1. Comparison of serum cytokine concentrations in patients with acute sciatica secondary to lumbar disc herniation choosing surgery with those choosing nonoperative treatment

BACKGROUND CONTEXT The interpretation of research studies comparing clinical outcomes from surgical and nonoperative treatment of patients with acute sciatica secondary to herniated nucleus pulposus (AS/ HNP) remain controversial. Recent studies have concluded that a subset of AS/HNP patients have identifiable biological characteristics that may predict favorable clinical nonoperative treatment outcomes. The mechanism of spinal nerve root injury associated with AS/HNP is mediated at least in part, through an acute inflammatory response that involves the up regulation of specific inflammatory cytokines (eg, TNFα, IL-1β, IL-8 and RANTES). Serum concentrations of these key cytokines measured at standardized points in the clinical course of AS/HNP patients have potential early predictive value in determining favorable clinical outcomes from nonoperative care. PURPOSE To compare serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES in AS/HNP patients who elected to have surgery with those who chose nonoperative care. STUDY DESIGN/SETTING Prospective cohort. PATIENT SAMPLE Inclusion: AS/HNP of less than 16 weeks duration who declined a selective nerve root steroid injection; spinal nerve root motor score of >3/5; McCulloch score of 5/5 Exclusion: red flag condition; prior lumbar surgery; other active inflammatory diseases. OUTCOME MEASURES Serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES at baseline, 6, 12 and 24 weeks post baseline. METHODS Patients meeting the inclusion and exclusion criteria were recruited to the study through an Acute Disc Clinic in a hospital-based spine program outpatient clinic. After providing informed consent, blood samples were obtained by venipuncture (baseline) and at 6, 12 and 24 weeks post baseline. Serum cytokine concentrations were measured by ELISA immunoassay. Patient preference to have surgery or nonoperative treatment was recorded. Patient use of oral medications, including NSAIDS was recorded at each data collection date. Research ethics approval was obtained. RESULTS Forty patients were enrolled over a period of 18 months, with 24 electing to undergo laminectomy discectomy surgery. Time of surgery from baseline ranged from 11-14 weeks. 6/40 patients reporting taking oral NSAIDS for less than one week in total for the duration of the study. At 24 weeks post baseline, 8/40 patients reported persisting thigh symptoms and 2/40 patients reported symptoms below the knee and had positive nerve root tension signs. Degree of up regulation of serum levels concentrations of TNFα, IL-1β, IL-8 and RANTES concentrations (pg/ml) at each data collection point were compared to 24-week levels for each patient. In patients 22/24 electing to undergo surgery, RANTES and IL-1β concentrations were increased 10-14fold compared to asymptomatic (ie, 24 week) levels, and in 13/16 patients by 5-7fold in patients choosing nonoperative care. TNFα concentrations were increased by 3-5fold in both surgical and nonoperative groups at baseline. Elevated concentrations of RANTES and IL-1β were maintained or were increased at 6 weeks post baseline in the same 22/24 patients undergoing surgery and diminished by an average of 28% in the same 13/16 patients electing to have nonoperative treatment. CONCLUSIONS In this study population, patients with highly up regulated baseline serum concentrations of RANTES and IL-1β that did not diminish at 6 weeks post baseline were associated with patient treatment choice to have surgery. TNFα serum concentrations were not associated with patient treatment preference. A larger scale study is required to further investigate these findings. Funded by a research grant from the National Institutes of Health, Bethesda, MD, USA. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. The interpretation of research studies comparing clinical outcomes from surgical and nonoperative treatment of patients with acute sciatica secondary to herniated nucleus pulposus (AS/ HNP) remain controversial. Recent studies have concluded that a subset of AS/HNP patients have identifiable biological characteristics that may predict favorable clinical nonoperative treatment outcomes. The mechanism of spinal nerve root injury associated with AS/HNP is mediated at least in part, through an acute inflammatory response that involves the up regulation of specific inflammatory cytokines (eg, TNFα, IL-1β, IL-8 and RANTES). Serum concentrations of these key cytokines measured at standardized points in the clinical course of AS/HNP patients have potential early predictive value in determining favorable clinical outcomes from nonoperative care. To compare serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES in AS/HNP patients who elected to have surgery with those who chose nonoperative care. Prospective cohort. Inclusion: AS/HNP of less than 16 weeks duration who declined a selective nerve root steroid injection; spinal nerve root motor score of >3/5; McCulloch score of 5/5 Exclusion: red flag condition; prior lumbar surgery; other active inflammatory diseases. Serum concentrations and patterns of up regulation of TNFα, IL-1β, IL-8 and RANTES at baseline, 6, 12 and 24 weeks post baseline. Patients meeting the inclusion and exclusion criteria were recruited to the study through an Acute Disc Clinic in a hospital-based spine program outpatient clinic. After providing informed consent, blood samples were obtained by venipuncture (baseline) and at 6, 12 and 24 weeks post baseline. Serum cytokine concentrations were measured by ELISA immunoassay. Patient preference to have surgery or nonoperative treatment was recorded. Patient use of oral medications, including NSAIDS was recorded at each data collection date. Research ethics approval was obtained. Forty patients were enrolled over a period of 18 months, with 24 electing to undergo laminectomy discectomy surgery. Time of surgery from baseline ranged from 11-14 weeks. 6/40 patients reporting taking oral NSAIDS for less than one week in total for the duration of the study. At 24 weeks post baseline, 8/40 patients reported persisting thigh symptoms and 2/40 patients reported symptoms below the knee and had positive nerve root tension signs. Degree of up regulation of serum levels concentrations of TNFα, IL-1β, IL-8 and RANTES concentrations (pg/ml) at each data collection point were compared to 24-week levels for each patient. In patients 22/24 electing to undergo surgery, RANTES and IL-1β concentrations were increased 10-14fold compared to asymptomatic (ie, 24 week) levels, and in 13/16 patients by 5-7fold in patients choosing nonoperative care. TNFα concentrations were increased by 3-5fold in both surgical and nonoperative groups at baseline. Elevated concentrations of RANTES and IL-1β were maintained or were increased at 6 weeks post baseline in the same 22/24 patients undergoing surgery and diminished by an average of 28% in the same 13/16 patients electing to have nonoperative treatment. In this study population, patients with highly up regulated baseline serum concentrations of RANTES and IL-1β that did not diminish at 6 weeks post baseline were associated with patient treatment choice to have surgery. TNFα serum concentrations were not associated with patient treatment preference. A larger scale study is required to further investigate these findings. Funded by a research grant from the National Institutes of Health, Bethesda, MD, USA.