Abstract
BackgroundThe cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood–cerebrospinal fluid barrier (B-CSF-B) permeability. For years QAlb was considered only as an age-related parameter but recently it has also been associated to sex. The aim of the present study was to explore the impact of sex in the determination of B-CSF-B dysfunction.MethodsThe analysis was retrospectively conducted on subjects consecutively admitted to the neurological ward. CSF and serum albumin levels were measured by immunonephelometry and pathological QAlb thresholds were considered: 6.5 under 40 years, 8.0 in the age 40–60 and 9.0 over 60 years.Results1209 subjects were included in the study. 718 females and 491 males (age: 15–88 years): 24.6% of patients had a diagnosis of multiple sclerosis, 23.2% suffered from other inflammatory neurological diseases, 24.6% were affected by non-inflammatory neurological diseases, and for 27.6% of patients the final neurological diagnosis could not be traced. Dysfunctional B-CSF-B was detected more frequently (44 vs. 20.1%, p < 0.0001) and median QAlb value were higher (7.18 vs. 4.87, p < 0.0001) in males than in females in the overall study population and in all disease subgroups. QAlb and age were positively correlated both in female (p < 0.0001) and male (p < 0.0001) patients, however the slopes of the two regression lines were not significantly different (p = 0.7149), while the difference between the elevations was extremely significant (p < 0.0001) with a gap of 2.2 units between the two sexes. Finally, in a multivariable linear regression analysis increased age and male sex were independently associated with higher QAlb in the overall study population (both p < 0.001) and after stratification by age and disease group.ConclusionsAccordingly, identification and validation of sex-targeted QAlb thresholds should be considered as a novel tool in an effort to achieve more precision in the medical approach.
Highlights
The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood–cerebrospinal fluid barrier (B-CSF-B) permeability
Albumin is produced in the liver and is not catabolised within the central nervous system (CNS), and it is generally thought that all albumin measured in CSF is of plasma derivation [6], there is some evidence that glial cells can produce albumin [7]
Patients characteristics The study was conducted on 1209 individuals, 718 women and 491 men, aged between 15 and 88 years: 297 (24.6%) patients had a diagnosis of multiple sclerosis (MS), 281 (23.2%) suffered from other inflammatory neurological diseases (OIND), 297 (24.6%) were affected by non-inflammatory neurological diseases (NIND), and for 334 (27.6%) the definite neurological diagnosis could not be traced (UNK)
Summary
The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood–cerebrospinal fluid barrier (B-CSF-B) permeability. Brain homeostasis is maintained by means of two different barriers: the blood–cerebrospinal fluid (CSF) barrier (B-CSF-B) formed by the choroid plexus epithelial cell, Castellazzi et al Fluids Barriers CNS (2020) 17:14 and the blood–brain barrier (BBB) formed by the cerebral blood vessel endothelium [1, 2]. Since both barriers are in chemical–physical equilibrium with each other and functionally overlap, the term ‘BBB’ is most commonly used to refer to the entire functional system separating blood from CSF and nervous tissue [3]. While the dependence between QAlb and age is clear [15], evidence of sex-related differences is less explored [16]
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