Koleske Joshua P, Pan Shelei, Meehan Thanda, Loe Maren, Morales Diego M, Lucey Brendan P, Musiek Erik, Strahle Jennifer M
Department of Neurosurgery, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Department of Neurology, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA.
Fluids Barriers CNS. 2025 Oct 16;22(1):102. doi: 10.1186/s12987-025-00686-1.
Known circadian variations in cerebrospinal fluid (CSF) flow and composition include fluctuations in electrolytes, hormones, and neurotransmitters. However, how commonly measured CSF constituents, such as protein and glucose, vary by time-of-day is understudied. Here, we identify and compare time-of-day differences in CSF protein and glucose from patients who underwent CSF collection during clinical care.
Patients with CSF collected between June 2018 and May 2023 at thirteen hospitals within our institution's health system were identified. Clinical, demographic and laboratory results were recorded. CSF results were divided into 1- and 4-hour intervals based on time-of-day and patient age. Patients were excluded if there was evidence of CSF infection, bleeding, as well as age criteria excluding neonates. One-way ANOVA with post-hoc Tukey was used to analyze differences between means.
15,272 patients underwent 26,397 CSF collection encounters. After exclusion, 8,210 CSF glucose and 10,103 CSF protein values remained. The CSF/blood glucose ratio showed time-of-day fluctuations; the mean ratio was higher from 00:00-04:00 (0.660), 04:00-08:00 (0.651), 16:00-20:00 (0.619), and 20:00-00:00 (0.633) than from 08:00-12:00 (0.588) and 12:00-16:00 (0.599). This pattern was also observed when dividing the time-of-day into 1-hour intervals and in every age cohort except patients 80 years and older. Children also exhibited time-of-day differences in CSF/blood glucose ratios, but the phase of their time-of-day pattern is shifted earlier to peak at 00:00-04:00. No clear time-of-day patterns were observed for CSF protein; however there was a significant association of age with CSF protein (R = 0.2182). There were no meaningful differences in CSF protein by time-of-day after separating patients by age.
Higher CSF glucose from 00:00-08:00 and 16:00-00:00 compared to 08:00-16:00 suggests diurnal fluctuations which may be driven by a circadian rhythm. A higher CSF protein concentration was strongly associated with increasing age, without clear time-of-day variations. These results have implications for clinical interpretation and future research of the role of CSF in health and disease.
已知脑脊液（CSF）流量和成分存在昼夜节律变化，包括电解质、激素和神经递质的波动。然而，蛋白质和葡萄糖等常用测量的脑脊液成分如何随一天中的时间变化尚未得到充分研究。在这里，我们识别并比较了在临床护理期间接受脑脊液采集的患者脑脊液蛋白质和葡萄糖的昼夜差异。
确定在我们机构医疗系统内的13家医院于2018年6月至2023年5月期间采集脑脊液的患者。记录临床、人口统计学和实验室结果。根据一天中的时间和患者年龄，将脑脊液结果分为1小时和4小时间隔。如果有脑脊液感染、出血的证据以及排除新生儿的年龄标准，则排除患者。使用带有事后Tukey检验的单因素方差分析来分析均值之间的差异。
15272名患者接受了26397次脑脊液采集。排除后，仍有8210个脑脊液葡萄糖值和10103个脑脊液蛋白质值。脑脊液/血糖比值显示出昼夜波动；00:00 - 04:00（0.660）、04:00 - 08:00（0.651）、16:00 - 20:00（0.619）和20:00 - 00:00（0.633）的平均比值高于08:00 - 12:00（0.588）和12:00 - 16:00（0.599）。当将一天中的时间分为1小时间隔时以及在除80岁及以上患者外的每个年龄组中也观察到了这种模式。儿童的脑脊液/血糖比值也表现出昼夜差异，但其昼夜模式的相位提前至00:00 - 04:00达到峰值。未观察到脑脊液蛋白质的明显昼夜模式；然而，年龄与脑脊液蛋白质存在显著关联（R = 0.2182）。按年龄对患者进行分组后，脑脊液蛋白质在一天中的时间上没有有意义的差异。
与08:00 - 16:00相比，00:00 - 08:00和16:00 - 00:00的脑脊液葡萄糖较高，表明昼夜波动可能由昼夜节律驱动。脑脊液蛋白质浓度较高与年龄增加密切相关，没有明显的昼夜变化。这些结果对脑脊液在健康和疾病中的作用的临床解释和未来研究具有启示意义。
