Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium.

Preoperative risk biomarkers for delirium may aid in identifying high-risk patients and developing intervention therapies, which would minimize the health and economic burden of postoperative delirium. Previous studies have typically used single omics approaches to identify such biomarkers. Preoperative cerebrospinal fluid (CSF) from the Healthier Postoperative Recovery study of adults ≥ 63 years old undergoing elective major orthopedic surgery was used in a matched pair delirium case-no delirium control design. We performed metabolomics and lipidomics, which were combined with our previously reported proteomics results on the same samples. Differential expression, clustering, classification, and systems biology analyses were applied to individual and combined omics datasets. Probabilistic graph models were used to identify an integrated multi-omics interaction network, which included clusters of heterogeneous omics interactions among lipids, metabolites, and proteins. The combined multi-omics signature of 25 molecules attained an AUC of 0.96 [95% CI: 0.85-1.00], showing improvement over individual omics-based classification. We conclude that multi-omics integration of preoperative CSF identifies potential risk markers for delirium and generates new insights into the complex pathways associated with delirium. With future validation, this hypotheses-generating study may serve to build robust biomarkers for delirium and improve our understanding of its pathophysiology.

Cerebrospinal Fluid Parameters Predicting Contralateral Isolated Lateral Ventricle in Adult Tuberculous Meningitis with Hydrocephalus Post-Ventriculoperitoneal Shunt.

OBJECTIVE: Hydrocephalus, a major complication in tuberculous meningitis (TBM) patients, often necessitates treatment via ventriculoperitoneal shunt (VPS). However, post-VPS, some patients develop a complication called contralateral isolated lateral ventricle (CILV), leading to persistent hydrocephalus symptoms. This study aims to evaluate cerebrospinal fluid (CSF) parameters in predicting CILV occurrence post-VPS in adult TBM patients. METHODS: A retrospective analysis was conducted, focusing on the relationship between preoperative CSF parameters and the development of CILV in 40 adult TBM patients who underwent VPS. The study compared CSF parameters from lumbar puncture after admission with those from ventricular CSF post-external ventricular drainage tube insertion. RESULTS: CILV was observed in 6 of the 40 patients following VPS. Statistical analysis showed no significant difference between the CSF parameters obtained via lumbar and ventricular punctures. Notably, the mean CSF glucose level in patients with CILV was significantly lower (1.92 mmol/L) compared to the non-CILV group (3.03 mmol/L). Conversely, the median adenosine deaminase (ADA) level in the CILV group was higher (5.69 U/L) compared to the non-CILV group (3.18 U/L). The optimal cutoff values for CSF glucose and ADA levels were 1.90 mmol/L and 4.80 U/L, respectively, with a sensitivity of 66.67% and 83.33% and a specificity of 88.24% and 79.41%. CONCLUSIONS: The study identified elevated ADA levels and decreased glucose levels in CSF as potential risk factors for CILV development in adult TBM patients post-VPS. These findings suggest the necessity for more tailored surgical approaches, in patients with altered CSF parameters to mitigate the risk of CILV.

Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.

BACKGROUND: This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery. METHODS: In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK. RESULTS: Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1ß levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses. CONCLUSION: Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.

Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.

OBJECTIVE: Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p-tau-181p, or Aß levels after non-cardiac, non-neurologic surgery in older adults. METHODS: Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6-week postoperative testing and were included in the analysis. RESULTS: There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: -1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p-tau-181p or Aß over this period. There was no change in cognitive index (mean [95% CI] 0.040 [-0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (-0.346 [-0.523, -0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p < 0.001). There were no significant correlations between preoperative to 6-week postoperative changes in cognition and CSF tau, p-tau-181p, or Aß42 changes over this interval (p > 0.05 for each). INTERPRETATION: Neurocognitive changes after non-cardiac, non-neurologic surgery in the majority of cognitively healthy, community-dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aß, tau or p-tau-181p levels or the p-tau-181p/Aß or tau/Aß ratios). TRIAL REGISTRATION: clinicaltrials.gov (NCT01993836).

Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study.

Intracranial bacterial infection remains a major cause of morbidity and mortality in neurosurgical cases. Metabolomic profiling of cerebrospinal fluid (CSF) holds great promise to gain insights into the pathogenesis of central neural system (CNS) bacterial infections. In this pilot study, we analyzed the metabolites in CSF of CNS infection patients and controls in a pseudo-targeted manner, aiming at elucidating the metabolic dysregulation in response to postoperative intracranial bacterial infection of pediatric cases. Untargeted analysis uncovered 597 metabolites, and screened out 206 differential metabolites in case of infection. Targeted verification and pathway analysis filtered out the glycolysis, amino acids metabolism and purine metabolism pathways as potential pathological pathways. These perturbed pathways are involved in the infection-induced oxidative stress and immune response. Characterization of the infection-induced metabolic changes can provide robust biomarkers of CNS bacterial infection for clinical diagnosis, novel pathways for pathological investigation, and new targets for treatment.

Phenotype, molecular characterisation and risk factors for postoperative meningitis caused by ESBL-producing-Enterobacteriaceae: a six years multi-Centre comparative cohort study.

BACKGROUND: To determine the phenotype, molecular characterisation and risk factors of postoperative meningitis induced by Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in China. METHODS: We performed a multi-centre comparative cohort study of postoperative meningitis patients infected with Enterobacteriaceae in 4 neurosurgical centres in China from January 2014 to December 2019. Phenotype and molecular characteristics of the isolates were reviewed and tested, and independent risk factors of the EPE meningitis were evaluated by binary logistic regression. RESULTS: In total, 220 Enterobacteriaceae include 78 EPE were available in this study. 85.6% (67/78) ESBL-related genes were tested, and blaSHV (14.9%) and blaSHV + blaTEM + blaCTX-M-9 (20.9%) were found to be the most frequent mono and combined ESBL-related genes harboured by Enterobacteriaceae. On binary logistic analysis, craniotomy (OR. 2.583, 95% C.I. 1.274-5.235, P = 0.008) and malignancy (OR. 2.406, 95% C.I. 1.299-4.456, P = 0.005) were the associated independent risk factors to meningitis induced by EPE. CONCLUSIONS: To the best of our knowledge, this is the largest series focusing on risk factors of EPE meningitis which has been conducted in China. Craniotomy and malignancy were independent risk factors for EPE meningitis. The risk factors identified may be further utilized in clinical practice and research to avoid and reduce the mortality in future.

Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors.

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

Higher Procalcitonin Level in Cerebrospinal Fluid than in Serum Is a Feasible Indicator for Diagnosis of Intracranial Infection.

Objective: To explore the value of the difference in procalcitonin (PCT) levels in serum and cerebrospinal fluid (CSF) for diagnosing intracranial infection in post-neurosurgical patients. Methods: Patients who were treated at our hospital after craniotomy from January 2015 to January 2019 were enrolled in this study. Twenty patients eventually diagnosed with intracranial infection were included in a study group and 22 patients with no intracranial infection were included in a control group. A t-test was used to compare the differences between serum and CSF PCT levels of PCT, and the diagnostic value of PCT was evaluated by receiver operating characteristic (ROC) curve analysis. Results: The serum PCT levels in the study and control groups were 0. 10 ± 0. 03 ng/mL and 0. 09 ± 0. 03 ng/mL, respectively, and they were not substantially different between the groups. The CSF PCT level in the study group was substantially higher than that in the control group, with values of 0. 13 ± 0. 03 ng/mL and 0. 07 ± 0. 02 ng/mL, respectively. The CSF/serum PCT ratio in the study group was substantially higher than that in the control group, with values of 1. 31 ± 0. 19 and 0. 79 ± 0. 23, respectively. The areas under the ROC curve for serum PCT, CSF PCT and the CSF/serum PCT ratio were 0. 56, 0. 92, and 0. 95, respectively, resulting in a substantial difference among the three groups. Conclusion: CSF PCT may be a valuable marker for diagnosing intracranial infection in patients after neurosurgery; in particular, the specificity of CSF PCT is higher if the CSF PCT level is higher than the serum PCT level.

The Role of Cerebrospinal Fluid Biomarkers in the Diagnosis of Post-Neurosurgical Meningitis.

AIM: To measure cytokine and lactate levels in the cerebrospinal fluid (CSF) of patients with suspected post-neurosurgical meningitis. MATERIAL AND METHODS: Interleukin (IL)-8,-12, and -13, interferon (IFN) gamma, and lactate concentrations were determined in the CSF of patients diagnosed with meningitis, who were undergoing follow-up after neurosurgical procedures at the Neurosurgery Clinic between May 2016 and November 2017. The demographic, clinical, biochemical, CSF cell count, CSF biochemistry, and CSF culture results of 119 patients were recorded. RESULTS: The study group consisted of 39 patients diagnosed with post-neurosurgical meningitis. The control group comprised of 80 patients without pleocytosis, who had undergone lumbar puncture due to various indications. In the study group, 59% of the patients had fever, 66.7% had deterioration in the level of consciousness, and 35.9% had neck stiffness. The levels of IL-8 (96.5 ng/L vs. 86.6 ng/L, p < 0.001), IL-12 (10.1 ng/L vs. 3 ng/L, p < 0.001), and lactate (5.9 mmol/L vs. 2.1 mmol/L, p < 0.001) were higher in the CSF of the patient group compared to the control group. However, IL-13 (32.7 ng/L vs. 42.5 ng/L, p=0.003) and IFN gamma (73.3 ng/L vs. 260.4 ng/L, p < 0.001) levels were lower in patients compared to controls. The mortality rate in post-neurosurgical meningitis patients was estimated to be 35.9%. CONCLUSION: Post-neurosurgical meningitis prolongs the duration of hospital stay and causes long-term sequelae. Therefore, measurement of CSF cytokine and lactate levels alongside meningitis diagnostic processes may facilitate early and accurate diagnosis. Measuring CSF lactate is inexpensive and cost effective, particularly in post-neurosurgical patients.

Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients.

BACKGROUND: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. OBJECTIVES: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. METHODS: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. RESULTS: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. CONCLUSIONS: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients.

Evaluation of Post-operative Meningitis: Comparison of Meningitis Caused by Acinetobacter spp. and Other Possible Causes.

AIM: To analyse postoperative meningitis (POM) after craniotomy, and to compare the clinical characteristics, treatment outcomes and mortality rates of POM that were caused by Acinetobacter spp. or other possible causes. MATERIAL AND METHODS: In this study, POM cases in our hospital between 2008 and 2016 were retrospectively reviewed. Cases were divided into three groups; Acinetobacter spp. meningitis (case group), non-Acinetobacter bacterial meningitis (control group 1) and culture negative meningitis (control group 2). Demographic, clinical, laboratory features, treatment modalities and mortality rates were compared between case and control groups. RESULTS: A total of 112 patients with POM were included in the study. Cerebrospinal fluid (CSF) culture results were negative in 50 (44.6%) patients; bacteria were isolated from CSF of 62 (55.3%) patients. Acinetobacter spp. was isolated from 28 (45%) patients, while bacteria other than Acinetobacter spp. were detected in 34 (55%) patients. No significant differences were observed between case and control groups in terms of age, gender, comorbidity and operation type. For the case group, change of treatment according to culture result was significantly different from control groups (p < 0.001). Mortality was 55.6% in the case group, 24.2% in control group 1 (p=0.013), and 24% in control group 2 (p=0.006). In multivariate analysis, isolation of Acinetobacter spp. from CSF culture [OR < sub > adj < /sub > 5.2, 95% confidence interval (CI):1.2-22.0, p=0.026] and inappropriate treatment (OR < sub > adj < /sub > 15.7, 95%CI:3.6-68.9, p < 0.001) were determined to be independent risk factors for mortality. CONCLUSION: Postoperative meningitis, especially caused by Acinetobacter spp., and its inappropriate empirical treatment are associated with high mortality.

CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study.

OBJECTIVE: To test the hypothesis that APOE ε4 status and cerebrospinal fluid (CSF) Aß42, T-tau and P-tau would independently predict the risk of postoperative delirium. BACKGROUND: Delirium following surgery is common and associated with adverse outcomes. Age and cognitive impairment are consistent risk factors for postoperative delirium. METHODS: This observational cohort study recruited 282 participants aged 65 years or older, without a diagnosis of dementia, admitted for primary elective hip or knee arthroplasty. Cognitive tests were undertaken preoperatively, blood and CSF were sampled at the time of spinal anesthesia, and participants were assessed daily postoperatively for delirium. RESULTS: Increasing age (P = 0.04), preoperative comorbidity (P = 0.03), type of surgery (P = 0.05), intravenous opioid usage (P = 0.04), and low CSF Aß42 (P < 0.01) were independent predictors of postoperative delirium. CONCLUSIONS: This study is the first to show an independent association between CSF Aß42 and delirium incidence in an elective surgical population, suggesting that postoperative delirium may indicate incipient Alzheimer disease.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

The combination of cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 concentrations for the diagnosis of postneurosurgical bacterial meningitis: A prospective study.

BACKGROUND: The differential diagnosis between postneurosurgical bacterial meningitis and aseptic meningitis remains challenging both for the clinician and the laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. METHODS: This prospective cohort study included patients with suspected bacterial meningitis after neurosurgery. The patients were divided into two groups according to the diagnostic criteria of meningitis involving a postneurosurgical bacterial meningitis group and a postneurosurgical aseptic meningitis group. Four biomarkers, including cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 were assayed separately, and three algorithms were constructed using a linear combination. The area under the receiver operating characteristic curve was used to compare their performances. RESULTS: A cohort of 112 patients was enrolled in our study. Forty-three patients were diagnosed with postneurosurgical bacterial meningitis, and the cerebrospinal fluid values of their biomarkers were higher in patients with postneurosurgical bacterial meningitis than with postneurosurgical aseptic meningitis. The area under the receiver operating characteristic curves for the detection of postneurosurgical bacterial meningitis were 0.803 (95% confidence interval [CI], 0.724-0.883) for procalcitonin; 0.936 (95% CI, 0.895-0.977) for lactate; 0.771 (95% CI, 0.683-0.860) for interleukin-8; 0.860 (95% CI, 0.797-0.929) for interleukin-10; 0.937 (95% CI, 0.897-0.977) for the composite two-marker test; 0.945 (95% CI, 0.908-0.982) for the composite three-marker test and 0.954 (95% CI, 0.922-0.989) for the composite of all tests. The area under the receiver operating characteristic curves of the combination tests were greater than those of the single markers. CONCLUSIONS: Combining information from several markers improved the diagnostic accuracy in detecting postneurosurgical bacterial meningitis.

Human herpesvirus 6 associated post-transplant acute limbic encephalitis: Clinical observations of biomarkers for risk of seizure in a pediatric population.

BACKGROUND: Human herpesvirus 6 (HHV6) is a cause of post-transplant acute limbic encephalitis (PALE). Seizures are associated with this disorder yet no predictive biomarkers have been identified. The objective of this study was to evaluate lab and neurodiagnostic biomarkers in patients with HHV6 associated PALE. METHODS: A retrospective chart review was performed at our institutions between 2000 and 2017. Patients were identified through a clinical database. Inclusion criteria included: age less than 18 years, HHV6 (quantitative real-time PCR or meningoencephalitis panel) tested in CSF and serum. Biomarkers of serum and CSF viral load, EEG, and MRI were reviewed along with clinical data. RESULTS: In total, 11 patients met inclusion criteria. All patients had undergone hematopoietic stem cell transplantation. Five of 11 patients had seizures as part of their clinical course, all being controlled with antiepileptic monotherapy. Seizure semiology was focal-onset in three cases and generalized in two. Neuroimaging was normal in all patients within seven days but six patients developed T2 signal intensities in the temporal lobes on repeat imaging between 14-28 days. The median CSF HHV6 viral load for all patients was 47 300 copies/mL although the median viral load was 2586 copies/mL in patients who had seizure compared to 473 969 copies/mL in those who had not (P = 0.02). Those with seizures tended to be younger (median 6.5 years compared to 11 years, P = 0.27). All patients with seizures had an EEG with 80% demonstrating abnormalities. CONCLUSION: In patients with post-hematopoietic stem cell transplant HHV6 associated PALE, lower CSF viral load may be associated with a higher likelihood to have seizures. This may indicate a primary infection as opposed to secondary reactivation phenomenon.

Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium.

BACKGROUND: Delirium is associated with new-onset dementia, suggesting that delirium pathophysiology involves neuronal injury. Neurofilament light (NFL) is a sensitive biomarker for neuroaxonal injury. METHODS: NFL was measured in cerebrospinal fluid (CSF) (n = 130), preoperative serum (n = 192), and postoperative serum (n = 280) in hip fracture patients, and in CSF (n = 123) and preoperative serum (n = 134) in cognitively normal older adults undergoing elective surgery. Delirium was diagnosed with the Confusion Assessment Method. RESULTS: Median serum NFL (pg/mL) was elevated in delirium in hip fracture patients (94 vs. 54 pre- and 135 vs. 92 postoperatively, both p < 0.001). Median CSF NFL tended to be higher in hip fracture patients with delirium (1,804 vs. 1,636, p = 0.074). Serum and CSF NFL were positively correlated (ρ = 0.56, p < 0.001). CONCLUSION: Our findings support an association between neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.