Association of cigarette smoking with cerebrospinal fluid biomarkers of insulin sensitivity and neurodegeneration.

INTRODUCTION: Cigarette smoking increases both the risk for insulin resistance and amyloid-ß (Aß) aggregation, and impaired brain insulin/insulin-like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aß42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers. METHODS: In this cross-sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured. Three polymorphisms regulating IGF1 were genotyped. Analysis of variance was used to compare differences of variables between groups. Partial correlation was performed to test the relationship between CSF biomarkers and smoking status. General linear models were applied to test the interaction of the effect of single nucleotide polymorphisms and cigarette smoking on CSF IGF1 levels. RESULTS: In the CSF from active smokers, IGF1 and lactate levels were significantly lower (p = .016 and p = .010, respectively), whereas Aß42 (derived from our earlier research) and insulin levels were significantly higher (p < .001 and p = .022, respectively) as compared to the CSF from nonsmokers. The AG + GG genotype of rs6218 in active smokers had a significant effect on lower CSF IGF1 levels (p = .004) and lower CSF insulin levels in nonsmokers (p = .016). CONCLUSIONS: Cigarette smoking as the "at-risk" factor for AD might be due to lower cerebral insulin sensitivity in CSF, and the subjects with rs6218G allele seem to be more susceptible to the neurodegenerative risks for cigarette smoking.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective, observational study.

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.

Discrepancy between ventricular and lumbar CSF in chronic meningitis.

Meningitis patient can present with various manifestation including hydrocephalus due to multiple reason. Diagnosis of meningitis mainly rely on CSF analysis which is usually obtained from lumbar puncture. In case of hydrocephalus CSF can be obtain from ventricles during VP shunt operation. Sometimes ventricular CSF can be normal in meningitis patient while lumbar CSF shows abnormality. Possible mechanisms behind this phenomenon are discussed here. Patients who present with hydrocephalus and have normal Ventricular CSF should investigated with lumbar CSF analysis in a view of delay in diagnosis and treatment.

Impaired consciousness and decreased glucose concentration of CSF as prognostic factors in immunocompetent patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system and has high morbidity and mortality. Almost studies about prognostic factors have largely focused on the immunocompromised population rather than immunocompetent patients. So that we sought to conduct a retrospective study to determine prognostic factors which predict the outcomes in immunocompetent patients with CM. METHODS: We retrospectively collected and analyzed the demographic and clinical data of 76 apparently immunocompetent patients with cryptococcal meningitis from January 2003 to June 2019 in China. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups, potential prognostic factors were analyzed. RESULTS: Non-parametric test confirmed that unfavorable outcome was associated with lower glucose level of CSF(P = 0.001), and Pearson's χ2 analysis confirmed that unfavorable outcome was associated with opening pressure of CSF(>300mmH20, P = 0.038), impaired consciousness (P = 0.001), hydrocephalus(P = 0.045), and Shunt surgery (P = 0.045), and then multiple logistic regression analysis confirmed that impaired consciousness(P = 0.015) and lower glucose concentration of CSF(P = 0.012) increased the likelihood of unfavorable outcome in CM patients. CONCLUSION: Impaired consciousness and decreased glucose concentration of CSF were independently prognostic factors which predict the unsatisfactory outcome in immunocompetent patients with CM.

Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer's disease.

Context: Alzheimer's disease is strongly associated with brain insulin signalling.Objective: Investigating the effect of amylin as a novel treatment in streptozotocin (STZ) rat model of AD.Materials and methods: Alzheimer's disease (AD) was induced in albino rats by intracerebroventricular injection of STZ (3 mg/kg). Rats received either amylin analogue (Pramlintide 200 µg/kg/day) or Metformin (30 mg/kg/day) for 5 weeks.Results: Both Pramlintide and Metformin improve learning and memory through enhancing insulin signalling (p-IR and p-PI3K) which lead to lowering level of CSF glucose, phosphorylated tau proteins, and amyloid-ß peptide (Aß) in hippocampus.Conclusions: Insulin sensitisers as Metformin and Pramlintide can improve learning and memory and decrease the pathological changes in STZ induced rat model of AD. However, Pramlintide is superior to Metformin in some memory tests which related to its action as an amylin analogue. Amylin improves learning and memory through an independent effect other than insulin sensitisation.

Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis / Comparação do lactato no líquido cefalorraquidiano com as características físicas, citológicas e outros marcadores bioquímicos, como fator prognostico nas meningites bacterianas agudas

ABSTRACT 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.

Valores del análisis citoquímico de líquido cefalorraquídeo en pacientes con derivación ventrículo-peritoneal / Values of cerebrospinal fluid cytochemistry in pediatric patients with ventriculoperitoneal shunt

Resumen Introducción: La derivación ventrículo-peritoneal (DVP) es el tratamiento para la hidrocefalia. El líquido cefalorraquídeo (LCR) se evalúa para el manejo de sus complicaciones; sin embargo, la información de los valores del citoquímico en esta población es insuficiente. Objetivo: Describir las características del citoquímico del LCR de niños en manejo con DVP. Materiales y Métodos: Estudio de tipo observacional descriptivo, desarrollado en Bogotá (Colombia), entre el año 2008 y 2016. Se revisaron los registros de procedimientos de DVP y relacionados. Se incluyeron pacientes entre 6 meses y 18 años de edad. Resultados: Se revisaron 285 registros e ingresaron 31 muestras. Los valores de LCR fueron, respectivamente, para la mediana y al percentil 90%: leucocitos totales: 0 y 7 céls/mm3, neutrófilos: 0 y 6,8 céls/mm3, linfocitos: 0 y 2 céls/mm3, proteínas: 13,4 y 67,2 mg/dL, glucosa: 59 y 27,4 mg/dL. Discusión: Los valores de glucosa presentan un rango normal hacia el extremo inferior más amplio, con valores de proteínas mayores a los valores esperados. El rango de celularidad es la variable que presenta menor variación. Conclusiones: Los valores del citoquímico de LCR en paciente con DVP no son equiparables a los de la población sana y deben interpretarse según las características propias de esta población.

Background: The ventriculo-peritoneal shunt (VPS) is the treatment for hydrocephalus, the cerebrospinal fluid (CSF) is evaluated for the management of its complications; however, information on the values of the cytochemistry in this population is insufficient. Aim: To describe the characteristics of the CSF cytochemistry of children in VPS management. Methods: Descriptive observational study, developed in Bogotá (Colombia), from 2008 to 2016. VPS and related procedures records were reviewed. Patients between 6 months and 18 years were included. Results: A total of 285 records were reviewed, 31 samples were entered. The CSF values were, respectively, for the median and 90% percentile: total leukocytes: 0 and 7 cells/mm3, neutrophils: 0 and 6.8 cells/mm3, lymphocytes: 0 and 2 cells/mm3, proteins: 13.4 and 67.2 mg/dL, glucose: 59 and 27.4 mg/dL. Discussion: Glucose values evinced a normal rank towards the widest inferior limit with protein values exceeding the values expected. Cellularity is the variable with the lowest variation. Conclusions: The values of the CSF cytochemistry in patients with VPS are not comparable to those of the healthy population and should be interpreted according to the characteristics of this population.

[A case of secondary central nervous system lymphoma presenting marked hypoglycorrhachia].

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. Abdominal computed tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with a combination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.

Association of vascular endothelial growth factor levels in CSF and cerebral glucose metabolism across the Alzheimer's disease spectrum.

The association of vascular endothelial growth factor (VEGF) levels in CSF and cerebral glucose metabolism across the Alzheimer's disease (AD) spectrum is unclear. CSF VEGF levels were cross-sectionally related to cerebral glucose metabolism, as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), using linear regression models. We found that VEGF levels were associated with cerebral glucose metabolism in patients with mild cognitive impairment (MCI) and AD, but not in cognitively normal older adults. Our data indicated that VEGF may play an important role in cerebral glucose metabolism.

The Causes of Postoperative Meningitis: The Comparison of Gram-Negative and Gram-Positive Pathogens.

AIM: To determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and to show the impact of Gram-negative rods and the differences between patient characteristics and the clinical and prognostic measures in Gram-negative and Gram-positive meningitis. MATERIAL AND METHODS: In this prospective, single-center study, we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. RESULTS: Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and a median age of 50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%) were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram-positives (p=0.034). The duration between surgery and meningitis was shorter in Gram-negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal fluid protein and lactate levels were higher and glucose level was lower in cases of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049). CONCLUSION: In NM, Gram-negative pathogens were seen more frequently; A. baumanni was the predominant pathogen; and NM caused by Gram-negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram-positives.

Electrolytes and Biochemical Changes in Cerebrospinal Fluid in Drowning: Experimental Rabbit Model.

The diagnosis of drowning is still a difficult task in forensic science. Biochemical changes in different body fluids have been examined for the identification of drowning. However, none of them alone gives accurate results in the diagnosis of drowning and differentiation of saltwater and freshwater drowning. This study aimed to examine cerebrospinal fluid changes in drowned rabbits. Six groups of rabbits were used including immersed dead rabbits in freshwater or saltwater (as control groups), alive fully conscious rabbits drowned in freshwater and saltwater, and anesthetized rabbits drowned in freshwater and saltwater. Cerebrospinal fluid electrolytes except for potassium levels were significantly higher in rabbits drowned consciously in saltwater than their level in the control group. In rabbit drowned in freshwater, the examined electrolytes decreased significantly. In addition, urea, creatinine, uric acid, glucose, and tumor necrosis factor were different in cases of freshwater and saltwater drowning from those of control rabbits. Electrolytes and biochemical changes of unconscious rabbits drowned in water showed no significant difference from those of control rabbits. Cerebrospinal fluid examination in drowning gives promising results in the diagnosis of drowning. In addition, the differentiation between freshwater and saltwater drowning was possible.

Gene therapy for Glut1-deficient mouse using an adeno-associated virus vector with the human intrinsic GLUT1 promoter.

BACKGROUND: We generated an adeno-associated virus (AAV) vector in which the human SLC2A1 gene, encoding glucose transporter type 1 (GLUT1), was expressed under the human endogenous GLUT1 promoter (AAV-GLUT1). We examined whether AAV-GLUT1 administration could lead to functional improvement in GLUT1-deficient mice. METHODS: We extrapolated human endogenous GLUT1 promoter sequences from rat minimal Glut1 promoter sequences. We generated a tyrosine-mutant AAV9/3 vector in which human SLC2A1-myc-DDK was expressed under the human GLUT1 promoter (AAV-GLUT1). AAV-GLUT1 was administered to GLUT1-deficient mice (GLUT1+/- mice) via intracerebroventricular injection (1.85 × 1010 vg/mouse or 6.5 × 1010 vg/mouse). We analyzed exogenous GLUT1 mRNA and protein expression in the brain and other major organs. We also examined improvements of cerebral microvasculature, motor function using rota-rod and footprint tests, as well as blood and cerebrospinal fluid (CSF) glucose levels. Additionally, we confirmed exogenous GLUT1 protein distribution in the brain and other organs after intracardiac injection (7.8 × 1011 vg/mouse). RESULTS: Exogenous GLUT1 protein was strongly expressed in the cerebral cortex, hippocampus and thalamus. It was mainly expressed in endothelial cells, and partially expressed in neural cells and oligodendrocytes. Motor function and CSF glucose levels were significantly improved following intracerebroventricular injection. Exogenous GLUT1 expression was not detected in other organs after intracerebroventricular injection of AAV-GLUT1, whereas it was detected in the liver and muscle tissue after intracardiac injection. CONCLUSIONS: Exogenous GLUT1 expression after AAV-GLUT1 injection approximated that of physiological human GLUT1 expression. Local central nervous system administration of AAV-GLUT1 improved CSF glucose levels and motor function of GLUT1-deficient mice and minimized off-target effects.

Evaluation of blood-brain barrier function by quotient alpha2 macroglobulin and its relationship with interleukin-6 and complement component 3 levels in neuropsychiatric systemic lupus erythematosus.

Although quotient of alpha2 macroglobulin (Qα2MG) was previously reported to be useful for the evaluation of blood-brain barrier (BBB) function, it is not commonly used. We therefore evaluated BBB function among the various subsets of neuropsychiatric systemic lupus erythematosus (NPSLE) using quotient Q α2MG. Furthermore, we determined the correlation between Q α2MG and cerebrospinal (CSF) interleukin (IL)-6 level and quotient complement component 3 (Q C3). To determine intrathecal production of C3, the C3 index (Q C3/Q α2MG) was also calculated. Fifty-six patients with SLE were included in this study. Of these, 48 were diagnosed with NPSLE, consisting of 30 diffuse NPSLE patients (acute confusional state (ACS): n = 14, non-ACS: n = 16) and 18 patients with focal NPSLE. CSF IL-6 concentration, and paired serum and CSF levels of α2MG and C3, were measured by enzyme-linked immuno solvent assay (ELISA). The Q α2MG, Q C3, and C3 index were then calculated. Q α2MG, Q C3, and IL-6 concentrations in the CSF were significantly elevated in NPSLE compared with non-NPSLE. Among the subsets of NPSLE, significant increases in Q α2MG, CSF IL-6, and Q C3 were observed in ACS compared with non-ACS or focal NPSLE. There was a positive correlation between CSF IL-6 level and Q α2MG, as well as between Q C3 and Q α2MG, in diffuse NPSLE. There were no significant differences in C3 index between NPSLE and non-NPSLE, as well as among the subgroups of NPSLE. Our study suggests that BBB disruption is present in ACS, and elevated levels of IL-6 and C3 in CSF in diffuse NPSLE, especially in ACS, might result from their entry to the CSF from the systemic circulation through the damaged BBB, as well as increased intrathecal production. Furthermore, Q α2MG might be useful for the evaluation of BBB integrity.

Tuberculosis/cryptococcosis co-infection in China between 1965 and 2016.

Cases of tuberculosis/cryptococcosis co-infection are rapidly increasing in China. However, most studies addressing this co-infection have been published in Chinese journals, and this publication strategy has obscured this disease trend for scientists in other parts of the world. Our investigation found that 62.9% of all co-infection cases worldwide were reported in the Chinese population (n=197) between 1965 and 2016, and 56.3% of these Chinese cases were reported after 2010. Nearly all cases originated from the warm and wet monsoon regions of China. HIV-positive subjects tended to correlate with more severe manifestations of a tuberculosis/cryptococcosis co-infection than those without HIV. Notablely, dual tubercular/cryptococcal meningitis was the most frequent (54.0%) and most easily misdiagnosed (95.2%, n=40/42) co-infection. We also found that the combined use of cerebrospinal fluid pressure and concentrations of glucose, protein and chlorine might be an inexpensive and effective indicator to differentiate tubercular/cryptococcal co-infection meningitis from tubercular meningitis and cryptococcal meningitis.

Increased cerebrospinal fluid levels of GABA, testosterone and estradiol in women with polycystic ovary syndrome.

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.

Magnetic resonance imaging study of cryptococcal neuroradiological lesions in HIV-negative cryptococcal meningitis.

Magnetic resonance (MR) scanning has become an important diagnostic and management tool in cryptococcal meningitis (CM). However, there are only isolated case reports documenting neuroradiological findings in human immunodeficiency virus (HIV)-negative patients with CM and none has clearly addressed the relationship between cerebral lesions on magnetic resonance imaging (MRI) and prognosis. The MR brain images available from 114 HIV-negative patients with CM were retrospectively analysed. Patients were divided into Group I with one or more CM-related lesions and Group II without CM-related lesions. Initial clinical and biochemical markers and prognosis were collected and compared between the two groups. In the present study, the most common pattern of CM-related lesions by MRI was radiological meningitis, following by Virchow-Robin (VR) dilatation, hydrocephalus, intracerebral nodules and pseudocysts, which was different from previous studies reporting that the main MR findings of cerebral cryptococcosis in HIV-infected patients include dilated VR spaces, masses and pseudocysts. Compared to the patients without CM-related lesions, patients with CM-related lesions presented with a higher percentage of male patients, a higher frequency of altered mental status, a higher positive rate of Cryptococcus culture in cerebrospinal fluid (CSF) and a lower ratio of CSF glucose/blood glucose. Poor outcomes were more frequent in patients with presence of CM-related lesions compared to patients without CM-related lesions. In conclusion, the main pattern of cryptococcosis-related lesions on MR scanning differ between non-HIV- and HIV-positive patients with CM. The presence of CM-related lesions was significantly associated with predictors for poor outcome. Neuroimaging on MR scanning is a useful tool to evaluate the initial severity and prognosis of CM without HIV infection.

Lower extremity weakness is associated with elevated blood and cerebrospinal fluid glucose levels following multibranched endovascular aortic aneurysm repair.

OBJECTIVE: Hyperglycemia is associated with worsened clinical outcomes after central nervous system injury. The purpose of this study was to examine the association between lower extremity weakness (LEW) and the glucose levels of blood and cerebrospinal fluid (CSF) in patients undergoing multibranched endovascular aneurysm repair (MBEVAR) of thoracoabdominal and pararenal aortic aneurysms. METHODS: Blood and CSF samples were collected preoperatively, immediately after aneurysm repair, and on postoperative day 1 in 21 patients undergoing MBEVAR. Data on demographics, operative repair, complications, and outcomes were collected prospectively. RESULTS: There were 21 patients who underwent successful MBEVAR. Two patients had pre-existing paraplegia from prior open aortic surgery and were excluded from the current analysis. The mean age was 73 ± 8 years, and 15 of 19 (79%) were men. In the postoperative period, 7 of 19 (37%) patients developed LEW. This was temporary in 5 of 19 (26%) patients and permanent in 2 of 19 (11%) patients. The LEW group was older than the non-LEW group (77 ± 6 vs 70 ± 9 years, respectively; P = .10), had a lower preoperative glomerular filtration rate (58.6 ± 18.5 vs 71.4 ± 23.5 mL/min per 1.73 m2; P = .24), and was more likely to be taking a statin (100% vs 67%, respectively; P = .13), but these did not reach statistical significance. There was no significant difference in the prevalence of diabetes mellitus, hypertension, coronary artery disease, lung disease, or peripheral artery disease between the LEW and non-LEW groups. There was also no difference in operative time, blood loss, contrast material volume, or fluoroscopy times between the two groups. Preoperative blood and CSF glucose levels were similar in those with and without LEW. During the postoperative period, glucose values in the blood and CSF were significantly higher in those patients who developed LEW compared with those who did not develop LEW. In all patients with LEW, the elevation in the blood or CSF glucose level preceded the development of LEW. In a multivariable logistic regression model, CSF glucose concentration on postoperative day 1 was significantly and independently associated with the development of LEW (odds ratio, 2.30 [1.03-5.14] per 10 mg/dL increase in CSF glucose; P = .04). CONCLUSIONS: Elevated blood glucose and CSF glucose levels are associated with postoperative LEW in patients undergoing MBEVAR. The protective effect of euglycemia deserves further study in patients at risk for spinal cord ischemia.

Time-dependent changes in epidural catheter aspirate after injection of a local anesthetic.

STUDY OBJECTIVE: A glucose check is used for investigation of a suspected accidental dural puncture in epidural anesthesia. However, glucose-positive clear fluid is sometimes aspirated from an epidural catheter in cases without clinical evidence of puncture. The goal of the study was to investigate time-dependent changes in the aspirate composition after injection of a local anesthetic into the epidural space. DESIGN: Observational study. SETTING: Operating rooms at Hamamatsu University Hospital. PATIENTS: The subjects were 30 patients (ASA I or II) undergoing surgery with combined epidural and general anesthesia. INTERVENTIONS: After epidural injection of local anesthetics, aspiration through the catheter was performed every 10min until fluid could not be aspirated. pH, Na, K, Cl, Ca and glucose were measured in fluid samples using a blood gas analysis apparatus. MAIN RESULTS: No patients had pain or clinical signs suggesting dural puncture throughout the perioperative period. Fluid aspiration was possible in 15 patients (50%) after 10min and in 7, 3, 2 and 2 patients after 20, 30, 40 and 50min, respectively. Glucose was detected in each aspirated fluid sample and gradually increased with time to become closer to the level in cerebrospinal fluid (CSF). Each electrolyte also changed to approach the level found in CSF. CONCLUSIONS: A glucose check may increase the risk of a false-positive finding for accidental dural puncture with increasing time after local anesthetic injection. Conversely, detection of glucose at the time of epidural catheter placement may provide useful information for detection of accidental dural puncture.