Search

Introduction. Nosocomial meningitis (NM) is one of the leading complications in neurosurgery due to high mortality and disability rates.Objective. The study was aimed to determine the reference values of laboratory parameters to diagnose NM in neurosurgical patients in the intensive care unit (ICU).Results. The incidence of NM in neurosurgical patients in ICU was 8.4 (95% CI 6.8–10. 0) per 100 patients. The dominant microbial agents of NM were coagulase-negative staphylococci, A. baumannii, and K. pneumoniae. We revealed the increase in leukocytosis, C-reactive protein, and blood procalcitonin in patients with infectious complications of other systems, regardless of NM presence. Episodes of hyponatremia and an increase in body temperature ≥ 38.0 occurred signifcantly more often in patients with NM. Changes in cerebrospinal fluid (CSF) cytosis, glucose, lactate, and the CSF/blood glucose ratio can serve as reliable criteria in the NM diagnosis.Conclusions. The diagnosis of NM is most likely when the increase in CSF cytosis > 65 cells/μL, CSF lactate > 4.2 mmol/L is observed, the decrease in the CSF glucose < 2.6 mmol, and CSF/blood glucose ratio < 0.45 is found.

Primary immunodeficiencies are disorders that cause clinical findings ranging from mild diseases to life-threatening diseases in a wide age range. Infections are the most common complications of primary immunodeficiencies. Caspase associated recruitment domain-9 (CARD9) is a protein that plays a role in fungal immune response. CARD9 deficiency is one of the primary immunodeficiency disorders that show autosomal recessive inheritance and can cause different clinical pictures. It has been associated with various fungal infections such as superficial or deep dermatophytosis, invasive pheohifomycosis, cutaneous mucormycosis, extrapulmonary aspergillosis, mucocutaneous or invasive candidiasis. The most common infections in CARD9 deficiency are caused by Candida spp. In this report, a case of Candida albicans meningoencephalitis due to CARD9 deficiency was presented. It was learned from the medical story that a 37 years old male patient had no known disease or drug use, but had recurrent oral candidiasis and cutaneous fungal infections since childhood, and received liposomal amphotericin B treatment with the diagnosis of C.albicans meningoencephalitis two months ago. It was learned that he was discharged with voriconazole treatment after clinical improvement, and he stopped the voriconazole treatment after discharge and did not go for follow-up. The patient, who reapplied 1.5 months after discharge with complaints of headache, vomiting and altered consciousness, did not have fever and neck stiffness, and Kerning and Bruzinski sign was negative. An external ventricular drainage (EVD) catheter was inserted after hydrocephalus was detected in the brain computerized tomography (CT). In the cerebrospinal fluid (CSF) examination, erythrocyte count was detected as 340/mm3, and no leukocytes were seen. CSF protein level was 28 mg/dl, CSF glucose level was 59 mg/dl (simultaneous blood glucose level was 104 mg/dl). There was no yeast or bacteria in CSF Gram staining and no acidfast bacteria in Ziehl-Neelsen staining. It was learned that there was no growth in the Mycobacterium tuberculosis culture made from CSF sample taken at the first admission of the patient. Serum human immunodeficiency virus antibody was negative. Upon learning of fluconazole-susceptible C.albicans growth in the control CSF culture of the patient, the EVD catheter was changed, and liposomal amphotericin B treatment was started. CSF culture was repeated. Fluconazole-susceptible C.albicans continued to grow in CSF cultures repeated in the follow-ups. No pathology in favor of abscess was detected in the brain magnetic resonance imaging. Fluconazole was added to the current liposomal amphotericin B treatment. Having a history of recurrent mucocutaneous fungal infection in the patient and his siblings, whose parents were third-degree relatives, suggested CARD9 deficiency. In the molecular test studied from blood samples, homozygous p.Q295X mutation due to CARD9 deficiency was detected in the patient and his sister. However, the patient died on the 62nd day of hospitalization due to delayed diagnosis, cerebral complications due to recurrent C.albicans meningoencephalitis, and insufficient treatment as a result of failure to receive the granulocyte colony stimulating factor (G-CSF) treatment. Persistent fungal infections that develop in CARD9 deficiency cause serious complications and mortality. Considering the frequency of CARD9 deficiency in the Turkish population and the lack of diagnostic testing in our country, it is thought that there may be many patients who cannot be diagnosed and who progress with mortality or morbidity. In conclusion, this case was presented to emphasize the consideration of CARD9 deficiency in case of persistent invasive fungal infection or recurrent invasive fungal infection after treatment despite effective antifungal treatment in children and adults who do not have known risk factors for invasive fungal infections.

Background: Yearly, about two million infants die during the first 28 days of life. Most of these deaths occur in sub-Saharan Africa and a third of those are caused by severe infections. The early identification of infants at risk of death is important when trying to prevent poor outcomes. Objective: The aim of this study was to identify risk factors for death among young infants with possible serious bacterial infection (pSBI) at hospital admission. Methods: This prospective, observational, single-site, descriptive study forms part of a larger study on bacterial meningitis in infants

Paroxysmal abnormal eye movement in early infancy is one of the initial symptoms of glucose transporter 1 deficiency syndrome (GLUT1DS). We describe four early infants with transient hypoglycorrhachia presenting with abnormal eye movements. Their symptoms disappeared after the introduction of a ketogenic diet (KD), and their development was normal. Since no variants in SLC2A1 were detected, the CSF-to-blood glucose ratios (C/B) were re-examined, and within normal range. None of the four patients displayed recurrent symptoms after withdrawal from the KD. Because long-term KD has potential adverse effects and could affect the quality of life of patients and their families, re-examination of CSF glucose during late infancy should be considered in the case of absence of the SLC2A1 pathogenic variant.

Introduction The ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population. Methods Prospective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia. Results 97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%. Conclusion Glucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.

Background: Guillain-Barré syndrome (GBS) is an acute autoimmune polyneuroradiculopathy characterized by flaccid paralysis which may lead to respiratory failure requiring intensive care. Objective: The purpose of the present study was to explore the relationship between the fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and disease severity of GBS patients who are not known to have DM. Methodology: This cross-sectional study included adult GBS patients without having DM [age 35 (22-48) years, median (interqurtile range, IQR); 39 male 22 female] who were admitted to Neurology department, National Institute of Neurosciences and Hospital, Dhaka, Bangladesh from July 2018 to June 2019. Demographics, clinical data were noted and FPG, HbA1c were measured. Disease severity were assessed by the GBS disability scale ranging from 0 to 6 with increasing score reflecting increased disability. Results: Patients with more severe GBS (disability score ≥4, unable to walk) had higher frequency of elevated FPG >5.5 mmol/L (61.2%; 30/49) in comparison to those with less severe GBS (disability score ≤3, able to walk; FPG >5.5 mmol/L in 16.7%, 2/12; p=0.006). But distribution of HbA1c category was not different across the groups (disability score ≥4 vs. ≤3: HbA1c 6.4: 10% vs. 17%; p=0.296). Participants with elevated FPG were elder [elevated vs. normal FPG: 40 (28-54) vs. 25 (19-43) years; median (IQR), p=0.012] and had higher CSF glucose (p=0.002) than those with normal FPG, but there was no difference in respct of gender, MRC sum score, requirement of assisted ventilation, CSF protein, GBS subtypes and duration of hospital stay (p=not significant for all). Conclusions: Patients with severe GBS have higher frequency of elevated FPG but not HbA1c. An acute change in glucose metabolism may occur in GBS which needs further study. Journal of National Institute of Neurosciences Bangladesh, 2020;6(2): 96-100

Subdural empyema (SDE) is a rare condition which can appear secondary to meningitis in childhood, especially in infants. This study was planned to evaluate and compare clinical and laboratory features, treatment, and outcome of children with SDE to those with acute bacterial meningitis (ABM) without SDE. The electronic medical files of 266 patients diagnosed with ABM between January 2009 and December 2019 were evaluated. Patients' demographic and clinical features, laboratory results, cranial imaging findings, treatment, and outcomes were recorded. SDE was identified in 10 patients, 3.7% of all diagnosed with meningitis. The etiology of SDE was identified in eight (80%). The most common responsible pathogen was Streptococcus pneumoniae. Cranial imaging was performed between the 2nd and 13th days of admission, and the most common reason of performing cranial imaging was persistence of fever. Two patients were healed with 4-6 weeks of antibiotic treatment without surgery, eight (80%) needed surgical intervention.Conclusion: The clinical signs and symptoms of SDE may be subtle. If the fever persists or focal neurological findings are seen during the treatment of bacterial meningitis, SDE should be suspected. Furthermore, patients with ABM who are determined to have a protein-to-glucose ratio in the cerebrospinal fluid above 4.65 should be carefully monitored for SDE development. What is known: • Subdural empyema may develop subsequently to meningitis, especially in the infant age group in whom very little is known in terms of disease characteristics. • Delay in diagnosis and treatment can cause long-term neurologic sequelae and mortality. What is new: • Persistence or relapse of fever during the treatment of acute meningitis is an important warning sign for SDE even if there are no other symptoms. • Children with subdural empyema secondary to bacterial meningitis have higher protein-to-glucose ratio in the CSF, and a threshold of ˃ 4.65 was determined to demonstrate 100% sensitivity and 50.7% specificity.

Background: Meningitis is an inflammation of the leptomeninges. The inflammation may be caused by infection with viruses, bacteria, other micro-organisms, or non-infective causes. Objective: The aim of this study was to evaluate the role of CSF-Presepsin in diagnosis of bacterial meningitis and in differentiation between bacterial and viral meningitis or aseptic meningitis. Patients and methods: The present study was a cross sectional study conducted in Intensive Care Unit and Pediatric Departments of El-Hommyat Hospital in Zagazig in the period from January 2017 to November 2017. The study included 50 patient of children with age from 6 months to 14 years with symptoms of CNS infection. Among the studied subjects there were 30 cases already diagnosed as bacterial meningitis and 20 cases already diagnosed to have viral meningitis (controls). Full history, clinical examination, and full laboratory tests were taken (Complete blood count (CBC) with differential leukocytic count, random blood sugar, serum CRP, and CSF analysis, CSF presepsin (psp) and CRP). Results: There was a significant increase in Presepsin and CRP in the CSF of cases of bacterial when compared to viral group. Additionally, there were significant direct correlation between CSF presepsin and CSF CRP to blood CRP, CSF total leucocytic count (TLC) and CSF protein and indirect correlation between CSF presepsin and hemoglobin level, platelet count and CSF glucose. Conclusion: CSF-Presepsin and CSF-CRP can be used in diagnosis of bacterial meningitis and can differentiate between them in bacterial and viral patients.

BACKGROUND AND PURPOSE: Bacterial meningitis most commonly affects young children and can result in critical adverse outcomes, including sensorineural hearing loss (SNHL). The purpose of this study is to determine the diagnostic accuracy of MR imaging for predicting the development of SNHL among infants with bacterial meningitis. MATERIALS AND METHODS: A retrospective review was performed among infants (age

Background: Pituitary apoplexy (PA) is a rare but potentially life-threatening condition that may require urgent surgical intervention.Case Presentation: We report a case of a patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, but was eventually diagnosed with PA. We present a summary of other cases reported in the literature of PA mimicking ME and analyze their clinical features and CSF findings.Results: Among all 22 PA cases reviewed, headache was the most commonly reported symptom. Hypopituitarism was seen in 94.4% of the cases; of these, panhypopituitarism was noted in 38.9%. The sensitivity of magnetic resonance image (MRI) for detecting PA was 94.7%, much higher than that of computed tomography (CT), which was only 31.6%. Neutrophil predominant pleocytosis was present in all cases with a neutrophil percentage ranging from 73% to 98%. CSF leukocyte count was less than 1000/ul in 86% of the cases. CSF erythrocytosis was seen in 92.9% of the cases with a count ranging from 15 to 2030/ul. Elevated CSF protein was present in all cases with a range of 69.8 to 239 mg/dl. CSF glucose level varied with a range between 12 and 136 mg/dl; the level was greater than 40 mg/dl in 73% of the cases.Conclusion: PA tends to be misdiagnosed as ME due to the similarities of semiology and CSF findings. PA should be considered in refractory acute headache cases, especially those with visual and endocrine abnormalities. Early recognition and treatment may lead to significant reduction in morbidity and mortality.Abbreviations: ACTH: adrenocorticotropic hormone; CSF: cerebrospinal fluid; CT: computed tomography; GRE: gradient echo; HRT: hormone replacement therapy;HSV: Herpes Simplex Virus; IV: intravenous; ME: meningoencephalitis; MRI: magnetic resonance image; PA: pituitary apoplexy; RBC: red blood cell; WBC: white blood cell.

Systemic infection triggers a spectrum of metabolic and behavioral changes, collectively termed sickness behavior, which while adaptive, can affect mood and cognition. In vulnerable individuals, acute illness can also produce profound, maladaptive, cognitive dysfunction including delirium, but our understanding of delirium pathophysiology remains limited. Here, we used bacterial lipopolysaccharide (LPS) in female C57BL/6J mice and acute hip fracture in humans to address whether disrupted energy metabolism contributes to inflammation-induced behavioral and cognitive changes. LPS (250 µg/kg) induced hypoglycemia, which was mimicked by interleukin (IL)-1β (25 µg/kg) but not prevented in IL-1RI−/− mice, nor by IL-1 receptor antagonist (IL-1RA; 10 mg/kg). LPS suppression of locomotor activity correlated with blood glucose concentrations, was mitigated by exogenous glucose (2 g/kg), and was exacerbated by 2-deoxyglucose (2-DG) glycolytic inhibition, despite preventing IL-1β synthesis. Using the ME7 model of chronic neurodegeneration in female mice, to examine vulnerability of the diseased brain to acute stressors, we showed that LPS (100 µg/kg) produced acute cognitive dysfunction, selectively in those animals. These acute cognitive impairments were mimicked by insulin (11.5 IU/kg) and mitigated by glucose, demonstrating that acutely reduced glucose metabolism impairs cognition selectively in the vulnerable brain. To test whether these acute changes might predict altered carbohydrate metabolism during delirium, we assessed glycolytic metabolite levels in CSF in humans during inflammatory trauma-induced delirium. Hip fracture patients showed elevated CSF lactate and pyruvate during delirium, consistent with acutely altered brain energy metabolism. Collectively, the data suggest that disruption of energy metabolism drives behavioral and cognitive consequences of acute systemic inflammation. SIGNIFICANCE STATEMENT Acute systemic inflammation alters behavior and produces disproportionate effects, such as delirium, in vulnerable individuals. Delirium has serious short and long-term sequelae but mechanisms remain unclear. Here, we show that both LPS and interleukin (IL)-1β trigger hypoglycemia, reduce CSF glucose, and suppress spontaneous activity. Exogenous glucose mitigates these outcomes. Equivalent hypoglycemia, induced by lipopolysaccharide (LPS) or insulin, was sufficient to trigger cognitive impairment selectively in animals with existing neurodegeneration and glucose also mitigated those impairments. Patient CSF from inflammatory trauma-induced delirium also shows altered brain carbohydrate metabolism. The data suggest that the degenerating brain is exquisitely sensitive to acute behavioral and cognitive consequences of disrupted energy metabolism. Thus “bioenergetic stress” drives systemic inflammation-induced dysfunction. Elucidating this may offer routes to mitigating delirium.

Bacterial meningitis (BM) is associated with a high morbidity and mortality. Cerebrospinal fluid (CSF) lactate may be used as a prognostic marker of this condition. We hypothesized that CSF lactate levels would remain elevated in participants who died of acute BM compared with those who recovered from this disease. Objective: To evaluate the potential use of lactate and other CSF biomarkers as prognostic markers of acute BM outcome. Methods: This retrospective, longitudinal study evaluated dynamic CSF biomarkers in 223 CSF samples from 49 patients who fulfilled the inclusion criteria of acute BM, with bacteria identified by CSF culturing. The participants were grouped according to outcome: death (n = 9; 18.37%) and survival (n = 40; 81.63%). All participants received appropriate antibiotic treatment. Results: In the logistic regression model, lactate concentration in the final CSF sample, xanthochromia, and CSF glucose variation between the first and last CSF samples were predictors of a poor outcome (death). In contrast, decrease in CSF white blood cell count and CSF percentage of neutrophils, increase in the percentage of lymphocytes, and normalization of the CSF lactate concentration in the last CSF sample were predictors of a good prognosis. Conclusion: The study confirmed the initial hypothesis. The longitudinal analysis of CSF lactate is an important predictor of prognosis in acute BM. RESUMO As meningites bacterianas (MB) estão associadas à alta morbidade e mortalidade. O lactato no líquido cefalorraquidiano (LCR) pode ser usado como biomarcador de prognóstico nas MB. A hipótese desse estudo é que os níveis de lactato no LCR se mantém elevados entre pacientes com MB aguda que evoluem para óbito, ao contrário do que ocorre em pacientes com bom prognóstico. Objetivo: Avaliar o uso potencial do lactato e outros marcadores no LCR como indicador de prognóstico na MB aguda. Métodos: Foi realizado um estudo retrospectivo longitudinal da dinâmica dos biomarcadores bioquímicos, celulares e físicos no LCR. Foram analisadas 223 amostras de 49 pacientes com MB aguda com bactérias identificadas por cultura do LCR. Os participantes foram divididos em dois grupos de acordo com o desfecho: óbito (n = 9; 18,37%) e não óbito (n = 40; 81,63%). Todos os participantes receberam antibioticoterapia adequada. Resultados: No modelo de regressão logística, as variáveis que diferiram significativamente entre os dois grupos foram concentração de lactato na amostra final de LCR, xantocromia e variação da concentração de glicose entre a primeira e a última amostra de LCR. A alteração desses fatores indicou desfechos negativos (óbito), enquanto a diminuição do número de leucócitos e da porcentagem de neutrófilos, assim como a normalização da concentração de lactato no LCR foram preditores de bom prognóstico. Conclusão: O estudo confirmou a hipótese inicial. A análise longitudinal do lactato no LCR é um importante preditor de prognóstico na MB aguda.

This study sought to determine the previously undescribed cytologic and metabolic alterations that accompany endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC). Cerebrospinal fluid (CSF) samples were collected from infant patients with hydrocephalus at the time of index ETV/CPC and again at each reintervention for persistent hydrocephalus. Basic CSF parameters, including glucose, protein, and cell counts, were documented. A multivariable regression model, incorporating known predictors of ETV/CPC outcome, was constructed for each parameter to inform time-dependent normative values. A total of 187 infants were treated via ETV/CPC for hydrocephalus; initial laboratory values were available for 164 patients. Etiology of hydrocephalus included myelomeningocele (53, 32%), intraventricular hemorrhage of prematurity (43, 26%), aqueductal stenosis (24, 15%), and others (44, 27%). CSF parameters did not differ significantly with age or etiology. Glucose levels initially drop below population average (36 to 32 mg/dL) post-operatively before slowly rising to normal levels (42 mg/dL) by 3 months. Dramatically elevated protein levels post-ETV/CPC (baseline of 59 mg/dL up to roughly 200 mg/dL at 1 month) also normalized over 3 months. No significant changes were appreciated in WBC. RBC counts were very elevated following ETV/CPC and quickly declined over the subsequent month. CSF glucose and protein deviate significantly from normal ranges following ETV/CPC before normalizing over 3 months. High RBC values immediately post-ETV/CPC decline rapidly. Age at time of procedure and etiology have little influence on common clinical CSF laboratory parameters. Of note, the retrospective study design necessitates ETV/CPC failure, which could introduce bias in the results.

Background Ventriculoperitoneal (VP) shunting is a permanent form of cerebrospinal fluid (CSF) diversion that can be performed for hydrocephalus. Sterility of the CSF is an important prerequisite for permanent shunt placement. It has been hypothesised that in early stage of meningitis, ventricular CSF remains sterile. A study is conducted on the first CSF sample taken from patients suspected to have meningitic hydrocephalus. Method A retrospective review case records of patients who had undergone external ventricular drainage (EVD) for suspected meningitic hydropcephalus in Hospital Sultanah Aminah Johor Bahru (HSAJB), Johor, Malaysia. Results Fifty-one cases were analysed. Mean age of patients was 37.27 years old, with 64.7% of them was male. Univariate analysis revealed that the main parameters to determine CSF sterility were CSF glucose (95% CI, 0.852, 10.290, P = 0.001), CSF protein (CI 95%, 0.722, 14.898, P < 0.001), CSF gram stain (95% CI, 16.437, 0.877, P < 0.001 ) and CSF appearance ( 0.611, 6.362, P = 0.012). Multivariate analysis had proven that gram stain was the main parameter in the CSF analysis (CI 95%, 16.437, 0.029, P = 0.016). No significant differences in CSF results were observed from EVD and lumbar puncture. Conclusion The most significant parameter in CSF to determine infection was gram stain.

Introduction and importancy Meningitis happening in post spinal anesthesia is rare. But it has potentially life threatening or permanent neurological sequel if delayed or left untreated. The cause can be infectious or noninfectious. In this case, uncommon pathogen is described causing bacterial meningitis. Incidence varies from 0% to 0.04%. Case presentation A term pregnant lady came to the Operation room (OR) for an emergency caesarian section(C/S) because of cervical dystocia. She has no history of known medical illness. The anesthetist planned to administer spinal anesthesia. Under aseptic technique, the senior anesthetist wore a tight-fitting surgical mask, cap, and sterile gloves after hand hygiene with alcohol-based solutions. In sitting positioning between L(lumbar) 3 and L4 interspaces 10 mg bupivacaine +10 μg fentanyl was administered. Surgery and anesthesia were uneventful, 16 h into the postoperative period the mother develop severe headache, agitation, confusion, and forgetfulness. She has no fever but meningeal sign was positive. Lumbar puncture (LP) reveals purulent cerebrospinal fluid (CSF). Immediately, empirical treatment began. CSF sent for analysis and Culture, hematology, urinalysis, and organ function tests requested. Diagnosis was confirmed by clinical picture, low CSF glucose, and high body fluid protein, culture growth; showed Escherichia coli (E.coli). Treatment was instituted and patient has recovered fully. Clinical discussion E.coli is a very rare cause of bacterial meningitis but manifests a similar clinical picture like other bacterial meningitis but in our case no pyrexia. We believe there is a sterility breach somewhere in the process. The use of hospital sterilized spinal set, multidose antiseptics; institute sterility practice might be challenged. Conclusion The use of modern packaging is recommended. Despite absent of pyrexia empiric treatment must start earlier besides the application of national guideline developed by the Joint Commission of different associations including America society of regional anesthesia (ASRA) is recommended., Highlights • Bacterial meningitis post spinal anesthesia is rare but can result life threatening complication. • In this case, uncommon pathogen e.coli1 is causing bacterial meningitis .as to me no reported cases (obstetric and non-obstetric ) e.coli bacteria as causative agent in PDPBM 2.most clinical picture of bacterial meningitis reveled but in our case no pyrexia . • Immediately after LP3 which appears purulent Empirical therapy began resulting in full recovery, no long term neurological sequel. • It raises questions regarding the use of locally sterilized spinal pack, wearing of sterile gown &adherence in check list in order to prevent contamination of both the site of LP and the equipment used

Objective Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). Methods A total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. Results Contrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. Conclusions CSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

The diagnosis of bacterial meningitis (BM) is problematic in young infants, as clinical features may be nonspecific or even absent. Cerebrospinal fluid (CSF) analysis usually confirms the diagnosis, but the CSF parameters can be normal also in culture-proven BM. Our objective was to identify the clinical and CSF indices, that quickly and without laboratory likely lead to the diagnosis of confirmed of probable BM in young infants in Angola.We conducted a prospective, observational, single-site study from February 2016 to October 2017 in the Pediatric Hospital of Luanda. All assessed infants showed symptoms and signs compatible of BM or neonatal sepsis and were90 days of age.Of the 1088 infants, 212 (19%) showed bacteria in CSF, while 88 (8%) had probable BM. Independent clinical indicators of BM were not-clear CSF, seizures, weight2500 g and illness7 days. In infants with BM, CSF leukocytes were10 × 106/L in 46%, CSF glucose25 mg/dL in 43% and CSF protein120 mg/dL in 58%. All measured parameters were in normal range in 25% of patients. In 515 infants with normal CSF parameters, bacteria were found in 74 (14%). In these infants, illness7 days, weight2500 g and malnutrition increased the probability of BM.Our study confirms and underlines the problems in diagnosing BM in young infants. While the CSF parameters were normal in 25% of infants, the easily recognizable unclear appearance of CSF was the single strongest predictor of BM.

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants.Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test.Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p < 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p > 0.05).Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.

BACKGROUND Infection is one of the most common complications of ventriculoperitoneal (VP) shunts. Its optimal management is controversial. We aimed to report current practice within a large pediatric neurosurgical center. METHODS We retrospectively studied a cohort of children

BackgroundEncephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens.MethodsHospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database.ResultsTwenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis.ConclusionWe describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.

To evaluate the utility of the corrected CSF white blood cell (WBC) count, cell index, CSF lactate, CSF glucose and a newly developed diagnostic model for the diagnosis of healthcare-associated ventriculitis or meningitis (HCAVM) in the setting of intracranial hemorrhage (ICH).A case-control study of 111 adult patients with ICH with HCAVM (cases) or without HCAVM (controls) matched 1:2 by age, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score enrolled in a large tertiary care center from 2003 to 2016.Subjects were appropriately matched by age, GCS, and APACHE II score (P 0.2). Cases had significantly higher CSF WBC count (uncorrected and corrected), cell index, and CSF lactate, but lower CSF glucose levels than controls (P 0.05). There were no differences between CSF protein, CSF neutrophilic pleocytosis, and serum C-reactive protein between cases and controls (P 0.1). The diagnostic accuracy as analyzed by the area under the receiver operating characteristic curve (AUC of ROC) was found to be good for the cell index (0.825), fair for the corrected CSF WBC count (0.770), and poor for the diagnostic model and uncorrected CSF WBC count (0.652 and 0.653, respectively).The diagnosis of HCAVM in patients with ICH remains challenging and although no single parameter is sufficient for diagnosis the cell index proved to be an important indicator of infection in our study.

Background Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection. Methods We conducted a retrospective chart review of children with culture-confirmed CSF shunt infection at Children’s Hospital and Medical Center from July 2013 to December 2015. CSF cytokine analysis was performed for those patients with CSF in frozen storage from the same sample that was used for diagnostic culture. Results A total of 12 infections were included in this study. Patients with shunt infection had a median C-reactive protein (CRP) of 18.25 mg/dL. Median peripheral white blood cell count was 15.53 × 103 cells/mL. Those with shunt infection had a median CSF WBC of 332 cells/mL, median CSF protein level of 406 mg/dL, and median CSF glucose of 35.5 mg/dL. An interesting trend was observed with gram-positive infections having higher levels of the anti-inflammatory cytokine interleukin (IL)-10 as well as IL-17A and vascular endothelial growth factor (VEGF) compared to gram-negative infections, although these differences did not reach statistical significance. Conversely, gram-negative infections displayed higher levels of the pro-inflammatory cytokines IL-1β, fractalkine (CX3CL1), chemokine ligand 2 (CCL2), and chemokine ligand 3 (CCL3), although again these were not significantly different. CSF from gram-positive and gram-negative shunt infections had similar levels of interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8. Conclusions This pilot study is the first to characterize the CSF cytokine profile in patients with CSF shunt infection and supports the distinction of chemokine and cytokine profiles between gram-negative and gram-positive infections. Additionally, it demonstrates the potential of CSF chemokines and cytokines as biomarkers for the diagnosis of shunt infection.

Glucose transporter type 1 (GLUT1) deficiency syndrome is a well recognised genetic neurometabolic disorder typically presenting with progressive encephalopathy, acquired microcephaly and drug-resistant epilepsy. Imaging is normal in the majority. Here we describe a 5-month-old boy who presented with motor delay, myoclonic jerks and tonic-clonic seizures. His MRI brain scan revealed confluent symmetrical T2 hyperintense signal abnormality in both anterior frontal lobes and delayed myelination. Neurometabolic screen revealed low CSF glucose and lactate levels. A pathogenic de novo heterozygous mutation in SLC2A1 (c.275+1G > A) confirmed the diagnosis of GLUT1 deficiency. Ketogenic diet resulted in a dramatic termination of his seizures at 72 h. At 15 months, he continued to be seizure free with marked developmental catch up. Repeat imaging revealed a significant resolution of the previously seen changes. This case suggests that GLUT1 deficiency should be considered in the differential diagnosis of infants with suspected genetic leukoencephalopathies with important treatment implications.

Background Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. Case presentation A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600–800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. Conclusions CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.

Objectives. To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. Methods. We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. Results. We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5,550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; p=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (p=0.01). Conclusions. Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and pre-existing conditions, as well as in case of meningitis following neurosurgical procedures.

Glucose transporter type 1 deficiency syndrome (Glut1-DS) is a rare neurometabolic disorder caused by mutations of the SLC2A1 gene. Paroxysmal exercise-induced dyskinesia is regarded as a representative symptom of Glut1-DS. Paroxysmal non-kinesigenic dyskinesia is usually caused by aberrations of the MR1 and KCNMA1 genes, but it also appears in Glut1-DS. We herein document a patient with Glut1-DS who suffered first from paroxysmal exercise-induced dyskinesia and subsequently paroxysmal non-kinesigenic dyskinesia and experienced a recent worsening of symptoms accompanied with a low fever. The lumbar puncture result showed a decreased glucose concentration and increased white blood cell (WBC) count in cerebrospinal fluid (CSF). The exacerbated symptoms were initially suspected to be caused by intracranial infection due to a mild fever of

This study aimed to explore the correlation of elevated glucose levels in the blood and cerebrospinal fluid with the progression and short-term prognosis of Guillain-Barr�� syndrome (GBS). The medical records of 982 patients who were diagnosed with GBS in 31 representative tertiary hospitals, located in 14 provinces in southern China, were collected and retrospectively reviewed. Patients were grouped according to the levels of fasting plasma glucose (FPG) and cerebrospinal fluid (CSF) glucose, as well as the concentration of blood hemoglobinAlc (HbA1c). The Hughes grade scale was used to quantify functional outcomes. Compared to patients with normal FPG and CSF glucose levels, those in the high FPG and high CSF glucose groups were characterized by a higher proportion of severe patients (HFGS ��� 3) at admission (58.8 vs. 73.1, P = 0.000; 57.6 vs. 71.2, P = 0.000), at nadir (67.4 vs. 83.0, P = 0.000; 66.2 vs. 80.4, P = 0.000), and at discharge (29.8 vs. 46.3, P = 0.000; 26.4 vs. 45.0, P = 0.000). Patients in the high HbA1c group also had more severe disability at admission (74.6 vs. 56.1, P = 0.005) and at nadir (80.3 vs. 64.3, P = 0.012) compared to the normal HbA1c group. Moreover, elevated levels of FPG and CSF glucose were significantly correlated with more severe disability at admission, at nadir, and at discharge. The present study showed that elevated glucose levels in the blood and cerebrospinal fluid were associated with the severity and short-term prognosis of GBS. chicTR-RRc-17,014,152. GBS, Guillain-Barr�� syndrome; FPG, fasting plasma glucose; CSF, cerebrospinal fluid; HFGS, Hughes Functional Grading Scale; HbA1c, hemoglobin A1c. DM, diabetes mellitus; NCS, nerve conduction study; AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor sensory axonal neuropathy; MV, mechanical ventilation.

In parenchymal neuro-Behcet disease (NBD), CSF opening pressure is usually normal. CSF pleocytosis is usually less than 200/mm3. Pleocytosis could be lymphocyte dominant or less frequently PMN dominant. However, CSF cytochemistry could be completely normal. CSF protein content is usually increased, but it could be normal. CSF glucose is often normal, which can be helpful in differentiation of acute NBD from infectious processes. In NBD presenting with cerebral venous sinus thrombosis, it is better to withhold the lumbar puncture; however, if CSF is taken, CSF opening pressure is elevated, but CSF constituents are usually normal. Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behcet disease. The absence of more than two oligoclonal IgG bands may help differentiate NBS from multiple sclerosis (MS). Oligoclonal bands are less stable in the setting of NBD compared with MS and can be easily suppressed by corticosteroid treatment. However, rarely in young MS patients, oligoclonal IgG bands could be absent in the early stages of the disease or can present as a weak single band. Therefore, the presence of oligoclonal bands cannot rule out NBD. CSF IL-6 might be a marker of disease activity in parenchymal NBD patients. That IL-6 is more increased in chronic progressive NBD patients is a matter of debate. Also, CSF IL-6 is not increased in patients with non-parenchymal NBD.

Background Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative cerebrospinal fluid (CSF) cultures. Data on effective treatment are limited. Methods Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky performance scores, magnetic resonance imaging (MRI) brain scanning, ophthalmic and audiologic exams, and CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion. Results The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (P Conclusions PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.

Objective This study aimed to create a prediction model with a radiographic score, serum, and cerebrospinal fluid (CSF) values for the occurrence of shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and to review and analyze literature related to the prediction of the development of SDHC. Methods Sixty-three patients with aSAH who underwent external ventricular drain insertion were included and separated into 2 subgroups: non-SDHC and SDHC. Patient characteristics, computed tomography scoring system, and serum and CSF parameters were collected. Multivariate logistic regression was conducted to illustrate a nomogram for determining the predictors of SDHC. Furthermore, we sorted and summarized previous meta-analyses for predictors of SDHC. Results The SDHC group had 42 cases. Stepwise logistic regression analysis revealed 3 independent predictive factors associated with a higher modified Graeb (mGraeb) score, lower level of estimated glomerular filtration rate group, and lower level of CSF glucose. The nomogram, based on these 3 factors, was presented with significant predictive performance (area under curve = 0.895) for SDHC development, compared with other scoring systems (AUC = 0.764–0.885). In addition, a forest plot was generated to present the 12 statistically significant predictors and odds ratio for correlations with the development of SDHC. Conclusions First, the development of a nomogram with combined significant factors had a good performance in estimating the risk of SDHC in primary patient evaluation and assisted in clinical decision making. Second, a narrative review, presented with a forest plot, provided the current published data on predicting SDHC.

Background The objective of the study was to assess the cerebrospinal fluid (CSF) findings in COVID-19 patients. Aims This was an observational retrospective cohort from electronic medical records of hospitalized patients (n = 2655) with confirmed COVID-19 between February 15, 2020, and April 15, 2020, in 182 hospitals from a large health system in the USA. The review of data yielded to a total of 79 patients in 20 hospitals who had CSF analysis. Methods Outcomes during hospitalization, including hospital length of stay, disease severity, ventilator time, and in-hospital death were recorded. Independent variables collected included patient demographics, diagnoses, laboratory values, and procedures. Results A total of 79 patients underwent CSF analysis. Of these, antigen testing was performed in 73 patients. Ten patients had CSF analysis for general markers such as total protein, cell count, glucose, clarity, and color. Seven of the 10 cases (70%) had normal total cell count and normal white blood cell count in CSF. Sixty-three percent (5/8) had elevated total protein. Two patients had normal levels of lactate dehydrogenase (LDH) and 1 patient had significantly elevated (fourfold) neuron-specific enolase (NSE) level in CSF. Conclusion Unlike bacterial infections, viral infections are less likely to cause remarkable changes in CSF glucose, cell count, or protein. Our observations showed no pleocytosis, but mild increase in protein in the CSF of the COVID-19 patients. The fourfold elevation of NSE may have diagnostic/prognostic value as a biomarker in CSF for COVID-19 patients who have altered mental status. Graphical abstract

BackgroundTuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The“Thwaites’ system” and “Lancet consensus scoring system” are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown.MethodsA multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The “Thwaites’ system” and “Lancet consensus scoring system” scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The “Thwaites’ system” and “Lancet consensus scoring system” suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively.ResultsA total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P P P ConclusionBoth criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

A 53-year-old woman presented with acute onset of bifrontal headache with fever and vomiting, and a 6-week history of unilateral, left-sided, clear, salty rhinorrhoea. She worked as a veterinary pathologist. On examination, her neck movements were painful, but there were no localising neurological signs. She was obese with a body mass index of 36.5 kg/m2(height 162 cm, weight 96 kg). Cerebrospinal fluid (CSF) examination identified a pleocytosis with a white cell count of 2910/µL (≤5), 91% polymorphs and 9% lymphocytes. The level of CSF glucose was low at 3.9 mmol/L, with a CSF/serum ratio of 0.66. CSF protein was markedly raised at 3.38 g/L (0.15–0.45). We made a presumptive diagnosis of bacterial meningitis and started antimicrobial cover as per local guidelines. This did not include corticosteroids or anti-tuberculous therapy. Given her occupation, and recent travel to Yosemite National Park, California, we excluded an extensive list of pathogens. CSF PCR was negative for Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli , Streptococcus agalactiae , Haemophilus influenzae , Listeria monocytogenes , cytomegalovirus, enterovirus, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), human herpesvirus 6, varicella zoster virus, …

Introduction Glucose hypometabolism and tau formation are key features of Alzheimer's disease (AD). Less is known about the relationship between fasting glucose and regional tau accumulation. Methods Cerebrospinal fluid (CSF) glucose was linearly regressed on regional tau (flortaucipir) among 169 Alzheimer's Disease Neuroimaging Initiative (ADNI3) participants. Flortaucipir uptake was examined by Braak stages and regions of interest (ROIs). Interactions were explored between CSF glucose and AD risk factors including regional amyloid beta (Aβ), sex, Apolipoprotein E ε4 (APOEε4) status, AD parental family history (AD FH), and cognitive impairment (CI). Results Interactions found higher CSF glucose tracked less tau in ROIs or Braak stages I/II (women, APOE ε4+, regional Aβ), III/IV (AD FH+, regional Aβ), and V/VI (AD FH+). CI drove Braak III‐VI associations. Discussion Among women and APOE ε4 carriers, higher CSF glucose tracked less early‐stage tau. Higher CSF glucose may reflect compensation against tau spreading in CI, Aβ+, or AD FH+.

Background: Few data are available on the risk factors involved in nosocomial meningitis from multi-drug-resistant Gram-negative bacteria (MDR-GNB). Our aim was to identify the risk factors of prognosis for MDR-GNB nosocomial meningitis.Methods: Retrospective study of patients undergoing neurosurgery and with positive cerebrospinal fluid culture results post operation between January 2012 and January 2017 in a tertiary hospital in China.Results: In total, 3533 patients were screened. Forty patients with meningitis and completed data were included and divided into two groups, 29 who survived in the successful group (SG) and 11 who died in the failed group (FG). Statistically significant different factors involved in treating successful and failed were pathogen types, highest body temperature in the first 24h of symptoms, CSF glucose content and meropenem susceptibility (for Acinetobacter baumannii). The most common pathogen in the failed ones is Acinetobacter baumannii with meropenem MIC ≥ 16mg/L.Conclusions: Treatment of MDR-GNB nosocomial meningitis is more likely to fail in patients with severe condition when symptoms occur and infected by Acinetobacter baumannii. Researches with larger population are needed to find more factors to improve patient outcome.

BACKGROUND: Studies in which brain metabolism has been monitored using microdialysis have indicated decreases in cerebral glucose concentration and increases in lactate concentration in patients with traumatic brain injury (TBI). However, few data are available on glucose and lactate concentrations in the cerebrospinal fluid (CSF) of TBI patients. This study investigates the relationship between CSF glucose and lactate concentrations and outcomes after TBI.; METHODS: Consecutive adult (>18y) TBI patients were admitted to our 35-bed medicosurgical between 2011 and 2014 and were included in the study if they met the following inclusion criteria: presence of an external ventricular drain (EVD) for intracranial pressure monitoring, daily analysis of CSF glucose and lactate concentrations for 4 consecutive days, and concomitant measurements of blood glucose/lactate concentrations. Neurological outcome was assessed at 3 months using the extended Glasgow Outcome Scale (GOS), and unfavorable outcome defined as a GOS 1 to 4.; RESULTS: Of 151 TBI patients who had an EVD, 56 met the inclusion criteria. Most EVDs were placed on the day of intensive care unit admission, and maintained for 10 (interquartile range: 6 to 14) days. On day 1, there was a weak but significant correlation between blood and CSF glucose concentrations (R=0.07, P=0.04), and a greater correlation between blood and CSF lactate (R=0.32, P

Background Growth failure and growth hormone deficiency (GHD) have been reported as one accessory feature of GLUT1 deficiency syndrome (GLUT1DS), considered so far as a long-term adverse effects of ketogenic diet which is used to treat this condition. Case presentation We report the case of a 10-year-old Caucasian boy referred for short stature (height − 2.56 SDS) and delayed growth (growth velocity − 4.33 SDS) who was diagnosed with GHD and started treatment with recombinant human growth hormone (rhGH). Because of his history of seizures with infantile onset, deceleration of head growth with microcephaly, ataxia, and moderate intellectual disability, a lumbar puncture was performed, which revealed a low CSF glucose concentration with a very low CSF-to-blood glucose ratio (SLC2A1 gene exon 1 deletion confirming a diagnosis of GLUT1DS. Ketogenic diet was started. After 5.5 years of rhGH treatment his height was normalized (− 1.15 SDS). No side effects were reported during treatment, particularly on glycemic metabolism. Conclusions This is the first case of GHD in a Caucasian boy with GLUT1DS diagnosed before starting ketogenic diet, with a good response to rhGH treatment and absence of side effects. We speculate that GHD may represent a poorly recognized clinical feature of GLUT1DS rather than a complication due to ketogenic diet. Under-diagnosis may derive from the fact that growth failure is usually ascribed to ketogenic diet and therefore not further investigated. Pediatric neurologists need to be alerted to the possible presence of GHD in patients with GLUT1DS with slow growth, while pediatric endocrinologist need to refer GHD patients with additional features (motor and cognitive developmental delay, seizures with infantile onset, deceleration of head growth with acquired microcephaly, movement disorder with ataxia, dystonia, and spasticity) that may suggest GLUT1DS.

In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = −0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = −0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95%: 0.77–0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease.

Objective: To describe cerebrospinal fluid (CSF) characteristics in tuberculous meningitis (TBM) with hydrocephalus patients as diagnostic criteria of TBM. Methods: A cross-sectional using retrospective method was applied in this study by obtaining medical records of TBM with hydrocephalus patients that were treated at Department of Neurosurgery Dr. Hasan Sadikin General Hospital, Bandung from January 2014–September 2016. Results: Sixty one records were included in the study. Patient characteristics such as age, gender, and CSF laboratory features such as color and clarity, cells and differential count, protein, and glucose were recorded and descriptively analyzed. The majority of CSF macroscopic appearance was seen to be clear (88%) and colorless (88%). Median for CSF cell count was 25 cells/mm3 with lymphocyte predominance (median: 76%). Increased protein from normal value range was seen in CSF (median: 50 mg/dL) while the mean for CSF glucose in this study remained in its normal value range (mean: 58.9±26.68 mg/dL) with lower CSF to blood glucose ratio (mean: 0.41±0.27). Conclusions: Clear CSF with colorless appearance, lymphocyte pleocytosis, high protein level, and low CSF glucose as well as blood glucose ratio remain typical CSF characteristics of TBM patients found at the Department of Neurosurgery, Dr. Hasan Sadikin General Hospital, Bandung. Keywords: Cerebrospinal fluid, hydrocephalus, tuberculous meningitis DOI: 10.15850/ijihs.v6n2.1129

Introduction The duration of treatment is not well established, especially in the negative cerebrospinal fluid (CSF) culture. The aim of this study is to explore the influence of duration of treatment in neonatal bacterial meningitis. Material and methods This is a retrospective analysis of 200 CSF specimens. Two hundred full-term neonates with bacterial meningitis admitted to the clinical status were evaluated using the Glasgow Outcome Scale (GOS) on the day of discharge. Results Neonates were identified as having bacterial meningitis based on the results of CSF culture tests of all suspected cases. According to the GOS, neonates were divided into two outcome groups: 77.5% good (GOS = 5) (shorter than 3 weeks' administration) and 22.5% unfavorable (GOS = 1-4) (longer than 3 weeks' administration). The duration of antibiotic treatment ranged from 4 to 43 days, and the mean therapy time was 19.74 ±7.32 days. Duration longer than 3 weeks for neonatal bacterial meningitis with negative CSF culture had no impact on prognosis. The unfavorable outcome group had more prenatal infections and premature rupture of membranes cases than the good outcome group. High CSF protein and CSF glucose and CSF cell count increase were associated with unfavorable outcome in 167 non-prenatal infection infants. High CSF cell count increase was associated with unfavorable outcome in 33 prenatal infection infants. In term infants, the positive rate of blood cultures was 24.5%. Conclusions Third generation cephalosporin therapy does not have a different prognosis for negative CSF culture of neonatal bacterial meningitis in term infants in this study.

Background: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD. Objective: Evaluate AD hypotheses by comparing neurotransmitter and metabolite marker concentrations in normal versus AD CSF. Methods: Meta-analysis allows for statistical comparison of pooled, existing cerebrospinal fluid (CSF) marker data extracted from multiple publications, to obtain a more reliable estimate of concentrations. This method also provides a unique opportunity to rapidly validate AD hypotheses using the resulting CSF concentration data. Hubmed, Pubmed and Google Scholar were comprehensively searched for published English articles, without date restrictions, for the keywords “AD”, “CSF”, and “human” plus markers selected for synaptic and metabolic pathways. Synaptic markers were acetylcholine, gamma-aminobutyric acid (GABA), glutamine, and glycine. Metabolic markers were glutathione, glucose, lactate, pyruvate, and 8 other amino acids. Only studies that measured markers in AD and controls (Ctl), provided means, standard errors/deviation, and subject numbers were included. Data were extracted by six authors and reviewed by two others for accuracy. Data were pooled using ratio of means (RoM of AD/Ctl) and random effects meta-analysis using Cochrane Collaboration’s Review Manager software. Results: Of the 435 identified publications, after exclusion and removal of duplicates, 35 articles were included comprising a total of 605 AD patients and 585 controls. The following markers of synaptic and metabolic pathways were significantly changed in AD/controls: acetylcholine (RoM 0.36, 95% CI 0.24-0.53, p Conclusion: This study provides proof of concept for the use of meta-analysis validation of AD hypotheses, specifically via robust evidence for the cholinergic hypothesis of AD. Our data disagree with the other synaptic hypotheses of glutamate excitotoxicity and GABAergic resistance to neurodegeneration, given observed unchanged glutamate levels and decreased GABA levels. With regards to metabolic hypotheses, the data supported upregulation of anaerobic glycolysis, pentose phosphate pathway (glutathione), and anaplerosis of the tricarboxylic acid cycle using glutamate. Future applications of meta-analysis indicate the possibility of further in silico evaluation and generation of novel hypotheses in the AD field.

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The novel coronavirus, named SARS-CoV-2, is known to have emerged in Wuhan, China in late 2019. A wide variety of organs have been found to be involved with SARS-CoV-2 infection. Recent reports indicate that the CNS is not spared. Headache, dysguesia and hyposmia, some more serious neurologic manifestations including encephalopathy Guillain Barre syndrome and stroke are now being reported as the number of patients with COVID-19 across the globe. We report a case of meningoencephalitis associated with SARS-CoV-2 who presented with altered mental status. CASE PRESENTATION: 43-year-old male with a PMH significant for insulin-dependent diabetes presented with altered mental status. In Emergency department was noted to have rhythmic jerking movements and his gaze was deviated to the right, concerning for seizure activity. Upon admission it was confirmed to have COVID-19 via detection of SARS-CoV-2 viral nucleic acid in a nasopharyngeal swab specimen using the Simplexa SARS-CoV-2 assay. Neurological examination revealed confusion with orientation only to self, inability to follow commands, and no apparent focal neurological deficits. Otherwise, general examination was unremarkable and vital signs were within normal. CT head was negative for any acute pathology. His cerebrospinal fluid (CSF) was clear and color less with an elevated CSF cell count and lymphocytic predominance suspicious for viral encephalitis.The CSF glucose (70 mg/dL) was increased and CSF protein levels (19 mg/dL) were decreased. A CSF PCR panel including Cryptococcus neoformans, HSV, varicella zoster virus, Streptococcus pneumoniae, Neisseria meningitidis and enterovirus was negative. The SARS-CoV-2 CSF PCR was negative. Labs were significant for elevated ferritin, LDH, C reactive protein and Di dimer. EEG shows diffuse slowing in the theta range indicative of encephalopathy and lacked any epileptogenic activity. Patient started on steroids, Remedesivir with concern of COVID 19 meningoencephalitis. Within the next 3 days, his mentation progressively improved;he was able to communicate, and was following commands. DISCUSSION: The neuroinvasive nature of human coronavirus has been previously reported during the 2002–2003 SARS-CoV pandemic when viral nucleic acids were found in the human brain upon autopsies. It was postulated by scientists in China that SARS-CoV-2, a novel coronavirus from the SARS-CoV family, could also infect the brain when they observed neurologic signs among patients with COVID-19 related respiratory illness. CONCLUSIONS: Although rare, meningoencephalitis should be considered as a possible manifestation of COVID-19 disease. A suspicion for SARS-CoV-2 meningitis or encephalitis should be high among patients presenting with neurological symptoms during this era of pandemic. SARS-CoV-2 testing should be included as part of the workup in addition to other infectious causes. REFERENCE #1: Gu J., Gong E., Zhang B. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202(3):415–424. doi: 10.1084/jem.20050828 REFERENCE #2: Moriguchi T., Harii N., Goto J. A first case of meningitis/encephalitis associated with SARS-coronavirus-2. Int J Infect Dis. 2020;94:55–58. doi: 10.1016/j.ijid.2020.03.062 DISCLOSURES: No relevant relationships by Ajay Adial, source=Web Response No relevant relationships by Muhammad Azaz Cheema, source=Web Response No relevant relationships by Asma Iftikhar, source=Web Response No relevant relationships by Hamza Quadri, source=Web Response

STUDY QUESTION Do cerebrospinal fluid (CSF) concentrations of gamma-aminobutyric acid (GABA), testosterone (T) and estradiol (E2) differ in women with polycystic ovary syndrome (PCOS) as compared to eumenorrheic, ovulatory women (EW)? SUMMARY ANSWER Women with PCOS displayed higher CSF levels of GABA and E2, and possibly T, than EW. WHAT IS KNOWN ALREADY The chronic anovulation characteristic of PCOS has been attributed to increased central GnRH drive and resulting gonadotropin aberrations. Androgens are thought to regulate GABA, which in turn regulates the neural cascade that modulates GnRH drive. STUDY DESIGN, SIZE, DURATION This cross-sectional observational study included 15 EW and 12 non-obese women with PCOS who consented to a lumbar puncture in addition to 24 h of serum blood collection at 15-min intervals. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 27 women were studied at a the General Clinical Research Center (GCRC) at the University of Pittsburgh. Serum analytes included T, E2 and androstenedione. CSF analytes included GABA, glutamate, glucose, T and E2. MAIN RESULTS AND THE ROLE OF CHANCE Women with PCOS had higher CSF GABA as compared to EW (9.04 versus 7.04 μmol/L, P < 0.05). CSF glucose and glutamate concentrations were similar between the two groups. CSF T was 52% higher (P = 0.1) and CSF E2 was 30% higher (P < 0.01) in women with PCOS compared to EW. Circulating T was 122% higher (P < 0.01) and circulating E2 was 75% higher (P < 0.01) in women with PCOS than in EW. LIMITATIONS REASONS FOR CAUTION The study is limited by its small sample size and the technical limitations of measuring CSF analytes that are pulsatile and have short half-lives. WIDER IMPLICATIONS OF THE FINDINGS Women with PCOS displayed significantly higher circulating levels of T and E2, significantly higher CSF levels of E2, and higher levels of CSF testosterone, although the latter was not statistically significant. A better understanding of the central milieu informs our understanding of the mechanisms mediating increased the GnRH drive in PCOS and lends a new perspective for understanding the presentation, pathogenesis and potential health consequences of PCOS, including gender identity issues. STUDY FUNDING/COMPETING INTEREST(S) No conflicts of interest. The study was funded by NIH grants to SLB (RO1-MH50748, U54-HD08610) and NIH RR-00056 to the General Clinical Research Center of the University of Pittsburgh. TRIAL REGISTRATION NUMBER NCT01674426.