Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies.

Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome. Therefore, there is an urgent need to develop and validate reliable and minimally invasive biomarkers for CNS tumours that can be used alone or in combination with current clinical practices. Blood-based biomarkers can be informative in the diagnosis and monitoring of various types of cancer. However, blood-based biomarkers have proven suboptimal for analysis of CNS tumours. In contrast, circulating biomarkers in cerebrospinal fluid (CSF), including circulating tumour DNA, microRNAs and metabolites, hold promise for accurate and minimally invasive assessment of CNS tumours. This review summarises the current understanding of these three types of CSF biomarkers and their potential use in neuro-oncologic clinical practice.

Pragmatic and evidence-based approach to paediatric cerebrospinal fluid reference limits for white cell count and concentrations of total protein and glucose.

BACKGROUND: It is often impractical for each laboratory to establish its own paediatric reference intervals. This is particularly true for specimen types collected using invasive procedures, for example, cerebrospinal fluid (CSF). METHODS: Published CSF reference intervals for white cell count, and concentrations of total protein and glucose were reviewed by stakeholders in a paediatric hospital. Consensus reference intervals for the three CSF parameters were then subjected to verification using guidelines from the Clinical Laboratory Standards Institute and residual CSF specimens. RESULTS: Consensus paediatric reference intervals adapted from published studies with minor modifications were locally verified as follows. White cell count (x106 cells/L): 0-20 (<1 month); 0-10 (1-2 months); 0-5 (>2 months). Total protein (g/L): 0.3-1.2 (<1 month); 0.2-0.6 (1-3 months); 0.1-0.4 (>3 months). Glucose (mmol/L): 2.0-5.6 (<6 months); 2.4-4.3 (6 months or older).

Historical perspectives in clinical pathology: a history of glucose measurement.

This is the second in the series of historical articles dealing with developments in clinical pathology. As one of the most commonly measured analytes in pathology, the assessment of glucose dates back to the time of the ancient Egyptians. It was only in the 19th century that advances in chemistry led to the identification of the sugar in urine being glucose. The following century witnessed the development of more chemical and enzymatic methods which became incorporated into the modern analysers and point-of-care instruments which are as ubiquitous as the modern day cellphones. Tracking the milestones in these developments shows the striking paradigms and the many parallels in the development of other clinical chemistry methods.

CSF xanthochromia: correlation with brain imaging and its usefulness as an out-of-hours test.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a spontaneous bleed into the subarachnoid space which is investigated by CT head and cerebrospinal fluid (CSF) xanthochromia. The aim of this study was to compare CSF xanthochromia with brain imaging and evaluate the need for out of hours (OOH) testing for CSF xanthochromia. METHOD: Discharge summaries and brain imaging of patients with positive xanthochromia screen were reviewed over 12 months retrospectively. Timings of CSF xanthochromia and hospital discharge of 30 consecutive patients with negative xanthochromia screen were also examined. RESULTS: From 289 xanthochromia requests, 23 were positive but only 2 patients had an actual bleed. In 30 consecutive negative xanthochromia results, all brain imaging results suggested no bleed. Eight of these requests were performed OOH, and as a result, 1 patient was discharged early. CONCLUSIONS: CSF xanthochromia has a poor positive predictive value (8.7%) but has a good negative predictive value (100%) for SAH. Analysis of CSF xanthochromia OOH, in patients with negative CT head, did not speed up the discharge process from the hospital.