Ian Holbrook

Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage

Abstract It is crucially important to detect subarachnoid haemorrhage (SAH) in all patients in whom it has occurred to select patients for angiography and preventative surgery. A computerized tomography (CT) scan is positive in up to 98% of patients with SAH presenting within 12 h, but is positive in only 50% of those presenting within one week. Cerebrospinal fluid (CSF) bilirubin spectrophotometry can be used to determine the need for angiography in those few CT-negative patients in whom clinical suspicion of SAH remains high; it may remain positive up to two weeks after the event. A lumbar puncture (LP) should only be performed >12 h after the onset of presenting symptoms. Whenever possible collect sequential specimens. Always ensure that the least blood-stained CSF sample taken (usually the last) is sent for bilirubin analysis. Protect the CSF from light and avoid vacuum tube transport systems, if possible. Always use spectrophotometry in preference to visual inspection. All CSF specimens are precious and should always be analysed unless insufficient sample is received. Centrifuge the specimen at >2000 rpm for 5 min as soon as possible after receipt in the laboratory. Store the supernatant at 4°C in the dark until analysis. An increase in CSF bilirubin is the key finding, which supports the occurrence of SAH but is not specific for this. In most positive cases, bilirubin will occur with oxyhaemoglobin.

A comparison of urinary mercury between children with autism spectrum disorders and control children.

Background Urinary mercury concentrations are used in research exploring mercury exposure. Some theorists have proposed that autism is caused by mercury toxicity. We set out to test whether mercury concentrations in the urine of children with autism were significantly increased or decreased compared to controls or siblings. Methods Blinded cohort analyses were carried out on the urine of 56 children with autism spectrum disorders (ASD) compared to their siblings (n = 42) and a control sample of children without ASD in mainstream (n = 121) and special schools (n = 34). Results There were no statistically significant differences in creatinine levels, in uncorrected urinary mercury levels or in levels of mercury corrected for creatinine, whether or not the analysis is controlled for age, gender and amalgam fillings. Conclusions This study lends no support for the hypothesis of differences in urinary mercury excretion in children with autism compared to other groups. Some of the results, however, do suggest further research in the area may be warranted to replicate this in a larger group and with clear measurement of potential confounding factors.

Is the presence of urinary indolyl-3-acryloylglycine associated with autism spectrum disorder?

To test whether the presence of indolyl‐3‐acryloylglycine (IAG) is associated with autism, we analyzed urine from population‐based, blinded cohorts. All children in York, UK with autism spectrum disorders (ASDs), diagnosed using ICD‐10 research diagnostic criteria, were invited to participate. Fifty‐six children on the autism spectrum (mean age 9y 8mo, SD 3y 8mo; 79% male) agreed to participate, as did 155 children without ASDs (mean age 10y, SD3y 2mo; 54% male) in mainstream and special schools (56 of whom were age‐, sex‐, and school‐matched to children with ASDs). IAG was found at similar levels in the urine of all children, whether IAG concentrations or IAG: ereatinine ratios were compared. There was no significant difference between the ASD and the comparison group, and no difference between children at mainstream schools and those at special schools. There is no association between presence of IAG in urine and autism; therefore, it is unlikely to be of help either diagnostically or as a basis for recommending therapeutic intervention with dietary manipulation. The significance of the presence of IAG in urine has yet to be determined.

What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid haemorrhage in computed tomography-negative patients?

Abstract Background Spectrophotometry of cerebrospinal fluid (CSF) for bilirubin is the recommended method for investigation in suspected cases of subarachnoid haemorrhage (SAH), when a computed tomography (CT) of the head is negative for blood. There is a potential need for a simpler alternative. Measurement of CSF ferritin might fulfil this need. Method We have measured ferritin in the CSF from 252 patients with suspected SAH who were negative on a CT of the head for blood, recruited on a consecutive intention to recruit basis from four centres. CSF spectrophotometry was performed on all samples. A positive outcome was taken as an aneurysm found on angiography that was treated or a discharge diagnosis of non-aneurysmal SAH. Results A final diagnosis of aneurysmal SAH was made in six patients, an arteriovenous malformation in one and non-aneurysmal SAH in nine. Receiver operating characteristic (ROC) analysis showed that at 6.4 μg/L, sensitivity, specificity, positive and negative predictive values were 1.0, 0.48, 0.12 and 1.0, respectively. At 12 μg/L, these values were 0.81, 0.91, 0.38 and 0.98, respectively. Conclusions At an appropriate negative predictive value (1.0) for a rule-out test, ferritin has too low a specificity to function as a stand-alone test and we cannot recommend it as an initial screen to be followed by spectrophotometry.

National audit of cerebrospinal fluid testing

Background: UK National External Quality Assessment Service (NEQAS) Specialist Advisory Group for EQA of CSF Proteins and Biochemistry was interested in current practice for the biochemical investigation of cerebrospinal fluid (CSF) in the UK. Methods: A questionnaire was sent to laboratories via regional audit committees and the results collated. Results: Most laboratories were analysing CSF in a satisfactory manner. There was some variation in the reference ranges used for glucose, protein and lactate. There was concern about the rejection policies of some laboratories on these unrepeatable samples and the wavelengths used to measure bilirubin. The survey revealed the lack of spectrophotometric scanning for haem pigments and bilirubin in some hospitals. Conclusions: The current practice for the measurement of CSF samples in the UK is satisfactory in most laboratories responding to the questionnaire. National agreement on reference ranges for glucose, protein and lactate should be achievable. Those performing spectrophotometric scanning of the CSF were doing so in concordance with the national guidelines. Some hospitals in the UK may not have responded to the questionnaire because they did not offer spectrophotometric scanning.

The British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea, 2nd edition

The prevalence of chronic diarrhoea has been estimated at 4-5% in Western populations and is one of the most common reasons for referral to a gastroenterological clinic. Investigation of patients was rationalized in 2003 with the publication by the British Society of Gastroenterology of guidelines for the investigation of chronic diarrhoea. The guidelines may also be viewed at www.bsg.org.uk/clinical_prac/guidelines/chronic_diarr.htm.

Cerebrospinal fluid lactate: measurement of an adult reference interval

Background Differentiating bacterial meningitis from viral meningitis is a diagnostic challenge. Cerebrospinal fluid lactate has been proposed as a valuable test to differentiate disease states; however, its use in adults is limited by a lack of robust reference interval data. Methods Cerebrospinal fluid samples with no cells or organisms detected, no culture growth after 48 h, and no increase in cerebrospinal fluid bilirubin were used to derive reference interval data for cerebrospinal fluid lactate in adults (n = 120). Results A cerebrospinal fluid lactate reference interval of 1.0 (90% CI 0.9–1.1) – 2.2 mmol/L (90% CI 2.0–2.6) was defined. Conclusions Cerebrospinal fluid lactate results are rapidly available to the clinician. When interpreted against the adult reference interval derived in this study, results can help to triage patients presenting with symptoms of meningitis.

Cerebrospinal fluid total protein cannot reliably distinguish true subarachnoid haemorrhage from other causes of raised cerebrospinal fluid net bilirubin and net oxyhaemoglobin absorbances

Background In cerebrospinal fluid (CSF) spectrophotometry, if the net bilirubin absorbance (NBA) and net oxyhaemoglobin absorbance (NOA) are both raised with a visible oxyhaemoglobin peak, the revised national guidelines for analysis of CSF bilirubin advise interpreting the results as ‘Consistent with subarachnoid haemorrhage (SAH)’ regardless of the CSF total protein concentration of the specimen. We wanted to study the range of CSF total protein concentrations found in confirmed SAH to establish if the CSF total protein value can give further guidance on the likelihood of SAH. Methods Consecutive cases from five different hospital sites were included if the CSF NBA was greater than 0.007 AU and the NOA was greater than 0.02 AU with a visible oxyhaemoglobin peak. For the cases identified, the laboratory information management system and patient records were interrogated to identify the total protein concentration of the CSF specimen and whether SAH had ultimately been confirmed or excluded by other methods and supporting evidence. Results Results from 132 patients were included. The CSF total protein range in confirmed SAH was 0.23–3.08 g/L with a median concentration of 0.7 g/L (n = 51). In the SAH excluded group, the CSF total protein range was 0.43–29 g/L with a median concentration of 1.9 g/L (n = 81). Conclusions Although confirmed SAH was not associated with the very highest concentrations of CSF total protein, a definite CSF protein cut-off concentration above which SAH could reliably be excluded cannot be recommended.

Positive Screening Tests for Barbiturates in Urine Samples in the York Area over a 1-Year Period

Following the screening of urine samples for a panel of drugs over a period of 1 year, a peak was observed during December 1999 and January 2000 in the numbers of samples testing positive for both morphine and barbiturates. This increase may be due to the adulteration of street heroin with barbiturate during this period.