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

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.