Cerebrospinal Fluid Spectrophotometry Research Articles

Visual inspection versus spectrophotometry for xanthochromia detection in patients with sudden onset severe headache-A diagnostic accuracy study.

There is still disagreement about whether to routinely use spectrophotometry to detect xanthochromia in cerebrospinal fluid (CSF) or whether visual inspection is adequate. We aimed to evaluate the diagnostic accuracy of these methods in detecting an aneurysmal subarachnoid hemorrhage in patients with sudden onset severe headache. When a patient presents to the emergency department with a headache for which there is suspicion of a subarachnoid hemorrhage, the gold standard to rule this out is to perform a CSF analysis for xanthochromia with or without spectrophotometry if the cranial non-contrast computed tomography (CT) upon admission is negative. Having applied the gold standard, we retrospectively included patients with acute headache who underwent both CT scan and CSF spectrophotometry at our hospital in the period 2002-2020. Patients were excluded if the cranial CT was interpreted as positive, there was a bloody CSF, or if visual assessment data of the CSF was unavailable. We scrutinized the patients' medical records and evaluated the benefit of spectrophotometry compared to visual inspection. The net bilirubin absorbance cut-off for support of subarachnoid hemorrhage was set at >0.007 absorbance units. The spectrophotometry was also considered positive if the net bilirubin absorbance was ≤0.007 and net oxyhemoglobin absorbance was ≥0.1 absorbance units. We calculated and compared the sensitivity and specificity of CSF spectrophotometry and visual inspection of the CSF. In total, 769 patients, with a mean age of 42.3 ± (standard deviation [SD] = 17.3) years, were included. The headache onset was classified as a thunderclap headache in 41.5%, and 4.7% had a sudden loss of consciousness. Fifteen patients (2%) were finally diagnosed with a subarachnoid hemorrhage, six (0.8%) had an aneurysmal subarachnoid hemorrhage, seven (0.9%) had a perimesencephalic hemorrhage, one (0.1%) had a cortical cerebral sinus venous thrombosis, and one (0.1%) had a spinal epidural hematoma. Four patients (0.5%) had a subarachnoid hemorrhage that was not detected by visual inspection, and two were caused by an aneurysmal rupture. One of these two patients died just before intervention, and the other underwent coiling for an anterior communicating aneurysm. The number needed for lumbar puncture to detect a subarachnoid hemorrhage was 51, but 128 to detect an aneurysmal hemorrhage. The corresponding numbers needed for CSF spectrophotometric analysis were 192 and 385, respectively. Spectrophotometry was positive in 31 patients (4.0%), of whom 18 (2.3%) also had visually detected xanthochromia (11 true positive). The mean net bilirubin absorbance in the 13 samples with visually clear CSF was 0.0111 ± (SD = 0.0103) absorbance units, compared to 0.0017 ± (SD = 0.0013) in the CSF with negative spectrophotometry. The corresponding figures for net oxyhemoglobin absorbance were 0.0391 ± (SD = 0.0522) versus 0.0057 ± (SD = 0.0081). The sensitivity of spectrophotometric xanthochromia detection was 100% (95% confidence interval [CI], 78-100), compared to 73% (95% CI, 45-92) for visual xanthochromia detection. The specificity of spectrophotometric xanthochromia detection was 98% (95% CI, 97-99) compared to 99% (95% CI, 98-100) for visual xanthochromia detection. Both methods had high negative predictive values: 100% (95% CI, 99.5-100) versus 99.5% (95% CI, 98.6-99.9), respectively. Both visual inspection and spectrophotometry have high diagnostic accuracy for detecting CSF xanthochromia, but the lower sensitivity of visual assessment makes it unreliable, and we recommend the use of spectrophotometry in clinical practice.

Detection of subarachnoid haemorrhage with spectrophotometry of cerebrospinal fluid- a comparison of two methods.

Spectrophotometric absorption curve analysis of cerebrospinal fluid (CSF) for oxyhaemoglobin and bilirubin is necessary to accurately diagnose subarachnoid haemorrhage (SAH) in patients with typical symptoms but with negative findings on X-ray examinations. In this study, we evaluated the performance of two methods for interpreting absorption curves; one method from the United Kingdom National External Quality Assessment Service (UK-NEQAS) and the other from the national quality assurance programme in Sweden (Equalis). Consecutive absorbance curves (n=336) were interpreted with two different methods, and their performance was compared to the diagnosis as stated in the patient records. The UK-NEQAS method displayed equal sensitivity to the Equalis method, but the specificity of the UK-NEQAS method was significantly higher than the Equalis method resulting in fewer false positive results. For UK-NEQAS, a positive predictive value (PPV) of 84.6% and a negative predictive value (NPV) of 99.7% were observed, whereas the Equalis method had a PPV of 27.5% and an NPV of 99.7%. The semi-automated method based on the guidelines from UK-NEQAS provides an efficient and correct interpretation of absorbance curves with short turn-around times. We propose using this method for the routine interpretation of CSF spectrophotometric curves.

The value of repeated lumbar puncture to test for xanthochromia, in patients with clinical suspicion of subarachnoid haemorrhage, with CT-negative and initial traumatic tap

Objectives For the diagnosis of subarachnoid haemorrhage (SAH), the presence of cerebrospinal fluid (CSF) xanthochromia is still considered the gold standard for patients with a thunderclap headache, in the absence of blood on brain CT scan. However, a traumatic lumbar puncture (LP) typically results in high concentrations of oxyhaemoglobin in CSF, impairing the detection of xanthochromia and preventing the reliable exclusion of SAH. In this context, the value of a repeat lumbar puncture has not yet been described. Materials and methods A retrospective case series of suspected SAH patients, with a negative CT scan and initial traumatic LP, managed with a repeat LP to assess for CSF xanthochromia. Clinical notes, laboratory and imaging results were reviewed. Results Between August 2011 and January 2020, 31 patients with suspected SAH were referred to our neurosurgical unit following negative CT and traumatic LP. A repeat LP was performed in 7 of the 31 patients, 2.4 days (±0.79 SD) after the first traumatic LP. CSF spectrophotometry analysis from repeated LP in all 7 patients was negative for xanthochromia. No adverse clinical events were recorded on average 18 months following discharge. Conclusion A repeat LP performed following a traumatic tap can still yield xanthochromia-negative CSF, thereby, excluding SAH, avoiding unnecessary invasive angiography and overall promoting the safer management of these patients.

Added value of cerebrospinal fluid spectrophotometry associated with computed tomography angiogram for suspected subarachnoid hemorrhage in the emergency department.

Added value of cerebrospinal fluid spectrophotometry associated with computed tomography angiogram for suspected subarachnoid hemorrhage in the emergency department.

Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for subarachnoid bleeding but adds little to computed tomography

Subarachnoid hemorrhage (SAH) is a serious neurological event associated with high morbidity and mortality. Computed tomography of the cerebrum (CTC) is the diagnostic method of choice, but in case of negative CTC but strong suspicion of SAH, lumbar puncture with spectrophotometric analysis of cerebrospinal fluid (CSF) for xanthochromia is performed. We wanted to examine the diagnostic properties of CSF spectrophotometry for xanthochromia testing. We performed a retrospective study of the diagnostic properties of CSF analysis for xanthochromia using spectrophotometry in the diagnosis of SAH. A total of 489 CSF samples were analyzed for xanthochromia, according to international guidelines, from 2009 until 2014 and for 411 of these the patient files were retrieved and examined for final clinical diagnosis and result of CTC. One patient with SAH did not have a positive spectrophotometry report and another patient with SAH had an equivocal report. In four patients did initial CTC not correctly identify SAH. For patients with a negative CTC within six hours of symptom onset spectrophotometry for xanthochromia in the CSF had a diagnostic sensitivity of 100% and a diagnostic specificity of 98.5%. The positive predictive value was 16.7% and the negative predictive value 100%. We conclude that spectrophotometry of CSF for xanthochromia is a sensitive and specific test for diagnosing SAH. However, it seems that an initial CTC identifies almost all patients with SAH. This suggests that in our and similar diagnostic settings, lumbar puncture and testing for xanthochromia might only be relevant in very few cases, if not obsolete.

Evaluation of Automated Determination of Bilirubin and Oxyhemoglobin in Cerebrospinal Fluid Using the DrugLog© Instrument.

In a heterogenous group of patients with acute headache it is important to diagnose subarachnoid hemorrhage (SAH), a potentially lethal but treatable condition, with short turnaround time and high precision. Spectrophotometry of cerebrospinal fluid (CSF) is an essential part in the investigation of patients with suspected SAH but the analysis is slow and operator dependent. We have evaluated a new instrument for ultraviolet and visible light (UV-VIS) spectroscopy (DrugLog©, Pharmacolog, Uppsala, Sweden) for automatic determination of oxyhemoglobin and bilirubin in CSF samples. The instrument incorporates software for calculating the absorbance values thus eliminating operator bias. Bilirubin and oxyhemoglobin in CSF was analyzed both with DrugLog© and traditional spectrophotometry at 415 and 476 nanometers (A415 and A476) using patient samples containing varying amounts of bilirubin and oxyhemoglobin. The DrugLog© method showed a strong correlation both for bilirubin (Pearson's r = 0.996) and oxyhemo-globin (Pearson's r = 0.993). The DrugLog© method had good linearity and precision, offering an automated determination of bilirubin and oxyhemoglobin, eliminating operator bias. The DrugLog© instrument has a short assay time and showed good agreement with traditional spectrophotometry.

Benefit of cerebrospinal fluid spectrophotometry in the assessment of CT scan negative suspected subarachnoid haemorrhage: A diagnostic accuracy study

This study aimed to determine if performing cerebrospinal fluid spectrophotometry in addition to visual inspection detects more ruptured cerebral aneurysms than performing cerebrospinal fluid visual inspection alone in patients with a normal head CT scan but suspected of suffering an aneurysmal subarachnoid haemorrhage (SAH). We performed a single-centre retrospective study of patients presenting to the emergency department of a tertiary hospital who underwent both head CT scan and lumbar puncture to exclude SAH. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an approach utilising both spectrophotometry and visual inspection (combined approach) was compared to visual inspection alone. A total of 409 patients (mean age 37.8years, 56.2% female) were recruited and six (1.5%) had a cerebral aneurysm on angiography. The sensitivity of visual inspection was 50% (95% confidence interval [CI]: 12.4–82.6%), specificity was 99% (95% CI: 97.5–99.7%), PPV was 42.9% (95% CI: 10.4–81.3%) and NPV was 99.2% (95% CI: 97.8–99.8%). The combined approach had a sensitivity of 100% (95% CI: 54.1–100%), specificity of 79.7% (95% CI: 75.4–83.5%), PPV of 6.8% (95% CI: 2.6–14.3%) and a NPV of 100% (95% CI: 98.8–100%). The sensitivity of the combined approach was not significantly different to that of visual inspection alone (p=0.25). Visual inspection had a significantly higher specificity than the combined approach (p<0.01). The combined approach detected more cases of aneurysmal SAH than visual inspection alone, however the difference in sensitivity was not statistically significant. Visual xanthochromia should prompt angiography because of a superior specificity and PPV. Due to its reduced sensitivity, caution should be applied when using only visual inspection of the supernatant.

Likelihood of aneurysmal subarachnoid haemorrhage in patients with normal unenhanced CT, CSF xanthochromia on spectrophotometry and negative CT angiography

Patients with suspected subarachnoid haemorrhage, a normal noncontrast computed tomography (CT) and cerebrospinal fluid (CSF) evidence of haemoglobin breakdown products often undergo CT angiography (CTA). If this is normal, then invasive catheter angiography may be offered. In current clinical practice, haemoglobin breakdown products are detected by spectrophotometry rather than visible xanthochromia, and CTA is performed on multidetector scanners. The aim of this study was to determine if such patients should still have a catheter angiography, given the associated risks. Patients positive for CSF spectrophotometry (n=26) were retrospectively identified from the clinical biochemistry information system and imaging data from the electronic radiology records were reviewed. Discharge letters were consulted to relate the biochemistry and radiology results to the final diagnosis. 15 patients with CT angiography were found. Nine patients had normal CT angiography. No causative aneurysms had been missed. One patient had small, coincidental aneurysms missed on initial reading of the CTA. The likelihood of a clinically significant aneurysm in a patient who is CT negative, lumbar puncture positive and CTA negative is low. Double reporting of negative CT angiograms may be advisable.

Time-Dependent Test Characteristics of Head Computed Tomography in Patients Suspected of Nontraumatic Subarachnoid Hemorrhage

A recent study suggested that in patients with acute headache suspicious of nontraumatic subarachnoid hemorrhage (SAH), cerebrospinal fluid (CSF) analysis is not needed to rule out SAH if head CT performed ≤6 hours after ictus is negative. Before implementation in daily practice, these results need replication. Therefore, we investigated test characteristics of head CT in patients with a clinical suspicion of SAH. Patients suspicious of SAH and a normal level of consciousness presenting to our tertiary care hospital between 2005 and 2012 were included. All patients had a head CT interpreted by experienced neuroradiologists and CSF spectrophotometry if head CT was negative or inconclusive. We determined test characteristics with 95% confidence intervals (CI) for nontraumatic SAH of head CT performed ≤6 or >6 hours after onset of headache. Sensitivity of head CT ≤6 hours after ictus (n=137) was 98.5% (95% CI, 92.1%-100%), diagnosing all patients with aneurysmal and perimesencephalic SAH, but not with a cervical arteriovenous malformation. Sensitivity of head CT performed >6 hours after ictus (n=113) was 90.0% (95% CI, 76.3-97.2). After exclusion of patients with an atypical presentation without headache, sensitivity, specificity, negative predictive value, and positive predictive value of head CT ≤6 hours were all 100%. In patients presenting with acute headache and a normal head CT ≤6 hours after ictus, as interpreted by experienced neuroradiologists, there is no added value of CSF analysis. In patients with an atypical presentation without headache and in patients presenting >6 hours after ictus, CSF analysis is still indicated.

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

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. 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. 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 microg/L, sensitivity, specificity, positive and negative predictive values were 1.0, 0.48, 0.12 and 1.0, respectively. At 12 microg/L, these values were 0.81, 0.91, 0.38 and 0.98, respectively. 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.

Should Spectrophotometry Be Used to Identify Xanthochromia in the Cerebrospinal Fluid of Alert Patients Suspected of Having Subarachnoid Hemorrhage?

To the Editor: We read with interest the article by Perry and colleagues.1 There appears to be a reluctance in North America to embrace what we believe to be the most sensitive method for demonstrating bilirubin in cerebrospinal fluid (CSF), spectrophotometry, on the basis that it is not requested, that the equipment does not exist and that it is difficult to interpret.1,2 It is then somewhat disingenuous to criticize spectrophotometry by using 4 methods, the first of which (‘traditional’) has many deficiencies which have been well documented3,4; the second of which (‘Chalmers and Kiley’)5 has been superseded by the third (‘Chalmers revised’) …

Is Cerebrospinal Fluid Spectrophotometry Useful in CT Scan-Negative Suspected Subarachnoid Haemorrage?

Missed cerebral aneurysms in CT-negative patients can have serious implications. We set out to determine the usefulness of cerebrospinal fluid (CSF) spectrophotometry and the individual significance of CSF oxyhaemoglobin, bilirubin and methaemoglobin in 463 CT scan-negative patients with suspected subarachnoid haemorrhage (SAH) and normal neurological examination. CSF spectrophotometry resulted in the diagnosis of an intracranial aneurysm in 2% (9/463) of patients with CT-negative suspected SAH. No aneurysms were found in patients in whom spectrophotometry was negative for haem pigments. Less than 1% of patients with oxyhaemoglobin alone had aneurysms diagnosed, whilst 21% of patients with bilirubin had an aneurysm. CSF spectrophotometry is an important investigation in patients with CT-negative suspected SAH, particularly where clinical suspicion is strong. Patients positive for bilirubin are likely to provide a high yield of aneurysmal bleed and should undergo angiography. Patients with oxyhaemoglobin alone in whom SAH is strongly suspected may benefit from angiography. Based on a small number of patients, we recommend that patients with methaemoglobin should also be investigated. Patients with negative spectrophotometry are unlikely to benefit from further investigation.

Current status of laboratory diagnosis of subarachnoid haemorrhage in Northern Ireland

Studies have shown that computed tomography (CT) scanning is 95% positive in patients scanned within 1 day of a suspected subarachnoid haemorrhage (SAH). However, generalized cerebral oedema can cause false‐positive diagnosis of SAH on CT, while it is estimated that up to 2% of patients with SAH can have negative scans as a result of the small amounts of subarachnoid blood involved. Because of the risks involved, there is a reluctance to identify aneurysms in CT‐negative patients by cerebral angiography without the supportive evidence of spectrophotometric examination of cerebrospinal fluid (CSF). CSF spectrophotometry is widely regarded as the best technique available for diagnosis of SAH and has replaced the visual inspection of CSF for xanthochromia that many accept as being inadequate. The test is now being carried out in an increasing number of centres throughout the UK and, in Northern Ireland, five hospital laboratories are involved in monitoring its performance by regional audit and a pilot NEQAS scheme. These have identified the limitations of CSF spectrophotometry, one of which is the time it takes for blood pigments to appear in the CSF, and has standardized issues of specimen requirements, laboratory procedures and the level of interpretation when reporting results.

Detection of Xanthochromia in Cerebrospinal Fluid,

Lumbar puncture (LP) still has an important role to play in the diagnosis of subarachnoid hemorrhage. Although computed tomography (CT) scanning has replaced LP as the investigation of first choice, within 24 h of ictus 5% of cases will show no evidence of hemorrhage on CT scanning; this percentage is as high as 50% by 1 week, 30% after 2 weeks, and 0% after 3 weeks (1). By definition, xanthochromia is the yellow discoloration indicating the presence of bilirubin in the cerebrospinal fluid (CSF) and is used by some to differentiate in vivo hemorrhage from a traumatic LP. In contrast to CT, CSF xanthochromia is present in all patients up to 2 weeks postictus and is still present in 70% of patients at 3 weeks (1)(2). A minimum period for CSF bilirubin detection is 12 h postictus (2). Thus, the detection of bilirubin in CSF appears to be the test of choice at late time points. Spectrophotometry of CSF in the visible region is, in general, considered more sensitive than visual examination, with peaks at 415 and ∼440–460 nm indicating the presence of hemoglobin (Hb) and bilirubin, respectively (1)(2). The problem with this test is that it is not known which CSF bilirubin absorbance indicates a clinically significant bleed. We have developed a simple quantitative method that attempts to address this question. CSF was collected aseptically by LP for routine biochemical …

Comparative studies of the diagnostic value of cerebrospinal fluid spectrophotometry and computed tomographic scanning in subarachnoid hemorrhage.

Serial spectrophotometric scans of cerebrospinal fluid (CSF) and computed tomographic (CT) scans of 99 patients with a subarachnoid hemorrhage (SAH) were examined. The xanthochromic index (i.e., the sum of the absorption values at 416 nm (oxyhemoglobin) and 460 nm (bilirubin)) yielded an accurate diagnosis in 82%, as did the CT scan. When both spectrophotometric and CT scans were used, the accuracy of SAH diagnosis increased to 96%. The xanthochromic index was valuable in estimating the date of hemorrhage and also correlated well with the clinical outcome of these patients. Only 42% of the recurrent hemorrhages were diagnosed by CSF spectrophotometry; in this capacity, its role seems less clear. However, a positive diagnosis of recurrent hemorrhage by CT scan was made in 83%.

Comparative studies of the diagnostic value of cerebrospinal fluid spectrophotometry and computed tomographic scanning in subarachnoid hemorrhage

Comparative studies of the diagnostic value of cerebrospinal fluid spectrophotometry and computed tomographic scanning in subarachnoid hemorrhage

Isoelectric focusing of cerebrospinal fluid proteins in ischemic cerebrovascular disease.

The cerebrospinal fluid (CSF) protein patterns, in ischemic cerebrovascular disease (ICD), of varying extension were studied by isoelectric focusing (IEF) in 100 patients at different intervals after the onset of symptoms. The diagnoses were based on conventional clinical examinations and CSF spectrophotometry in all cases. Computed tomography was performed on 52 cases. One or more CSF protein aberrations were noted in 94 patients. Some of these findings were most common with small lesions including TIA. Other aberrations were most frequent with the more extensive infarctions. A regional increase in the gammaglobulin range was found in six cases. The findings were most frequent in the first days after the stroke except for barrier damage which reached a maximum during the second week. The IEF findings of CSF seem to be of diagnostic value. Taken together with the clinical signs and CT findings, they could conceivably give prognostic information.

Diagnostic significance of CSF spectrophotometry and computer tomography in cerebrovascular disease. A comparative study in 231 cases.

Two hundred and thirty-one patients with cerebrovascular disease were examined by spectrophotometry of the cerebrospinal fluid (CSF) and by computer tomography. Many were followed by repeated examinations. Specific diagnoses --- bleeding as opposed to non-hemorrhagic or hemorrhagic infactions --- were indicated in 97% by spectrophotometry and in 65% by CT scan in 201 of the 231 cases (excluding 25 patients with transient ischemic attacks and five patients with cerebral tumors with cerebrovascular onset). Comparison between the two methods revealed agreement in most cases, with disagreement in only a few. The specific diagnosis was generally established on only one examination by both methods: repeated examinations were necessary in only a few cases. The results indicated that a combination of the two complementary methods established the diagnosis in almost all cerebrovascular disorders. This was particularly evident if the examinations were performed 24 hours to 21 days after onset of disease.

Computer Tomography Compared with Spectrophotometry of Cerebrospinal Fluid in Cerebrovascular Diseases

Eighty patients with cerebrovascular diseases were examined by computer tomography and spectrophotometry of CSF, most cases being followed by repeat examinations. Specific diagnoses were obtained in 76 per cent of the cases at tomography and in 95 per cent at spectrophotometry, generally at one examination. In cases examined angiographically or by isotope encephalography, the corresponding figures were 60 and 58 per cent. Twenty patients with confirmed haemorrhage or infarction examined only at tomography further indicated the high diagnostic significance of this method. The combination of tomography and spectrophotometry, being complementary to each other, obviously means a break-through in the diagnosis of cerebrovascular diseases, which is a prerequisite for a more rational therapy of these common and frequently disabling disorders.

Spectrophotometry of cerebrospinal fluid in subacute and chronic subdural haematomas.

Spectrophotometric examinations were performed on cerebrospinal and subdural fluids in subacute (five patients) and chronic (20 patients) subdural haematomas, with special reference to the diagnostic aid of CSF spectrophotometry. Spectrophotometric xanthochromia of haemorrhagic origin was found in all CSFs examined, while definite visible xanthochromia was observed in only 28% and the CSF was judged as colourless in 52% of those cases. Characteristic bleeding patterns were found spectrophotometrically in all the 20 CSFs examined within 24 hours after lumbar puncture, haematoma patterns being detected in 90-95% of the cases. In many cases the electrophoretically separated protein fractions of CSF and subdural fluids were spectrophotometrically examined. In conclusion, CSF spectrophotometry is a simple, fast, and extremely sensitive method, which in our opinion should be used routinely in the diagnosis of suspected subdural haematomas, if lumbar puncture is not contraindicated.