Inflammatory cerebrospinal fluid markers in schizophrenia spectrum disorders: A systematic review and meta-analysis of 69 studies with 5710 participants.

BACKGROUND: There is increasing evidence of immune dysregulation and neuroinflammation occurring in schizophrenia. The aim of this study is to combine studies on routine CSF parameters, as well as cytokines and inflammatory proteins, in individuals with schizophrenia spectrum disorders. METHODS: CSF parameters were summated and inverse variance meta-analyses using a random effects model were performed comparing mean difference or odds ratios. Between study heterogeneity was assessed using the I2 statistic. Quality assessment and sensitivity analyses were performed. RESULTS: There were 69 studies of 5710 participants, including 3180 individuals with schizophrenia spectrum disorders. Averaged CSF parameters were within normal limits, however, between 3.1 % and 23.5 % of individual cases with schizophrenia spectrum disorders had an abnormal CSF result: Protein (abnormal in 23.5 % cases), albumin (in 18.5 %), presence of oligoclonal bands (in 9.3 %), white blood cell count (in 3.6 %), and IgG levels (3.1 %). Meta-analysis of 55 studies with non-psychiatric controls demonstrated a significant increase in CSF total protein (MD: 3.50, CI: 0.12-6.87), albumin ratio (MD: 0.55, CI: 0.02-0.09), white cell count (MD: 0.25, CI: 0.05-0.46), IL-6 (SMD: 0.53, CI: 0.29 to 0.77) and IL-8 (SMD: 0.56, CI: 0.11 to 1.01). Sensitivity analysis did not alter findings. CONCLUSION: Abnormal CSF parameters, cytokines and inflammatory proteins were found in a significant proportion of individuals with schizophrenia spectrum disorders. This may indicate alterations to blood brain barrier function and permeability, CSF flow dynamics or neuroinflammation. Further research is needed to explore these potential mechanisms.

Does a single dose of intravenous dexamethasone reduce Symptoms in Emergency department patients with low Back pain and RAdiculopathy (SEBRA)? A double-blind randomised controlled trial.

OBJECTIVE: To assess the effect of a single dose of intravenous dexamethasone in addition to routine treatment on visual analogue scale (VAS) pain scores at 24 h in emergency department (ED) patients with low back pain with radiculopathy (LBPR). METHODS: Double-blind randomised controlled trial of 58 adult ED patients with LBPR, conducted in one tertiary and one urban ED. The intervention was 8 mg of intravenous dexamethasone (or placebo) in addition to current routine care. The primary outcome was the change in VAS pain scores between presentation and 24 h. Secondary outcomes included VAS pain scores at 6 weeks, ED length of stay (EDLOS), straight leg raise (SLR) angles and Oswestry functional scores. RESULTS: Patients treated with dexamethasone had a 1.86 point (95% CI 0.31 to 3.42, p=0.019) greater reduction in VAS pain scores at 24 h than placebo (dexamethasone: -2.63 (95% CI -3.63 to -1.63) versus placebo: -0.77 (95% CI -2.04 to 0.51)). At 6 weeks, both groups had similar significant and sustained decrease in VAS scores compared with baseline. Patients receiving dexamethasone had a significantly shorter EDLOS (median: 3.5 h vs 18.8 h, p=0.049) and improved SLR angle at discharge (14.7°, p=0.040). There was no difference in functional scores. CONCLUSIONS: In patients with LBPR, a single dose of intravenous dexamethasone in addition to routine management improved VAS pain scores at 24 h, but this effect was not statistically significant at 6 weeks. Dexamethasone may reduce EDLOS and can be considered as a safe adjunct to standard treatment. TRIAL REGISTRATION NUMBER: ACTRN12611001020976.