Mathematical Simulation and Numerical Computation of the Temperature Profiles in the Peripherals of Human Brain during the Tepid Sponge Treatment to Fever.

BACKGROUND: Fever is one of the frequently occurring diseases in human beings, and the body is said to have befallen in fever if the arterial or internal body temperature rises to 38°C. The patient who suffers from fever is either given paracetamol or tepid sponging or both. OBJECTIVE: This paper is aimed at studying the effects of the tepid sponge in normalizing the high temperature of the human body during fever. Among the various available methods for tepid sponging, the impact of holding a cool wet cloth on the forehead for reducing the fever is analyzed and pictured graphically. METHOD: For analyzing the effects of tepid sponge on the temperature distribution of the domain consisting of scalp, skull, and cerebrospinal fluid (CSF), a cool wet cloth is brought in contact with the skin allowing the heat to transfer from the brain to the wet cloth through these layers. The heat transfer in living biological tissues is different from ordinary heat transfer in other nonliving materials. Therefore, a model based on the bioheat equation has been constructed. The model has been solved by numerical methods for both steady- and unsteady-state cases. The domain, which consists of the scalp, skull, and CSF layers of the human head, has been discretized into four equal parts along the axes of the three-dimensional coordinate system. The forward difference and forward time centered space approximations were employed for numerical temperature distribution results at the nodal points. RESULTS: The effects of tepid sponge in reducing the body temperature with fever at 38°C, 39.5°C, and 41°C have been numerically calculated, and the results were pictured graphically. For transient cases, the corresponding calculations have been carried out at times t = 2 minutes, 4 minutes, and 6 minutes. CONCLUSION: Among all the available remedies to fever, tepid sponging has shown a significant effect in controlling fever.

Prolonged Fever: An Atypical Presentation in MOG Antibody-Associated Disorders.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelinating disorders (MOGAD) are increasingly being recognized in the pediatric age group. Over time, unusual presentations have expanded the clinical presentation. We report 12 cases of MOGAD where prolonged fever (PF) was an important part of the symptom complex during the course of the illness. METHODS: After initial recognition of this atypical clinical presentation, more patients were recruited over 2 years and followed up prospectively. RESULTS: Eight of twelve patients had no clinical/imaging evidence of demyelination until much later in the course. Three clinical presentations recognized were fever of unknown origin (4 of 12), aseptic meningitis (4 of 12), and PF seen concurrently with established acute demyelination syndrome (4 of 12). Leukocytosis, raised inflammatory markers, and cerebrospinal fluid pleocytosis were almost universal. The first two presentations frequently caused diagnostic confusion, as MOGAD was not considered until several weeks after disease onset. The third group was more a therapeutic conundrum on how to manage the PF. Early seizures without encephalopathy were not uncommon and were probably independent of the later-appearing demyelination. CONCLUSIONS: This case series highlights PF as an important component of the pediatric MOGAD symptom complex. MOGAD could be considered in the differential diagnosis of these clinical presentations.

Clinical characterization of benign enterovirus infection in neonates.

ABSTRACT: Enteroviruses is a group of positive single-stranded RNA viruses ubiquitous in the environment, which is a causative agent of epidemic diseases in children and infants. But data on neonates are still limited. The present study aimed to describe the clinical characteristics of enterovirus infection in neonates and arise the awareness of this disease to general public.Between March 2018 and September 2019, data from all of the neonates diagnosed with enterovirus infection were collected and analyzed from neonatal intensive care unit of Zhangzhou Hospital in Fujian, China.A total of 23 neonates were enrolled. All of them presented with fever (100%), and some with rashes (39.1%). The incidence of aseptic meningitis was high (91.3%), but only a small proportion (28.6%) presented with cerebrospinal fluid (CSF) leukocytosis. The positive value for nucleic acid detection in CSF was significantly higher than throat swab (91.3% vs 43.5%, P = .007). Five of the infected neonates presented with aseptic meningitis (23.8%) underwent brain magnetic resonance imaging examination and no craniocerebral injuries were found. Subsequent follow-ups were performed in 15 of them (71.4%) and no neurological sequelae was found.Aseptic meningitis is a common type of enterovirus infection in neonates with a benign course. Nucleic acid detection of CSF has an important diagnostic value. Febrile neonates would be suggested to screen for enterovirus infection in addition to complete septic workup. An unnecessary initiation or earlier cessation of antibiotics could be considered in enterovirus infection, but that indications still need further studies to guarantee the safety.

Listeria rhombencephalitis mimicking acute disseminated encephalomyelitis in a patient without predisposing medical conditions.

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.

Predictors of hospital discharge outcome from the presenting clinical characteristics and the first cerebrospinal fluid analysis among the patients with cryptococcal meningitis.

OBJECTIVE: Prognosticators of the outcome of patients with cryptococcal meningitis (CM) at variable follow-up time has been reported. We aimed to identify prognosticators of an outcome on hospital discharge of treated CM. PATIENTS AND METHODS: The presenting characteristics of CM patients admitted in Songklanagarind Hospital from 2002 to 2017 were retrospectively reviewed. The unfavorable outcome was defined as no improvement or death after starting treatment. The significant differences in clinical presentations between the patients with favorable and unfavorable outcomes were descriptively analyzed. The significant independent predictors from the clinical presentations and the first results of cerebrospinal fluid (CSF) analysis with cut-off values were further defined by multiple logistic regression analysis and shown in adjusted odds ratios (p < 0.05). RESULTS: Sixty-two CM patients were enrolled and 33 (53.2%) of them were females. Their median (IQR) age was 37 (30, 46) years old. HIV serology was positive in 71.0%. Concurrent immunosuppressant use and systemic malignancies were 6.5 and 4.8%, respectively. The median (IQR) days of hospital stay was 18.0 days (12.8, 23.0). Eleven patients had unfavorable outcomes at hospital discharge (8 died, 3 no neurological improvement). Cranial nerve palsy and high CSF protein were dependent predictors for the unfavorable outcome, while high CSF glucose was a protective factor. In addition, CSF protein >270 mg/dL was an independent predictor for the unfavorable outcome when adjusted for other CSF analysis results (adjusted odds ratio 27.1, 95% confidence interval 1.1-678.5, p = 0.034). CONCLUSION: Elevated CSF protein was a significant independent predictor for an unfavorable outcome.

Etiology is the key determinant of neuroinflammation in epilepsy: Elevation of cerebrospinal fluid cytokines and chemokines in febrile infection-related epilepsy syndrome and febrile status epilepticus.

OBJECTIVE: To investigate intrathecal inflammation using cerebrospinal fluid (CSF) cytokines and chemokines in a subgroup of pediatric epilepsy patients with frequent daily seizures. METHODS: We measured 32 cytokines/chemokines using multiplex immunoassay in CSF collected from pediatric patients with febrile infection-related epilepsy syndrome (FIRES)/FIRES-related disorders (FRD; n = 6), febrile status epilepticus (FSE; n = 8), afebrile status epilepticus (ASE; n = 8), and chronic epilepsy with frequent daily seizures (n = 21) and compared the results with noninflammatory neurological disorders (NIND; n = 20) and encephalitis (n = 43). We also performed longitudinal CSF cytokine/chemokine studies in three cases with FIRES/FRD. RESULTS: The median age of onset of seizures was 2.4 years (range = 0.08-12.5). Median CSF timing from the onset of seizures was longer in chronic epilepsy (540 days), whereas FIRES, FSE, and ASE had CSF tested within 1-2 days of onset of seizures (P < .001). The elevation of cytokines/chemokines was higher in FIRES followed by FSE, when compared to chronic epilepsy and NIND controls. Th1-associated cytokines/chemokines (TNF-α, CXCL9, CXCL10, CXCL11), IL-6, CCL2, CCL19, and CXCL1 (P < .05) were elevated in FIRES, in contrast to the elevation of a broader network of cytokines/chemokines in encephalitis. The cytokines/chemokines (CXCL9, CXCL10, CXCL11, and CCL19) were elevated in FSE when compared to ASE despite the similar median seizure duration and timing of CSF testing in relation to seizures. Chronic epilepsy generally lacked significant elevation of cytokines/chemokines despite frequent daily seizures. The median concentrations of the cytokines/chemokines rapidly declined on serial testing during the course of illness in all three FIRES/FRD cases. SIGNIFICANCE: We identify significant differences in CSF cytokine/chemokine profile between FIRES/FRD and encephalitis. The prominent elevation of CSF cytokines and chemokines in FIRES/FRD and to a lesser extent FSE highlights that the cytokine/chemokine elevation is significantly associated with the etiology of the underlying process rather than purely reactive. However, it is unclear whether the immune activation contributes to the disease process.

Cerebrospinal fluid protein and glucose levels in neonates with a systemic inflammatory response without meningitis.

BACKGROUND: It has been estimated that paediatric meningitis without elevated CSF white cell count (pleocytosis) accounts for 0.5-12% of all cases of bacterial meningitis. CSF protein and glucose measurements are therefore essential in management but may be neglected in clinical practice. In order to improve recognition of bacterial meningitis in neonates and to enable adequate management and audit, we investigated whether a systemic inflammatory response in the absence of meningitis is associated with elevated CSF protein and reduced CSF glucose levels. A further aim was to determine whether abnormal levels of these parameters were associated with increased incidence of neurological damage. METHODS: As part of an audit into management of abnormal CSF findings in neonates, we conducted a retrospective analysis of neonates without meningitis as evident from normal CSF white blood cell counts and negative CSF culture. We compared data from neonates with fever (temperature > 38.0 °C) and/or elevated C-reactive protein (CRP) levels (> 5 mg/l) (possible sepsis) with data from neonates without fever or CRP elevation. RESULTS: We analysed results from a total of 244 neonates. CSF protein levels were 0.89 g/l (SD 0.37) in neonates without fever or elevated CRP (n = 26) and not significantly different from neonates with possible sepsis (n = 218) with 0.92 g/l (SD 0.40). CSF glucose levels in infants with possible sepsis were 2.71 (SD 0.83) mmol/l and not significantly different from infants without sepsis with 2.55 mmol/l (SD 0.34). CONCLUSIONS: CSF protein and glucose levels are not affected by a systemic inflammatory response syndrome if there is no meningitis.

Cerebrospinal fluid features in adults with enteroviral nervous system infection.

OBJECTIVES: The aim of this study was to investigate the clinical and laboratory features of adults with nervous system infections caused by enteroviruses, with special emphasis on cerebrospinal fluid (CSF). METHODS: The data of 46 patients who were PCR-positive for enteroviruses in the CSF between 2002 and 2017 were evaluated. RESULTS: Meningitis was the most common clinical manifestation (89%), followed by encephalitis (7%) and isolated cranial nerve involvement (4%). Twenty percent of patients reported a sudden onset of severe headache that led to the initial suspected diagnosis of subarachnoid haemorrhage. General signs of infection, such as fever, elevated C-reactive protein, and an elevated white blood cell count, were found in only 61%. Most patients exhibited consistent inflammatory CSF changes, with elevated cell counts (85%) and blood-CSF barrier dysfunction (83%). Patients with normal CSF cell counts were significantly older, less frequently presented with meningitis, and exhibited lower peripheral white blood cell counts. Sequencing revealed species Enterovirus B in all patients, with most sequences related to echovirus 30. CONCLUSIONS: The absence of CSF pleocytosis, isolated cranial nerve involvement, and only infrequent general signs of infection may impede the diagnosis of enteroviral nervous system infections. A thorough CSF analysis including PCR is essential for a reliable diagnosis.

Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection.

Effects of Binge-Like Ethanol Exposure During Adolescence on the Febrile Response in Rats.

BACKGROUND: Ethanol (EtOH) exposure during different phases of life may increase the risk of infections and cause alterations in the central nervous system. The present study investigated the effects of binge-like EtOH exposure in adolescent rats on the febrile response that was induced by lipopolysaccharide (LPS) and interleukin-1ß (IL-1ß). METHODS: Male rats were exposed to EtOH from postnatal days 25 to 38 in a binge-like pattern. Fever was induced by LPS (5 and 50 µg/kg, intraperitoneally) and evaluated on postnatal days 51 and 63, or by IL-ß (3 ng) and evaluated on postnatal day 51. Hematological parameters, the status of peritoneal macrophages, and plasma and cerebrospinal IL-1ß levels were also evaluated on postnatal day 51. RESULTS: EtOH exposure during adolescence did not alter normal body temperature. However, a significant reduction in the febrile response that was induced by LPS at both doses was observed on postnatal day 51. However, no changes in the febrile response were observed on postnatal day 63 in EtOH-exposed animals. The febrile response that was induced by intracerebroventricular IL-1ß also significantly decreased in animals that received binge-like EtOH exposure during adolescence. Acute oral treatment with EtOH 24 h prior to LPS administration did not alter the febrile response that was induced by LPS. Binge-like EtOH exposure during adolescence did not alter hematological parameters or the number or viability of peritoneal macrophages. Binge-like EtOH exposure did not alter plasma IL-1ß levels but reduced the cerebrospinal fluid levels of this cytokine. CONCLUSIONS: These results suggest that binge-like EtOH exposure during adolescence causes changes in the central nervous system that can impair the febrile response that can be observed after the cessation of EtOH exposure. These changes were reversible and appeared to involve the LPS/IL-1ß system.

Afebrile Infants Evaluated in the Emergency Department for Serious Bacterial Infection.

OBJECTIVES: Afebrile infants 0 to 60 days of age are sometimes evaluated for serious bacterial infection (SBI). Our objective was to describe the clinical and laboratory findings in this population and compare them to their febrile counterparts. METHODS: We performed a retrospective observational study comparing afebrile infants undergoing an SBI evaluation to those evaluated for fever. RESULTS: We included infants who were admitted to the hospital and had at least 2 of 3 following bacterial cultures: blood, urine, or cerebrospinal fluid. Of the 1184 infants presenting to the emergency department with chief complaints that may prompt an SBI evaluation, 579 patients met our inclusion criteria with 362 in the fever group and 217 in the afebrile group. The most common chief complaints in the afebrile group were respiratory symptoms (27%), seizure (22%), vomiting/diarrhea (21%), and apparent life-threatening event (11%). Rates of true-positive blood, urine, and cerebrospinal fluid cultures were 2%, 2.4%, and 0.9% respectively. All cases of bacterial meningitis were in the fever group antibiotics (P = 0.16). Infants with fever were more likely to receive antibiotics (P < 0.001), although there were no statistical differences between the 2 groups in the rates of positive blood or urine cultures. CONCLUSIONS: Afebrile infants make up a significant percentage of SBI evaluations in the emergency department. Respiratory symptoms, vomiting, and seizure-like activity are common presentations. Although rates of bacteremia and urinary tract infection are higher in the febrile group, this did not reach statistical significance, and therefore afebrile infants should still be considered at risk for SBI.

Association between Clinical Outcomes and Hospital Guidelines for Cerebrospinal Fluid Testing in Febrile Infants Aged 29-56 Days.

OBJECTIVE: To describe the association between clinical outcomes and clinical practice guidelines (CPGs) recommending universal cerebrospinal fluid (CSF) testing in the emergency department for febrile infants aged 29-56 days. STUDY DESIGN: Using 2007-2013 administrative data from 32 US children's hospitals, we performed a difference-in-differences analysis comparing 7 hospitals with CPGs recommending universal CSF testing for older febrile infants aged 29-56 days (CPG group) with 25 hospitals without such CPGs (control group). We compared differences in clinical outcomes between older febrile infants with the corresponding differences among younger febrile infants aged 7-28 days. The primary outcome was the occurrence of an adverse event, defined as a delayed diagnosis of bacterial meningitis, mechanical ventilation, placement of a central venous catheter, extracorporeal membrane oxygenation, or in-hospital mortality. Analyses were adjusted for race/ethnicity, sex, median annual household income by zip code, primary insurance source, discharge season, and discharge year. RESULTS: The proportion of older febrile infants undergoing CSF testing was higher (P < .001) in the CPG group (64.8%) than the control group (47.8%). CPGs recommending universal CSF testing for older febrile infants were not associated with significant differences in adverse events (difference-in-differences: +0.31 percentage points, 95% CI -0.18 to 0.85; P = .22). CONCLUSIONS: Hospital CPGs recommending universal CSF testing for febrile infants aged 29-56 days were not associated with significant differences in clinical outcomes.

Management of Hospitalized Febrile Neonates Without CSF Analysis: A Study of US Pediatric Hospitals.

OBJECTIVE: Management of febrile neonates includes obtaining blood, urine, and cerebrospinal fluid (CSF) cultures with hospitalization for empiric parenteral antibiotic therapy. Outcomes and management for neonates were compared based on whether CSF was obtained. METHODS: This multicenter retrospective review of the 2002 to 2012 Pediatric Health Information System database included hospitalized infants aged ≤28 days (neonates) admitted to an inpatient ward with a diagnosis code for fever or neonatal fever. Patients admitted to an ICU or with a complex chronic condition diagnosis code were excluded. Neonates were categorized as full septic workup (FSW; charge codes for blood, urine, and CSF culture or cell count) or as partial septic workup (PSW; charge codes for blood and urine cultures only), and their data were compared. RESULTS: Of 27 480 neonates with a diagnosis code for fever, 14 774 underwent the FSW and 3254 had a PSW. Median length of stay was 2 days for both groups, with no significant difference in readmissions, disposition, or parenteral antibiotic administration. Neonates with a PSW had significantly greater odds of having charge codes for additional laboratory testing and imaging, and they were more likely to receive a diagnosis code for sepsis, meningitis, or bronchiolitis. CONCLUSIONS: Neonates with PSW had lengths of stay and readmission rates similar to those with FSW but were more likely to undergo additional laboratory testing and imaging. Future studies including information about clinical severity and test results may provide additional insight into the variation in practice for this patient population.

Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.

OBJECTIVE: The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients. DESIGN: Prospective, open-label, observational, cohort study. SETTING: Neurosurgical ICU, Chang Gung Memorial Hospital. PATIENTS: Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis. INTERVENTION: Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1ß, interleukin-6, interleukin-8, transforming growth factor-ß, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques. MEASUREMENT AND MAIN RESULTS: Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1ß, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever. CONCLUSION: The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1ß, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.