Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway

Aims/hypothesis: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. Methods: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. Results: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. Conclusions/interpretation: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities. Graphical abstract: [Figure not available: see fulltext.

The Anaesthetic Biobank of Cerebrospinal fluid:a unique repository for neuroscientific biomarker research

Background: The pathophysiology of numerous central nervous system disorders remains poorly understood. Biomarker research using cerebrospinal fluid (CSF) is a promising way to illuminate the neurobiology of neuropsychiatric disorders. CSF biomarker studies performed so far generally included patients with neurodegenerative diseases without an adequate control group. The Anaesthetic Biobank of Cerebrospinal fluid (ABC) was established to address this. The aims are to (I) provide healthy-control reference values for CSF-based biomarkers, and (II) to investigate associations between CSF-based candidate biomarkers and neuropsychiatric symptoms.&amp; nbsp; &amp; nbsp;Methods: In this cross-sectional study, we collect and store CSF and blood from adult patients undergoing spinal anaesthesia for elective surgery. Blood (20.5 mL) is collected during intravenous cannulation and CSF (10 mL) is aspirated prior to intrathecal local anaesthetic injection. A portion of the blood and CSF is sent for routine laboratory analyses, the remaining material is stored at &amp; minus;80 ?. Relevant clinical, surgical and anaesthetic data are registered. A neurological examination and Montreal Cognitive Assessment (MoCA) are performed pre-operatively and a subset of patients fill in questionnaires on somatic and mental health (depression, anxiety and stress).&amp; nbsp; Results: Four-hundred-fifty patients (58% male; median age: 56 years) have been enrolled in the ABC. The planned spinal anaesthetic procedure was not attempted for various reasons in eleven patients, in fourteen patients the spinal puncture failed and in twelve patients CSF aspiration was unsuccessful. A mean of 9.3 mL CSF was obtained in the remaining 413 of patients. Most patients had a minor medical history and 60% scored in the normal range on the MoCA (median score: 26).&amp; nbsp; Conclusions: The ABC is an ongoing biobanking project that can contribute to CSF-based biomarker research. The large sample size with constant sampling methods and extensive patient phenotyping provide excellent conditions for future neuroscientific research.</p

The Anaesthetic Biobank Of Cerebrospinal Fluid: A Repository For Neuroscientific Research

Background: The pathophysiology of numerous central nervous system disorders remains poorly understood. Biochemical analyses of cerebrospinal fluid (CSF) may identify novel biomarkers and help illuminate the neurobiology of common neuropsychiatric disorders. Studies of CSF biomarkers have so far generally included small numbers of patients with neurodegenerative diseases without adequate control groups. The Anaesthetic Biobank of Cerebrospinal Fluid (ABC) is an ongoing project in which we are storing CSF collected from patients undergoing spinal anaesthesia, a relatively neurologically healthy population. Our aim is to provide reference values for CSF-based biomarkers and to investigate associations between candidate markers and neuropsychiatric symptoms. We here present our methods and initial technical results.Methods: All patients ≥ 18 years scheduled for elective surgery under spinal anaesthesia are invited to participate, except for patients scheduled for caesarean section. A Montreal Cognitive Assessment (MoCA) and screening neurological examination are performed preoperatively. During intravenous cannulation, 20 ml blood is collected. During the spinal puncture, prior to intrathecal local anaesthetic administration, 10 ml of CSF is aspirated. Sensory block height is measured 10 minutes after spinal injection. A portion of the blood and the first 2 ml of CSF is sent for routine laboratory analyses. The remaining material is stored at -80°C. Relevant clinical, surgical and anaesthetic data are registered. A subset of patients have completed questionnaires on somatic and mental health (depression, anxiety and stress).Results: Four-hundred-fifty patients (58% male; median age: 56 years, IQR: 37 - 67) were enrolled between October 2016 and March 2020. Body mass index (BMI) ranged from 18 to 51 with a median of 27 kg/m2. Almost half of patients were ASA status I and were discharged home on the day of surgery. MoCA scores ranged from 14 to 30 and 60% of patients had a MoCA score ≥ 26. Blood was collected in 445 (99%) of patients. The planned spinal anesthetic procedure was not attempted for various reasons in eleven patients, in fourteen patients the spinal puncture failed and in twelve patients CSF aspiration was unsuccessful. In the remaining 413 patients, mean CSF volume aspirated was 9.3mL (range 0.1 - 13.0). CSF aspiration required a mean (range) of 2 minutes (1 - 10). A vasovagal response occurred in 7% of all patients, the spinal block was insufficient in 3% of patients and post-dural puncture headache was reported for 3 patients. Median (IQR) [range] block height was T8 (T6 - T10) [L5 - C4]. Type of local anaesthetic used had a significant effect on the extent of block (isobaric bupivacaine T6, hyperbaric bupivacaine T8, hyperbaric prilocaine T9; p&lt;0.001).Conclusion: Banking of CSF from a surgical population is ongoing and feasible and does not appear to pose any significant additional risks to participating patients as sensory block height and the incidence of complications were consistent with that reported in earlier studies. Our large sample size, standardized sampling methods and extensive patient phenotyping provide excellent conditions for future neuroscientific research. So far, we are studying the relationships among CSF biochemistry and block height, and also with depression scores, and remain open to suggestions for collaborations with other interested groups.Copyright © 2020 American Society of Anesthesiologist