Cerebrospinal Fluid Glucose Levels Research Articles

Protocol for the study of bedside CSF analysis by urinary reagent strips and comparison with traditional laboratory measurements in a tertiary care centre in rural India

Abstract* Background Meningitis is an infection of leptomeninges. It is an emergency life-threatening condition that requires prompt treatment initiation. Diagnosis is the rate-limiting step because cerebrospinal fluid (CSF) analysis requires experienced personnel. Therefore, this study was conducted to assess the utility of urinary reagent strips for the rapid bedside diagnosis of CSF glucose, proteins, and leukocytes. Objective To determine the efficacy of a urinary reagent strip for bedside analysis of cerebrospinal fluid (CSF) samples. Methods This prospective comparative study will be conducted in the Department of Neonatology and Pediatrics, Jawaharlal Nehru Medical College, Sawangi, Wardha. CSF samples from patients suspected of infection of the central nervous system (CNS) and awaiting diagnosis will be subjected to semi-quantitative analysis using a urinary reagent strip (for glucose, proteins, and leukocytes). The results were compared with the laboratory results of the individual samples. Result After completing the study, we determined the efficacy of the urinary reagent strips in bedside estimation of CSF glucose, protein, and leukocyte levels in terms of sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. Conclusion This study provides insight into the utility of urinary reagent strips for rapid bedside diagnosis of CSF samples from patients suspected of having an infection.

Ventriculoperitoneal shunting obstruction: a multicentre clinical audit for cerebrospinal fluid parameters and its prediction role.

Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failurefromother factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing.

Implantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors mainly requires transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces biocompatibility, or limits portability. Here, we develop a set of millimeter-scale, chip-less, and battery-less magnetic implants paired with a fully integrated wearable device for measuring biophysical and biochemical signals. The wearable device can induce a large amplitude damped vibration of the magnetic implants and capture their subsequent motions wirelessly. These motions reflect the biophysical conditions surrounding the implants and the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities of measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure, and CSF glucose levels. This miniaturized system opens the possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4weeks estimated gestational age. PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Gene polymorphisms of IL-17A and bacterial meningitis in Angolan children

Interleukin (IL)-17 A plays a crucial role in protecting hosts from invading bacterial pathogens. In this study, we investigated if single nucleotide polymorphisms (SNPs) in IL-17A are associated with susceptibility and outcome of bacterial meningitis (BM) in Angolan children. The study sample comprised 241 confirmed BM patients and 265 controls, which were matched for age and ethnicity. Three IL-17A SNPs – rs2275913 (−197G > A), rs8193036 (-737C > T) and rs4711998 (−877 A > G) – were determined by high-resolution melting analysis (HRMA). The frequency of variant genotype rs4711998 was significantly higher in patients with BM caused by Haemophilus influenzae (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.49–8.23; P = 0.0025) than in controls. Also, patients with BM caused by Gram-negative bacteria and who carried the variant genotype rs2275913 had a lower glucose level (P = 0.0051) in cerebrospinal fluid (CSF). Patients with BM caused by Streptococcus pneumoniae who carried the variant type rs8193036 had a reduced risk for severe neurological sequelae (OR: 0.14; 95% CI: 0.029–0.68; P = 0.0079), blindness (OR: 0.012; 95% CI: 0.012–0.87; P = 0.017) and ataxia (OR: 0.28; 95% CI: 0.091–0.83; P = 0.023). This study suggests an association of IL-17A genetic variations with susceptibility and outcome of bacterial meningitis in Angolan children.

Clinical and imaging features of lymphomatosis cerebri: analysis of 8 cases and systematic review of the literature

Lymphomatosis cerebri (LC) is a rare type of primary central nervous system lymphoma with diffuse, nonenhancing infiltrative lesions and is often misdiagnosed. Our study aimed to investigate the clinical characteristics and prognosis of LC through analyzing patients from the literature and our own center, so as to improve early diagnosis and treatment. PubMed, Web of Science and our hospital databases were reviewed, and information on demographic, clinical, pathological, cerebrospinal fluid (CSF), neuroimaging and treatment options was extracted. Univariate survival analysis was conducted by generating survival curves and comparing them using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to identify the prognostic predictors. A total of 81 patients (median age: 58 years; interquartile range, IQR: 50–66.5 years), 45 males and 36 females, were included. The most common symptoms were cognitive impairment (65.4%) and gait impairment (50.6%). Imaging studies indicated that all 81 patients had supratentorial structure involvement, and 93.8% (76/81) had bilateral hemisphere involvement. There were 53.3% (32/60) patients with CSF pleocytosis and 65% (39/60) patients with increased CSF protein levels. The median time of diagnosis was 4.8 months (IQR: 2.3–6.9 months). Compared with 4 (95% CI: 1.78–6.22) months for all 81 patients, the median OS was 20 (95% CI: 8.24–31.76) months for those who had chemotherapy plus radiotherapy. Multivariate Cox analysis revealed that chemoradiotherapy (HR: 0.12; 95% CI: 0.02–0.68) and higher CSF glucose level (HR: 0.01; 95% CI: 0.00–0.26) were inversely associated with death. The diagnosis of LC should be alerted when neuroimaging with bilateral hemispheric involvement and CSF abnormality with pleocytosis and increased protein. Once the diagnosis is confirmed, the combination of chemotherapy and radiotherapy can be considered if the patient’s physical condition permits.Journal standard instruction requires an unstructured abstract. Kindly check and confirm.We have checked and confirmed that there is no problem.

SAT043 Chronically High Cerebrospinal Fluid Glucose Levels Impair Memory In Male Mice

Abstract Disclosure: M.U. Raza: None. K.H. Chhabra: None. Diabetes doubles the risk of cognitive decline and Alzheimer’s disease (AD). Whether this is mediated by an increase in blood glucose or cerebrospinal fluid (CSF) glucose levels, or by other metabolic factors such as changes in plasma insulin levels is unclear. To clarify the contribution of high blood glucose versus high CSF glucose levels toward increasing the risk of cognitive decline in mice, we have developed a method through which glucose concentration can be increased selectively in CSF. We implanted 8 weeks old male mice (n= 7-8 / group) with cannula attached to osmotic minipumps to directly infuse either artificial CSF (aCSF/sham group) or 50% glucose solution (treatment group) into the right lateral ventricle for eight weeks at a flow rate of 0.25ul/hr. CSF glucose was measured two and eight weeks after initiating the infusion in these mice. We also performed oral glucose tolerance tests (OGTT) in these mice to assess their peripheral glucose metabolism and uptake. Moreover, these mice were tested through the Morris water maze (MWM) to investigate the effects of high CSF glucose on learning and memory. Mice in the treatment group showed a significant increase (p&amp;lt;0.0001, unpaired t-test) in CSF glucose levels (mean=328±30.15 and 358±15.03mg/dl post-2, and 8 weeks of implantation, respectively) as compared to the sham group (mean=56±2.63 and 73±8.61mg/dl post-2, and 8 weeks of implantation, respectively). There was no significant change in body weight and food intake during the study. In OGTT, the treatment group showed significantly lower blood glucose levels (p&amp;lt;0.05, two-way ANOVA repeated measures design, Bonferroni’s multiple comparisons) at 15 minutes post-gavage (mean=336.3±24.41mg/dl) as compared to the sham group (mean=478.6±30.06 mg/dl). Mice in the treatment group made significantly fewer entries to the correct quadrant (i.e. the quadrant where the hidden platform was placed during training) (mean=12.43±1.55 entries, p&amp;lt;0.05, unpaired t-test) in the MWM test, as compared to the sham group (mean=18.4±1.84 entries). Additionally, mice in the treatment group were significantly less likely to revisit the correct quadrant (mean=10.7±1.50 revisits, p&amp;lt;0.05, unpaired t-test) than the mice in the sham group (mean=16.8±1.78 revisits). Importantly, there was no significant difference in the overall locomotor activity between the groups as measured through the open field test. To summarize, we have developed a method to test the effects of high CSF glucose levels on learning and memory in mice. Our results show that high CSF glucose levels for up to two months cause memory deficits in mice. This mouse model of chronically high CSF glucose presents a useful tool to investigate how diabetes-associated dysregulation of glucose homeostasis in the brain may contribute to AD and other neurodegenerative disorders. Presentation: Saturday, June 17, 2023

A-057 Cerebrospinal Fluid Prolactin in Patients with Neurological Disorders

Abstract Introduction Prolactin a 23 kDa glycoprotein produced by the anterior pituitary among other cells with possible immunological properties. The presence and significance of prolactin in cerebrospinal fluid (CSF) is not widely known. This study examined prolactin levels in CSF from patients being investigated for neurological disorders. Methods CSF samples (leftover) from patients being investigated for neuropathy were obtained and stored at 4 °C or at −20 °C if not analyzed within one week of collection. Prolactin levels were measured using a high sensitivity prolactin ELISA (R and D Systems, Inc., MN, USA) according to manufacturer’s instructions. CSF samples reported total protein and glucose levels were obtained and correlated with measured prolactin levels. Statistical analysis were performed using NCSS statistical software. Results A total of 53 CSF (leftover samples) were analyzed for prolactin content. Prolactin was detectable and levels ranged from 2.68 ng/mL to 12.1 ng/mL (mean 4.49 ng/mL). Total protein ranged from 21 mg/dL to 219 mg/dL (mean 67.5 mg/dL). CSF glucose levels ranged from 16 mg/dL to 114 mg/dL (mean 63.9 mg/dL). Although there was poor (r = 0.66) but significant (P &amp;lt; 0.003) correlation between CSF prolactin and total protein levels, there was no correlation (r = −0.1) between CSF prolactin and CSF glucose levels (P = 0.6). Conclusion Prolactin levels was detected in CSF from patients being investigated for neurological dysfunction. There was correlation with total protein and glucose levels. The clinical significance of CSF prolactin is unknown and remains to be elucidated.

Prominent cerebral veins on susceptibility-weighted angiography in acute meningoencephalitis.

We have commonly observed prominent cerebral veins on susceptibility-weighted angiography (SWAN) in acute meningoencephalitis. This study aimed to investigate the clinical significance of these findings. Cerebral veins on SWAN of 98 patients with acute meningoencephalitis diagnosed from February 2016 through October 2020 were classified into three groups according to the degree of venous prominence (mild, 23; moderate, 53; and prominent, 22). Clinical variables and laboratory findings were compared between these groups. The influence of variables on the prediction of prominent cerebral veins was measured by random forest (RF) and gradient boosting machine (GBM). As cerebral veins became more prominent, cerebrospinal fluid (CSF) glucose level decreased (69.61±29.05vs. 59.72±22.57vs. 48.36±20.29mg/dL, p=.01) and CSF protein level increased (100.73±82.98vs. 104.73±70.99vs. 159.12±118.15mg/dL, p=.03). The etiology of meningoencephalitis, neurological symptoms, and increased intracranial pressure (ICP) signs differed between groups (p<.05). RF and GBM demonstrated that CSF protein level was the variable with the highest power to predict the prominent cerebral vein (mean decrease in node impurity: 4.19, relative influence: 50.66). The presence of prominent cerebral veins on SWAN in acute meningoencephalitis was significantly associated with a low CSF glucose level and a high CSF protein level, as well as ICP. Thus, the visual grade of the cerebral veins on SWAN may be utilized for the management of patients with acute meningoencephalitis.

Relationship between catheter related cerebrospinal fluid infections and systemic immune-inflammation index.

This study investigated the relationship between the systemic immune inflammation index (SII) and catheter-related infections and their effects on prognosis in pediatric patients. A total of 56 pediatric patients diagnosed with ventriculoperitoneal (V-P) shunt infection between January 2017 and October 2019 were included. V-P shunt infection diagnosis was made based on clinical findings. All cerebrospinal fluid (CSF) samples were subjected to direct microscopic examination and culture. Protein, glucose, and sodium levels in CSF, CSF leukocytes, and hematological and biochemical parameters were measured. Fifty-six patients with growth in CSF culture were included in this study. 55.4% of the cases were female and 44.6% male. V-P shunt was detected in 82.1% of the cases and external ventricular drainage (EVD) catheter-related infection in 17.9%. The CSF/blood glucose ratio was significantly lower (p=0.046), and SII was significantly increased (p=0.002) in non-coagulase-negative staphylococci. Early and appropriate antibiotic therapy reduces morbidity and mortality in catheter-related infections. However, it is important to start empirical antibiotherapy until culture results are expected. Therefore, further research on the estimation of possible factors is needed.

A rare case of Elizabethkingia meningoseptica infection in a neonate

Background: Elizabethkingia infections were reportedly rare, but if it was found, it had been known to cause neonatal meningitis, bloodstream infections and respiratory infections. Elizabethkingia meningoseptica had a unique antibiotic susceptibility pattern, usually resistant to most antibiotics. Elizabethkingia infections were associated with a high mortality rate because of the lack of effective therapeutic regimens, antibiotic resistance and virulence. Case Presentation: Fourteen days old boy patient came with the chief complaint of seizure, which occurred twice. Before the seizure, the patient had a fever with the highest temperature was 39°C. The patient looked lethargic, tended to sleep more often, cried occasionally and was not as active as previously. Septic marker revealed an Immature to Total neutrophil (IT) ratio of 0.2 and C-Reactive Protein (CRP) 49.30 mg/dL. A blood smear examination showed toxic granules, vacuolization of the leucocyte and reactive thrombocytosis. Cerebrospinal fluid analysis revealed a cell number of 2520 cell/uL, polymorphonuclear (PMN) cell 80%, mononuclear (MN) cell 20%, Nonne and Pandy was positive, protein level at 300 mg/dL and cerebrospinal fluid glucose level below 20 mg/dL. The patient was initially diagnosed with sepsis and meningitis and was given ampicillin and gentamicin. Blood and cerebrospinal fluid culture isolated Elizabethkingia meningoseptica and significantly as the infection-causing agent. The antibiotic sensitivity of the blood culture was ciprofloxacin and levofloxacin. The antibiotic sensitivity of the cerebrospinal fluid culture was levofloxacin. During the treatment, there were several inappropriate results between clinical manifestation and laboratory results; the antibiotic was changed to levofloxacin according to the sensitivity of the blood and cerebrospinal fluid culture. Conclusion: Elizabethkingia meningoseptica was a rare case, and the nature of this bacteria was resistant to multiple antibiotics. Treatment should be considered carefully.

Correlation of levels of lactic acid and glucose in cerebrospinal fluid of cerebral hemorrhage patients with the occurrence of postoperative intracranial infection and clinical prognosis.

Cerebral haemorrhage is a critical condition that often requires surgical treatment, and postoperative intracranial infection can significantly impact patient outcomes. The aim of the study was to examine the relationship between the levels of lactic acid and glucose in cerebrospinal fluid (CSF) of patients with cerebral haemorrhage and their postoperative intracranial infection and clinical prognosis. The study selected the clinical data of 324 patients with cerebral haemorrhage who underwent surgical treatment in our hospital from March 2020 to March 2022 for retrospective analysis and divided these patients into the intracranial infection group (Group A, n=22, leukocyte values in CSF>5×106/L) and the non-intracranial infection group (Group B, n=302, leukocyte values in CSF 5×106/L) according to the occurrence of postoperative intracranial infection in patients to detect the levels of lactic acid and glucose in CSF at different times in the two groups. Pearson method was adopted to analyze the correlation of the levels of lactic acid and glucose in CSF of patients with intracranial infection, and the Glasgow Outcome Scale (GOS) was used to assess the clinical prognosis of patients. According to their scores, these patients were divided into the good prognosis group (GPG, scores of 4-5 points, n=178) and the poor prognosis group (PPG, scores of 1-3 points, n=146). The levels of lactic acid and glucose in the CSF of patients in the two groups were measured, and the Pearson method was adopted to analyze the relationship between these levels and clinical prognosis.

Correlation between blood glucose and cerebrospinal fluid glucose levels in patients with differences in glucose metabolism.

We aimed to determine a method to identify normal cerebrospinal fluid (CSF) glucose levels by examining the correlation between blood and CSF glucose levels in patients with normal and abnormal glucose metabolism. One hundred ninety-five patients were divided into two groups according to their glucose metabolism. The glucose levels were obtained from CSF and fingertip blood at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. SPSS 22.0 software was used for the statistical analysis. In both the normal and abnormal glucose metabolism groups, CSF glucose levels increased with blood glucose levels at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. In the normal glucose metabolism group, the CSF/blood glucose ratio range was 0.35-0.95 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.43-0.74. In the abnormal glucose metabolism group, the CSF/blood glucose ratio range was 0.25-1.2 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.33-0.78. The CSF glucose level is influenced by the blood glucose level 6 h before lumbar puncture. In patients with normal glucose metabolism, direct measurement of the CSF glucose level can be used to determine whether the CSF level is normal. However, in patients with abnormal or unclear glucose metabolism, the CSF/average blood glucose ratio should be used to determine whether the CSF glucose level is normal.

RT-QuIC Testing for Prions: Applying a Sensitive but Imperfect Test in Clinical Practice (P5-12.010)

<h3>Objective:</h3> Identify the clinical, laboratory, and pathologic features associated with false negative real-time quaking-induced conversion (RT-QuIC) testing for prions. <h3>Background:</h3> Heterogeneity in clinical presentation, abundant mimics, and potential for iatrogenic transmission emphasize the need for accurate diagnostic tests for Creutzfeldt-Jakob disease (CJD). While RT-QuIC is an excellent test, false negative results are recognized in clinical practice. <h3>Design/Methods:</h3> One-hundred twelve patients with probable or definite prion disease were assessed at two tertiary care centers from 2013–2021. RT-QuIC testing for prions was performed in cerebrospinal fluid (CSF) in all patients via the National Prion Disease Pathology Surveillance Center (Cleveland, OH). Demographic data, clinical features, and results of common tests and laboratory studies were abstracted from electronic medical records, and differences between RT-QuIC positive and negative patients considered using univariate statistics. <h3>Results:</h3> Initial RT-QuIC testing was negative in 12/112 patients (sensitivity 89%). Median age at presentation was younger in RT-QuIC negative patients (56.9 vs 66 years, p&lt;0.01), who were also less likely to present with ataxia (3/12 vs 61/100, p=0.03). CSF cell count, protein, and glucose levels were similar between cohorts, while rates of 14-3-3 positivity (2/12 vs 77/100, p&lt;0.01) and median CSF total tau levels were lower in RT-QuIC negative patients (2318 vs 4001 pg/mL, p&lt;0.01). RT-QuIC negative patients also had a longer median days from symptom onset to first presentation (125 vs 47, p=0.04), and longer symptomatic disease duration (530 vs 148, p&lt;0.01). Two RT-QuIC-negative patients underwent repeat testing, of which both were positive. <h3>Conclusions:</h3> RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when prion disease is suspected. Patients with negative RT-QuIC had lower CSF biomarkers of neuronal damage (total-tau and 14-3-3) and longer symptomatic duration of prion disease raising the possibility that false negative RT-QuIC testing may associate with a more indolent disease course. <b>Disclosure:</b> Dr. Jones has nothing to disclose. Dr. Lazar has nothing to disclose. Dr. Porter has nothing to disclose. Dr. Prusinski has nothing to disclose. Dr. Brier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Brier has received research support from NIH. Dr. Bucelli has received personal compensation for serving as an employee of Biogen. Dr. Bucelli has received personal compensation for serving as an employee of Biogen. Dr. Bucelli has received personal compensation for serving as an employee of Neuroquestions. Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen . Dr. Bucelli has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bucelli has stock in Neuroquestions.com. An immediate family member of Dr. Bucelli has stock in Neuroquestions.com. The institution of Dr. Bucelli has received research support from Biogen. The institution of Dr. Bucelli has received research support from Ionis. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.

Autoimmune glial fibrillary acidic protein astrocytopathy: clinical analysis and review of 15 cases

BackgroundTo review clinical characteristics, auxiliary examination results, treatment effects, and outcomes of patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).MethodsWe collated and retrospectively analyzed clinical data of 15 patients admitted with clinical characteristics of an autoimmune GFAP-A acute encephalitis or meningitis phenotype.ResultsAll patients were diagnosed with acute-onset meningoencephalitis and meningoencephalomyelitis. Initial presentations included pyrexia and headache at onset; dual symptoms of prominent tremor with urinary and bowel dysfunction; ataxia, psychiatric and behavioral abnormalities, and impaired consciousness; neck resistance; reduced extremity muscle strength; blurred vision; epileptic seizures; and reduced basic blood pressure. Cerebrospinal fluid (CSF) examination showed that the degree of protein elevation was significantly higher than the degree of increase in white blood cells. Moreover, in the absence of obvious low chloride and glucose levels, CSF chloride levels decreased in 13 patients, accompanied by a CSF glucose level decrease in four. Brain abnormalities were found in magnetic resonance imaging of ten patients, with a linear radial perivascular enhancement present in the lateral ventricles of two patients and symmetric abnormalities in the splenium of the corpus callosum in three patients.ConclusionsAutoimmune GFAP-A may be a spectrum disorder, with acute- or subacute-onset meningitis, encephalitis, and myelitis being the main phenotypes. When used for acute stage treatment, combined hormone and immunoglobulin therapy was superior to hormone pulse therapy or immunoglobulin pulse therapy alone. However, hormone pulse therapy alone without immunoglobulin pulse therapy was associated with a greater number of remaining neurological deficits.

Autosomal Recessively Inherited Glucose Transporter-1 Deficiency Syndrome with Acanthocytosis: A Case Report

AbstractGlucose transporter-1 deficiency syndrome (GLUT-1DS) is a rare, autosomal dominantly inherited disorder due to a heterozygous mutation in the gene solute channel 2A1 (SLC2A1).This gene encodes the glucose transporter protein-1. Autosomal recessive inheritance is extremely rare. Similarly, only very few reports are found in the literature of hematological manifestations in this syndrome. We report an autosomal recessively inherited GLUT-1DS, due to a de novo mutation, with the classical infantile presentation associated with concomitant acanthocytosis. In this case report, the second child born to consanguineous parents with initial refractory neonatal seizures and subsequent poorly controlled epilepsy and developmental regression is discussed. The most notable investigation findings supportive of his underlying diagnosis were very low cerebrospinal fluid (CSF) glucose and CSF lactate levels. His CSF:plasma glucose ratio was 1:7.6. He was anemic with a hemoglobin of 8.8 g/dL with his blood film showing marked acanthocytosis. His elder brother who also had refractory epilepsy and developmental regression had similar hypoglycorrhachia, low CSF:plasma glucose ratio, and mild anemia with acanthocytosis, and he died before establishment of a diagnosis. Our patient was diagnosed to have a novel mutation SLC2A1 c.184A &gt; G p.(Thr62Ala), for which both parents were heterozygous, confirming autosomal recessive inheritance. Commencement of a ketogenic diet resulted in improvement of his seizures and slow gain in development. It also resulted in gradual disappearance of acanthocytes from his peripheral blood. This case describes a rare case of classical GLUT-1DS, autosomal recessively inherited, due to a novel mutation. The acanthocytosis in his blood smear is another rare association minimally reported in GLUT-1DS. The cause of his abnormal red blood cell morphology is unclear. It is possibly related to cation leakage reported in some rare mutations of the SLC2A1 gene needs reference.

Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid

Diabetes increases the risk of cognitive decline and impairs brain function. Whether or not this relationship between high glucose and cognitive deficits is causal remains elusive. Moreover, whether these deficits are mediated by an increase in glucose levels in cerebrospinal fluid (CSF) and/or blood is also unclear. There are very few studies investigating the direct effects of high CSF glucose levels on central nervous system (CNS) function, especially on learning and memory, since current diabetes models are not sufficiently developed to address such research questions. This article describes a method to chronically increase CSF glucose levels for 4 weeks by continuously infusing glucose into the lateral ventricle using osmotic minipumps in mice. The protocol was validated by measuring glucose levels in CSF. This protocol increased CSF glucose levels to ~328 mg/dL after infusion of a 50% glucose solution at a 0.25 µL/h flow rate, compared to a CSF glucose concentration of ~56 mg/dL in mice that received artificial cerebrospinal fluid (aCSF). Furthermore, this protocol did not affect blood glucose levels. Therefore, this method can be used to determine the direct effects of high CSF glucose on brain function or a specific neural pathway independently of changes in blood glucose levels. Overall, the approach described here will facilitate the development of animal models for testing the role of high CSF glucose in mediating features of Alzheimer's disease and/or other neurodegenerative disorders associated with diabetes.

Real-Time Quaking-Induced Conversion Assays for Prions: Applying a Sensitive but Imperfect Test in Clinical Practice.

Real-time quaking-induced conversion (RT-QuIC) assays offer a sensitive and specific means for detection of prions, although false negative results are recognized in clinical practice. We profile the clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays and extend these to frame the diagnostic approach to patients with suspected prion disease. 113 patients with probable or definite prion disease were assessed at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ) or Washington University School of Medicine (St. Louis, MO) from 2013-2021. RT-QuIC testing for prions was performed in CSF at the National Prion Disease Pathology Surveillance Center (Cleveland, OH). Initial RT-QuIC testing was negative in 13/113 patients (sensitivity 88.5%). RT-QuIC negative patients were younger (median 52.0 years vs 66.1 years, p<0.001). Other demographic and presenting features, and CSF cell count, protein, and glucose levels were similar in RT-QuIC negative and positive patients. Frequency of 14-3-3 positivity (4/13 vs 77/94, p<0.001) and median CSF total tau levels were lower in RT-QuIC negative patients (2517 vs 4001 pg/mL, p=0.020), while time from symptom onset to first presentation (153 vs 47 days, p=0.001) and symptomatic duration (710 vs 148 days, p=0.001) were longer. RT-QuIC is a sensitive yet imperfect measure necessitating incorporation of other test results when evaluating patients with suspected prion disease. Patients with negative RT-QuIC had lower markers of neuronal damage (CSF total-tau and protein 14-3-3) and longer symptomatic duration of disease suggesting that false negative RT-QuIC testing associates with a more indolent course.

383 Artificial Neural Network Modeling of Outcomes in Subarachnoid Hemorrhage

INTRODUCTION: Aneurysmal subarachnoid hemorrhage is a devastating neurological condition which requires complex neurocritical care and neurosurgical decision-making yet results in remarkably variable outcomes. Robust methods of identifying patients who may need operative and critical care interventions, such as those who develop hydrocephalus requiring long-term shunting or cerebral vasospasm, or predicting patients who may go on to have long-term disability or worsened neurological outcomes are lacking. METHODS: Data used to train our models included demographic data (gender, age and race), history of medical conditions (hypertension, diabetes, coronary artery disease, hyperlipidemia, tobacco use), Hunt and Hess scale, ventriculostomy data (external ventricular drain (EVD) output, EVD level, EVD age), and cerebrospinal fluid (CSF) lab values (CSF protein and glucose levels). The models were trained on a subpopulation of 85% of subjects and then individually validated in a training-naive subset of 15% of subjects with high accuracy. RESULTS: Using this data, we have generated artificial neural network classifiers with hyperparameter tuning which predict the need for long-term cerebrospinal fluid (CSF) diversion via placement of a shunt (receiver operating characteristic area under the curve) (ROC AUC) = 0.8312), vasospasm (ROC AUC = 0.8058), and the categorical outcome of patient disposition (model accuracy = 0.7786). CONCLUSIONS: We hope the use of artificial intelligence and machine learning techniques will continue to demonstrate power in predicting complex medical outcomes and ultimately help neurosurgeons and neuro-critical care personnel prognosticate and provide appropriate and timely treatment.

The Diagnostic Value of Cerebrospinal Fluid Lactate for Detection of Sepsis in Community-Acquired Bacterial Meningitis.

Community-acquired bacterial meningitis conveys significant morbidity and mortality due to intracranial and systemic complications, and sepsis is a major contributor to the latter. While cerebrospinal fluid (CSF) analysis is essential in the diagnosis of bacterial meningitis, its predictive utility for detection of sepsis is unknown. We investigated the diagnostic performance of CSF parameters for sepsis defined by the Sepsis-3 criteria in a retrospective cohort of patients with community-acquired bacterial meningitis. Among 103 patients, 69.5% developed sepsis. CSF lactate was associated with sepsis with an odds ratio of 1.11 (p = 0.022), while CSF cell counts, glucose and protein levels were not (all p > 0.4). Employing the optimal cutoff of 8.2 mmol/L, elevated CSF lactate resulted in a sensitivity of 81.5% and specificity of 61.5% for sepsis. In exploratory analyses, CSF lactate was also associated with in-hospital mortality with an odds ratio of 1.21 (p = 0.011). Elevated CSF lactate might contribute to early diagnosis of sepsis as well as prognostication in patients with community-acquired bacterial meningitis.