Cerebrospinal Fluid Laboratory Research Articles

Neonatal CSF glucose measured by blood gas analyzer, glucometer, and standard laboratory methods.

To determine agreement between neonatal cerebrospinal fluid (CSF) glucose measured by standard laboratory method versus blood gas analyzers (BGA) and glucometers. This prospective, observational, cross-sectional study was conducted in a level III neonatal unit on 97 neonates undergoing lumbar puncture. Agreement was estimated by Lin's coefficient of concordance and Bland-Altman plot. Lin's coefficient of concordance between the CSF laboratory and BGA glucose values was higher than that between CSF laboratory and glucometer glucose {P value < 0.001}. Bland-Altman plot of CSF glucose values by laboratory and BGA methods showed a bias of -0.137 mmol/l. The plot of laboratory versus glucometer methods showed a bias of -0.863 mmol/l. A linear regression equation to predict laboratory CSF glucose from BGA values and glucometer values had an R2 of 0.975 and 0.971 respectively. CSF glucose measured by blood gas analyzers may be used as a point-of-care test among neonates. Not applicable.

Research progress on antibody index in the diagnosis and treatment of central nervous system diseases

Cerebrospinal fluid (CSF) laboratory tests are important for diagnosing central nervous system (CNS) diseases. Research on intrathecal immunoglobulin-related indexes has gradually attracted attention. The antibody index, which corrects for the effect of individual blood-brain barrier function on CSF antibody test results, is of great significance in the differential diagnosis, efficacy monitoring and prognostic assessment of CNS diseases. It is expected to become a new index for the diagnosis of CNS diseases. This article reviews the concept of antibody index and the research progress of differential diagnosis and treatment of various CNS diseases in order to provide references for the diagnosis, efficacy monitoring and disease progression assessment of CNS diseases.

Assessment of Preanalytical Cerebrospinal Fluid Handling and Storage Factors on Measurement of Aβ1-42, Aβ1-40, and pTau181 Using an Automated Chemiluminescent Platform.

Standardizing cerebrospinal fluid (CSF) laboratory protocols will improve the reliability and availability of clinical biomarker testing required for prescription of novel Alzheimer disease (AD) therapies. This study evaluated several preanalytical handling and storage factors common to β-amyloid1-42 (Aβ1-42), β-amyloid1-40 (Aβ1-40), and phosphorylated tau (pTau181) concentrations including storage at different temperatures, extended cap contact, various mixing methods, and multiple freeze-thaw cycles. Aβ1-42, Aβ1-40, and pTau181 concentrations were measured using LUMIPULSE G1200 automated assays. Samples were collected in polypropylene tubes of various volumes. Sample cap-contact was evaluated by storing samples in upright and inverted positions at either 4°C for 1 week or -80°C for 1 month. To assess mixing methods, samples were freeze-thawed and mixed by inversion, vortex, horizontal roller, or unmixed prior to assay sampling. The impact of successive freeze-thaw cycles was assessed through freezing, thawing, and analyzing CSF samples. Short-term storage at 4°C did not affect Aβ1-42, Aβ1-40, or pTau181 measurements in any tube type. Tube cap contact affected Aβ1-42 in 2.5 mL tubes and pTau181 levels in 10 mL tubes. No difference was observed between mixing methods. After 4 freeze-thaw cycles, Aβ1-42 significantly decreased but Aβ1-40 remained unchanged. Utilizing the Aβ1-42/Aβ1-40 ratio, Aβ1-42 values normalized, maintaining ratio values within ±5% of baseline measurements. Storage of CSF at 4°C for 1 week or -80°C for 1 month did not significantly affect Aβ1-42, Aβ1-40, pTau181, or associated ratio measurements. Tube cap-contact impacted pTau181 and pTau181/Aβ1-42 values in larger tubes. Mixing methods are equivalent. The Aβ1-42/Aβ1-40 ratio compensates for freeze-thaw variability up to 4 cycles.

Concordance rate between oligoclonal bands and the Kappa index in patients with suspected multiple sclerosis (MS).

Oligoclonal bands (OCBs) and Kappa free light chains (FLCs) in the cerebrospinal fluid (CSF) are sensitive markers of intrathecal immunoglobulin (Ig)G synthesis in patients with multiple sclerosis. To evaluate the concordance rate between OCBCs and the Kappa index (KI) in patients with suspected multiple sclerosis (MS). Patients with suspected MS were referred to a specialized CSF laboratory as part of their diagnostic investigation. Paired CSF and serum samples were collected and submitted to detection of OCBs and determination of the KI. Positive and negative results were determined with both methods, and the percentage of agreement between them was established. In total, 171 serum and CSF samples from 171 patients were included in the analysis. The mean age of the patients was of 40 ± 14.2 years; 18.9% of them were male, and 81.1% were female. The OCBs and KI presented concordant results in 161 (94.2%) samples: in 74 (43.3%), both were positive, and in 87 (50.9%), both were negative. In 10 cases, the results were discrepant: KI positive/OCB negative in 8 and OCB positive/KI negative in 2 cases. The KI and OCBs presented high concordance level. Currently, the detection of OCBs in the CSF is the standard method for MS diagnosis, but it is time-consuming, and its visual interpretation can be difficult. The results suggest that the KI is a good alternative for the detection of intrathecal immunoproduction in cases of suspected MS.

Characterizing the association between CSF biomarkers and risk for ventriculoperitoneal shunt following posterior fossa tumor resection in a case-control study

BackgroundRecalcitrant hydrocephalus necessitating permanent cerebrospinal fluid (CSF) diversion is a known complication after resection of a posterior fossa tumor (PFT). Various CSF contents, such as protein and other markers, have been variably correlated with the need for permanent CSF diversion. This study aims to evaluate which CSF laboratory values are associated with permanent CSF diversion following PFT resection in adults. MethodsThis study queried our multi-institutional database (Central Nervous System Tumor Outcome Registry at Emory; CTORE) consisting of 617 adult patients with PFT resections from 2006 to 2021. Retrospective data was collected from the 89 patients of this cohort that required EVD placement. Patients were stratified into two groups: those that required a shunt following EVD removal (n = 30) and those that did not (n = 40). CSF variables collected included glucose, protein, nucleated cell count, and presence of infection. An unadjusted logistic regression was performed to assess exposures associated with shunt requirement and unadjusted odds ratios (ORs) and their associated 95 % confidence intervals (CIs) were obtained. ResultsImmediately following surgery, no CSF variables were significantly associated with shunt placement. Except for post-operative CSF being not-clear (OR: 4.15 (1.47–12.56), p = 0.009) and CSF glucose (OR: 0.97 (1.03–1.07), p = 0.031) all other variables were not significantly associated with shunt at time point 2. ConclusionIn our retrospective analysis, most routinely collected CSF values were not associated with permanent CSF diversion via a ventriculoperitoneal shunt following PFT resection. Further research is needed to identify other potential predictive markers.

Diagnostic Utility of Cerebrospinal Fluid White Blood Cell Components for the Identification of Bacterial Meningitis in Infants.

To evaluate the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). We identified a cohort of infants discharged from a Pediatrix NICU between 1997 and 2020 who did not have an immunodeficiency, had at least 1 CSF culture collected within the first 120 days of life, and at least 1 CSF laboratory specimen obtained on the day of culture collection. We only included an infant's first CSF culture and excluded cultures from CSF reservoirs and those growing contaminants or nonbacterial organisms. We examined the utility of CSF WBC components to diagnose or predict bacterial meningitis by calculating sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating curve (AUC) at different cutoff values for each parameter. We performed subgroup analysis excluding infants treated with antibiotics the day before CSF culture collection. Of the 20 756 infants that met the study inclusion criteria, 320 (2%) were diagnosed with bacterial meningitis. We found (AUC [95% CI]) CSF WBC count (0.76 [0.73-0.79]), CSF neutrophil count (0.74 [0.70-0.78]), and CSF neutrophil percent (0.71 [0.67-0.75]) had the highest predictive values for bacterial meningitis, even when excluding infants with early antibiotic administration. No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.

Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: a retrospective analysis

BackgroundFew studies have analyzed the clinical characteristics and adverse factors affecting prognosis in older patients with tuberculous meningitis (TBM). This study aimed to compare the clinical characteristics of TBM in older patients with those in younger and middle-aged patients.MethodsThis single-center retrospective study extracted data on the clinical features, cerebrospinal fluid changes, laboratory results, imaging features, and outcomes of patients with TBM from patient medical records and compared the findings in older patients (aged 60 years and older) with those of younger and middle-aged patients (aged 18–59 years).ResultsThe study included 197 patients with TBM, comprising 21 older patients aged 60–76 years at onset, and 176 younger and middle-aged patients aged 18–59 years at onset. Fever was common in both older (81%) and younger and middle-aged patients (79%). Compared with younger and middle-aged patients, older patients were more likely to have changes in awareness levels (67% vs. 40%), peripheral nerve dysfunction (57% vs. 29%), changes in cognitive function (48% vs. 20%), and focal seizures (33% vs. 6%), and less likely to have headache (71% vs. 93%), neck stiffness on meningeal stimulation (38% vs. 62%), and vomiting (47% vs. 68%). The Medical Research Council staging on admission of older patients was stage II (52%) and stage III (38%), whereas most younger and middle-aged patients had stage I (33%) and stage II (55%) disease. Neurological function evaluated on the 28th day of hospitalization was more likely to show poor prognosis in older patients than in younger and middle-aged patients (76% vs. 25%). Older patients had significantly higher red blood cell counts and blood glucose levels, and significantly lower serum albumin and sodium levels than those in younger and middle-aged patients. The cerebrospinal fluid protein levels, nucleated cell counts, glucose levels, and chloride levels did not differ significantly by age.ConclusionIn patients with TBM, older patients have more severe clinical manifestations, a higher incidence of hydrocephalus and cerebral infarction, and longer hospital stays than younger and middle-aged patients. Older patients thus require special clinical attention.

Quantitative evaluation of the thickened dura mater impacting clinical signs in immune-mediated hypertrophic pachymeningitis

ObjectiveThis study evaluated the volume of thickened dura mater lesions and their impact on clinical findings in immune-mediated hypertrophic pachymeningitis (HP). MethodsThe volume of contrast-enhanced dura mater on magnetic resonance imaging was evaluated using the imaging feature quantification system in 19 patients with immune-mediated HP, including 12 with antineutrophil cytoplasmic antibody-related, 4 with IgG4-related, and 3 with idiopathic HP, as well as 10 with multiple sclerosis (MS) as controls. The implications of HP volume on neurological manifestations and cerebrospinal fluid (CSF) laboratory markers were statistically analyzed in patients with immune-mediated HP. ResultsThe volumes of the contrast-enhanced dura mater in the convexity, cranial fossa, and tentorium cerebelli were significantly higher in patients with immune-mediated HP than in those with MS. Among patients with immune-mediated HP, those with cranial nerve (CN) VIII neuropathy had a significantly higher volume of the contrast-enhanced dura mater in the cranial fossa than those without CN VIII neuropathy. The volume of the contrast-enhanced dura mater in the tentorium cerebelli was positively correlated with CSF protein levels. ConclusionQuantification of the thickened dura mater is useful for elucidating the relationship with the clinical findings in immune-mediated HP. Thickened dura mater lesions in the cranial fossa may be implicated in the development of CN VIII neuropathy. The enlargement of HP lesions in the tentorium cerebelli can increase CSF protein levels.

Concomitant West Nile Virus Encephalitis and Ischemic Strokes – A Case Report and Review of the Literature. (P8-10.004)

<h3>Objective:</h3> We report a case of concomitant West Nile virus (WNV) encephalitis and acute ischemic strokes and review the literature documenting cases of WNV encephalitis with associated cerebrovascular disease. <h3>Background:</h3> Cases of WNV have risen since 2002, but neuroinvasive disease in uncommon, occurring in 1 in 150. The most common presentation of neuroinvasive WNV is a meningo-encephalitis. Cerebrovascular presentations are exceedingly rare. <h3>Design/Methods:</h3> We report a case of concomitant neuro-invasive WNV infection and acute stroke. We include magnetic resonance imaging (MRI), serologic and cerebrospinal fluid (CSF) laboratory data, and electroencephalogram (EEG) findings. We also present a review of PubMed, Embase, and Web of Science databases for cases of WNV encephalitis associated with cerebral infarctions. <h3>Results:</h3> A 70-year-old woman without significant cardiovascular history was admitted with depressed level of consciousness, hypophonia, and inability to participate in examination. MRI and computed tomography angiography demonstrated bilateral corona radiata strokes without obvious large vessel occlusion. Transthoracic echocardiogram demonstrated a patent foramen ovale; lower extremity ultrasound did not reveal any venous thrombosis. Low-density lipoprotein was elevated. Urine toxicology screen was positive for cocaine. Poor mental status could not be explained by the infarcts alone thus further testing was pursued. Testing for toxic and metabolic abnormalities was unrevealing. EEG demonstrated mild generalized delta slowing. CSF testing showed elevated WNV IgM and IgG. Upon discharged to a rehabilitation facility, her examination was unchanged from presentation. A review of the literature yielded 28 cases of WNV encephalitis complicated by cerebrovascular disease. Most cases were multi-territorial ischemic strokes but etiology of infarction appears varied. <h3>Conclusions:</h3> Pursuit of uncommon etiologies is imperative when presenting symptoms and imaging are not explained by routine testing. The association of neurotropic viruses and strokes may be underappreciated, and possible pathophysiologic connections remain unexplained. <b>Disclosure:</b> Dr. Hingorani has nothing to disclose. Dr. Feske has received publishing royalties from a publication relating to health care. Dr. Cervantes-Arslanian has nothing to disclose.

Nosocomial outbreaks of aseptic meningitis: A public health concern

Nosocomial outbreaks of aseptic meningitis: A public health concern

Lack of Association between YEASTONE Antifungal Susceptibility Tests and Clinical Outcomes of Cryptococcus Meningitis.

The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species.

A CASE OF COMBINED CENTRAL AND PERIPHERAL DEMYELINATION IN A PATIENT WITH PEDIATRIC MULTIPLE SCLEROSIS AFTER SARS-COV-2 VACCINATION

We present a case of combined central and peripheral demyelination in a patient with pediatric multiple sclerosis after the first dose of ChAdOx1-S (Chimpanzee Adenovirus Oxford 1) vaccination. The patient presented with ascending flaccid quadriparesis with respiratory failure that required mechanical ventilation. The lumbar puncture revealed albuminocytological dissociation, was negative for presence of JCV (John Cunningham Virus) in the CSF (Cerebrospinal Fluid) and ruled out other infections. A few days later he developed anisocoria and multiple new enlarging acute demyelinating lesions in the brain MRI (Magnetic Resonance Imaging). He was treated with intravenous immunoglobulin, corticosteroids and plasma exchange with gradual improvement. All other diseases were excluded via MR Spectroscopy, MR Angiography and serum and CSF laboratory investigations. Seven months later, the patient is under intense physiotherapy and is improving every day.

Diagnostic Accuracy of Urinary Reagent Strip to Determine CSF Chemistry and Cellularity

Background: Cerebrospinal Fluid (CSF) examination is a common investigation to diagnose and evaluate different neurological diseases. The gold standard method of CSF examination is microscopy, biochemistry and culture in a standard laboratory, which require an experienced microscopist and laboratory support. Urinary reagent strip can be a point of care test in such condition. The study aimed to document the diagnostic accuracy of urinary reagent strip for the semi-quantitative analysis of CSF chemistry and cellularity.&#x0D; Materials and methods: One hundred hospitalized patients from the Department of Neurology, Chittagong Medical College Hospital were included in this study. CSF samples of the patients were subjected for the de nitive test (CSF microscopy and laboratory biochemical values) and the index test [Combur-10 urinary reagent strip was used as the index test for protein, glucose, leukocytes and erythrocytes. The diagnostic accuracy of each index test was calculated using different cut-off levels (Glucose 1+ vs. CSF glucose &gt;50 mg/dL, protein 1+ vs. CSF protein &gt;30 mg/dL, leukocyte esterase 1+ positivity vs. &gt;10 granulocytes/mm3 and erythrocyte 1+ positivity versus &gt;5 RBC/mm3 in CSF sample).&#x0D; Results: The diagnostic accuracy of protein estimation by reagent strip shows 100% sensitivity, 84.21% specificity for detection of CSF protein at level 30mg/dl. Glucose reagent strip positivity had 98.8% sensitivity and 75% specificity for detection of CSF glucose at level 50 mg/dl. Leukocyte esterase positivity by test strip had sensitivity of 60% and specificity of 100% for the detection of CSF granulocyte of &gt;10 granulocytes/mm3. The diagnostic accuracy of erythrocyte estimation by reagent strip show 92% sensitivity, 92% specificity for detection of CSF RBC &gt;5 cells/mm3.&#x0D; Conclusion: Urinary reagent strip can be used routinely for rapid analysis of CSF.A resource-limited hospital might find it useful as a point-of-care laboratory workup of CSF.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.21 (2); July 2022; Page 9-13

Cerebrospinal fluid lactate as a predictive biomarker for tuberculous meningitis diagnosis.

The definitive diagnosis of tuberculous meningitis (TBM) is achieved by identifying Mycobacterium tuberculosis (MTb) in cerebrospinal fluid (CSF); however, diagnostic confirmation is difficult due to the inability ofcurrent tests for an effective diagnosis. Our objective was to retrospectively assess the characteristics of CSF lactate (CSF-LA) as an adjunct biomarker in the diagnosis of TBM. 608 CSF laboratory reports were assessed. Of these, 560 had clinically suspected TBM. These were classified as definite (n=36), probable (23), possible (278),or non-TBM (223) according to the international consensus TBM case definitions. An additional 48 CSF samples were negative controls with normal CSF. Against a reference standard of definite TBM, the cut-off value for CSF-LA was 4.0mmol/L, the area under the ROC curve was 0.88 (95% CI, 0.82-0.94; p=0.0001), sensitivity was 69%, specificity 90%, negative predictive value 98%. These diagnostic parameters decreased when calculated against those of the other categories of TBM. CSF-LA exhibited high specificity, efficiency, negative predictive value, and clinical utility index in all the groups studied. CSF-LA is a useful diagnostic marker to rule out TBM when associated with conventional microbiology tests, nucleic acid amplification assays, and clinical algorithms, particularly in endemic areas.

Treatment of Carbapenem-Resistant Multidrug-Resistant Gram-Negative Bacilli with Intracerebroventricular Injection of Polymyxin B: A Retrospective Study.

We evaluated the efficacy and administration time of intraventricular (IVT) polymyxin B in the treatment of carbapenem-resistant and multidrug-resistant/extensively drug-resistant (MDR/XDR) Gram-negative bacilli in central nervous system (CNS) infections and investigated prognostic factors. This retrospective analysis comprised 41 post-surgical carbapenem-resistant CNS infections from October 2016 to October 2021. All patients were treated with effective intravenous antibiotics and IVT polymyxin B. Patient characteristics, therapeutic procedure, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were recorded. The effectiveness of IVT polymyxin B was evaluated using temperature, Glasgow Coma Scale, CSF contents, bacterial clearance rate, cure rate, and mortality. Mortality between early (7 days) and late administration of IVT polymyxin B was compared. Prognostic factors were evaluated using the pupillary light reflex and multiloculated hydrocephalus. The 41 patients acquired carbapenem-resistant MDR/XDR bacteria, including 24 Klebsiella pneumoniae, 15 Acinetobacter baumannii, 3 Pseudomonas aeruginosa, and 1 Enterobacter cloacae. The bacterial clearance rate was 32/41 (78.0%), and 9 patients (22.0%) with uncured bacterial infections died. Adverse events included 1 case of skin pigmentation. Among the 32 cured patients, 31 received a ventriculoperitoneal shunt, and 1 patient had an extraventricular drainage tube removed. Mortality in the late (>7 days) group was higher (39.1% vs 0%, P < 0.05). The group without pupillary light reflex showed a higher death rate (41.2% vs 8.3%; P < 0.05). The multiloculated hydrocephalus group had a higher mortality rate than that of the normal group (34.8% vs 5.6%, P < 0.05). All 32 cured patients were followed up for 9 to 66 months, and all survived without recurrent infections. Intraventricular polymyxin B is an effective treatment for carbapenem-resistant MDR/XDR Gram-negative bacilli, with a 78% cure rate and significant mortality reduction if administered within 7 days of bacterial identification. Multiloculated hydrocephalus and the pupillary light reflex may be used as prognostic indicators of mortality.

A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis.

We performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid (CSF) samples. The intrathecal fraction (IF) of FLCκ was calculated in relation to the hyperbolic reference range. 679 patient samples were used as a discovery cohort (DC). The sensitivity and negative predictive value (NPV) of the FLCκ-IF for the detection of an intrathecal humoral immune response (CSF-specific OCB and/or IF IgG/A/M > 0%) was determined. Based on these data, a diagnostic algorithm was developed and prospectively validated in an independent validation cohort (VC, n = 278). The sensitivity of the FLCκ-IF was 98% in the DC and 97% in the VC with a corresponding NPV of 99%. The use of the FLCκ-IF as a first line analysis would have reduced the Ig and OCB analysis by 62% in the DC and 74% in the VC. The absence of a FLCκ-IF predicts the absence of a humoral intrathecal immune response with a very high NPV of 99%. Thus, integration of our proposed algorithm into routine CSF laboratory analysis could help to reduce analytical efforts.

Etiological Risk Factors Profile of Arterial Ischemic Stroke in Children at A Tertiary Care Children's Hospital

Objective: To determine the etiological risk factors of arterial ischemic stroke (AIS) in children. Study Design: An observational cohort study. Place and Duration of the Study: Neurology department of “The Children's Hospital and Institute of Child Health, Multan”, from January 2020 to December 2020. Methods: Children in the age group from one month of age to 12 years with a history of acute onset of focal neurological deficit of upper motor nerve and positive findings on neuroimaging were included in the study. The workup included baseline lab testing, neuroimaging, cardiac evaluation, and cerebro-spinal fluid (CSF) laboratory testing. We used predesigned proforma for recording the patient's details and the possible etiology of the stroke. Results: In a total of 84 children, 28 (33.3%) were male and 56 (66.7%) were female. Age ranged from 4 months to 11 years with a mean age of 3.4±2.2 years. Etiological risk factors identified in 62 (73.8%) patients and were remained undetermined in 22 (26.2%) patients. The risk factors identified were central nervous system infection arteriopathy in 22 (26.2%), iron deficiency anemia 20 (23.8%), cardiac disorders 11 (13.1%), moyamoya disease in 5 (6.0%), and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes in 4 (4.8%) patients. Practical Implications: It is essential to know the etiology of risk factors responsible for AIS as the management and prognosis are directly influenced by them. Conclusion: Infection-associated arteriopathy was the most common etiological risk factor for arterial ischemic stroke in our study population. Keywords: Anemia, arterial ischemic stroke, central nervous system, moamoya

Immunization Status and the Management of Febrile Children in the Pediatric Emergency Department: What Are We Doing?

Widespread Haemophilus influenzae and Streptococcus pneumoniae immunization has decreased occult bacteremia and bacterial meningitis rates. Practice has evolved in pediatric emergency departments (PEDs) to favor fewer diagnostic tests for and empiric treatment of invasive bacterial infection. We lack evidence-based guidance on evaluation and treatment of unimmunized (UnI) or underimmunized (UnderI) febrile children. This study aims to determine how parental report of immunization status in febrile PED patients impacts rates of diagnostic testing, interventions, and hospital admissions. This is a retrospective cohort study with chart review of encounters of children aged 3 to 36 months presenting to an academic, tertiary care PED in 2019 using International Classification of Diseases-10 code for fever (R50.9). Inclusion criteria were documented fever of 38°C and higher and well appearance. Encounters were excluded if there was a history of chronic illness or documentation of ill appearance or hemodynamic instability. Encounters were grouped by provider-documented immunization status. Fischer exact test and logistic regression compared rates of diagnostic testing (serum, urine or cerebrospinal fluid laboratory studies, and chest radiographs), interventions (intravenous fluid bolus, intravenous antibiotic or steroid administration, respiratory support, or breathing treatment), and hospital admissions between UnderI, UnI, and fully immunized (FI) groups. Of the 1813 encounters reviewed, 1093 (60%) included provider-documented immunization status and 788 (43%) met final inclusion criteria: 23 (2.1%) UnI, 44 (5.8%) UnderI, and 721 (92.1%) FI. The UnderI and UnI children experienced significantly higher rates of laboratory evaluation including complete blood count and blood culture, medical intervention, and antibiotic prescriptions while in the PED. No significant differences were observed for rates of chest radiographs, hospital admissions, or 72-hour PED return visits. Higher rates of laboratory testing and interventions were observed in UnderI and UnI versus FI febrile patients at a PED, likely demonstrating increased clinical suspicion for invasive bacterial infection in this group despite lacking national guidelines. Given continued vaccine hesitancy, further studies are needed for guiding management of febrile UnI and UnderI children presenting for emergency care.

Outcome of Using Intraventricular Plus Intravenous Polymyxin B in Post-neurosurgical Patients With Multi/Extensively Drug-Resistant Gram-Negative Bacteria-Induced Intracranial Infection

IntroductionPost-neurosurgical central nervous system (CNS) infection caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacteria remains a major clinical challenge. This study describes our experience of treating such patients with combined intraventricular (IVT) and intravenous (IV) polymyxin B administration.MethodsThis retrospective study included six patients with post-neurosurgical CNS infections of carbapenem-resistant Acinetobacter baumannii (CRAB) or carbapenem-resistant Klebsiella pneumoniae (CRKP). All patients were treated in the intensive care unit (ICU) of First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between November 2020 and November 2021, and all received IVT plus IV polymyxin B. Data including patients' characteristics, therapeutic process, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were collected.ResultsSix patients with post-neurosurgical CNS infection were enrolled in the study. The patients comprised five males and one female, and the average age was 58 years (range, 38–73 years). Four out of the six cases were CRAB-positive in CSF culture, while two cases were CRKP-positive. The mean duration of polymyxin B administration was 14 ± 5.69 days (range, 6–20 days). The average period of patients reaching CSF sterilization was 10.33 ± 3.67 days (range, 5–14 days). All six cases were cured without acute kidney injury or epilepsy.ConclusionIVT plus IV polymyxin B is a safe and effective treatment for post-neurosurgical patients with intracranial infection caused by MDR/XDR Gram-negative bacteria.

Clinical and Magnetic Resonance Imaging Characteristics of Pediatric Acute Disseminating Encephalomyelitis With and Without Antibodies to Myelin Oligodendrocyte Glycoprotein.

BackgroundMyelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated disorders (MOGADs) have been considered as a new inflammatory disease entity of the central nervous system (CNS) and have heterogeneous clinical and imaging presentations. Acute disseminated encephalomyelitis (ADEM) is one of the most important phenotypes. Our research is aimed to compare the clinical and magnetic resonance imaging (MRI) characteristics of ADEM with or without MOG-IgG in pediatric-acquired demyelinating syndromes (ADSs).Methods and ResultsWe retrospectively reviewed the clinical characteristics, MRI features, and outcomes of pediatric patients with ADSs from March 2017 to February 2021 in our center. MOG-IgG was analyzed by transfected cell-based assay (CBA). Among 46 children with ADEM, 21 children (11 girls and 10 boys) were positive for MOG-IgG. Headache, fever, vomiting, vertigo, ataxia, and decreased muscle strength were common in all enrolled children. No significant difference existed in demographic characteristics, symptoms at an initial episode, or laboratory cerebrospinal fluid (CSF) findings between children with MOG-IgG and children without MOG-IgG. For children with MOG-IgG seropositive ADEM, cerebral MRI showed widespread, poorly demarcated bilateral lesions, especially in cortical and subcortical white matter, and spinal MRI often showed lesions spanning more than three segments. The significant difference in MRI features between the two groups was the presence of lesions in the thalamus and cortical area (p < 0.05). Most children in both groups showed clinical improvement 1 week after immunotherapy and achieved recovery during their hospital stay. Three children with MOG-IgG and four children without MOG-IgG had one or more relapsing courses with median interattack intervals of 4 (range: 1–7) months and 10 (range: 1–24) months, respectively. New clinical symptoms and lesions on cerebral and spinal MRI were found during relapsing courses in two groups. No recurrences were recorded 6–51 months after each patient’s last episode.ConclusionsThere was no significant difference in clinical characteristics between ADEM children with MOG-IgG and ADEM children without MOG-IgG. For children with MOG-IgG seropositive ADEM, cerebral MRI showed large, bilateral lesions and spinal MRI often showed lesions spanning more than three segments. Children achieved a favorable outcome regardless of MOG-IgG serostatus.