Point-of-Care Cerebrospinal Fluid Detection

SLAS TECHNOLOGY: Translating Life Sciences Innovation

Cerebrospinal fluid (CSF) leaks can occur when there is communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient’s risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions postoperatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and noninvasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample be sent to a tertiary site for analysis, where days to weeks may pass before results return. To address this, our group recently developed a semiquantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-...

Clinica Chimica Acta, 2011

Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition.

The American Journal of Medicine, 1983

The cerebrosplnal fluk! Is a dynamic, metabolically active substance that has many Important functions. It Is Invaluable as a diagnostic aid In the evaluation of inflammatory conditions, infectious or noninfectious, involving the brain, spinal cord, and menlnges. The cerebrosplnal fluid may be obtained with relatlve ease with the use of lumbar puncture, but falling this, alternative techniques are available. Wfth the judlclous use of the computerized axial tomographic scan, the removal of cerebrosplnal fluid has little attendant risk. Age-related and compartmental varlatlons In chemical and cellular composition are important conslderatlons in the interpretation of results. Afteratlons in cerebrosplnal flukl constituents from different pathologic processes may be similar in certain ctrcumstances and cause Interpretation dlfflcufties.

European Journal of Neurology, 2006

A great variety of neurological diseases require investigation of cerebrospinal fluid (CSF) to prove the diagnosis or to rule out relevant differential diagnoses. The objectives were to evaluate the theoretical background and provide guidelines for clinical use in routine CSF analysis including total protein, albumin, immunoglobulins, glucose, lactate, cell count, cytological staining, and investigation of infectious CSF. The methods included a Systematic Medline search for the above-mentioned variables and review of appropriate publications by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. It is recommended that CSF should be analysed immediately after collection. If storage is needed 12 ml of CSF should be partitioned into three to four sterile tubes. Albumin CSF/serum ratio (Q alb ) should be preferred to total protein measurement and normal upper limits should be related to patientsÕ age. Elevated Q alb is a non-specific finding but occurs mainly in bacterial, cryptococcal, and tuberculous meningitis, leptomingeal metastases as well as acute and chronic demyelinating polyneuropathies. Pathological decrease of the CSF/serum glucose ratio or increased lactate concentration indicates bacterial or fungal meningitis or leptomeningeal metastases. Intrathecal immunoglobulin G synthesis is best demonstrated by isoelectric focusing followed by specific staining. Cellular morphology (cytological staining) should be evaluated whenever pleocytosis is found or leptomeningeal metastases or pathological bleeding is suspected. Computed tomography-negative intrathecal bleeding should be investigated by bilirubin detection.

Otolaryngologic Clinics of North America, 2005

Cerebrospinal fluid (CSF) leakage is a rare but potentially lifethreatening condition that requires thorough and timely intervention. It occurs when the barriers retaining CSF around the brain are breached. Otorrhea occurs only when there is violation of these barriers within the temporal bone. Thus, there is breach of the arachnoid membrane, dura mater, bone, and mucosal lining of the mastoid and middle ear. To complete the route of egress there must be a defect in the external auditory canal or perforation of the tympanic membrane. If this defect is not present, CSF, once in the middle ear cleft, can flow down the eustachian tube and present as otorhinorrhea. A physician therefore must remember that rhinorrhea does not always come from the anterior skull base and must be vigilant for an otologic cause. In this article, CSF leaks are categorized as either nontraumatic or traumatic. The article explains the physiology of the milieu of CSF that surrounds the brain and spinal cord. It then discusses the detection, assessment, causes, clinical presentation, and management related to clinical pathologies. Physiology The bulk of the CSF is formed in the choroid plexuses of the lateral and, to a lesser extent, in the third and fourth ventricles. The remainder of the intracranial production occurs in the interstitial space. Extrachoroidal production occurs in the ventricular ependyma, and some CSF may be derived from the capillaries on the surface of the brain and spinal medulla.

An Easy Guide for Practical Biochemistry, 2018

Cerebrospinal fluid analysis Cerebrospinal fluid (CSF) analysis is a set of laboratory tests that examine a sample of the fluid surrounding the brain and spinal cord. This fluid is an ultrafiltrate of plasma. It is clear and colorless. It contains glucose, electrolytes, amino acids, and other small molecules found in plasma, but has very little protein and few cells. CSF protects the central nervous system from injury, cushions it from the surrounding bone structure, provides it with nutrients, and removes waste products by returning them to the blood. CSF is withdrawn from the subarachnoid space through a needle by a procedure called a lumbar puncture or spinal tap. CSF analysis includes tests in clinical chemistry, hematology, immunology, and microbiology. Usually three or four tubes are collected. The first tube is used for chemical and/or serological analysis and the last two tubes are used for hematology and microbiology tests. This reduces the chances of a falsely elevated white cell count caused by a traumatic tap (bleeding into the subarachnoid space at the puncture site), and contamination of the bacterial culture by skin germs or flora.

Journal of Neurosurgery, 2016

OBJECT The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown. METHODS A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined. RESULTS Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% ...

Acta Otorhinolaryngologica Italica, 2021

Cerebrospinal fluid (CSF) leak remains a rare condition, characterized by serious complications and potentially fatal. According to different etiologies, CSF leaks may be classified into two main categories: traumatic and spontaneous. Spontaneous fistulas seem to be mainly related to obesity and idiopathic intracranial hypertension. Diagnosis is both clinical and radiological. During the last three decades, surgical treatment has mostly shifted to endonasal endoscopic approach, which widely demonstrated to be more effective than invasive intracranial ones. Post-operative complications, long-term sequelae and hospital stay are strongly reduced thanks to endoscopic approach. The diagnosis and treatment of CSF leaks represent a difficult and challenge task. The main effort seems to be related to the precise localization of the leak. An accurate assessment of both predisposing factors and comorbidities is mandatory in case of spontaneous leaks. However, a clinical multidisciplinary evaluation as well as treatment, is essential to decrease the rate of failure of surgery. The presence of a dedicated instruments, the Skull Base Team, the knowledge of reconstructive materials and techniques represents a decisive result in therapeutical management even if for each patient an effective therapeutic algorithm can be obtained considering the correct leak detection and characteristics. In conclusion the strict teamwork with neurosurgeons, neuroradiologists, ophtalmologists will enable the development also of innovative biomaterials, which could spread and standardize multi-layer techniques, nowadays still related to surgeon preferences.

International Forum of Allergy & Rhinology, 2011

The association of spontaneous cerebrospinal fluid (CSF) leaks with increased intracranial pressure (ICP) is well-documented. Accurate assessment of CSF pressure is paramount to optimal long-term outcomes, as failure of surgical repair or recurrent leaks may be associated with untreated intracranial hypertension. Many surgeons utilize a single opening pressure measured at the onset of the surgical procedure to determine if long-term acetazolamide or shunt placement will be necessary. However, preoperative measurement of CSF pressure may be inaccurate secondary to active drainage. The purpose of this study is to determine the accuracy of preoperative CSF pressure measurement in the se ing of active CSF rhinorrhea.

European Handbook of Neurological Management, 2006

Background A great variety of neurological diseases require investigation of the cerebrospinal fluid (CSF) to prove the diagnosis or to rule out relevant differential diagnoses. Objectives To evaluate the theoretical background and provide guidelines for clinical use in routine CSF analysis including total protein, albumin, immunoglobulins, glucose, lactate, cell count, cytological staining, and investigation of infectious CSF. Methods Systematic Medline search for the above mentioned variables. Review of appropriate publications by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. CSF should be analysed immediately after collection. If storage is needed 12 ml of CSF should be partitioned into three to four sterile tubes.