Cerebrospinal Fluid Red Blood Cell Count Research Articles

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage.

Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis. Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study. Longitudinal CSF samples were collected as part of routine diagnostics. RBC count and CSF TP at the time of admission (RBCfirst, TPfirst), in Week 1 (RBCDays1-7, TPDays1-7), Week 2 (RBCDays8-14, TPDays8-14), and Week 3 or thereafter (RBCDay>14, TPDay>14), the highest detected value (RBChighest, TPhighest), as well as the RBC count adjusted for disease duration (RBCadjusted) were assessed. Primary outcomes were good functional outcome after 3 months, defined as modified Rankin scale score ≤2 and ICU survival. A total of 183 SAH patients with a female predominance (69%), a median (interquartile range [IQR]) age of 60 (50-70) years and median (IQR) Hunt and Hess score of 4 (3-5) were included. Multivariable analyses revealed that lower values of RBCfirst, RBCadjusted, RBChighest, TPfirst and TPhighest were associated with good functional outcome and hospital survival. Lower TP concentrations in Weeks 1, 2 and 3 were associated with good functional outcome, and in Weeks 1 and 2 with ICU survival. Early RBC measurements (Week 1) were associated with good functional outcome and ICU survival. Low CSF RBC counts and TP concentrations were associated with good functional outcome and ICU survival in a real-world cohort of SAH patients requiring external ventricular drainage.

Subarachnoid haemorrhage or traumatic lumbar puncture. Differentiation by cerebrospinal fluid parameters in a multivariable approach

Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP. CSF red blood cell (RBC), white blood cell (WBC) count, total protein, CSF colour and supernatant were used for group comparisons of patients with SAH and ‘symptomatic controls’. Due to variable time intervals between bleeding onset and LP in SAH patients in contrast to patients with traumatic LP, where blood contamination of CSF occurs at the time of LP, CSF variables were adjusted for decay in time to allow comparability. Logistic regression analysis identified bloody CSF [odds ratio (OR) 32.6], xanthochromic supernatant [OR 15.5] and WBCadjusted [OR 4.5 (per increase of 100/µl)] as predictors of SAH, while age, sex and CSF total proteinadjusted were no predictors. Optimal cut-point of RBCadjusted (determined at day 1 after bleeding) was > 3667/µl to identify SAH patients with a 97% sensitivity and 94% specificity. Combination of low RBC and clear CSF supernatant was found in none of SAH patients. Combined CSF RBC count and CSF supernatant reliably distinguished traumatic LP from SAH.

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage.

Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients. A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2. Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61-0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60-0.96, p = 0.020). CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH.

Cerebrospinal fluid immunoglobulins are increased in neonates exposed to Zika virus during foetal life

ObjectiveTo compare immunoglobulin levels in cerebrospinal fluid (CSF) of neonates exposed to Zika virus (ZIKV) during foetal life (cases) with levels in CSF of control neonates. MethodsWe identified 16 neonates who underwent lumbar puncture (LP), during the ZIKV epidemic (December/2015 to March/2016) whose mothers reported ZIKV clinical symptoms during gestation (cases). Congenital microcephaly was defined as head circumference ≤31.9 cm (boys) and ≤31.5 cm (girls) for term neonates, or ≤2 standard deviations below the mean for premature (<37 weeks) neonates. Subsequently, we identified neonates who underwent LP in the same lab and fulfilled criteria to be controls: age ≤4 days, CSF white blood cell count ≤8/mm3, CSF protein ≤132 mg/dL, CSF red blood cell count ≤1,000/mm3, neither central nervous system illness, nor congenital infection, nor microcephaly. CSF immunoglobulin concentrations were measured by mass spectrometry. Results13 controls were included. IgM, IgA, IgG, IgK, and IgL were significantly higher among cases (p < 0.001). Eight (50%) ZIKV exposed infants had congenital microcephaly. These showed the strongest immunoglobulin elevation of the IgM and IgA classes. ConclusionNeonates exposed to ZIKV infection during gestation present with elevated distinct immunoglobulins in CSF, both in cases that developed microcephaly and in cases that did not.

Elevated Cerebrospinal Fluid Protein Is Associated with Unfavorable Functional Outcome in Spontaneous Subarachnoid Hemorrhage

Background/objective: Subarachnoid hemorrhage (SAH) is a devastating neurologic event for which markers to assess poor outcome are needed. Elevated cerebrospinal fluid (CSF) protein may result from inflammation and blood-brain barrier (BBB) disruption that occurs during SAH. We sought to determine if CSF protein level is associated with functional outcome after SAH. Methods: We prospectively collected single-center demographic and clinical data for consecutive patients admitted with spontaneous SAH. Inclusion required an external ventricular drain and daily CSF protein and cellular counts starting within 48 hours of symptom onset and extending through 7 days after onset. Seven-day average CSF protein was determined from daily measured values after correcting for contemporaneous CSF red blood cell (RBC) count. Three-month functional outcome was assessed by telephone interview with good outcome defined as modified Rankin score 0-3. Variables univariately associated with outcome at P less than .25 and measures of hemorrhage volume were included for binary logistic regression model development. Results: The study included 130 patients (88% aneurysmal SAH, 69% female, 54.8 ± 14.8 years, Glasgow Coma Scale [GCS] 14 [7-15]). Three-month outcome assessment was complete in 112 (86%) patients with good functional outcome in 74 (66%). CSF protein was lower in good outcome (35.3 [20.4-49.7] versus 80.5 [40.5-115.5] mg/dL; P < .001). CSF protein was not associated with cerebral vasospasm, but delayed radiographic infarction on 3 to 12-month neuroimaging was associated with higher CSF protein (46.3 [32.0-75.0] versus 30.2 [20.4-47.8] mg/dL; P = .023). Good 3-month outcome was independently associated with lower CSF protein (odds ratios [OR] .39 [.23-.70] for 75th versus 25th percentile of protein; P = .001) and higher admission GCS (OR 1.23 [1.10-1.37] for good outcome per GCS point increase; P < .001). Parenchymal hematoma predicted worse outcome (OR 6.31 [1.58-25.25]; P = .009). Results were similar after excluding nonaneurysmal SAH and after including CSF RBC count, CT score, and intraventricular hemorrhage volume in models. Conclusions: Elevated average CSF protein is associated with poor outcome after spontaneous SAH. Further research should investigate if elevated CSF protein identifies patients in whom mechanisms such as BBB disruption contribute to poor outcome.

Cerebrospinal Fluid Profiles of Infants ≤60 Days of Age With Bacterial Meningitis.

We aimed to describe the cerebrospinal fluid (CSF) profiles of infants ≤60 days old with bacterial meningitis and the characteristics of infants with bacterial meningitis who did not have CSF abnormalities. We included infants ≤60 days old with culture-positive bacterial meningitis who were evaluated in the emergency departments of 11 children's hospitals between July 1, 2011, and June 30, 2016. From medical records, we abstracted clinical and laboratory data. For infants with traumatic lumbar punctures (CSF red blood cell count of ≥10 000 cells per mm3), we used a red blood cell count/white blood cell (WBC) count correction factor of 1000:1 to determine the corrected CSF WBC count. We calculated the sensitivity for bacterial meningitis of a CSF Gram-stain and corrected CSF pleocytosis (≥16 WBCs per mm3 for infants ≤28 days old and ≥10 WBCs per mm3 for infants 29-60 days old). Among 66 infants with bacterial meningitis, the sensitivity of a CSF Gram-stain was 71.9% (95% confidence interval [CI]: 59.2-82.4), and the sensitivity of corrected CSF pleocytosis was 80.3% (95% CI: 68.7-89.1). The sensitivity of combining positive Gram-stain results with corrected CSF pleocytosis was 86.4% (95% CI: 75.7-93.6). Of 9 infants with meningitis who had a negative Gram-stain result and no corrected CSF pleocytosis, 8 (88.9%) had either an abnormal peripheral WBC count (>15 000 or <5000 cells per μL) or bandemia >10%. Most infants ≤60 days old with bacterial meningitis have CSF pleocytosis or a positive Gram-stain result. Infants with no CSF pleocytosis and a negative Gram-stain result are unlikely to have bacterial meningitis in the absence of other laboratory abnormalities.

Assessment of Diagnostic Yield of Nonculture Infection Testing on Cerebrospinal Fluid in Immune-Competent Children

Nonculture infection tests of cerebrospinal fluid (CSF) samples using polymerase chain reaction and antigen or antibody assays are frequently ordered on lumbar puncture specimens concurrently with routine CSF cell counts, but the value of CSF infection testing in otherwise healthy children is unknown. To determine the value of nonculture CSF infection testing in immune-competent children with normal CSF cell counts. This cross-sectional study reviewed screening and diagnostic tests in the electronic medical record system of a large academic tertiary care children's hospital. Records of children aged 0.5 to 18.9 years (n = 4083) who underwent lumbar puncture (n = 4811 procedures) in an inpatient or outpatient facility of Children's Hospital of Philadelphia between July 1, 2007, and December 31, 2016, were reviewed. Those with indwelling CSF shunts or catheters; those with active or past oncologic, immunologic, or rheumatologic conditions; or those taking immune-suppressing medications were excluded from analysis. This study was conducted from July 20, 2017, to March 13, 2019. Outcome variables included frequency of nonculture CSF infection testing and frequency of positive results in the entire cohort, and among those with normal cell counts. Normal cell counts were defined as CSF white blood cell counts lower than 5 cells/μL and CSF red blood cell counts lower than 500 cells/μL. In total, 4811 lumbar puncture procedures were performed on 4083 unique children, with a median (range) age of 7.4 (0.5-18.9) years, 2537 boys (52.7%), and 3331 (69.2%) with normal CSF cell counts. At least 1 nonculture CSF infection test was performed on 1270 lumbar puncture specimens with normal cell counts (38.1%; 95% CI, 36%-40%), and more tests were performed in the summer months. Only 18 (1.4%; 95% CI, 0.9%-2.2%) of 1270 lumbar puncture specimens with normal cell counts had at least 1 nonculture infection test with a positive result; 2 of these 18 children required clinical intervention for their positive results, but each also had other clear clinical signs of infection. Nonculture CSF infection testing appeared to be common in immune-competent children with normal CSF cell counts, but positive results were uncommon and were not independently associated with clinical care; delaying the decision to send nonculture infection tests until CSF cell counts are available could reduce unnecessary diagnostic testing and medical costs, which may improve value-based care.

Prevalence of Concomitant Acute Bacterial Meningitis in Neonates with Febrile Urinary Tract Infection: A Retrospective Cross-Sectional Study

To describe the frequency of concomitant acute bacterial meningitis (ABM) in neonates with febrile urinary tract infection (UTI). This was a retrospective cross-sectional study from 2005 to 2013 of infants ≤30 days old evaluated in the emergency department of a quaternary care children's hospital with fever and laboratory-confirmed UTI. Definite ABM was defined as cerebrospinal fluid (CSF) culture with growth of pathogenic bacteria and probable ABM if pleocytosis with ≥ 20 white blood cell was present in an antibiotic-pretreated patient. The timing of lumbar puncture and first antibiotic dose was recorded to assess for antibiotic pretreatment. A total of 236 neonates with UTI were included. Mean age was 18.6 days (SD 6.2); 79% were male infants. Twenty-three (9.7%) had bacteremia. Fourteen (6%) were pretreated. No neonate (0%; 95% CI 0%-1.6%) had definite ABM and 2 (0.8%; 95% CI 0.1%-3.0%) neonates with bloody CSF had probable ABM. CSF white blood cell count was 25 and 183 for these 2 infants, and CSF red blood cell count was 3100 and 61 932, respectively. Another neonate had herpes simplex virus meningoencephalitis. The frequency of ABM in neonates with febrile UTI is low. Further prospective studies are needed to evaluate the safety of a tiered approach to evaluate for serious bacterial infection, in which lumbar puncture potentially could be avoided in well-appearing febrile neonates with suspected UTI.

Significance of routine cerebrospinal fluid analysis in subarachnoid hemorrhage.

The aim of this paper was to determine the diagnostic value of cerebrospinal fluid (CSF) analysis in the setting of aneurysmal subarachnoid hemorrhage (aSAH), hypothesizing that CSF analysis is only critical in confirming suspected infection and may be useful in predicting and/or detecting delayed cerebral ischemia (DCI). Retrospective review of consecutive adult patients diagnosed with aSAH from 1/2000 to 12/2013 at Mayo Clinic, Rochester, MN, USA with cerebral aneurysm(s) identified by vascular imaging, and CSF drawn within 14 days of the date of hemorrhage. We identified 741 patients during the study period, 167 met inclusion criteria and 356 samples were collected. First Median CSF samples were taken 5 (4-8) days postbleed. Multiple samples were taken in 94 (54.5%) patients and the mean number of samples per patient was 2.1. Ventriculitis, confirmed by growth of organism from CSF culture was present in 2 (1.2%) patients and one patient (0.6%) developed meningitis. CSF WBC count remained elevated throughout the 14 days, even when corrected for red blood cell count (RBC). Peak CSF RBCs occurred 2-4 days post bleed, and then gradually normalized. Maximum CSF RBCs did not correlate with modified Fisher grades (P=0.422). Delayed cerebral ischemia (DCI) was present in 86 (51.5%) patients and there was no difference in the CSF profile of patients with DCI compared with those without. Routine CSF sampling for cell count and chemistry in the setting of temporary diversion following aSAH appears to have little clinical benefit beyond the evaluation for infection.

Validation of cerebrospinal fluid findings in aneurysmal subarachnoid hemorrhage

BackgroundRecently proposed cutoff criteria for cerebrospinal fluid (CSF) analyses might safely exclude a diagnosis of aneurysmal subarachnoid hemorrhage (aSAH). ObjectiveThe objective of this study was to examine the sensitivity of a CSF red blood cell (RBC) count greater than 2000 × 106/L (ie, 2000 RBCs per microliter) or the presence of visible CSF xanthochromia in identifying patients with aSAH. MethodsWe identified a retrospective case series of patients diagnosed with aSAH after lumbar puncture (LP) in an integrated health delivery system between January 2000 and June 2013 by chart review. All identified patients had at least 1 cerebral aneurysm that was treated with a neurosurgical or endovascular intervention during the index hospitalization. The lowest CSF RBC count was used for validation analysis. Cerebrospinal fluid color was determined by visual inspection. Xanthochromia was defined as pink, orange, or yellow pigmentation of CSF supernatant. ResultsSixty-four patients met study inclusion criteria. Of these, 17 (33%) of 52 underwent LP within 12 hours of headache onset, and 49 (84%) of 58 exhibited CSF xanthochromia. The median CSF RBC count was 63250 × 106/L. The sensitivity of a CSF RBC count of greater than 2000 × 106/L in identifying aSAH was 96.9% (95% confidence interval, 89.3%-99.1%). Additional consideration of CSF xanthochromia resulted in a sensitivity of 100% (95% confidence interval, 94.3%-100%). ConclusionsAll patients in this case series of patients with aSAH had either a CSF RBC count greater than 2000 × 106/L or visible CSF xanthochromia, increasing the likelihood that this proposed cutoff strategy may safely identify patients who warrant further investigation for an aneurysmal cause of subarachnoid hemorrhage.

The Effect of Traumatic Lumbar Puncture on Hospitalization Rate for Febrile Infants 28 to 60 Days of Age

The authors measured the effect of a traumatic or unsuccessful lumbar puncture (LP) on the management of febrile infants. This was a 10-year retrospective cross-sectional study of low-risk infants by the "Boston" criteria 28 to 60days of age presenting to the emergency department for evaluation of fever. "Normal LP" infants had cerebrospinal fluid (CSF) WBC < 10×10(6) cells/L. "Traumatic" or "unsuccessful LP" infants had CSF red blood cell count ≥ 10×10(9) cells/L or no CSF cell counts obtained, respectively. A serious bacterial infection (SBI) was defined as growth of a bacterial pathogen from culture. The hospitalization and SBI rates were compared between infants with normal versus traumatic or unsuccessful LPs. Of the 929 study infants, 756 (81.4%) had normal LPs, and 173 (18.6%) had traumatic or unsuccessful LPs. Infants with traumatic or unsuccessful LPs had a higher hospitalization rate (72.3% traumatic or unsuccessful LP vs. 18.1% normal LP; difference= 54.1%; 95% confidence interval [CI] = 46.4% to 60.8%), but a similar SBI rate (2.9% vs. 4.1%; difference= 1.2%; 95% CI = -2.7% to 3.6%). No infant had proven bacterial meningitis (0% risk, 95% CI = 0 to 0.3%). Low-risk infants aged 28 to 60days with traumatic or unsuccessful LPs are more frequently hospitalized, although SBI rates were similar to those of infants with normal LPs.

Analysis of infant lumbar puncture success rates: sitting flexed versus lateral flexed positions.

The primary objective was to determine whether the sitting flexed position yields higher success rates of obtaining cerebrospinal fluid (CSF) for culture. The secondary objectives were to determine whether the sitting flexed position yields higher success rates of obtaining the following: CSF for cell count, non-traumatic CSF, and CSF on the first attempt. The study investigator performed a retrospective chart review of infants 0 to 365 days of age who had a lumbar puncture (LP) performed from January 1 to December 31 of 2010. Data on the LP position and the number of attempts were abstracted from procedure notes. Twenty-one LPs were excluded because of incomplete data on LP position and/or number of attempts. Spinal fluid count results were obtained from electronic medical records. Non-traumatic LPs were defined in 2 categories: CSF red blood cell counts of 500 cells per cubic millimeter or less and 10,000 cells per cubic millimeter or less. One hundred thirty-two LPs were included: 30 sitting flexed and 102 lateral flexed. There were no differences in success rates between positions for the primary objective of obtaining CSF for culture and the secondary study objectives of obtaining CSF for cell count and non-traumatic CSF. A significant secondary objective was that operators who performed the LP in the sitting flexed position were more likely to obtain CSF on the first attempt (odds ratio, 2.74; confidence interval, 1.17-6.45). The sitting flexed position was as successful as the lateral flexed position in the primary objective of obtaining CSF for culture and the secondary objectives of obtaining CSF for cell count and non-traumatic CSF. For the secondary objective of obtaining CSF on the first attempt, the sitting flexed position was associated with a higher rate of obtaining CSF on the first attempt in infants younger than 12 months.

Normal reference values for testing of cerebrospinal fluid in term and preterm infants

Srinivasan et al have provided a valuable service to clinicians and infants worldwide by performing and analyzing in an exacting way the cerebrospinal fluid (CSF) findings of preterm and term infants who did not have central nervous system infections. Their findings provide most reliable, clinically relevant cutpoints for normal findings that we ever have had or likely will have in the future. Contrary to tenets from previously published data, CSF white blood cell counts in preterm and term infants are similar and are low (upper bound cutpoints of 14 cells/mm3), even in the first week of life. This study is superior to others in the past, most notably because of careful exclusion criteria and prospective approach that aided correct patient categorization and minimized missing data. An important caveat is that infants with CSF red blood cell counts of >500 cells/mm3, presumably from hemorrhage, birth trauma, or traumatic lumbar puncture, were excluded. Inclusion of such infants in prior studies speculatively could be a major reason why we held as “normal” higher limits of white blood cell counts and protein concentrations. It is noteworthy that 30% of infants evaluated for inclusion in the study were excluded because of high red blood cell counts. Findings are not generalizable to this group.The additional finding that short-term antibiotic therapy prior to lumbar puncture did not affect cutpoints in a clinically meaningful way will be most useful in settings in the neonatal intensive care unit, when cardiorespiratory instability precludes CSF examination prior to therapy and when CSF is only successfully obtained 1-2 days after treatment of neonates admitted from emergency departments.Article page 729▶ Srinivasan et al have provided a valuable service to clinicians and infants worldwide by performing and analyzing in an exacting way the cerebrospinal fluid (CSF) findings of preterm and term infants who did not have central nervous system infections. Their findings provide most reliable, clinically relevant cutpoints for normal findings that we ever have had or likely will have in the future. Contrary to tenets from previously published data, CSF white blood cell counts in preterm and term infants are similar and are low (upper bound cutpoints of 14 cells/mm3), even in the first week of life. This study is superior to others in the past, most notably because of careful exclusion criteria and prospective approach that aided correct patient categorization and minimized missing data. An important caveat is that infants with CSF red blood cell counts of >500 cells/mm3, presumably from hemorrhage, birth trauma, or traumatic lumbar puncture, were excluded. Inclusion of such infants in prior studies speculatively could be a major reason why we held as “normal” higher limits of white blood cell counts and protein concentrations. It is noteworthy that 30% of infants evaluated for inclusion in the study were excluded because of high red blood cell counts. Findings are not generalizable to this group. The additional finding that short-term antibiotic therapy prior to lumbar puncture did not affect cutpoints in a clinically meaningful way will be most useful in settings in the neonatal intensive care unit, when cardiorespiratory instability precludes CSF examination prior to therapy and when CSF is only successfully obtained 1-2 days after treatment of neonates admitted from emergency departments. Article page 729▶ Cerebrospinal Fluid Reference Ranges in Term and Preterm Infants in the Neonatal Intensive Care UnitThe Journal of PediatricsVol. 161Issue 4PreviewTo determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit. Full-Text PDF

Adjustment of cerebrospinal fluid protein for red blood cells in neonates and young infants

To determine the relationship between cerebrospinal fluid (CSF) red blood cell (RBC) count and CSF protein in neonates and young infants undergoing lumbar puncture. Cross-sectional study. Urban tertiary care children's hospital. Infants 56 days of age and younger who had a lumbar puncture in the emergency department between January 1, 2005 and July 31, 2009 were eligible for inclusion. Infants with missing laboratory data, exceedingly high CSF red blood cell counts, or conditions known to elevate CSF protein were excluded. Linear regression was used to determine the association between CSF RBC and CSF protein. Of 1986 infants, 56 days of age or younger, who underwent lumbar puncture in the emergency department during the study period, 1241 (62.5%) met inclusion criteria. The median age was 34 days (interquartile range: 19-46 days); 45% of patients were male. The median CSF RBC count was 40 cells/mm(3) (interquartile range: 2-1080 cells/mm(3)); 11.8% of patients had a CSF RBC >10,000 cells/mm(3). CSF protein increased by 1.9 mg/dL (95% confidence interval: 1.7-2.1 mg/dL) per 1000 CSF RBCs for all included patients. Restricting analysis to patients without pleocytosis yielded comparable results, as did subanalyses by age and delivery type. We found that CSF protein concentrations increased by approximately 2 mg/dL for every 1000 CSF RBCs. These data may assist clinicians in interpreting CSF protein concentrations in infants 56 days of age and younger in the context of traumatic lumbar punctures.

Incidence of post-dural puncture headache in research volunteers.

To determine the frequency and risk factors of post-dural puncture headache (PDPH) in research volunteers. Despite increasing interest in measuring cerebrospinal fluid (CSF) biomarkers to investigate disease pathogenesis and diagnosis, previous case series have evaluated lumbar puncture (LP) safety only in clinical care. PDPH is a common complication after LP. We determined the frequency of PDPH in neurologically unselected HIV seropositive and seronegative adults volunteering for research, as well as the variables associated with the development of PDPH. Variables studied were body mass index (BMI), HIV serostatus, volume of CSF removed, number of previous LPs, use of pre-medication, LP position, lumbar space, number of needle passes, whether or not aspiration was used, CSF white blood cell counts, CSF red blood cell counts, CD4 count, CD4 nadir, CSF HIV viral load, plasma HIV viral load, and race. Of 675 LPs performed over 1 year, headache developed in 38 (5.6%; 95% CI 4.2, 7.1). Most PDPH (92%) resolved spontaneously or with conservative medical management; 3 required epidural blood patch. Greater headache risk was associated with lower BMI (BMI ≤25 vs >25) (OR 3.3; CI 95% 1.5, 7.0; P = .001) and less prior LP experience (previous LPs ≤2 vs >2) (OR 2.1; CI 95% 1.1, 4.1; P = .03). PDPH was not significantly (P > .05) related to HIV serostatus, CSF volume, or gender. In this study, where tolerance to risk was low because LPs were done for research rather than clinical purposes and healthy controls were included, adverse effects were mild and self-limited.

CSF cytokine levels in preterm infants may reflect systemic inflammation and are independent of gestation

Background Among preterm infants, high concentrations of inflammatory mediators in cerebrospinal fluid (CSF) are associated with poor outcome. Previous studies have not indicated whether CSF concentrations of inflammatory mediators are associated with important confounders such as gestational age. Aims To examine associations between CSF concentrations of inflammatory mediators and gestational age, maternal features suggestive of inflammation, characteristics of the CSF sample or the presence of a systemic inflammatory response. Study design and subjects Aliquots of CSF obtained during routine investigation of potential sepsis among infants born before 35 weeks gestation were assayed for 17 mediators of inflammation using a fluorescent multi-bead analyser. Other information was collected from routine clinical records. Results 39 infants were assessed. CSF levels of mediators of inflammation were not correlated with gestational age. CSF red blood cell counts were correlated with CSF concentrations of IL-6, GM-CSF and IL-17 (each p < 0.003). CSF lactate was correlated with CSF concentrations of IL-1β, IL-6, GM-CSF, G-CSF, IFN-γ and MIP-1β. CSF concentrations of IL-1β, IL-6, G-CSF, TNF-α and IFN-γ were higher in infants with a raised CRP within 24 h of delivery (each p < 0.003). Conclusions CSF concentrations of inflammatory mediators most probably reflect inflammatory pathologies and are not influenced by gestational age. They may also, however, reflect contamination with blood or systemic inflammation. CSF concentrations of inflammatory mediators may not provide a specific indicator of CNS inflammation.

Xanthochromia is not pathognomonic for subarachnoid hemorrhage

To test the hypothesis that xanthochromia may be observed in traumatic lumbar puncture (LP). Xanthochromia, the yellow discoloration of cerebrospinal fluid (CSF) caused by hemoglobin catabolism, is classically thought to arise within several hours after subarachnoid hemorrhage (SAH). The presence of xanthochromic supernatant is often used to distinguish the elevated red blood cell (RBC) count observed in the CSF of SAH from the elevated RBC count observed after traumatic LP. The authors developed a model of traumatic LP by adding whole blood to pigment-free CSF to obtain RBC concentrations of 0, 5000, 10000, 20000, 30000, and 40000 RBC/ microL. Supernatant from centrifuged samples was assessed for xanthochromia by spectrophotometry. Xanthochromia was considered present if the absorption followed a characteristic oxyhemoglobin curve with a maximal absorption greater than 0.023 at 415 nm. Samples with at least 30000 RBC/ microL demonstrated xanthochromia immediately. Samples with 20000 RBC/ microL demonstrated xanthochromia within one hour, and samples with 10000 RBC/ microL or less, within two hours. Cerebrospinal fluid xanthochromia may be observed within two hours after traumatic LP and sooner in samples with greater than 10000 RBC/ microL. Conversely, xanthochromia in traumatic LP with less than 5000 RBC warrants further investigation for SAH. When the CSF RBC count is elevated above 10000 RBC/ microL, or the time between sample acquisition and analysis is prolonged, the clinician should not rely on xanthochromia to confirm SAH.

The diagnostic utility of cerebrospinal fluid creatine kinase activity in the horse.

We evaluated creatine kinase (CK) activity in the cerebrospinal fluid (CSF) of 128 horses with various neurological disorders. No association was found between CSF CK activity and CSF red blood cell count, CSF nucleated cell count, CSF total protein concentration, or serum CK activity. The sensitivity and specificity of CSF CK activity as a diagnostic test for protozoal myelitis in horses (61% and 56%, respectively) was higher than for cervical stenotic myelopathy, degenerative myelopathy, or motor neuron disease, but was considered to be inadequate to be of use diagnostically. Contamination of CSF with whole blood, hemolyzed red blood cells, or serum did not substantially contribute to increases in CSF CK activity. Addition of epidural fat or dura to CSF significantly increased CSF CK activity in all cases. We suggest that the use of CSF CK activity as a diagnostic indicator of neurological disease in the horse in unreliable, and that CSF CK activity may be falsely increased by contamination of CSF with epidural fat or dura during CSF collection.