The incidence of acute and chronic spinal cord injury (SCI) in the United States is more than 10,000 per year, resulting in 720 cases per million persons enduring permanent disability each year. The economic impact of SCI is estimated to be more than 4 billion dollars annually. Preclinical studies, case reports, and small clinical trials suggest that early treatment may improve neurological recovery. To date, no proven therapeutic modality exists that has demonstrated a positive effect on neurological outcome. Emerging data from recent preclinical and clinical studies offer hope for this devastating condition. This review gives an overview of current basic research and clinical studies for the treatment of SCI.

STUDY DESIGN.: Retrospective cohort study. OBJECTIVE.: To identify predictors of early mortality following traumatic spinal cord injury (TSCI). SUMMARY OF BACKGROUND DATA.: Limited information is available on factors associated with early mortality following TSCI. Ability to identify high risk individuals can help to appropriately treat them, and reduce mortality. METHODS.: Early mortality was defined as death occurring during the initial hospital admission. Retrospective analysis of 1995 patients with TSCI, admitted to various hospitals of South Carolina from 1993 to 2003, was performed. There were 251 patients with early mortality. Multivariable logistic regression was used in modeling of early death following TSCI with gender, race, age, Frankel grade, trauma center, level of injury, injury severity score (ISS), traumatic brain injury (TBI), and medical comorbidities as covariates. RESULTS.: Increasing age after 20 years (OR: 1.2, P = <0.0001), male gender (OR: 1.6, P = 0.016), severe (ISS > or =15) systemic injuries (OR: 1.9, P = 0.012), TBI (OR: 3.7, P < 0.0001), 1 or more comorbidities (P < 0.0001), poor neurologic status (P = 0.015), and level 1 trauma center (OR: 1.4, P = 0.026) were significantly associated with early mortality, after adjusting for other covariates. CONCLUSION.: Early mortality following TSCI is influenced by multiple factors. Timely recognition of these factors is crucial for improving survival in the acute care setting. Severe systemic injuries, medical comorbidities, and TBI continue to be the main limiting factors affecting the outcome. These findings also suggest the need to allocate resources for trauma prevention, and promote research towards improving the care of acutely injured patients.

Loss of motoneurons may underlie some of the deficits in motor function associated with CNS injuries and diseases. We tested whether melatonin, a potent antioxidant and free radical scavenger, would prevent motoneuron apoptosis following exposure to toxins and whether this neuroprotection is mediated by melatonin receptors. Exposure of VSC4.1 motoneurons to either 50 μM H 2 O 2 , 25 μM glutamate (LGA), or 50 ng/ml tumor necrosis factor-alpha (TNF-α) for 24 h caused significant increases in apoptosis, as determined by Wright staining and ApopTag assay. Analyses of mRNA and proteins showed increased expression and activities of stress kinases and cysteine proteases and loss of mitochondrial membrane potential during apoptosis. These insults also caused increases in intracellular free [Ca 2+ ] and activities of calpain and caspases. Cells exposed to stress stimuli for 15 min were then treated with 200 nM melatonin. Post-treatment of cells with melatonin attenuated production of reactive oxygen species (ROS) and phosphorylation of p38, MAPK, and JNK1, prevented cell death, and maintained whole-cell membrane potential, indicating functional neuroprotection. Melatonin receptors (MT1 and MT2) were upregulated following treatment with melatonin. To confirm the involvement of MT1 and MT2 in providing neuroprotection, cells were post-treated (20 min) with 10 μM luzindole (melatonin receptor antagonist). Luzindole significantly attenuated melatonin-induced neuroprotection, suggesting that melatonin worked, at least in part, via its receptors to prevent VSC4.1 motoneuron apoptosis. Results suggest that neuroprotection rendered by melatonin to motoneurons is receptor mediated and melatonin may be an effective neuroprotective agent to attenuate motoneuron death in CNS injuries and diseases.

Additional FGR increased completeness of resection and enabled more consistent resections between cases.

Fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have previously been investigated separately with the objectives, respectively, of increasing the extent of brain tumour resection and of selectively destroying residual tumour post-resection. Both techniques have demonstrated trends towards improved survival, pre-clinically and clinically. We hypothesize that combining these techniques will further delay tumour re-growth. In order to demonstrate technical feasibility, we here evaluate fluorescence imaging and PDT treatment techniques in a specific intracranial tumour model. The model was the VX2 carcinoma grown by injection of tumour cells into the normal rabbit brain. An operating microscope was used for white light imaging and a custom-built fluorescence imaging system with co-axial excitation and detection was used for FGR. PDT treatment light was applied by intracranially-implanted light emitting diodes (LED). The fluorescent photosensitizer used for both FGR and PDT was ALA-induced PpIX. For PDT, ALA (100 mg kg(-1)) and low light doses (15 and 30 J) were administered over extended periods, which we refer to as metronomic PDT (mPDT). Eighteen tumour bearing rabbits were divided equally into three groups: controls (no resection); FGR; and FGR followed by mPDT. Histological whole brain sections (H&E stain) showed primary and recurrent tumours. No bacteriological infections were found by Gram staining. Selective tumour cell death through mPDT-induced apoptosis was demonstrated by TUNEL stain. These results demonstrate that the combined treatment is technically feasible and this model is a candidate to evaluate it. Further optimization of mPDT treatment parameters (drug/light dose rates) is required to improve survival.