Systemic manifestations of traumatic brain injury.

Traumatic brain injury (TBI) affects functioning of various organ systems in the absence of concomitant non-neurologic organ injury or systemic infection. The systemic manifestations of TBI can be mild or severe and can present in the acute phase or during the recovery phase. Non-neurologic organ dysfunction can manifest following mild TBI or severe TBI. The pathophysiology of systemic manifestations following TBI is multifactorial and involves an effect on the autonomic nervous system, involvement of the hypothalamic-pituitary axis, release of inflammatory mediators, and treatment modalities used for TBI. Endocrine dysfunction, electrolyte imbalance, and respiratory manifestations are common following TBI. The influence of TBI on systemic immune response, coagulation cascade, cardiovascular system, gastrointestinal system, and other systems is becoming more evident through animal studies and clinical trials. Systemic manifestations can independently act as risk factors for mortality and morbidity following TBI. Some conditions like neurogenic pulmonary edema and disseminated intravascular coagulation can adversely affect the outcome. Early recognition and treatment of systemic manifestations may improve the clinical outcome following TBI. Further studies are required especially in the field of neuroimmunology to establish the role of various biochemical cascades, not only in the pathophysiology of TBI but also in its systemic manifestations and outcome.

Treatment of mild traumatic brain injury with an erythropoietin-mimetic peptide.

Mild traumatic brain injury (mTBI) results in an estimated 75-90% of the 1.7 million TBI-related emergency room visits each year. Post-concussion symptoms, which can include impaired memory problems, may persist for prolonged periods of time in a fraction of these cases. The purpose of this study was to determine if an erythropoietin-mimetic peptide, pyroglutamate helix B surface peptide (pHBSP), would improve neurological outcomes following mTBI. Sixty-four rats were randomly assigned to pHBSP or control (inactive peptide) 30 µg/kg IP every 12 h for 3 days, starting at either 1 hour (early treatment) or 24 h (delayed treatment), after mTBI (cortical impact injury 3 m/sec, 2.5 mm deformation). Treatment with pHBSP resulted in significantly improved performance on the Morris water maze task. Rats that received pHBSP required 22.3±1.3 sec to find the platform, compared to 26.3±1.3 sec in control rats (p=0.022). The rats that received pHBSP also traveled a significantly shorter distance to get to the platform, 5.0±0.3 meters, compared to 6.1±0.3 meters in control rats (p=0.019). Motor tasks were only transiently impaired in this mTBI model, and no treatment effect on motor performance was observed with pHBSP. Despite the minimal tissue injury with this mTBI model, there was significant activation of inflammatory cells identified by labeling with CD68, which was reduced in the pHBSP-treated animals. The results suggest that pHBSP may improve cognitive function following mTBI.

Gross and microscopic study of the filum terminale: does the filum contain functional neural elements?

OBJECT: The filum terminale (FT) is considered a fibrous structure that extends from conus medullaris of the spinal cord to coccyx. Based on previous studies and from their own experience with intraoperative electrophysiological monitoring of the sacral nervous system, the authors postulate that the FT contains functional neural elements in some individuals. METHODS: The FT was dissected from 13 fresh stillborn cadavers (7 male, 6 female; mean gestational age 36 weeks and 1 day). The gross anatomical features were recorded, and connections between the FT and the nerve roots of the cauda equina were noted. These connections, when present, were sectioned for histological studies. The fila (both interna and externa) were also sectioned for histological and immunohistochemical studies. In addition, FT specimens were obtained from 5 patients undergoing sectioning of the FT in an untethering surgical procedure. RESULTS: There were 5 gross connections between the FT and nerve roots demonstrating nerve fibers that were positive for S100. The FT showed islands of cells that were positive for GFAP in 10 cases, synaptophysin in 3 cases, S100 in 11 cases, and nestin in 2 cases. The nerve fibers in the FT were myelinated in 2 cases. The conus ended at the L-1 or L-2 vertebral level in all 13 specimens. The dural sac terminated at the S-2 vertebral level in most of the specimens. The 5 FT specimens that were obtained from patients revealed nerve bundles that were positive for S100 in 4 cases and cells that were positive for GFAP in 3 cases. CONCLUSIONS: There are gross anatomical connections between the FT and nerve roots that contain nerve fibers. Apart from fibrous stroma, the FT may contain nerve bundles and cells that stain positive for GFAP, synaptophysin, S100, and nestin. These microscopic findings and previous intraoperative electrophysiological studies suggest a probable functional role for the FT in some individuals. At birth, the conus ends at a higher vertebral level (lower L-1 or upper L-2) than L-3.