < 0.05).ConclusionsMMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0726-6) contains supplementary material, which is available to authorized users.

Chronic and Subacute Meningitis

This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail. With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke. Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.

Clinical characteristics, risk factors and pre‐surgical evaluation of post‐infectious epilepsy

Epilepsy is a frequent complication of central nervous system (CNS) infections. Post-infectious epilepsy is commonly refractory to medical treatment and plays a pivotal role for the poor long-term outcome of CNS infections. To provide an overview of clinical characteristics and risk factors of seizures associated with CNS infections. In addition, to summarize the state of the art of anticonvulsive treatment and the pre-surgical evaluation process in refractory cases. A comprehensive literature search for articles published between January 1970 and December 2011 was carried out. The occurrence of seizures during the acute course of meningitis, encephalitis and brain abscess is the main risk factor for the development of post-infectious epilepsy. There is a shortage of trials evaluating the efficacy of prophylactic and symptomatic treatment during the course of acute infection. Moreover, there are no randomized-controlled trials studying anticonvulsive drugs and their combinations for the management of post-infectious epilepsy. In a selected group of patients, however, medically refractory focal epilepsy is potentially curable by surgery. Further studies are required to improve the pathogenetic understanding of post-infectious epilepsy in order to develop preventive measures as well as to evaluate additional medical and surgical treatment strategies for the patients currently not considered for surgery.

Astrocytic tissue remodeling by the meningitis neurotoxin pneumolysin facilitates pathogen tissue penetration and produces interstitial brain edema

Astrocytes represent a major component of brain tissue and play a critical role in the proper functioning and protection of the brain. Streptococcus pneumoniae, the most common cause of bacterial meningitis, has a high lethality and causes serious disabilities in survivors. Pneumolysin (PLY), a member of the cholesterol-dependent cytolysin group and a major S. pneumoniae neurotoxin, causes deterioration over the course of experimental S. pneumoniae meningitis. At disease-relevant sub-lytic concentrations, PLY produces actin and tubulin reorganization and astrocyte cell shape changes in vitro. In this article, we show that sub-lytic amounts of PLY remodel brain tissue and produce astrocytic process retraction, cortical astroglial reorganization and increased interstitial fluid retention, which is manifested as tissue edema. These changes caused increased tissue permeability to macromolecules and bacteria. The pore-forming capacity of PLY remained necessary for these changes because none of the nonpore-forming mutants were capable of producing similar effects. We suggest that PLY can increase the permeability of brain tissue toward pathogenic factors and bacteria in the course of meningitis, thus contributing to the deterioration caused by the disease.

Meningitis Following Lateral Skull Base Surgery

Objective: 1) Determine the clinical course of meningitis in the following lateral skull base surgery. 2) Examine risk factors leading to meningitis following lateral skull base surgery. Method: Retrospective review of patients undergoing lateral skull base surgery between February 1999 and March 2010. All subjects had culture-proven meningitis in the postoperative period. Medical records were compared with the lateral skull base patients who did not develop meningitis. Results: Fourteen of 508 patients (2.8%) developed meningitis following lateral skull base surgery. The most common diagnosis was acoustic neuroma in 78.5%. A total of 64.3% of patients had a CSF leak prior to meningitis onset, and 42.9% received a lumbar drain. The mean time to onset of meningitis was 16.1 days. The most common pathogens were staphylococcus, streptococcus, and enterococcus species; each in 14.3% of cases. A total of 10.3% of patients with postoperative CSF leakage and 9.2% with lumbar drains developed meningitis. The odds ratio of developing meningitis in the setting of a postoperative CSF leak is 7.3. There were no meningitis associated mortalities. Conclusion: Postoperative meningitis was seen in 2.8% of lateral skull base surgeries. As expected a CSF leak and placement of a lumbar subarachnoid drain are significant risk factors for developing meningitis. No mortality was associated with meningitis.

Clinical characteristics and therapeutic outcomes of nosocomial super-infection in adult bacterial meningitis

BackgroundSuper-infection in adult bacterial meningitis (ABM) is a condition wherein the cerebrospinal fluid (CSF) grows new pathogen(s) during the therapeutic course of meningitis. It is an uncommon but clinically important condition rarely examined in literature.MethodsTwenty-seven episodes of super-infection states in 21 ABM patients collected in a 9.5-year study period (January 2001 to June 2010) were evaluated. The clinical characteristics, implicated pathogens, results of antimicrobial susceptibility tests, and therapeutic outcomes were analyzed.ResultsTwenty-one patients (13 men, 8 women) aged 25-73 years (median, 45 years) had post-neurosurgical state as the preceding event and nosocomial infection. The post-neurosurgical states included spontaneous intracranial hemorrhage (ICH) with craniectomy or craniotomy with extra-ventricular drainage (EVD) or ventriculo-peritoneal shunt (VPS) in 10 patients, traumatic ICH with craniectomy or craniotomy with EVD or VPS in 6 patients, hydrocephalus s/p VPS in 2 patients, and one patient each with cerebral infarct s/p craniectomy with EVD, meningeal metastasis s/p Omaya implant, and head injury. All 21 patients had EVD and/or VP shunt and/or Omaya implant during the whole course of ABM. Recurrent fever was the most common presentation and the implicated bacterial pathogens were protean, many of which were antibiotic resistant. Most patients required adjustment of antibiotics after the pathogens were identified but even with antimicrobial therapy, 33.3% (7/21) died. Morbidity was also high among survivors.ConclusionsSuper-infection in ABM is usually seen in patients with preceding neurosurgical event, especially insertion of an external drainage device. Repeat CSF culture is mandatory for diagnostic confirmation because most of the implicated bacterial strains are non-susceptible to common antibiotics used. Unusual pathogens like anaerobic bacteria and fungi may also appear. Despite antimicrobial therapy, prognosis remains poor.

Acute Deafness as the Presenting Symptom of Bacterial Meningitis

Hearing loss has long been documented to occur during the course of meningitis. We report a case of a child presenting with deafness as the principal complaint of bacterial meningitis.

Systemic manifestations in the course of meningococcal disease

Meningococcal disease most often manifests itself as meningitis or sepsis. During the course of these diseases, other clinical events sometimes develop such as pneumonia, pericarditis, arthritis, and they are referred to as extrameningeal or systemic manifestations of the meningococcal disease. The aim of this study was to investigate the type and the incidence of particular extrameningeal/systemic manifestations among patients with meningococcal meningitis and sepsis, including time of their onset and the influence on the disease outcome. The retrospective study of the medical records of 246 patients treated for meningococcal disease over the 25-year period in the Institute for Infectious and Tropical Diseases, Belgrade was conducted. The patients, aged 3 months to 82 years both sexes, were divided into two groups. Out of 246 patients extrameningeal/systemic manifestations were found in 42 (17.1%) patients: 35 (14.2%) occurred during meningitis, and seven (2.8%) during sepsis. Pulmonary manifestations (mostly pneumonia) were the most prevalent, found in 12 (4.9%) patients, followed by heart involvement in nine (3.6%) patients (mostly pericarditis, in seven or 2.8% patients). Various ophthalmic manifestations occurred in seven (2.8%), arthritis in 4 (1.6%) and sinusitis in six (2.4%) patients. Otitis, multiple renal embolisms with hematuria, osteomyelitis and thrombophlebitis were evidenced in one patient, each. Most of the systemic manifestations (30 patients or 71.4%), developed within the initial three days of the disease (p < 0.01), suggesting direct pathogenic mechanism induced by meningococci per se, while only three (7.1%) developed after seven days, when immune-mediated disease was more likely. Even though these manifestations complicate and prolong treatment of the meningococcal disease, they had no major influence on the disease outcome. Lethal outcome occurred in 2 (4.76%) patients, both with the meningococcal type of the disease. Extrameningeal or systemic manifestations are uncommon complications during the course of both meningococcal meningitis and sepsis. The onset of pneumonia, pericarditis, eye involvement, and arthritis, within the initial seven days of the disease, were most prevalent in the course of meningitis. They had no major influence on the disease outcome.

The relation of cerebrospinal fluid and plasma glycine levels in propionic acidaemia, a ‘ketotic hyperglycinaemia’

The characteristic elevation of plasma glycine concentrations observed in propionic acidaemia (PA) and other 'ketotic hyperglycinaemias' has been attributed to secondary inhibition of the hepatic glycine cleavage system (GCS) by accumulating CoA derivatives of branched-chain amino acid metabolites. In nonketotic hyperglycinaemia (NKH), cerebrospinal fluid (CSF) and plasma glycine levels and their ratio are increased due to primary deficiency of central nervous system (CNS) as well as hepatic GCS. Whether the GCS in the CNS is also inhibited in PA is unclear, as there are scant data available on CSF glycine levels in this disorder. We studied the relation of CSF and plasma glycine levels in 6 paired samples from 4 PA patients, including one PA patient with bacterial meningitis who underwent ventriculoperitoneal shunting and multiple CSF analyses (n = 26). In contrast to the CSF glycine levels which were generally elevated in all four PA patients, the CSF/plasma glycine concentration ratios in paired samples were normal (0.016-0.029), with the exception of a single sample (0.132) with extremely high CSF protein concentration (2010 mg/L) during the course of meningitis indicating a disturbed blood-brain barrier. This finding of normal CSF/plasma glycine ratio in PA suggests that the observed elevations of CSF glycine levels are a reflection of the concurrent hyperglycinaemia resulting from secondary inhibition of hepatic GCS, but that brain GCS is not affected, in contrast to the situation in NKH. The neurological sequelae in PA are therefore unlikely to be related to disturbed glycine metabolism.

Response to ‘Benefits of glucocorticoids in the treatment of bacterial meningitis in children: End of the controversy?’

Response to ‘Benefits of glucocorticoids in the treatment of bacterial meningitis in children: End of the controversy?’