A Survey of Cerebrospinal Fluid Total Protein Upper Limits in Canada: Time for an Update?

Abstract

ABSTRACT:Background: The antiquated standard reference range of 0.15–0.45 g/L for cerebrospinal fluid total protein (CSF-TP) is well entrenched in medical literature and laboratory operating procedures across the world. Methods: We conducted a web-based survey with a response rate of 34.9% through the listserv of the Canadian Neurological Sciences Federation. Additional laboratory reference data were collated by telephone interview of hospital laboratory technologists across Canada. Results: A total of 142 site responses were obtained: 64.1% from academic/tertiary hospitals and 35.9% from community hospitals. A strong majority (80.4%) of both types of institutions reported using a CSF-TP upper reference limit of 0.45 g/L or less. As a rule, no age adjustments were implemented in CSF-TP-level interpretation. Conclusions: Recent well-powered laboratory reference studies have documented CSF-TP upper reference limits that are above 0.6 g/L starting at age 50, with incremental limits partitioned by subsequent decades of age. The conventional 0.45 g/L limit could lead to false positive results. Our survey suggests there is a need to consider a wide adoption of data-driven, rather than historical, reference values.

Cerebrospinal Fluid Protein Concentration in Healthy Older Japanese Volunteers

“…The current gold standard, the reference range of 15-45 mg/dL (0.15-0.45 g/L) for lumbar CSF-TP dates back to 1938, and it has been adopted for a wide range of population for almost a century [1,2]. However, recent Western studies have started to report that the concentration of CSF-TP in adults is considered to increase gradually with age, and the concentrations in the older population are significantly higher than the current standard upper reference limit [1,[3][4][5].…”

“…To our knowledge, only two studies have reported on CSF-TP in Japanese patients, but these were presented over 30 years ago [11,12]. Since the CSF measuring methods and the accuracy of testing have been greatly improved in the past decades, it is crucial to review the CSF-TP reference interval for various populations [2,11,12]. In addition, even though the available data from a healthy population are often limited [1,3,6,13] because of the invasive nature and the potential risks of the sampling procedure, using the data of healthy subjects is desirable to properly interpret the laboratory data [14].…”

Cerebrospinal Fluid Protein Concentration in Japanese Healthy Older Volunteers

“…Worldwide, the concentration of cerebrospinal fluid total protein (CSF-TP) is used for the diagnosis of various life-threatening neurological emergencies, such as infectious, inflammatory, and immune diseases of the central/peripheral nervous systems; thus, a valid reference interval of CSF-TP concentrations is crucial for precise diagnosis and treatment. The current gold standard, the reference range of 15-45 mg/dL (0.15-0.45 g/L) for lumbar CSF-TP dates back to 1938, and it has been adopted for a wide range of population for almost a century [1,2]. However, recent Western studies have started to report that the concentration of CSF-TP in adults is considered to increase gradually with age, and the concentrations in the older population are significantly higher than the current standard upper reference limit [1,[3][4][5].…”