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BACKGROUND: Orbital roof fractures are often the result of high-velocity collisions and are seen in 1-9% of patients with craniofacial trauma. Although the majority of orbital roof fractures are displaced superiorly, a subset results in inferior displacement of fracture fragments, posing a risk for muscle/nerve entrapment and possible blindness. Many of these patients have severe traumatic brain injury (TBI) and, in addition to orbital fractures, also have elevated intracranial pressure (ICP). Management of depressed orbital roof fractures in the setting of severe TBI with elevated ICP represents a management dilemma. CASE DESCRIPTION: Two cases of severe TBI with associated downward displacement of orbital roof fractures were reviewed. Both cases exhibited elevated ICP correlated with the degree of orbital roof fracture depression. Surgical intervention involving elevation and repair of the fractures was undertaken when there was a significant risk of injury to the extraocular muscles and/or the optic nerve due to the extent of the fracture depression. CONCLUSION: Depressed orbital roof fractures may migrate in response to changes in ICP. Serial computed tomography scans and eye examinations may aid with determining the need for and timing of surgical intervention.

International guidance on bioanalytical method validation recommends the practice of partial validation when introducing a new matrix from the same species into a previously fully validated assay. Planning the partial validation protocol should include an evaluation of analyte chemistry, consideration of sample container materials, and a comparison of properties between the relevant biological matrices. Transition of a serum/plasma‐validated bioanalytical method to analysis from a low‐protein matrix, such as urine, cerebral spinal fluid, or oral fluid can result in inconsistent analyte recovery. The low recovery can potentially be mistaken for signal suppression or lack of drug stability and may be more pronounced in low‐concentration or low‐volume samples. In addition, adsorption and absorption interactions with containers may be exacerbated in low‐protein matrices. Several possibilities exist for mitigating the impact of non‐specific binding and low‐protein matrices, including surfactants, bovine serum albumin, and β‐cyclodextrin. Finally, higher matrix protein can facilitate analyte stability. Given all this, matrix protein content should not be overlooked when anticipating a partial bioanalytical method validation. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid leakage (CSFL) is a common complication during spinal surgery. This study aimed to compare dural closure with different suture types, sizes, and techniques, and adhesives to reduce the occurrence of CSFL. Using a pig spine model, the PDS II 4-0, 5-0, 6-0, Vicryl 4-0, 5-0, 6-0, and Prolene 4-0, 5-0, 6-0 sutures were compared by calculating the permeability after suturing. Spraying bioprotein glue was also tried. Next, 120 patients who underwent surgery for intraspinal subdural tumors were enrolled and received 5-0 PDSII, Vicryl, or Prolene for dura repair. In the animal model study, Vicryl 5-0 showed a reduced leakage flow rate compared with 5-0 Prolene and 5-0 PDS II. In the clinical study, postoperative drainage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05). Drainage volume of patients with postoperative cerebrospinal fluid leakage in the Vicryl group was smaller than that in the other groups during the first 3 days after surgery (p < 0.05). There were 12 patients (23.1%, 12/52) in the Vicryl group, 20 patients (55.6%, 20/36) in the PDS group, and 16 patients (50.0%, 16/32) in the Prolene group who had CSFL.The incidence of CSFL was significantly reduced in Vicryl group compared with the other groups(P < 0.05). 5-0 Vicryl sutures significantly reduced the dural leakage flow rate in an animal spine model. Fibrin glue can reinforce dural repair after surgery. 5-0 Vicryl was associated with a lower occurrence of CSFL in patients. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28–73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one‐third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape. [ABSTRACT FROM AUTHOR]

Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b-values and ultra-long echo time (dynDTIlow-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17–28 years; seven men, one woman) underwent dynDTIlow-b using a 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7 % and 4.94 %, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTIlow-b signal intensity at b=0 s/mm2 (i.e., T2-weighted, [S(b=0 s/mm2)]) decreased in systole, but this change was ∼7.5 % of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b=0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of apparent diffusivity in pCSF was present, suggesting that dynDTIlow-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTIlow-b technique can capture various pCSF dynamics in artery pulsation.

INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults. METHODS: We constructed a protein co‐expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically‐relevant outcomes. RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p‐tau181 (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = −2.00, p = 0.005, M7: β = −2.39, p < 0.001). DISCUSSION: In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post‐translational modifications for early cognitive and pathological changes. [ABSTRACT FROM AUTHOR]

Tarlov cysts were thought to be anatomic variants of uncertain etiology and clinical significance when initially described over 80 years ago. They are often detected in routine lumbosacral imaging and generally not reported in a differential diagnosis. There is increasing evidence that at least some Tarlov cysts are symptomatic and can have a significant adverse impact on patients' health and well-being. Women are disproportionately affected with this condition, often presenting with long-standing pain and neurological dysfunctions. Significant gender bias has been a concern in the management of these patients. Unfortunately, there is no consensus on patient selection or management approaches for symptomatic Tarlov cysts. This review article updates information on the prevalence, diagnosis, clinical significance, and treatments of these cysts. Based on these findings and experience with over 1000 patient referrals, a treatment decision algorithm for symptomatic Tarlov cysts was constructed to provide guidance for appropriate management of patients with these complex cysts. [ABSTRACT FROM AUTHOR]

Objectives: Nosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. Methods: From May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. Results: There was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. Conclusion: This pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis.

This retrospective study evaluated canine patients with presumptively diagnosed meningoencephalomyelitis (ME) based on neurological clinical signs, cerebrospinal fluid (CSF) analysis, cross-sectional imaging, and infectious disease testing with a limited neurological-focused polymerase chain reaction (PCR) panel performed on blood and CSF. The first goal was to determine the proportion of dogs where the condition was caused by an infectious agent versus a probable immune-mediated etiology (i.e., meningoencephalomyelitis of unknown origin; MUO) in our geographic region. The secondary goals of this study were to examine and define associations between abnormal CSF test results and cross-sectional neuroimaging findings, in addition to defining the age and most common neurological clinical signs in each group of ME. A total of 168 dogs matched the inclusion criteria with magnetic resonance imaging (MRI) performed in 130 dogs and computed tomography (CT) performed in 38 dogs. Presumptive MUO was observed in 152/168 (90.5%) of dogs and infectious ME was identified in 16/168 (9.5%) of dogs (p

Introduction Nosocomial ventriculitis is a severe infection that habitually plagues neurological intensive care units. It is usually associated with external ventricular drains. Unfortunately, classic cerebral spinal fluid parameters are less specific and sensitive compared to community acquired meningitis. This is in part secondary to indolent bacteria commonly infecting external ventricular drains leading to ventriculitis. Case report Herein, a rare case of Sphingomonas paucimobilis ventriculitis in an immunocompetent host is reported. The patient had classic symptoms of ventriculitis, but her cerebral spinal fluid parameters were benign and initial cultures were negative. Consequently, treatment was tailored to an assumed respiratory infection only to have recurrence of her symptoms. Repeat analysis of her cerebral spinal fluid was again benign, but her cerebral spinal fluid culture grew S. paucimobilis. Subsequently, the patient was treated with cefepime, which resolved her symptoms. She completed a two-week course and has had no recurrence of her infection. Conclusions This case reinforces the need for clinicians to have heightened awareness of this emerging pathogen, its antibiotic resistance patterns, and the unique composition of this bacterium's cell wall which has ramifications on disease presentation. [ABSTRACT FROM AUTHOR]

Aims: Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment. Methods: A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development. Results: Research on biomarkers mainly focused on amyloid‐β (Aβ) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aβ42, total Tau (t‐Tau), and phosphorylated Tau (p‐Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aβ have shown some efficacy and those that target BACE1 and Tau are still undergoing development. Conclusion: Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis. [ABSTRACT FROM AUTHOR]

• Conventional ventriculitis diagnostics lack sensitivity and specificity. • Alpha-defensins are a novel diagnostic that can aid in diagnosing ventriculitis. • Significantly higher levels of α-defensins were present in the ventriculitis cohort. • Levels of α-defensins were not affected by blood or species of bacteria. Nosocomial ventriculitis is a difficult infectious condition to diagnose given that typical cerebral spinal fluid (CSF) parameters, commonly used in the diagnosis of meningitis, lack sensitivity and specificity in nosocomial ventriculitis. Consequently, novel diagnostics are needed to aid in diagnosing this condition. Herein a pilot study using alpha-defensins (α-defensins) to diagnose ventriculitis is discussed. From May 01, 2022, to December 30, 2022, ten patients with culture-proven external ventricular drain (EVD)-associated ventriculitis and ten patients without EVD-associated ventriculitis had CSF preserved. Levels of α-defensins were compared between the two cohorts with enzyme-linked immunosorbent assay. There was a statistically significant (P ˂0.0001) higher level of CSF α-defensins in the ventriculitis cohort compared to the non-ventriculitis cohort. The levels of α-defensins were not affected by blood in CSF or bacterial virulence. Patients with other infectious conditions had increased levels of α-defensins but these levels were still statistically significantly (P ˂0.001) less than those seen in the ventriculitis cohort. This pilot study shows that α-defensins have promise as a biomarker to aid in the diagnosis of ventriculitis. If larger studies support the findings here, this biomarker can help improve diagnostic accuracy and decrease unwarranted empirical broad-spectrum antibiotic use in suspected EVD-associated ventriculitis. [ABSTRACT FROM AUTHOR]

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.

Background: Meningitis is a severe infection affecting the central nervous system requiring early management to prevent debilitating consequences and death. Detection of meningitis can be done by the analysis of cerebrospinal fluid cellularity and biochemistry (glucose and protein concentration). Urine reagent strips can be used to assess these variables and reach to the diagnosis of meningitis early, thereby, reducing the delay in the initiation of its treatment. Aims and Objectives: The current study aimed to determine the efficacy of urine reagent strips for the analysis of CSF. Materials and Methods: The current prospective study was done in a tertiary care center in Rewa, M.P., on 100 cerebral spinal fluid (CSF) samples obtained from the children suspected of meningitis, which were, then, analyzed by both the conventional methods of CSF analysis (including routine biochemical and microscopic analysis) the index test, utilizing the Combur-10 urine reagent strips for the estimation of CSF cell, protein, and glucose. These results were, then, correlated to calculate the diagnostic utility of urine reagent strips for the rapid diagnosis of meningitis. Results: The sensitivity, specificity, and diagnostic accuracy of urine reagent strips for the detection of cell count >10/cumm were 81.81%, 98.21%, and 91%, respectively, and 78.57%, 81.25%, and 79% for detection of protein >30 mg/dL. Reagent strips showed a sensitivity and specificity of 96.85% and 79.41% for the detection of glucose levels

Background Human chorionic gonadotropin (hCG) detection in cerebrospinal fluid (CSF) can provide additional value in the diagnosis of germinoma. However, matrix effects can influence the results when alternative sample types are used. Therefore, modified-cleared/approved methods, which are standard methods used outside their intended scope, are of interest. The aim of the present study was to establish a model to validate modified-approved methods in agreement with the College of American Pathologists (CAP) accreditation requirements. Methods Concentrations of hCG in CSF were determined by means of electrochemiluminescence immunoassay using a Roche Cobas e 602 immunoassay analyzer. Based on the intended use, the following performance characteristics were evaluated: precision, the limit of quantitation (LoQ), and the analytical measurement range (AMR). The reference interval (RI) was also established. For the clinical application study, CSF and serum hCG were measured in 10 patients diagnosed with germinoma. Results The intra- and inter-assay precisions at two levels (10, 250 IU/L) were 0.64 and 0.57% and 4.26 and 3.54%, respectively. The LoQ for hCG was determined to be 0.25 IU/L. The AMR was set from 0.2 to 1,200 IU/L. The RI for hCG in CSF was below 0.40 IU/L. The CSF hCG levels of 10 patients were all above 0.4 IU/L before therapy. Conclusion Modified-approved methods were validated and showed that the quality specifications of the medical laboratory have a positive value in the clinical context. The illustration of quantification of hCG in CSF resulted in compliance with the CAP accreditation requirements.

The IFN‐γ/STAT1 immune signaling pathway impacts many homeostatic and pathological aspects of neurons, beyond its canonical role in controlling intracellular pathogens. Well known for its potent pro‐inflammatory and anti‐viral functions in the periphery, the IFN‐γ/STAT1 pathway is rapidly activated then deactivated to prevent excessive inflammation; however, neurons utilize unique IFN‐γ/STAT1 activation patterns, which may contribute to the non‐canonical neuron‐specific downstream effects. Though it is now well‐established that the immune system interacts and supports the CNS in health and disease, many aspects regarding IFN‐γ production in the CNS and how neurons respond to IFN‐γ are unclear. Additionally, it is not well understood how the diversity of the IFN‐γ/STAT1 pathway is regulated in neurons to control homeostatic functions, support immune surveillance, and prevent pathologies. In this review, we discuss the neuron‐specific mechanisms and kinetics of IFN‐γ/STAT1 activation, the potential sources and entry sites of IFN‐γ in the CNS, and the diverse set of homeostatic and pathological effects IFN‐γ/STAT1 signaling in neurons has on CNS health and disease. We will also highlight the different contexts and conditions under which IFN‐γ‐induced STAT1 activation has been studied in neurons, and how various factors might contribute to the vast array of downstream effects observed. [ABSTRACT FROM AUTHOR]

Background: Acute neuropsychiatric disorders are heterogeneous conditions resulting from interaction between genetic and environmental features. Among these, post infectious forms like Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are common. Preclinical studies suggest a role of CNS T-helper-17/interleukin-17 (IL-17) inflammatory mediated response in the pathogenesis of these disorders. We analyze serum and cerebral-spinal fluid (CSF)-IL-17 concentrations in a cohort of patients with acute neuropsychiatric disease., Methods: We retrospectively included patients <14 years with acute neuropsychiatric symptoms from 2016 to 2020. IL-17 was determined on serum and CSF by means of quantitative sandwich enzyme immunoassay technique, and values were compared to serum and CSF controls. Variables were identified using univariate analysis with Pearson's regression test and X 2 test., Results: 58 subjects were included (67.8 % males, average age: 8.5 years). 50.8 % were classified as PANDAS, 11.8 % as PANS. Mean concentrations of serum IL-17 were higher in the study group compared to controls (p < 0.0001). We observe a trend of increasing IL-17 in post-pubertal children both on serum (p = 0.05) and on CSF (p = 0.04). Coupled IL-17 concentration were higher in the CSF than in serum (p = 0.003), with a marked significance in the PANDAS and PANS group (p < 0.001)., Conclusion: IL-17 is elevated in children and adolescents with acute neuropsychiatric conditions, both on serum and CSF. IL-17 could be involved in the pathogenesis of acute neuropsychiatric disorders in childhood. Further studies are necessary to validate its potential role as a diagnostic or prognostic biomarker., Competing Interests: Competing interests The Authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Meningitis is a severe infection affecting the central nervous system requiring early management to prevent debilitating consequences and death. Detection of meningitis can be done by the analysis of cerebrospinal fluid cellularity and biochemistry (glucose and protein concentration). Urine reagent strips can be used to assess these variables and reach to the diagnosis of meningitis early, thereby, reducing the delay in the initiation of its treatment. Aims and Objectives: The current study aimed to determine the efficacy of urine reagent strips for the analysis of CSF. Materials and Methods: The current prospective study was done in a tertiary care center in Rewa, M.P., on 100 cerebral spinal fluid (CSF) samples obtained from the children suspected of meningitis, which were, then, analyzed by both the conventional methods of CSF analysis (including routine biochemical and microscopic analysis) the index test, utilizing the Combur-10 urine reagent strips for the estimation of CSF cell, protein, and glucose. These results were, then, correlated to calculate the diagnostic utility of urine reagent strips for the rapid diagnosis of meningitis. Results: The sensitivity, specificity, and diagnostic accuracy of urine reagent strips for the detection of cell count >10/cumm were 81.81%, 98.21%, and 91%, respectively, and 78.57%, 81.25%, and 79% for detection of protein >30 mg/dL. Reagent strips showed a sensitivity and specificity of 96.85% and 79.41% for the detection of glucose levels <50 mg/dL. The two methods showed an almost perfect degree of agreement for the detection of leucocytes with Cohen's kappa value of 0.86. Conclusion: Reagent strips can be a helpful bedside screening test for the detection of meningitis and also in resource-limited settings. [ABSTRACT FROM AUTHOR]

External ventricular drains (EVDs) provide a temporary egress for cerebrospinal fluid (CSF) in patients with symptomatic hydrocephalus following aneurysmal subarachnoid hemorrhage. Before EVD removal, a wean trial, which involves clamping the EVD, is typically attempted to ensure that CSF self-regulation is achieved. Automated infrared pupillometry (AIP) has been shown to detect early neurologic decline. We sought to explore the use of AIP to detect early EVD clamping trial failure. This prospective observational pilot study enrolled aneurysmal subarachnoid hemorrhage patients before an EVD clamp trial. On initiating the clamp trial, nurses included hourly AIP assessment in documentation. Clamp trial outcome was based on neurologic examination and neuroimaging. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) models were constructed to explore computed tomography (CT) versus AIP as predictors of clamp trial outcome. Among the 30 subjects enrolled, there were 38 clamping trials and 22 successful EVD removals. CT scan as a predictor of clamp trial was found to have a sensitivity of 68.8% and specificity of 89.5% (PPV = 84.6%, NPV = 77.3%). AIP assessment as a predictor of wean trial outcome was found to have a sensitivity of 58.3% and specificity of 100% (PPV = 100%, NPV = 63.2%). The pilot study data support that Neurological Pupil index <3 is a potential indicator of early clamp trial failure, but a CT scan has a higher sensitivity and NPV for predicting successful EVD removal. This finding suggests the benefits of including AIP assessments during clamping trials. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the infection rates and catheterization duration of applying antibiotic-impregnated external ventricular drain (EVD) for the treatment of post-hemorrhagic hydrocephalus (PHH) in low birth weight infants (LBWI). Methods: This retrospective cohort study included 13 preterm LBWI with PHH. Data were collected from the patient's medical charts and included gender, gestational age, birth weight, intraventricular hemorrhage grade, ventriculostomy-associated infection (VAI), and the duration of catheterization. All patients were followed up for at least 6 months after EVD surgery. Results: The mean gestational age at birth was 27 ± 2.5 weeks, and the mean birth weight was 907 ± 220 g. Among all patients with IVH, two (6.7%) had grade 2 IVH, five (38.5%) had grade 3 IVH, and six (46.2%) had grade 4 IVH. EVD surgery was conducted once for six patients, twice for five patients, and three times for two patients. One patient (7.7%) had VAI post-EVD surgery at 14 days. Three patients (23%) expired due to sepsis, shock, and chylous ascites. Seven patients (53.8%) had hydrocephalus and needed a ventriculoperitoneal shunt over the following course. The longest EVD catheterization period was 57 days without sustained VAI. Conclusions: Antibiotic-impregnated EVD has a similar infection rate with the ventricular access device and ventriculosubgaleal shunt. The risk of VAI was not increased even with the EVD catheterization day approaching 2 months. Our study supports the evidence that antibiotic-impregnated EVD is safe and effective for the management of PHH in LBWI. However, this research has a small sample sized and a retrospective design. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is the most common pediatric malignant central nervous system tumor. Overall survival in MB depends on treatment tuning. There is aneed for biomarkers of residual disease and recurrence. We analyzed the proteome of waste cerebrospinal fluid (CSF) from extraventricular drainage (EVD) from six children bearing various subtypes of MB and six controls needing EVD insertion for unrelated causes. Samples included total CSF, microvesicles, exosomes, and proteins captured by combinatorial peptide ligand library (CPLL). Liquid chromatography-coupled tandem mass spectrometry proteomics identified 3560 proteins in CSF from control and MB patients, 2412 (67.7%) of which were overlapping, and 346 (9.7%) and 805 (22.6%) were exclusive. Multidimensional scaling analysis discriminated samples. The weighted gene co-expression network analysis (WGCNA) identified those modules functionally associated with the samples. A ranked core of 192 proteins allowed distinguishing between control and MB samples. Machine learning highlighted long-chain fatty acid transport protein 4 (SLC27A4) and laminin B-type (LMNB1) as proteins that maximized the discrimination between control and MB samples. Machine learning WGCNA and support vector machine learning were able to distinguish between MB versus non-tumor/hemorrhagic controls. The two potential protein biomarkers for the discrimination between control and MB may guide therapy and predict recurrences, improving the MB patients' quality of life. [ABSTRACT FROM AUTHOR]

Droplet microfluidics with push-pull and microdialysis sampling from brain slices, cultured cells and engineered tissues produce low volume mass limited samples containing analytes sampled from the extracellular space. This sampling approach coupled to mass spectrometry (MS) detection allows evaluation of time-dependent chemical changes. Our goal is an approach for continuous sampling and segregation of extracellular samples into picoliter droplets followed by the characterization of the droplets using nanoelectrospray ionization (nESI) MS. The main focus here is the optimization of the carrier oil for the microfluidic device that neither affects the stability of picoliter droplets nor compatibility with MS detection of a range of analytes. We developed and characterized a 1-octanol-assisted ultra-small volume droplet microfluidic nESI MS system for the analysis of neurotransmitters in distinct samples including cerebrospinal fluid (CSF). The use of a 1-octanol oil phase was effective for generation of aqueous droplets as small as 65 pL and enabled detection of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) in water and artificial CSF. Continuous MS analysis of droplets for extended periods up to 220 min validated the long-term stability of droplet generation and analyte detection by nESI-MS. As an example, ACh response demonstrated a linear working range (R2 = 0.99) between 0.4 μM and 25 μM with a limit of detection of 370 nM (24 amol), enabling its quantitation in rodent CSF. The established droplet microfluidics – nESI MS approach allows the analysis of microenvironments at high spatiotemporal resolution. The approach may allow microsampling and monitoring of spatiotemporal dynamics of neurochemicals and drugs in the brain and spinal cord of live animals. [Display omitted] • A pL droplet microfluidic-nESI MS system optimized for neurotransmitter detection. • The 1-octanol oil phase effectively generates aqueous droplets as small as 65 pL. • Long-term stability for droplet generation and analyte detection by MS. • Acetylcholine quantified from rat cerebral spinal fluid samples. • Characteristics of the system designed for in vivo monitoring of neurotransmitters. [ABSTRACT FROM AUTHOR]

• Diffusion tensor of the pCSF oriented parallel with the neighboring arterial flow. • Arterial dilation promotes pCSF flow in parallel and perpendicular directions. • DynDTI low-b could detect the volume and flow variance of pCSF within cardiac cycle. Perivascular cerebrospinal fluid (pCSF) flow is a key component of the glymphatic system. Arterial pulsation has been proposed as the main driving force of pCSF influx along the superficial and penetrating arteries; however, evidence of this mechanism in humans is limited. We proposed an experimental framework of dynamic diffusion tensor imaging with low b -values and ultra-long echo time (dynDTI low-b) to capture pCSF flow properties during the cardiac cycle in human brains. Healthy adult volunteers (aged 17–28 years; seven men, one woman) underwent dynDTI low-b using a 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) with simultaneously recorded cardiac output. The results showed that diffusion tensors reconstructed from pCSF were mainly oriented in the direction of the neighboring arterial flow. When switching from vasoconstriction to vasodilation, the axial and radial diffusivities of the pCSF increased by 5.7 % and 4.94 %, respectively, suggesting that arterial pulsation alters the pCSF flow both parallel and perpendicular to the arterial wall. DynDTI low-b signal intensity at b =0 s/mm2 (i.e., T2-weighted, [S(b =0 s/mm2)]) decreased in systole, but this change was ∼7.5 % of a cardiac cycle slower than the changes in apparent diffusivity, suggesting that changes in S(b =0 s/mm2) and apparent diffusivity arise from distinct physiological processes and potential biomarkers associated with perivascular space volume and pCSF flow, respectively. Additionally, the mean diffusivities of white matter showed cardiac-cycle dependencies similar to pCSF, although a delay relative to the peak time of apparent diffusivity in pCSF was present, suggesting that dynDTI low-b could potentially reveal the dynamics of magnetic resonance imaging-invisible pCSF surrounding small arteries and arterioles in white matter; this delay may result from pulse wave propagation along penetrating arteries. In conclusion, the vasodilation-induced increases in axial and radial diffusivities of pCSF and mean diffusivities of white matter are consistent with the notion that arterial pulsation can accelerate pCSF flow in human brain. Furthermore, the proposed dynDTI low-b technique can capture various pCSF dynamics in artery pulsation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.

PurposePatients with intraventricular tumors are more susceptible to postoperative meningitis (POM) than other intracranial tumors. In this study, we explored the risk factors of POM in lateral ventricular trigone meningiomas (LVTMs).MethodsClinical features of 64 patients with LVTMs were analyzed. Age, gender, body mass index, medical history, intraoperative blood loss (IBL), intraventricular drainage placement, surgical duration, tumor grade, postoperative tumor cavity hemorrhage, and tumor size were included in univariate and multivariate analyses of POM.ResultsOf the 64 patients, 14 patients (21.9%) received diagnosis of POM. The univariate analysis revealed IBL ≥400 mL (odds ratio [OR], 9.012; p = 0.003), tumor size ≥50 cm3 (OR, 3.071; p = 0.080), and surgical duration ≥5 h (OR, 2.970; p = 0.085) were considered possible risk factors for POM (p

BackgroundMitochondrial DNA (mtDNA) haplogroups are ancestry-related patterns of single-nucleotide polymorphisms that are associated with differential mitochondrial function in model systems, neurodegenerative diseases in HIV-negative populations, and chronic complications of HIV infection, including neurocognitive impairment. We hypothesized that mtDNA haplogroups are associated with neuroinflammation in HIV-infected adults.MethodsCNS HIV Antiretroviral Therapy Effects Research (CHARTER) is a US-based observational study of HIV-infected adults who underwent standardized neurocognitive assessments. Participants who consented to DNA collection underwent whole blood mtDNA sequencing, and a subset also underwent lumbar puncture. IL-6, IL-8, TNF-α (high-sensitivity), and IP-10 were measured in cerebrospinal fluid (CSF) by immunoassay. Multivariable regression of mtDNA haplogroups and log-transformed CSF biomarkers were stratified by genetic ancestry using whole-genome nuclear DNA genotyping (European [EA], African [AA], or Hispanic ancestry [HA]), and adjusted for age, sex, antiretroviral therapy (ART), detectable CSF HIV RNA, and CD4 nadir. A total of 384 participants had both CSF cytokine measures and genetic data (45% EA, 44% AA, 11% HA, 22% female, median age 43 years, 74% on ART).ResultsIn analyses stratified by the 3 continental ancestry groups, no haplogroups were significantly associated with the 4 biomarkers. In the subgroup of participants with undetectable plasma HIV RNA on ART, European haplogroup H participants had significantly lower CSF TNF-α (P = 0.001).ConclusionsLower CSF TNF-α may indicate lower neuroinflammation in the haplogroup H participants with well-controlled HIV on ART.

We aimed to investigate the CXCL13 concentration of the serum and cerebral spinal fluid (CSF) in human immunodeficiency virus (HIV)-negative latent syphilis patients with treatment failure and explore the change in CXCL13 after treatment. Sixty-eight latent syphilis patients with treatment failure (failure group), 68 syphilis patients with successful treatment (seroconversion group) and 18 patients with non-inflammatory diseases of the nervous system (control group) were included and serum and CSF were collected. Enzyme-linked immunosorbent assay was employed to detect the CXCL13 in the serum and CSF. Results showed that the serum CXCL13 concentration was comparable among three groups, and the CSF leukocyte count, IgG index and CXCL13 concentration in the failure group were significantly higher than those in the seroconversion group and control group (P < 0.05, P < 0.01). CSF CXCL13 concentration in the failure group was positively related to the CSF leukocyte count (r = 0.3594, P < 0.001). Of the 68 patients in the treatment failure group, neurosyphilis was found in 17 (25.0%). In conclusion, involvement of nervous system is one of the reasons for the treatment failure in patients with latent syphilis. Detection of CSF CXCL13 concentration is helpful for the diagnosis and therapeutic evaluation of HIV-negative latent syphilis patients with treatment failure and neurosyphilis.

Fast and accurate cerebrospinal fluid cytology is the key to the diagnosis of many central nervous system diseases. However, in actual clinical work, cytological counting and classification of cerebrospinal fluid are often time-consuming and prone to human error. In this report, we have developed a deep neural network (DNN) for cell counting and classification of cerebrospinal fluid cytology. The May-Grünwald-Giemsa (MGG) stained image is annotated and input into the DNN network. The main cell types include lymphocytes, monocytes, neutrophils, and red blood cells. In clinical practice, the use of DNN is compared with the results of expert examinations in the professional cerebrospinal fluid room of a First-line 3A Hospital. The results show that the report produced by the DNN network is more accurate, with an accuracy of 95% and a reduction in turnaround time by 86%. This study shows the feasibility of applying DNN to clinical cerebrospinal fluid cytology.

Introduction: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain., Materials and Methods: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus from 2017 (when the PACC last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations were based on the strength of evidence, and when evidence was scant, recommendations were based on expert consensus., Results: The PACC evaluated the published literature and established evidence- and consensus-based expert opinion recommendations to guide best practices in treating cancer pain. Additional guidance will occur as new evidence is developed in future iterations of this process., Conclusions: The PACC recommends best practices regarding the use of intrathecal drug delivery in cancer pain, with an emphasis on managing the unique disease and patient characteristics encountered in oncology. These evidence- and consensus-based expert opinion recommendations should be used as a guide to assist decision-making when clinically appropriate., Competing Interests: Conflict of Interest Shane E. Brogan acts as a paid consultant for Medtronic. Eric Buchser reports grants from the Swiss National Foundation and the Commission for Technology and Innovation; and grants, personal fees and nonfinancial support from Medtronic, during the conduct of the study. Timothy R. Deer reports no conflicts that pertain to intrathecal therapy; reports conflicts within the neuromodulation field that include consulting for Abbott, Saluda, Ethos, Nalu, PainTeq, and Cornorloc; he also holds a patent pending with Abbott; is on the advisory board of Abbott and Nalu; has stock options Saluda, Spinethera, and Nalu; and has institutional research grants from Abbott, Saluda, Vertiflex and Mainstay. Denis Dupoiron reports personal fees from Medtronic and Esteve during the conduct of the study. Amitabh Gulati reports personal fees from Medtronic, Flowonix, AIS HealthCare, SPR Therapeutics, Nalu Medical, Bausch Health, and Spark Medical, outside the submitted work. Jennifer Hah reports grants from NIH NIDA, outside the submitted work. Gladstone C. McDowell II reports personal fees and other from Medtronic Corporation; personal fees, nonfinancial support, and other from Flowonix Corporation and TerSera Therapeutics, outside the submitted work. Christophe Perruchoud reports grants and personal fees from Medtronic and Boston Scientific, during the conduct of the study; and personal fees from Medtronic and Boston Scientific, outside the submitted work. Fabian Piedimonte reports personal fees from Medtronic and Abbott, which stopped in June 2020. Julie G. Pilitsis reports grants and other from Boston Scientific, Nevro, Abbott, Medtronic, and TerSera; other from Saluda; grants from NIH 2R01CA166379-06, other from Aim Medical Robotics and Karuna Labs; and grants from NIH U44NS115111, outside the submitted work. Jason E. Pope reports other from Ethos Labs, Flowonix, Saluda, PainTeq, Aurora Spine, Thermaquil, Celeri Health, Spine Thera, AGR, NIS, Abbott, Medtronic, Biotronik, Mainstay, Muse, AIS, SPR Therapeutics, TerSera, Vertiflex, Boston Scientific, Vertos, SPARK, and WISE, outside the submitted work. Michael F. Saulino reports research grants from Medtronic and Flowonix; fellowship support from Medtronic, Piramal, and Saol. Peter S. Staats reports grants from Saluda, Nalu, AIS Therapeutics, Thermaquil, Biotronik, electroCore and Vertos, outside the scope of this work; royalties from the Averitas-Qutenza Patch, outside the scope of this work; payment or honoraria from Medtronic and SPR Therapeutics, outside the scope of this work; patents for vagus nerve and topical capsaicin products; participation in a Data Safety Monitoring or Advisory Board for Nalu and Saluda; a leadership role in the World Institute of Pain, American Society of Pain and Neuroscience, American Society of Interventional Pain Physicians, and the Florida Academy of Pain Management; and stock options in Saluda, Nalu and electroCore. Mark S. Wallace reports grants from NIH and is a consultant to TerSera. Tony L. Yaksh reports grants from NIH NINDS, other from CODA, IONIS, and Medtronic, during the conduct of the study; and grants from NIH-NINDS, IONIS, and Medtronic, outside the submitted work. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Orbital roof fractures are often the result of high-velocity collisions and are seen in 1-9% of patients with craniofacial trauma. Although the majority of orbital roof fractures are displaced superiorly, a subset results in inferior displacement of fracture fragments, posing a risk for muscle/nerve entrapment and possible blindness. Many of these patients have severe traumatic brain injury (TBI) and, in addition to orbital fractures, also have elevated intracranial pressure (ICP). Management of depressed orbital roof fractures in the setting of severe TBI with elevated ICP represents a management dilemma., Case Description: Two cases of severe TBI with associated downward displacement of orbital roof fractures were reviewed. Both cases exhibited elevated ICP correlated with the degree of orbital roof fracture depression. Surgical intervention involving elevation and repair of the fractures was undertaken when there was a significant risk of injury to the extraocular muscles and/or the optic nerve due to the extent of the fracture depression., Conclusion: Depressed orbital roof fractures may migrate in response to changes in ICP. Serial computed tomography scans and eye examinations may aid with determining the need for and timing of surgical intervention., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups whereas the Exe-9 and Glp-1r KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of early-onset sepsis (EOS) of the newborn remains a controversial issue among providers due to the non-infectious symptomology which exists in the newborn period. Pre/post interventional quality improvement project in a level III NICU to reduce antibiotic utilization and ancillary laboratory tests with the introduction of an evidence-based guideline for the evaluation of EOS in the NICU. Primary outcome measures include mean number of empiric antibiotic treatment days and utilization rate (AUR), number of laboratory tests ordered, and incidence of unwarranted antibiotic therapy beyond the 48-h rule out period. Mean empiric antibiotic treatment days decreased from 2.94 to 1.58 days and overall antibiotic use decreased from 73.7% to 57.1%. Likewise, the mean AUR decreased from 212.5 to 147.6 days of therapy per 1000 patient days. There was an 86% decline in the number of ancillary tests and unwarranted antibiotic use beyond 48- h was reduced by 74%. Guidelines for EOS of the newborn should include a thorough baseline evaluation of the drivers of antibiotic use to create an evidence-based foundation. Reducing unnecessary antibiotic use and EOS evaluations in a safe and effective manner have the potential to lower consumer and healthcare expenditures while improving the long-term health of the newborn in the NICU. These findings emphasize the importance of implementing an evidence-based protocol for antibiotic stewardship in the NICU. With further research there is the potential to improve the healthcare of newborns while reducing expenditures in a safe, effective evaluation of EOS in the newborn population. • Early-onset sepsis remains a large contributor of morbidity and mortality. • Evidence-based practices can facilitate change within healthcare organizations. • Antibiotic stewardship can impact healthcare outcomes during the newborn period. • The neonatal early-onset sepsis calculator can reduce empiric antibiotic use. [ABSTRACT FROM AUTHOR]

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke. [ABSTRACT FROM AUTHOR]

Background: CSF rhinorrhea refers to CSF leakage into the nasal cavity. Most commonly, CSF enters the nasal cavity through defects in the anterior skull base. CSF leak is a serious condition occurring spontaneously or as a result of increased ICP, head trauma, surgery, neoplastic invasion, inflammatory erosion of the skull base, or congenital malformations. Objective: Our meta-analysis study is to compare between free grafts and prdicled nasal flaps in repairing CSF rhinorrhea regarding success rate, complications, operative time and hospital stay. Methodology: The total number of patients in all the included studies was 524 patients; 339 in the free graft group and 185 in the vascularized flap group. Results: Our meta-analysis study showed that success rate in free graft group was 88.5%, while, in vascularized flap group was 93% and the complications rate in free graft group was 39%, while, in vascularized flap group was 39.3%. The result of our meta-analysis showed no significant difference between free grafts and vascularized nasal flaps in reconstruction of skull base in CSF rhinorrhea regarding success rate and complications rate. Data Sources: Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Conclusion: We found no significant difference between free grafts and vascularized nasal flaps in reconstruction of skull base in CSF rhinorrhea regarding success rate and complications rate. Choosing between them depends on the surgeon's experience and the location and the size of the defect. [ABSTRACT FROM AUTHOR]

Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM# 261600), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls. The CSF concentrations and CSF/plasma ratios for glucose and lactate were found to be below normal, similar to what has been reported for glucose transporter1 (GLUT1) deficiency patients who exhibit many of the same clinical symptoms as untreated PKU patients. CSF glucose and lactate levels were negatively correlated with CSF phenylalanine (Phe), while CSF glutamine and glutamate levels were positively correlated with CSF Phe levels. Plasma glucose levels were negatively correlated with plasma Phe concentrations in PKU subjects, which partly explains the reduced CSF glucose concentrations. Although brain glucose concentrations are unlikely to be low enough to impair brain glucose utilization, it is possible that the metabolism of Phe in the brain to produce phenyllactate, which can be transported across the blood-brain barrier to the blood, may consume glucose and/or lactate to generate the carbon backbone for glutamate. This glutamate is then converted to glutamine and carries the Phe-derived ammonia from the brain to the blood. While this mechanism remains to be tested, it may explain the correlations of CSF glutamine, glucose, and lactate concentrations with CSF Phe. • Adult phenylketonurics have low CSF, but normal plasma, glucose and lactate levels. • Similar findings occur in glucose transporter1 deficiency syndrome patients. • CSF glucose and lactate are negatively correlated with CSF phenylalanine level. • CSF glutamine level is positively correlated with CSF phenylalanine level. • Brain phenylalanine metabolism can consume glucose/lactate and generate glutamine. [ABSTRACT FROM AUTHOR]

Abstract Background For definitive diagnosis of cryptococcal meningitis, Cryptococcus neoformans and/or C. gattii must be identified within cerebral spinal fluid from the patients. The traditional methods for detecting Cryptococcus spp. such as India ink staining and culture are not ideal. Although sensitive and specific enough, detection of cryptococcal antigen polysaccharide has a high dose hook effect. Therefore, the aim of this study was to introduce a new rapid and simple detection method of Cryptococcus neoformans and C. gattii in cerebral spinal fluid. Methods The lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assay was constructed to detect the specific DNA sequences of C. neoformans and C. gattii. The detection limit was evaluated using serial dilutions of C. neoformans and C. gattii genomic DNA. The specificity was assessed by excessive amount of other pathogens genomic DNA. The optimal detection time and amplification temperature were also analyzed. The diagnostic parameters were first calculated using 114 clinical specimens and then compared with that of other diagnostic method. A brief analysis and comparison of different DNA extraction methods was discussed, too. Results The LF-RPA assay could detect 0.64 pg of genomic DNA of C. neoformans per reaction within 10 min and was highly specific for Cryptococcus spp.. The system could work well at a wide range of temperature from 25 to 45 °C. The overall sensitivity and specificity were 95.2 and 95.8% respectively. As amplification template for LF-RPA assay, both cell lysates and genomic DNA produce similar experimental results. Conclusions The LF-RPA system described here is shown to be a sensitive and specific method for the visible, rapid, and accurate detection of Cryptococcus spp. in cerebral spinal fluid and might be useful for clinical preliminary screening of cryptococcal meningitis.

Medulloblastoma (MB) is the most common pediatric malignant central nervous system tumor. Overall survival in MB depends on treatment tuning. There is aneed for biomarkers of residual disease and recurrence. We analyzed the proteome of waste cerebrospinal fluid (CSF) from extraventricular drainage (EVD) from six children bearing various subtypes of MB and six controls needing EVD insertion for unrelated causes. Samples included total CSF, microvesicles, exosomes, and proteins captured by combinatorial peptide ligand library (CPLL). Liquid chromatography-coupled tandem mass spectrometry proteomics identified 3560 proteins in CSF from control and MB patients, 2412 (67.7%) of which were overlapping, and 346 (9.7%) and 805 (22.6%) were exclusive. Multidimensional scaling analysis discriminated samples. The weighted gene co-expression network analysis (WGCNA) identified those modules functionally associated with the samples. A ranked core of 192 proteins allowed distinguishing between control and MB samples. Machine learning highlighted long-chain fatty acid transport protein 4 (SLC27A4) and laminin B-type (LMNB1) as proteins that maximized the discrimination between control and MB samples. Machine learning WGCNA and support vector machine learning were able to distinguish between MB versus non-tumor/hemorrhagic controls. The two potential protein biomarkers for the discrimination between control and MB may guide therapy and predict recurrences, improving the MB patients’ quality of life.

Background Subarachnoid neurocysticercosis (SANCC) represents the most severe and difficult to treat form of neurocysticercosis. The inflammatory response contributes significantly to the morbidity and mortality of the disease. This study sought to understand the nature and evolution of the inflammation associated with SANCC, and evaluate for predictors of time to cure. Methods There were 16 subjects with SANCC (basilar cistern, sylvian fissure, and/or spinal involvement) during active infection who had cerebrospinal fluid (CSF) cytokine and chemokine profiling, of whom 9 had a second CSF sample at (or following) the time of cure. The relationships between clinical parameters and cytokine/chemokine results were assessed. Results Compared to pools of healthy donor CSF, those with active SANCC showed a significant (P <.05) increase in chemokines and cytokines associated with Type 1 immunity (interferon [IFN] γ, interleukin [IL] 12p70, C-X-C Motif Ligand 10 CXCL-10); Type 2 immunity (IL-10, IL-13); IFNα2; and the chemokines Macrophage inflammatory protein MIP-1α/CCL3, MIP-1ß/CCL4, and Vascular Endothelial Growth Factor VEGF that appears to be locally (central nervous system [CNS]) produced. Compared to those with active disease, those with CSF taken at the time of cure showed a significant decrease in most of these chemokines and cytokines. Despite this, CSF from cured SANCC patients had levels of IL-10 (P =.039), CXCL-10 (P =.039), and IL-12p70 (P =.044) above those seen in CSF from uninfected subjects. High ratios of IL-12p70/IL-10 early in infections were associated with a shorter time to cure (r = −0.559; P =.027), and a high Taenia solium burden (by quantitative polymerase chain reaction) was associated with longer times to cure (r = 0.84; P =.003). Conclusions SANCC is associated with a marked, CNS-localized cytokine-/chemokine-driven inflammatory response that largely decreases with curative therapy, though some analytes persisted above the normal range. The relative balance between proinflammatory and regulatory cytokines may be an important determinant for a cure in SANCC. [ABSTRACT FROM AUTHOR]