High Cerebral Spinal Fluid Research Articles

The predictive value of CSF multiple assay in multiple sclerosis: A single center experience

BackgroundMultiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, neurodegenerative disorder. Many studies are investigating the potential role of body fluid biomarkers as prognostic factors for early identification of patients presenting with clinical isolated syndrome (CIS) at high risk for conversion to MS or to recognize RRMS patients at high risk for progression. ObjectivesTo evaluate the correlation between levels of BAFF, chitinase 3-like 1 (CHI3L1), sCD163, Osteopontin (OPN), both on serum and cerebral spinal fluid (CSF), and the disease activity and progression. We also want to explore a possible relationship between serological and CSF biomarker's levels. Patients and methodsWe enrolled 82 patients between June 2014 and June 2016. Seventy-one received a diagnosis of demyelinating disease of CNS (46 RRMS and 25 CIS), while 11 were affected by other neurological diseases. All patients underwent a neural axis MRI, lumbar puncture and blood samples. Levels of BAFF, CHI3L1, sCD163, OPN on serum and CSF were analyzed by Luminex xMAP system, with a kit 11-plex ad hoc. ResultsThe CSF CHI3L1, sCD163 and OPN levels were significantly higher in MS patients than in controls. We did not find significant differences in serum CHI3L1, sCD163 and OPN levels, nor CSF or serum BAFF levels between patient and control groups.We found significantly higher CSF level of sCD163 and CHI3L1 in all patients’ subgroups compared with controls, while OPN was higher in CIS and RR subgroups. We did not find significant differences for serum and CSF levels of all the markers between patients with or without clinical or radiological disease activity.CSF sCD163 and CHI3L1 levels was significant higher in CIS patients who converted to MS (p < 0.05).Using ROC curve analysis, CSF sCD163 resulted the best predictive factor. CSF CHI3L1 and OPN levels resulted useful independent predictors too. Combined ROCs of those three analytes demonstrated a better predictive value, with sCD163 and CHI3L1 resulting as the best combination. ConclusionsCSF sCD163 CHI3L1 and OPN levels were higher in MS patients whereas serum CHI3L1, sCD163 and OPN levels did not show differences compared with controls. This finding confirms the high CSF specificity with regards to the analysis of processes, inflammatory and non-inflammatory, that occur within the CNS.

Paramedian Forehead Flap for Repair of Refractory High-Flow Anterior Skull Base CSF Leak

Aim The paramedian forehead flap (PMFF) has been well described for nasal reconstruction. However, it has never been reported for use in the repair of high flow anterior skull base cerebral spinal fluid (CSF) leaks. Material and methods The patient is a 55 yo African American male cocaine abuser who initially presented with a high flow anterior skull base CSF leak, extensive pneumocephalus, and intra-cerebral and intra-ventricular abscesses with an oro-nasal-cerebral fistula. The patent initially underwent bi-frontal craniotomy, exenteration of the frontal sinus, abdominal fat graft, resection of intra-cerebral abscesses, and repair of high flow anterior skull base CSF leak with a pedicled pericranial flap (PF). 18 months after the patient's surgery he had resumed his use of cocaine and suffered necrosis of his PF. This caused his high flow CSF leak to recur. After extensive psychiatric treatment, he stopped cocaine use and was subsequently repaired with a pedicled de-epithelialized PMFF originating off the bilateral supratrochlear arteries. Results The patient has had no CSF leak for 3 years, and primary closure of the forehead was achieved with good cosmetic outcome. Conclusion This case highlights the use of PMFF for the treatment of recurrent high flow anterior skull base CSF leak. It also highlights the importance of treatment of the patient's underlying medical disorder, in this case, the patient's addiction to cocaine. We provide a detailed discussion for the use of the de-epithelialized PMFF and how it can be utilized as a vascularized reconstructive technique to repair complex refractory cerebral spinal fluid leaks.

Paramedian Forehead Flap for Repair of Refractory High-Flow Anterior Skull Base CSF Leak.

The paramedian forehead flap (PMFF) has been well described for nasal reconstruction. However, it has never been reported for use in the repair of high flow anterior skull base cerebrospinal fluid (CSF) leaks. The patient was a 55 year-old African American male cocaine abuser who initially presented with a high flow anterior skull base CSF leak, extensive pneumocephalus, and intra-cerebral and intra-ventricular abscesses with an oro-nasal-cerebral fistula. The patent initially underwent bi-frontal craniotomy, exenteration of the frontal sinus, abdominal fat graft, resection of intra-cerebral abscesses, and repair of high flow anterior skull base CSF leak with a pedicled pericranial flap (PF). Eighteen months after the patient's surgery, he had resumed his use of cocaine and suffered necrosis of his PF. This caused his high flow CSF leak to recur. After extensive psychiatric treatment, he stopped cocaine use and was subsequently repaired with a pedicled de-epithelialized PMFF originating off the bilateral supratrochlear arteries. The patient has had no CSF leak for 3 years, and primary closure of the forehead was achieved with good cosmetic outcome. This case highlights the use of PMFF for the treatment of recurrent high flow anterior skull base CSF leak. It also highlights the importance of treatment of the patient's underlying medical disorder, in this case, the patient's addiction to cocaine. We provide a detailed discussion for the use of the de-epithelialized PMFF and how it can be utilized as a vascularized reconstructive technique to repair complex refractory CSF leaks.

Operationalising elaboration theory for simulation instruction design: a Delphi study.

The aim of this study was to assess the feasibility of incorporating the Delphi process within the simplifying conditions method (SCM) described in elaboration theory (ET) to identify conditions impacting the complexity of procedural skills for novice learners. We generated an initial list of conditions impacting the complexity of lumbar puncture (LP) from key informant interviews (n=5) and a literature review. Eighteen clinician-educators from six different medical specialties were subsequently recruited as expert panellists. Over three Delphi rounds, these panellists rated: (i) their agreement with the inclusion of the simple version of the conditions in a representative ('epitome') training scenario, and (ii) how much the inverse (complex) version increases LP complexity for a novice. Cronbach's α-values were used to assess inter-rater agreement. All panellists completed Rounds 1 and 2 of the survey and 17 completed Round 3. In Round 1, Cronbach's α-values were 0.89 and 0.94 for conditions that simplify and increase LP complexity, respectively; both values increased to 0.98 in Rounds 2 and 3. With the exception of 'high CSF (cerebral spinal fluid) pressure', panellists agreed with the inclusion of all conditions in the simplest (epitome) training scenario. Panellists rated patient movement, spinal anatomy, patient cooperativeness, body habitus, and the presence or absence of an experienced assistant as having the greatest impact on the complexity of LP. This study demonstrated the feasibility of using expert consensus to establish conditions impacting the complexity of procedural skills, and the benefits of incorporating the Delphi method into the SCM. These data can be used to develop and sequence simulation scenarios in a progressively challenging manner. If the theorised learning gains associated with ET are realised, the methods described in this study may be applied to the design of simulation training for other procedural and non-procedural skills, thereby advancing the agenda of theoretically based instruction design in health care simulation.

Role of inflammasome component nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 in predicting outcome after severe traumatic brain injury

Objective To study the role of inflammasome component nucleotide oligomerization domain (NOD)-like receptor (NLR) family,pyrin domain containing 3 (NLRP3) in predicting outcome after severe traumatic brain injury (sTBI).Methods Cerebral spinal fluid (CSF) samples from 20 patients with sTBI were analyzed for NLRP3 by ELISA.Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6th month post injury.Clinical variables and GOS were related to the levels of NLRP3 in CSF.Results Patients with sTBI exhibited significantly higher CSF levels of NLRP3 [(33.8 ± 11.6) μg/L] compared to moderate TBI patients [(11.4 ± 2.9) μg/L,P ＜ 0.01] or non-trauma controls [(1.1 ± 0.3) μg/L,P ＜0.01].The mean NLRP3 level in sTBI patients with unfavorable outcome was (42.8 ± 14.4) μg/L,significantly higher than in those with favorable outcome [(29.9 ± 7.9) μg/L,P ＜ 0.05].The expression of NLRP3 was correlated significantly with CT finding (r =0.601,P ＜ 0.01) and GOS (r =0.665,P ＜ 0.01).Conclusion NLRP3 in CSF is potential biochemical marker to assess severity and outcome of patients with sTBI. Key words: Inflammasome; Nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 ; Traumatic brain injury ; Prognosis

Impact of aromatase genetic variation on hormone levels and global outcome after severe TBI.

Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality (p=0.019) and better GOS-6 scores (p=0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone (p≤0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores (p≤0.05, all comparisons), and those with>1 risk SNP variant had a higher risk for poor outcome, compared with those with ≤1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI.

Management of the young febrile child: a continuing controversy.

In 1975, Teele and colleagues1identified the risk factors for and occurrence of bacteremia in young febrile children presenting to a pediatric walk-in clinic. They found that 3.2% of children 4 weeks to 2 years of age were bacteremic and that the height of the temperature and white blood cell count were valuable predictors of bacteremia. The Teele report initiated a controversy regarding the management of young febrile children that continues today. Despite more than 20 years of research, the essential question remains unchanged—does obtaining a blood culture and initiating expectant therapy with oral or parenteral antibiotics prevent serious sequelae? In this issue of Pediatrics, Kramer and Shapiro2 argue that recently published guidelines for management of febrile children,3 which recommend blood culture and expectant therapy in infants and children with temperatures ≥39°C, are costly, intrusive, and do more harm than good.2 Good clinical practice guidelines have important attributes, including validity, reliability, and scheduled reviews.4 Since the publication of the fever guidelines there have been two developments that may affect their validity. First, there has been a dramatic reduction in the number of cases of meningitis, sepsis, and bacteremia specifically attributable to Haemophilus influenzae type B (Hib).5 The issue of expectant therapy and reduction in morbidity is now largely …

Localization of the cerebroventricular receptors involved in CNS-induced natriuresis.

Ventriculocisternal perfusion (VCP) or localized "push-pull" perfusion (PPP) was performed in pentobarbital-anesthetized dogs. Renal function was studied in protocols consisting of a 1-h experimental period bracketed by 1-h control and recovery periods. The animals were perfused with artificial cerebral spinal fluid (CSF) throughout the protocol but the sodium concentration was elevated (300 mM, high Na) during the experimental period. In the first series of experiments, prior to VCP, petroleum jelly plugs were injected into either the ventral third ventricle (V3V) or other brain regions. When petroleum jelly plugs were injected into the V3V prior to VCP, they prevented perfusates from reaching this area, as determined by subsequent dye perfusion. These V3V plugs blocked the natriuresis and ADH response otherwise induced by high Na VCP. In the second series of experiments, the anterior portion of the V3V (AV3V) was perfused by means of PPP. In some of the PPP experiments a V3V plug was also injected to ensure restriction of the stimulus to the AV3V. PPP of the AV3V with high Na CSF at 50 microliter/min did not induce a natriuresis (either with or without a V3V plug). However, when the high Na CSF was perfused at a very high rate (100 microliter/min) and the stimulus was not restricted to the AV3V by a V3V plug, a natriuresis did occur. These results suggest that the ventricular surface where high Na CSF acts to cause natriuresis and increased ADH secretion is within the V3V region but not in the AV3V.