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Cureus Jun 2021Inflammation of the meningeal linings of the central nervous system (CNS), also known as meningitis, is one of the serious presentations in the emergency because it...
Inflammation of the meningeal linings of the central nervous system (CNS), also known as meningitis, is one of the serious presentations in the emergency because it carries high morbidity and mortality. The most common cause is pus-producing organisms. However, non-suppurative meningitis, termed aseptic meningitis, is another cause of meningeal inflammation. Many etiologies stand behind aseptic meningitis. Those etiologies include viral and non-viral, drug-induced, malignancy, and systemic inflammation. Drug-induced aseptic meningitis is a rare type of meningitis. Although it is easily treated, it can be a challenging disease if not present in the differential diagnosis. It is commonly associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Nonetheless, other medications have been also reported to cause aseptic meningitis, including antibiotics. Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most prescribed antibiotics as a prophylactic and therapeutic drug due to its effectiveness and low cost. Although immunocompromised patients are at a higher risk to develop aseptic meningitis, immunocompetent patients are also at risk. Unrelated to the source of the infection, TMP-SMX carries a risk of aseptic meningitis and should be considered as an etiology in patients presenting with meningeal signs and symptoms. Hereby, we report a young immunocompetent patient who developed aseptic meningitis eight days after being prescribed TMP-SMX. Like all drug-induced aseptic meningitis, all his symptoms resolved two days after stopping the medication.
PubMed: 34327094
DOI: 10.7759/cureus.15869 -
Annals of Clinical and Translational... Dec 2021To determine whether the metabolites of Kynurenine pathway (KP) could serve as biomarkers for distinguishing between viral CNS infections and autoimmune...
OBJECTIVE
To determine whether the metabolites of Kynurenine pathway (KP) could serve as biomarkers for distinguishing between viral CNS infections and autoimmune neuroinflammatory diseases, especially anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and herpes virus encephalitis (HSE).
METHODS
This study enrolled CSF samples from 76 patients with viral CNS infections, autoimmune neuroinflammatory, and non-inflammatory neurological diseases. We measured cerebrospinal fluid (CSF) concentrations of tryptophan (Trp) and kynurenine (Kyn) by ELISA.
RESULTS
Kyn concentrations and Kyn/Trp ratios were highly increased (p < 0.001, viral vs. autoimmune) in viral CNS infections, whereas patients with autoimmune neuroinflammatory and non-inflammatory diseases exhibited low concentrations. Furthermore, Kyn concentrations and Kyn/Trp ratio turned out to be excellent biomarkers to distinguish between herpes simplex encephalitis (HSE) and NMDARE (AUC 0.920 and AUC 0.906), whereas Trp concentrations were similar in all three groups.
INTERPRETATION
The results suggest that elevated CSF Kyn concentrations and Kyn/Trp ratio may serve as biomarkers for distinguishing viral CNS infections from autoimmune neuroinflammatory diseases. In particular, the distinction between HSE and NMDARE is of great clinical relevance. Further studies are warranted to investigate the potential of CSF Kyn levels and Kyn/Trp ratio as routine parameters in patients with CNS diseases.
Topics: Adult; Aged; Aged, 80 and over; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Biomarkers; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; Humans; Hydrocephalus, Normal Pressure; Kynurenine; Male; Meningitis, Viral; Middle Aged; Multiple Sclerosis; Pseudotumor Cerebri; Signal Transduction; Tryptophan; Young Adult
PubMed: 34623755
DOI: 10.1002/acn3.51383 -
Annals of Medicine and Surgery (2012) Jan 2024Meningitis, an inflammatory disease affecting the meningeal layers of the brain and the spinal cord, poses a significant public health concern globally. Most meningitis... (Review)
Review
Meningitis, an inflammatory disease affecting the meningeal layers of the brain and the spinal cord, poses a significant public health concern globally. Most meningitis cases are caused by viral infections, bacterial infections being the second most common cause, while fungal or parasitic infections are deemed rare. Despite the decrease in bacterial meningitis because of vaccination and treatment, a recent meningitis outbreak in the United States and Mexico highlighted ongoing challenges. The current meningitis outbreak is caused by a pathogenic fungus and is associated with surgical procedures performed under spinal anaesthesia as reported by the Centers for Disease Control and Prevention (CDC) on the 11 May of 2023. Around 20 cases with clinical suspicion of meningitis, including two fatalities, have been attributed to this rampant outbreak. Timely diagnosis, utilising diagnostic modalities such as lumbar puncture and pathogen detection methods, is crucial for appropriate management. Iatrogenic meningitis must be avoided by enhancing surveillance, infection control procedures, and adherence to aseptic practices. To lessen the effects of meningitis and enhance patient outcomes, the WHO's roadmap and preventive interventions, such as targeted immunisations, are essential.
PubMed: 38222676
DOI: 10.1097/MS9.0000000000001463 -
Frontiers in Pediatrics 2022Meningitis is an inflammation of the brain and spinal cord meninges caused by infectious and non-infectious agents. Infectious agents causing meningitis include viruses,... (Review)
Review
Meningitis is an inflammation of the brain and spinal cord meninges caused by infectious and non-infectious agents. Infectious agents causing meningitis include viruses, bacteria, and fungi. Viral meningitis (VM), also termed aseptic meningitis, is caused by some viruses, such as enteroviruses (EVs), herpesviruses, influenza viruses, and arboviruses. However, EVs represent the primary cause of VM. The clinical symptoms of this neurological disorder may rapidly be observed after the onset of the disease, or take prolonged time to develop. The primary clinical manifestations of VM include common flu-like symptoms of headache, photophobia, fever, nuchal rigidity, myalgia, and fatigue. The severity of these symptoms depends on the patient's age; they are more severe among infants and children. The course of infection of VM varies between asymptomatic, mild, critically ill, and fatal disease. Morbidities and mortalities of VM are dependent on the early recognition and treatment of the disease. There were no significant distinctions in the clinical phenotypes and symptoms between VM and meningitis due to other causative agents. To date, the pathophysiological mechanisms of VM are unclear. In this scientific communication, a descriptive review was performed to give an overview of pediatric viral meningitis (PVM). PVM may occasionally result in severe neurological consequences such as mental retardation and death. Clinical examinations, including Kernig's, Brudzinski's, and nuchal rigidity signs, were attempted to determine the clinical course of PVM with various success rates revealed. Some epidemiological correlates of PVM were adequately reviewed and presented in this report. They were seen depending mainly on the causative virus. The abnormal cytological and biochemical features of PVM were also discussed and showed potentials to distinguish PVM from pediatric bacterial meningitis (PBM). The pathological, developmental, behavioral, and neuropsychological complications of PVM were also presented. All the previously utilized techniques for the etiological diagnosis of PVM which include virology, serology, biochemistry, and radiology, were presented and discussed to determine their efficiencies and limitations. Finally, molecular testing, mainly PCR, was introduced and showed 100% sensitivity rates.
PubMed: 35783317
DOI: 10.3389/fped.2022.923125 -
PloS One 2021Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for...
OBJECTIVES
Meningitis is a medical emergency with permanent disabilities and high mortality worldwide. We aimed to determine causative microorganisms and potential markers for differentiation between bacterial and viral meningitis.
METHODOLOGY
Adult patients with acute meningitis were subjected to lumber puncture. Cerebrospinal fluid (CSF) microorganisms were identified using Real-time PCR. PCT and CRP levels, peripheral and CSF-leucocyte count, CSF-protein and CSF-glucose levels were assessed.
RESULTS
Out of 80 patients, infectious meningitis was confirmed in 75 cases; 38 cases were bacterial meningitis, 34 cases were viral meningitis and three cases were mixed infection. Higher PCT, peripheral and CSF-leukocytosis, higher CSF-protein and lower CSF-glucose levels were more significant in bacterial than viral meningitis patients. Neisseria meningitides was the most frequent bacteria and varicella-zoster virus was the most common virus. Using ROC analyses, serum PCT and CSF-parameters can discriminate bacterial from viral meningitis. Combined ROC analyses of PCT and CSF-protein significantly improved the effectiveness in predicting bacterial meningitis (AUC of 0.998, 100%sensitivity and 97.1%specificity) than each parameter alone (AUC of 0.951 for PCT and 0.996 for CSF-protein).
CONCLUSION
CSF-protein and serum PCT are considered as potential markers for differentiating bacterial from viral meningitis and their combination improved their predictive accuracy to bacterial meningitis.
Topics: Adult; Biomarkers; Diagnosis, Differential; Female; Humans; Male; Meningitis, Bacterial; Meningitis, Viral
PubMed: 34115780
DOI: 10.1371/journal.pone.0251518 -
Frontiers in Neurology 2022Since December 2019, the time when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spotted, numerous review studies have been published on COVID-19... (Review)
Review
Since December 2019, the time when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spotted, numerous review studies have been published on COVID-19 and its neuro invasion. A growing number of studies have reported headaches as a common neurological manifestation of COVID-19. Although several hypotheses have been proposed regarding the association between headache and the coronavirus, no solid evidence has been presented for the mechanism and features of headache in COVID-19. Headache also is a common complaint with the omicron variant of the virus. COVID-19 vaccination also is a cause of new-onset headaches or aggravation of the previous headache in migraine or tension headache sufferers. In this review study, the types of headaches reported in previous studies and their possible pathogenic mechanisms are outlined. To accomplish this objective, various types of headaches are classified and their patterns are discussed according to ICHD-3 diagnostic criteria, including, headaches attributed to systemic viral infection, viral meningitis or encephalitis, non-infectious inflammatory intracranial disease, hypoxia and/or hypercapnia, cranial or cervical vascular disorder, increased cerebrospinal fluid (CSF) pressure, refractive error, external-compression headache, and cough headache. Then, their pathogeneses are categorized into three main categories, direct trigeminal involvement, vascular invasion, and inflammatory mediators. Furthermore, persistent headache after recovery and the predictors of intensity is further investigated. Post-vaccination headache is also discussed in this review.
PubMed: 35911910
DOI: 10.3389/fneur.2022.942956 -
BMC Neurology Dec 2021Depending on geographic location, causes of encephalitis, meningoencephalitis and meningitis vary substantially. We aimed to identify the most frequent causes, clinical... (Observational Study)
Observational Study
BACKGROUND
Depending on geographic location, causes of encephalitis, meningoencephalitis and meningitis vary substantially. We aimed to identify the most frequent causes, clinical presentation and long-term outcome of encephalitis, meningoencephalitis and meningitis cases treated in the Inselspital University Hospital Bern, Switzerland.
METHODS
In this monocentric, observational study, we performed a retrospective review of clinical patient records for all patients treated within a 3-year period. Patients were contacted for a telephone follow-up interview and to fill out questionnaires, especially related to disturbances of sleep and wakefulness.
RESULTS
We included 258 patients with the following conditions: encephalitis (18%), nonbacterial meningoencephalitis (42%), nonbacterial meningitis (27%) and bacterial meningoencephalitis/meningitis (13%). Herpes simplex virus (HSV) was the most common cause of encephalitis (18%); tick-borne encephalitis virus (TBEV) was the most common cause of nonbacterial meningoencephalitis (46%), enterovirus was the most common cause of nonbacterial meningitis (21%) and Streptococcus pneumoniae was the most common cause of bacterial meningoencephalitis/meningitis (49%). Overall, 35% patients remained without a known cause. After a median time of 16 months, 162 patients participated in the follow-up interview; 56% reported suffering from neurological long-term sequelae such as fatigue and/or excessive daytime sleepiness (34%), cognitive impairment and memory deficits (22%), headache (14%) and epileptic seizures (11%).
CONCLUSIONS
In the Bern region, Switzerland, TBEV was the overall most frequently detected infectious cause, with a clinical manifestation of meningoencephalitis in the majority of cases. Long-term neurological sequelae, most importantly cognitive impairment, fatigue and headache, were frequently self-reported not only in encephalitis and meningoencephalitis survivors but also in viral meningitis survivors up to 40 months after acute infection.
Topics: Communicable Diseases; Encephalitis; Humans; Meningitis, Bacterial; Meningoencephalitis; Retrospective Studies
PubMed: 34872509
DOI: 10.1186/s12883-021-02502-3 -
Frontiers in Neurology 2022Cryptococcal meningoencephalitis (CM) continues to cause major morbidity and mortality in a range of patients such as those immunosuppressed from HIV and with biologic... (Review)
Review
Cryptococcal meningoencephalitis (CM) continues to cause major morbidity and mortality in a range of patients such as those immunosuppressed from HIV and with biologic immunosuppressants, including treatments of autoimmunity, malignancies, and conditioning regimens for transplantation. It is currently the most common cause of non-viral meningitis in the United States. Infections in previously healthy patients also develop with autoantibodies to granulocyte-macrophage colony stimulating factor or with monogenetic defects. In all populations, mortality and significant long-term morbidity occur in 30-50% despite therapy, and immune reconstitution and post-infectious inflammatory response syndromes complicate management. To help with these difficult cases, we present here a practical tutorial of the care of a range of patients with CM in the absence of HIV/AIDS.
PubMed: 36530631
DOI: 10.3389/fneur.2022.994396 -
Frontiers in Immunology 2023In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give...
In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give rise to Tim-3+PD-1+ terminally differentiated CD8 T cells that retain their effector functions. Tpex cells are thus essential to maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation, and only they respond to PD-1-targeted therapy. Despite their potential as a crucial therapeutic target for immune interventions, the mechanisms controlling the maintenance of virus-specific Tpex cells remain to be determined. We observed approximately 10-fold fewer Tpex cells in the spleens of mice chronically infected with lymphocytic choriomeningitis virus (LCMV) one-year post-infection (p.i.) than at three months p.i. Similar to memory CD8 T cells, Tpex cells have been found to undergo self-renewal in the lymphoid organs, prominently the bone marrow, during chronic LCMV infection. Furthermore, treatment with IL-15 preferentially induced the proliferation of Tpex cells rather than the terminally differentiated subsets. Interestingly, single-cell RNA sequencing analysis of LCMV-specific exhausted CD8 T cells after IL-15 treatment compared with those before treatment revealed increased expression of ribosome-related genes and decreased expression of genes associated with the TCR signaling pathway and apoptosis in both Tpex and Ttex subsets. The exogenous administration of IL-15 to chronically LCMV-infected mice also significantly increased self-renewal of Tpex cells in the spleen and bone marrow. In addition, we assessed the responsiveness of CD8 tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma patients to IL-15. Similar to the data we obtained from chronic viral infection in mice, the expansion of the Tpex subset of PD-1+ CD8 TILs upon IL-15 treatment was significantly higher than that of the terminally differentiated subset. These results show that IL-15 could promote self-renewal of Tpex cells, which has important therapeutic implications.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Interleukin-15; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Programmed Cell Death 1 Receptor; Signal Transduction
PubMed: 37409128
DOI: 10.3389/fimmu.2023.1117092 -
Pediatric Emergency Care Jan 2022A sepsis workup is recommended in young infants 56 days or younger with fever to rule out a serious bacterial infection (SBI). Given the reduction in non-severe acute...
OBJECTIVES
A sepsis workup is recommended in young infants 56 days or younger with fever to rule out a serious bacterial infection (SBI). Given the reduction in non-severe acute respiratory syndrome - coronavirus 2 viral infections observed in multiple studies during the coronavirus diseases 2019 (COVID-19) pandemic, we sought to determine if the reduction in viral infections led to a change in the incidence of SBI in this vulnerable patient population.
METHODS
We performed a multicenter, retrospective study of infants 56 days or younger presenting with fever to emergency departments of 6 community hospitals. We compared the incidence of SBIs, viral meningitis, and viral bronchiolitis during March 2020 to February 2021 (pandemic year) with the same calendar months in the 2 preceding years (prepandemic years).
RESULTS
From March 2018 to February 2021, 543 febrile infants presented to the emergency departments, 95 during the pandemic year (March 2020 to February 2021) compared with 231 and 217 in the prepandemic years (March 2018 to February 2019 and March 2019 to February 2020, respectively).During the pandemic year, 28.4% of infants (27 of 95) were diagnosed with an SBI compared with 11.7% and 6.9% (P < 0.001) in the prepandemic years (27 of 231 and 15 of 217, respectively). Five patients were diagnosed with bacterial meningitis over the 3-year period, 4 of them during the pandemic year (4 of 95 [4.2%]). Positivity for viral cerebrospinal fluid polymerase chain reaction during the pandemic year was 6.4% (3 of 47) compared with 20.8% (25 of 120) and 20.4% (23 of 113) in prepandemic years (P = 0.070). During the pandemic year, 2.1% (2 of 95) febrile young infants were admitted with a comorbid diagnosis of bronchiolitis compared with 4.3% and 6.0% in the prepandemic years (P = 0.310).
CONCLUSIONS
The COVID-19 pandemic led to an increase in the incidence of SBIs in febrile infants 56 days or younger, likely a result of reduction in non-severe acute respiratory syndrome - coronavirus 2 viral infections. Greater vigilance is thus warranted in the evaluation of febrile infants during the COVID-19 pandemic.
Topics: Bacterial Infections; COVID-19; Humans; Infant; Infant, Newborn; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 34986582
DOI: 10.1097/PEC.0000000000002601