Surgical versus conservative treatment for lumbar disc herniation: a prospective cohort study.

OBJECTIVES Evidence comparing the effectiveness of surgical and conservative treatment of symptomatic lumbar disc herniation is controversial. We sought to compare short-term and long-term effectiveness of surgical and conservative treatment in sciatica symptom severity and quality of life in patients with lumbar disc herniation in a routine clinical setting. METHODS A prospective cohort study of a routine clinical practice registry consisting of 370 patients. Outcome measures were the North American Spine Society questionnaire and the 36-Item Short-Form Health Survey to assess patient-reported back pain, physical function, neurogenic symptoms and quality of life. Primary outcomes were back pain at 6 and 12 weeks. Standard open discectomy was assessed versus conservative interventions at 6, 12, 52 and 104 weeks. We filled in missing outcome variable values with multiple imputation, accounted for repeated measures within patients with mixed-effects models and adjusted baseline group differences in relevant prognostic indicators by inverse probability of treatment weighting. RESULTS Surgical treatment patients reported less back pain at 6 weeks than those receiving conservative therapy (-0.97; 95% CI -1.89 to -0.09), were more likely to report ≥50% decrease in back pain symptoms from baseline to 6 weeks (48% vs 17%, risk difference: 0.34; 95% CI 0.16 to 0.47) and reported less physical function disability at 52 weeks (-3.7; 95% CI -7.4 to -0.1). The other assessments showed minimal between-group differences with CIs, including the null effect. CONCLUSIONS Compared with conservative therapy, surgical treatment provided faster relief from back pain symptoms in patients with lumbar disc herniation, but did not show a benefit over conservative treatment in midterm and long-term follow-up

Lactate and glucose as energy substrates and their role in traumatic brain injury and therapy

Traumatic brain injury is a leading cause of disability and mortality worldwide, but no new pharmacological treatments are clinically available. A key pathophysiological development in the understanding of traumatic brain injury is the energy crisis derived from decreased cerebral blood flow, increased energy demand and mitochondrial dysfunction. Although still controversial, new findings suggest that brain cells try to cope in these conditions by metabolizing lactate as an energy substrate '‘on-demand ’ in lieu of glucose. Experimental and clinical data suggest that lactate, at least when exogenously administered, is transported from astrocytes to neurons for neuronal utilization, essentially bypassing the slow, catabolizing glycolysis process to quickly and efficiently produce ATP. Treatment strategies using systemically applied lactate have proved to be protective in various experimental traumatic brain injury studies. However, lactate has the potential to elevate oxygen consumption to high levels and, therefore, could potentially impose a danger for tissue-at-risk with low cerebral blood flow. The present review outlines the experimental basis of lactate in energy metabolism under physiological and pathophysiological conditions and presents arguments for lactate as a new therapeutical tool in human head injury

Repetitive cortical spreading depolarizations in a case of severe brain trauma

Objective and importance: Cortical spreading depolarizations (CSD) are waves of mass tissue depolarization that mediate progressive development of cortical infarction in animal models and occur in ∼50% of patients with acute brain injury. Here we performed multi-modal cerebral monitoring to investigate pathologies associated with CSD occurrence in a case of severe traumatic brain injury. Clinical presentation: A 20 years old male suffering severe traumatic brain injury from a fall had extensive frontal subdural and intraparenchymal hemorrhage with mass effect. Craniectomy was performed for hematoma evacuation and decompression. Intervention: During surgery, a subdural electrocorticography (ECoG) electrode strip, along with microdialysis and P ti O 2 probes, was placed beside injured cortex for CSD monitoring. Within 13-81 hours post-injury, 34 CSD occurred. CSD incidence increased during spontaneous hyperthermia and decreased during induced normothermia. Periods of CSD activity were also associated with low brain glucose (40 mmol/l) and lactate/pyruvate (>40), and P ti O 2 <10 mmHg. CSD caused progressive deterioration of ECoG activity only in regions with infarction at follow-up on day 27. Conclusion: Repetitive mass tissue depolarizations accompanied a negative course of hemorrhagic lesion progression in the presence of ischemic conditions after traumatic brain injury. Whether as cause or effect, CSD may represent an inherent component of progressive metabolic failure leading to tissue death, and temperature appears to be an important factor influencing their occurrence. Continuous ECoG is a valuable tool for monitoring subclinical events such as CSD and seizures and for translational research in acute brain injury mechanisms and therapeutics

Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells