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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]

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]

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]

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: 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]

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]

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 studywas 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 from0.2 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. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Background: Disability from migraine has a profound impact on the world's economy. Research has been ongoing to identify biomarkers to aid in diagnosis and treatment.Objective: The aim of this study was to highlight the purported diagnostic and therapeutic migraine biomarkers and their role in precision medicine.Methods: A comprehensive literature search was conducted using PubMed, Google Scholar, and clinicaltrials.gov using keywords: "migraine" OR "headache" combined with "biomarkers" OR "marker." Other keywords included "serum," "cerebral spinal fluid," "inflammatory," and "neuroimaging."Results: After a review of 88 papers, we find the literature supports numerous biomarkers in the diagnosis of migraine. Therapeutic biomarkers, while not as extensively published, highlight calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide-38 (PACAP-38) as biomarkers with the most substantiated clinical relevance. Genetic markers mainly focusing on gene mutations with resultant biochemical alterations continue to be studied and show promise.Conclusion: Although there are several proposed biomarkers for migraine, continued research is needed to substantiate their role in clinical practice. [ABSTRACT FROM AUTHOR]

Many previous studies have investigated the use of post-mortem biochemistry to estimate the post-mortem interval (PMI). Vitreous humour (VH) potassium and sodium/chloride levels are well recognized to increase and decrease, respectively, in the post-mortem period but have limited ability in estimating PMI. Cerebrospinal fluid (CSF) is described to have different post-mortem biochemical properties than VH, but is not well studied in relation to estimating PMI. This exploratory study examined 20 paired cases of VH and CSF to investigate their use in estimating PMI. Linear univariate analysis showed Na+, Cl− and K+ in VH and CSF share similar trends, but only K+ in VH and CSF collected via lumbar puncture (LP) showed a significant regression coefficient (p < 0.01). In subsequent linear multivariate analysis, the coefficient for K+ in VH remained positive and significant but not for K+ in CSF. Only minor improvement was observed in the multivariate analysis. Our study showed changes in analytes in VH and CSF follow similar trends. K+ in VH is most accurate in estimating the PMI, with no significant improvement in accuracy when K+ in CSF is combined. Thus, the role of CSF electrolytes in estimating PMI may be very limited. [ABSTRACT FROM AUTHOR]

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) and vitreous humour (VH) can be biochemically analysed post-mortem. CSF can be aspirated from the ventricular system (VA) and from lumbar puncture (LP), whereas, VH is aspirated from the orbits. This study compared the biochemical constituents between CSF and VH in 20 post-mortem subjects as well as the effect post-mortem interval and subject age have on these variables. VH samples had significantly higher sodium (Na) and chloride (Cl) and lower magnesium (Mg), potassium (K), urea (Ur) and creatinine (Cr) compared with CSF samples. No statistically significant difference was demonstrated with beta-hydroxybutyrate (BHB) and glucose levels in both VH and both CSF samples. Interestingly, some of the differences in the biochemical analysis correlated with age, but none with post-mortem interval. In addition to sampling and pre-analytical sample processing differences, there may also be ante- and post-mortem factors explaining these observations. This study suggests that post-mortem CSF and VH are biochemically different and reference ranges for VH are not recommended for use in CSF samples. [ABSTRACT FROM AUTHOR]

Summary: Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS‐directed therapies that are also associated with significant short‐ and long‐term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS. [ABSTRACT FROM AUTHOR]

Dravet syndrome (DS) is a neurodevelopmental genetic disorder caused by mutations in the SCN1A gene encoding the α subunit of the NaV1.1 voltage-gated sodium channel that controls neuronal action potential firing. The high density of this mutated channel in GABAergic interneurons results in impaired inhibitory neurotransmission and subsequent excessive activation of excitatory neurons. The syndrome is associated with severe childhood epilepsy, autistic behaviors, and sudden unexpected death in epilepsy. Here, we compared the rescue effects of an adeno-associated viral (AAV) vector coding for the multifunctional β1 sodium channel auxiliary subunit (AAV-NaVβ1) with a control vector lacking a transgene. We hypothesized that overexpression of NaVβ1 would facilitate the function of residual voltage-gated channels and improve the DS phenotype in the Scn1a+/− mouse model of DS. AAV-NaVβ1 was injected into the cerebral spinal fluid of neonatal Scn1a+/− mice. In untreated control Scn1a+/− mice, females showed a higher degree of mortality than males. Compared with Scn1a+/− control mice, AAV-NaVβ1-treated Scn1a+/− mice displayed increased survival, an outcome that was more pronounced in females than males. In contrast, behavioral analysis revealed that male, but not female, Scn1a+/− mice displayed motor hyperactivity, and abnormal performance on tests of fear and anxiety and learning and memory. Male Scn1a+/− mice treated with AAV-NaVβ1 showed reduced spontaneous seizures and normalization of motor activity and performance on the elevated plus maze test. These findings demonstrate sex differences in mortality in untreated Scn1a+/− mice, an effect that may be related to a lower level of intrinsic inhibitory tone in female mice, and a normalization of aberrant behaviors in males after central nervous system administration of AAV-NaVβ1. The therapeutic efficacy of AAV-NaVβ1 in a mouse model of DS suggests a potential new long-lasting biological therapeutic avenue for the treatment of this catastrophic epilepsy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Postoperative ventriculoperitoneal (VP) shunt complications in pediatric patients involves impaired absorption of CSF from the subarachnoid space to the venous circulation via the arachnoid villi. It also involves obstruction in flow of CSF from the ventricles to the subarachnoid space. Objective: To assess the proper management of postoperative shunt complications. Patients and Methods: Retrospective study conducted in the Neurosurgery Department of Al-Azhar University Hospitals and El-Sahel Teaching Hospital. Pediatric patients from both genders including infants and pediatric patients till 12 years old who were having postoperative ventriculoperitoneal shunt complications were assessed clinically and radiographically for the best management that include either surgical or medical ones or both .Results: The management of postoperative VP shunt malfunction is essential shunt revision of either proximal or distal catheters or the whole system if shunt disintegration is suspected. The most common organisms in shunt infection were gram positive organisms (coagulase negative staph. and staph. aureus). Conclusion: The most effective management plan is shunt revision. To prevent VP shunt malfunction, we have to make sure of intraoperative closed, sterile and functioning shunt system. [ABSTRACT FROM AUTHOR]

Aim: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results.Methods: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging-Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups.Results: The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones.Conclusion: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ghrelin is physiologically important for maintaining sleep rhythm. Cigarette smoking has been demonstrated to significantly increase the risk of insufficient sleep by regulating ghrelin at the central and peripheral levels. No research has been published to study the relationship between active smoking and sleep via ghrelin level in cerebrospinal fluid (CSF). A total of 139 Chinese males were recruited and divided into active smokers (n = 77) and non-smokers (n = 62). The levels of CSF and plasma ghrelin were measured. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep. Non-smokers had lower PSQI scores (1.71 ± 1.93) than active smokers (3.70 ± 1.78). Non-smokers have significantly lower plasma ghrelin levels and lower plasma/CSF ghrelin ratio but higher CSF ghrelin than active smokers. Among non-smokers, plasma ghrelin levels were not correlated with PSQI scores (all p > 0.05), CSF ghrelin levels were positively correlated with PSQI scores (r = 0.309, p = 0.019), and the plasma/CSF ghrelin ratio was negatively correlated with PSQI scores (r = −0.346, p = 0.008). This study is the first to reveal the relationship between cigarette smoking, high CSF ghrelin levels and insufficient sleep, suggesting that maintaining a normal plasma/CSF ghrelin ratio may be the physiological mechanism of healthy sleep, and the insufficient sleep population must quit smoking. • This is the first case-control study to probe the relationship of smoking with sleep and ghrelin both in CSF and plasma • A normal plasma/CSF ghrelin ratio may contribute to healthy sleep • Smoking may disturb the association between sleep and CSF ghrelin, as shown by the high plasma/CSF and PSQI scores in smokers [ABSTRACT FROM AUTHOR]

Primary Objective: Closed brain injuries are a common danger in contact sports and motorized vehicular collisions. Mild closed brain injuries, such as concussions, are not easily visualized by computed imaging or scans. Having a comprehensive head/brain model and using fluid-structure interaction (FSI) simulations enable us to see the exact movement of the cerebrospinal fluid (CSF) under such conditions and to identify the areas of brain most affected. Research Design: The presented work is based on the first FSI model capable of simulating the interaction between the CSF flow and brain. Methods and Procedures: FSI analysis combining smoothed-particle hydrodynamics and high-order finite-element method is used. Main Outcomes and Results: The interaction between the CSF and brain under rapid acceleration and deceleration is demonstrated. The cushioning effect of the fluid and its effect on brain are shown. Conclusions: The capability to locate areas (down to the exact gyri and sulci) of the brain the most affected under given loading conditions, and therefore assess the possible damage to the brain and consequently predict the symptoms, is shown. [ABSTRACT FROM AUTHOR]

A spontaneous remission of symptoms in women with multiple sclerosis is often associated with pregnancy. And sex hormones such are thought to play a crucial role in this. Both testosterone and estrogen have been studied extensively in the disease, but not relaxin. In an initial study of relaxin in multiple sclerosis elevated levels were detected in the sera of some, but not all subjects. Unfortunately, it was not possible to determine if this was relaxin 1, 2 or 3 du to the non-specificity of the assay. In this study we measured the levels of all three relaxins in matched sera and cerebral spinal fluid samples from subjects with multiple sclerosis. No relaxin 2 was detected in any of the samples. However, both relaxin 1 and 3 were detected in some of the samples. The presence of relaxin 3 was not remarkable. In contrast, the presence of relaxin 1 was notable. The presence of relaxin 1 in subjects with multiple sclerosis suggests that it has a biological function and is not a pseudogene has been previously suggested. [ABSTRACT FROM AUTHOR]

Objectives To assess the potential of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in rapid identification of bacteria from smear-positive cerebrospinal fluid (CSF) in a cohort of patients with meningitis. Methods Single-centre observational study, including adults and children with community-acquired or postneurosurgical bacterial meningitis. Meningitis was defined using established criteria. Samples of CSF that had a positive CSF Gram stain were directly examined by MALDI-TOF-MS. Identification was considered accurate when identical to the CSF culture or PCR results (species and genus level). Laboratory workers performing the MALDI-TOF-MS and interpreting its results were blinded to the direct smear results, except for the fact that it was positive. MALDI-TOF-MS results were not conveyed to clinicians. Results MALDI-TOF-MS was tested on 44 CSF samples; ten samples were obtained from patients with community-acquired meningitis, and 34 samples were from patients with postneurosurgical meningitis. The assay identified bacteria correctly in 17/21 of the samples with Gram-negative rods observed on the direct smear, all obtained from patients who had undergone neurosurgery, (sensitivity 81%, 95% CI 64.2%–97.7%). In the postneurosurgical group, Gram-positive cocci were identified correctly in only 1/11 (9.1%) of the samples, and Candida species were not identified in two samples. Among patients with community-acquired meningitis, the assay did not identify Streptococcus pneumoniae in eight of eight samples, Neisseria meningitidis in one sample (1/1), and Streptococcus agalactiae in one sample (1/1). Conclusions We found MALDI-TOF-MS to be useful in the rapid identification of Gram-negative rods directly from smear-positive CSF samples, but not of Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a public health problem that causes high mortality and disability worldwide. Secondary brain damage from this type of injury may cause brain edema, blood–brain barrier destruction, and neurological dysfunction. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and play vital roles in maintaining and regulating physiological function. Notably, studies suggest that miRNA levels are altered in the cerebral cortex and hippocampus of rats and mice after TBI. These miRNAs exhibit promoting or inhibiting effects on the formation of secondary brain damage, such as promotion of neuron regeneration and apoptosis, alleviation of leakage across the blood–brain barrier (BBB), disruption of intracellular transport, and decreasing the inflammatory response. miRNA levels are also altered in the blood and cerebral spinal fluid (CSF) of humans with TBI. Some special miRNAs in blood were used in clinical trials for TBI diagnosis and prognosis prediction. Treatment with miRNA agomirs or antagomirs alleviated the lesion volume and improved neurological deficits post-injury. We review the current progress of miRNA studies in TBI patients and animal models and identify the prospects and difficulties involved in the clinical applications of miRNAs. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis III type A (MPS IIIA; Sanfilippo syndrome), a genetic lysosomal disorder causing a deficiency of heparan N-sulfatase (HNS), leads to progressive cognitive decline from an early age. An effective enzyme replacement therapy (ERT) for MPS IIIA requires central nervous system (CNS) biodistribution. Recombinant human heparan N-sulfatase (rhHNS), an investigatory ERT for MPS IIIA, has been formulated for intrathecal (IT) administration since intravenous (IV) administration cannot cross the blood brain barrier (BBB) in sufficient amounts to have a therapeutic effect. In this study, systemic and CNS distribution of rhHNS in cynomolgus monkeys following IV and IT administration was evaluated by quantitation of rhHNS in serum, cerebral spinal fluid (CSF) and various tissues, and positron emission tomography (PET) imaging of live animals. Following IV administration, rhHNS levels were low to non-detectable in the CSF, and systemic clearance was rapid (≤2 h). With IT administration, rhHNS was observable in CNS tissues in ≤1 h, with varying Tmax (1-24 h). Appreciable systemic distribution was observed up to 7 days. This provides evidence that in this animal model, intrathecal administration of rhHNS delivers the replacement enzyme to therapeutically relevant tissues for the treatment of Sanfilippo Syndrome type A. Penetration into grey matter and cortex was 3-4 times greater than concentrations in white matter and deeper parenchymal regions, suggesting some limitations of this ERT strategy. [ABSTRACT FROM AUTHOR]

Purpose A gravitational valve (GV) may be used to treat hydrocephalus, offering possible advantages that include avoidance of over drainage and long-term complications. Because a GV is made from metal, there are potential safety and other problems related to the use of MRI. The objective of this investigation was to evaluate MRI-related issues (i.e., magnetic field interactions, heating, and artifacts) for a newly developed, metallic GV. Methods Tests were performed on the GV (GAV 2.0) using well-accepted techniques to assess magnetic field interactions (translational attraction and torque, 3-Tesla), MRI-related heating (1.5-T/64-MH and 3-T/128-MHz, whole body averaged SAR, 2.7-W/kg and 2.9-W/kg, respectively), artifacts (3-Tesla; gradient echo and T1-weighted, spin echo sequences), and possible functional changes related to exposures to different MRI conditions (exposing six samples each to eight different pulse sequences at 1.5-T/64-MHz and 3-T/128-MHz). Results Magnetic field interactions were not substantial (deflection angle 2°, no torque) and heating was minor (highest temperature rise, ≥ 1.9 °C, highest background temperature rise, ≥ 1.7 °C). Artifacts on the gradient echo pulse sequence extended approximately 10 mm from the size and shape of the GV. The different exposures to 1.5-T/64-MHz and 3-T/128-MHz conditions did not alter or damage the operational aspects of the GV samples. Conclusions The findings demonstrated that MRI can be safely used in patients with this GV and, thus, this metallic implant is deemed acceptable or “MR Conditional” (i.e., using current labeling terminology), according to the conditions used in this study. [ABSTRACT FROM AUTHOR]

Nusinersen is an antisense oligonucleotide intended for the treatment of spinal muscular atrophy. The pharmacokinetics of nusinersen, following intrathecal administrations, in the cerebrospinal fluid (CSF) and plasma of 72 pediatric patients (3 months to 17 years) with spinal muscular atrophy across 5 clinical trials was analyzed via population-based modeling. With sparse data in the CSF and profile data in the plasma, a linear 4-compartment model simultaneously described the time-concentration profiles in both matrices. The typical population parameters were: Qp = 0.572 L/h, QCSF = 0.069 L/h, CLp = 2.50 L/h, CLCSF = 0.133 L/hr, VCSF = 0.441 L, Vp = 32.0 L, Vsystemic_tissue = 429 L, and VCNS_tissue = 258 L. A full covariate modeling approach identified baseline body weight to be a statistically and clinically relevant covariate on VCSF, Vp, and CLp. The model predicted that the CSF volume of distribution increased steadily with age from 0 to 2 years but became relatively steady for children >2 years. Simulations from the final model showed that age-based dosing in children under 2 years ensured a more comparable exposure (peak concentration and area under the concentration-time curve) across subjects in the population relative to a fixed dosing scheme. However, because no dose-limiting toxicity has been reported in any of the trials, a fixed-dose scheme (12 mg across all age groups) was recommended. The median terminal half-life of nusinersen in the CSF was determined from the model to be 163 days, which supported infrequent dosing, once every 4 to 6 months in pediatric patients with spinal muscular atrophy. [ABSTRACT FROM AUTHOR]

Background: Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke.Methods: We included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression.Results: One hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta -0.50, 95% CI -565.9, -78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes.Conclusion: T-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons.Trial Registration: Clinicaltrials.gov NCT00506818 , July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007. [ABSTRACT FROM AUTHOR]

Diffuse Optical Tomography commonly neglects or assumes as insignificant the presence of optically clear regions in biological tissues, estimating their contribution as a small perturbation to light transport. The inaccuracy introduced by this practice is examined in detail in the context of a complete, based on realistic geometry, virtual fluorescence Diffuse Optical Tomography experiment where a mouse head is imaged in the presence of cerebral spinal fluid. Despite the small thickness of such layer, we point out that an error is introduced when neglecting it from the model with possibly reduction in the accuracy of the reconstruction and localization of the fluorescence distribution within the brain. The results obtained in the extensive study presented here suggest that fluorescence diffuse neuroimaging studies can be improved in terms of quantitative and qualitative reconstruction by accurately taking into account optically transparent regions especially in the cases where the reconstruction is aided by the prior knowledge of the structural geometry of the specimen. Thus, this has only recently become an affordable choice, thanks to novel computation paradigms that allow to run Monte Carlo photon propagation on a simple graphic card, hence speeding up the process a thousand folds compared to CPU-based solutions. [ABSTRACT FROM PUBLISHER]

Background The blood brain barrier (BBB) is an impediment to the development of large and highly charged molecules as therapeutics for diseases and injuries of the central nervous system (CNS). Antisense oligonucleotides (ASOs) are large (6000–8000 MW) and highly charged and therefore do not cross the BBB. A method of circumventing the blood brain barrier to test ASOs, and other non-BBB penetrant molecules, as CNS therapeutics is the direct administration of these molecules to the CNS tissue or cerebral spinal fluid. New method We developed a rapid, simple and robust method for the intrathecal catheterization of rats to test putatively therapeutic antisense oligonucleotides. This method utilizes 23-gauge needles, simply constructed ½ in. long 19-gauge guide cannulas and 8 cm long plastic PE-10 sized catheters. Comparison with existing methods Unlike the cisterna magna approach, this method uses a lumbar approach for intrathecal catheterization with the catheter residing entirely in the cauda equina space minimizing spinal cord compression. Readily available materials and only a few specialized pieces of equipment, which are easily manufactured, are used for this intrathecal catheterization method. Conclusions This method is easy to learn and has been taught to multiple in house surgeons, collaborators and contract laboratories. Greater than 90% catheterization success is routinely achieved with this method and as many as 100 catheters can be placed and test substance administered in one 6-h period. This method has allowed the pre-clinical testing of hundreds of ASOs as therapeutics for CNS indications. [ABSTRACT FROM AUTHOR]

Advances in medicine mean there are more women with complex medical histories giving birth. This may include women with conditions such as hydrocephalus requiring a cerebrospinal fluid shunt. Midwives should understand the principles of care for such women and work with the multidisciplinary team to provide indiviulaised care throughout the pregnancy and intrapartum period. [ABSTRACT FROM AUTHOR]

In the present paper a one-dimensional mathematical model of a cerebral aneurysm is considered. The model combines the interaction between the arterial wall structure, blood pressure and the cerebral spinal fluid (CSF) that is around the aneurysm. CSF is considered electrically conducting in the presence of a uniform magnetic field. Therefore, it may be possible to control pressure and its flow behavior by using an appropriate magnetic field. Hence, such studies have potential for the treatment of Cerebral aneurysms, diseases of heart and blood vessels. The modeled mathematical equations are solved algebraically and the displacement of the arterial wall is plotted to visualize the wall movement. It is evident from the graphs the inclusion of magnetic field reduce the movement of the arterial wall and in turn prevent the rupture of the cerebral aneurysm. The solution is also investigated using computational tools for various other parameters involve in the model. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs – miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p – that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the promising miRNA candidates and discussed their diagnostic properties and cellular functions in order to search for potential biomarker for AD. [ABSTRACT FROM AUTHOR]

Background: Postoperative intracranial hypotension-associated venous congestion (PIHV) is an uncommon cause of clinical deterioration after a neurosurgical procedure that is often unrecognized until late in its course. Functional outcomes range from remarkable neurological recovery to death. Little is understood about the reason for deterioration in certain patients compared with improvement in others. A 68-year-old man with a progressive cervical myelopathy underwent an uncomplicated cervical decompression and alignment restoration at our hospital and suffered violent generalized tonic-clonic seizures intraoperatively and postoperatively. A postoperative head CT showed a right parietal hematoma, but no other cranial findings. A subsequent MRI demonstrated what we describe as early PIHV with symmetric T2 signal changes in the bilateral deep gray structures. No diffusion restriction corresponded to these areas. A CT myelogram revealed a considerable CSF collection within the operative bed. Upon returning to the operating room to localize the source of the leak, a large dural tear was identified off of midline with a bone chip alongside the defect. The defect was repaired, and the patient remained comatose for over a week postoperatively. He made a remarkable gradual recovery, and after a month in the hospital and rehabilitation, he returned home with relatively minimal neurological deficits.Conclusions: We postulate that if caught early and treated aggressively, neurologic injury resulting from PIHV may be reversible despite initially ominous imaging. Neurosurgeons and neurointensivists should therefore be compelled to search for dural defects and return to the operating room for immediate repair. [ABSTRACT FROM AUTHOR]

An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer's disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium(Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium(V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers. [ABSTRACT FROM AUTHOR]

Postoperative continuous bloody cerebral spinal fluid drainage with external ventricular drainage catheter could decrease the incidence of inflammation. But the drainage catheter left in place will interrupt the watertight dura matter closure. To prevent the related cerebrospinal fluid leakage and subgaleal pseudomeningocele after the catheter removal, we developed a patched closure method to seal the dural outlet of the drainage catheter with a favorable clinical outcome. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a highly debilitating motor disorder and is the second most common neurodegenerative disease after Alzheimer's disease. Its current method of diagnosis mainly relies on subjective clinical rating scales in the presence of clinical motor features. Early detection of PD is a known challenge as neuronal cell death may range from 50% to 80% when a patient is first diagnosed with PD. Therefore, there is an urgent need to identify and develop biomarkers for early detection of this progressive disease. This mini review focuses on the recent developments of biofluid-based microRNAs (miRNAs) as molecular biomarkers for PD. A comprehensive list of miRNA biomarkers found in blood, plasma, serum, and cerebral spinal fluid is presented. Challenges and future perspectives of using these PD-related molecular biomarkers in a "real-world" clinical setting are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: Increased intracranial pressure (ICP) is associated with worse outcomes following traumatic brain injury (TBI). Studies have confirmed that ICP is correlated with optic nerve sheath diameter (ONSD) on ultrasound. The aim of our study was to assess the independent relationship between ONSD measured using CT and mortality in a population of patients admitted with severe TBI. Methods: We conducted a retrospective cohort study of patients with a TBI requiring ICP monitoring admitted to the ICU between April 2006 and May 2012 to two neurotrauma centers. ONSD was independently measured by two physicians blinded to patient outcomes. Multivariable logistic regression modeling was used to assess an association between ONSD and hospital mortality. Results: A total of 220 patients were included in the analysis. Overall, the cohort had a mean age of 35 (SD 17) years and 171 of 220 (79 %) were male. The median admission GCS was 6 (IQR 3-8). Intra-class correlation coefficient between raters for ONSD measurements was 0.92 (95 % CI 0.90-0.94, P < 0.0001). On multivariable analysis, each 1 mm increase in ONSD was associated with a twofold increase in hospital mortality (OR 2.0, 95 % CI 1.2-3.2, P = 0.007). Using linear regression, ONSD was independently associated with increased ICP in the first 48 h after admission ( β = 4.4, 95 % CI 2.5-6.3, P < 0.0001). Conclusions: In patients with TBI, ONSD measured on CT scanning was independently associated with ICP and mortality. [ABSTRACT FROM AUTHOR]

The B7 family consists of activating and inhibitory molecules that regulate immune responses. Recent research demonstrated the roles of soluble B7-H3 (sB7-H3) and soluble B7-H1 (sB7-H1) in the blood serum of various tumors; however, none of these studies investigated the expression of these proteins in the cerebral spinal fluid (CSF) and blood serum of patients with glioma. The aim of the present study was to investigate the expression of B7-H3 and B7-H1 in the CSF, blood serum and tissues of patients with glioma and their correlation with clinicopathological data. Between January 2012 and November 2012, samples were obtained from 78 patients with glioma, four CSF samples were obtained from patients with a moderate traumatic brain injury, four brain tissue samples were obtained from patients with a traumatic brain injury and 40 blood serum samples were obtained from healthy individuals. The expression of B7-H3 and B7-H1 in the CSF, blood serum and tumor samples of the patients with high-grade glioma was found to be higher than that in the patients with low-grade glioma. However, no significant differences in sB7-H3 and sB7-H1 expression were observed in the blood serum of the patients with glioma compared with the healthy control subjects. In addition, the expression of sB7-H3 and sB7-H1 in the CSF of the patients with glioma was higher than that in the CSF of the patients with a moderate traumatic brain injury. Furthermore, in the patients with glioma, B7-H3 and B7-H1 expression in the CSF and tumor tissue, although not in the blood serum, correlated with the glioma grade. [ABSTRACT FROM AUTHOR]

Antenatal betamethasone (BM) therapy accelerates lung development in preterm infants but may induce early programming events with long-term cardiovascular consequences. To elucidate these events, we developed a model of programming whereby pregnant ewes are administered BM (2 doses of 0.17 mg/kg) or vehicle at the 80th day of gestation and offspring are delivered at term. BM-exposed (BMX) offspring develop elevated blood pressure; decreased baroreflex sensitivity; and alterations in the circulating, renal, and brain renin-angiotensin systems (RAS) by 6 mo of age. We compared components of the choroid plexus fourth ventricle (ChP4) and cerebral spinal fluid (CSF) RAS between control and BMX male offspring at 6 mo of age. In the choroid plexus, high-molecular-weight renin protein and ANG I-intact angiotensinogen were unchanged between BMX and control animals. Angiotensinconverting enzyme 2 (ACE2) activity was threefold higher than either neprilysin (NEP) or angiotensin 1-converting enzyme (ACE) in control and BMX animals. Moreover, all three enzymes were equally enriched by approximately 2.5-fold in ChP4 brush-border membrane preparations. CSF ANG-(1-7) levels were significantly lower in BMX animals (351.8 ± 76.8 vs. 77.5 ± 29.7 fmol/mg; P ≤ 0.05) and ACE activity was significantly higher (6.6 ± 0.5 vs. 8.9 ± 0.5 fmol·min-1·ml-1; P ≤ 0.05), whereas ACE2 and NEP activities were below measurable limits. A thiol-sensitive peptidase contributed to the majority of ANG-(1-7) metabolism in the CSF, with higher activity in BMX animals. We conclude that in utero BM exposure alters CSF but not ChP RAS components, resulting in lower ANG-(1-7) levels in exposed animals. [ABSTRACT FROM AUTHOR]

Abstract: Background and Purpose: A new neurological implant, the Sensor-Reservoir, was developed to provide a relative measurement of ICP, which permits a noninvasive technique to detect and localize occlusions in ventricular drainage systems and, thus, to identify mechanical damage to shunt valves. The “reservoir” of this device can be used to administer medication or a contrast agent, to extract cerebral spinal fluid (CSF), and with the possibility of directly measuring ICP. The Sensor-Reservoir was evaluated to identify possible MRI-related issues at 1.5-T/64-MHz and 3-T/128-MHz. Materials and Methods: Standard testing techniques were utilized to evaluate magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3-T for the Sensor-Reservoir. In addition, 12 samples of the Sensor-Reservoir underwent testing to determine if the function of these devices was affected by exposures to various MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz. Results: Magnetic field interactions for the Sensor-Reservoir were not substantial. The heating results indicated a highest temperature rise of 1.8°C, which poses no patient risks. Artifacts were relatively small in relation to the size and shape of the Sensor-Reservoir, but may interfere diagnostically if the area of interest is near the device. All devices were unaffected by exposures to MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz. Conclusion: When specific guidelines are followed, the Sensor-Reservoir is “MR conditional” for patients undergoing MRI examinations at 3-T or less. [Copyright &y& Elsevier]

Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction ( p = 0.03) and consolidation ( p = 0.04), while lysophosphatidylcholine (LPC) increased following induction ( p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year ( p < 0.001), 2 years ( p = 0.001) and 3 years ( p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory ( p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity. [ABSTRACT FROM AUTHOR]