Traumatic brain injury (TBI) survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in many severe TBI patients, results in accumulation of amyloid precursor protein (APP). Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ) peptides, a hallmark finding in Alzheimer’s disease (AD). At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF) using cerebral microdialysis and/or cerebrospinal fluid (CSF) following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques, and the complexity of TBI in the available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using methods such as rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long-term consequences of TBI.

This study tested the hypotheses that (1) cervical total disc replacement with a compressible, sixdegree-of-freedom prosthesis would allow restoration of physiologic range and quality of motion, and (2) the kinematic response would not be adversely affected by variability in prosthesis position in the sagittal plane. Twelve human cadaveric cervical spines were tested. Prostheses were implanted at C5-C6. Range of motion (ROM) was measured in flexion-extension, lateral bending, and axial rotation under ±1.5 Nm moments. Motion coupling between axial rotation and lateral bending was calculated. Stiffness in the high flexibility zone was evaluated in all three testing modes, while the center of rotation (COR) was calculated using digital video fluoroscopic images in flexion-extension. Implantation in the middle position increased ROM in flexion-extension from 13.5 ± 2.3 to 15.7 ± 3.0°(p \ 0.05), decreased axial rotation from 9.9 ± 1.7 to 8.3 ± 1.6°(p \ 0.05), and decreased lateral bending from 8.0 ± 2.1 to 4.5 ± 1.1°( p \ 0.05). Coupled lateral bending decreased from 0.62 ± 0.16 to 0.39 ± 0.15°for each degree of axial rotation (p \ 0.05). Flexion-extension stiffness of the reconstructed segment with the prosthesis in the middle position did not deviate significantly from intact controls, whereas the lateral bending and axial rotation stiffness values were significantly larger than intact. Implanting the prosthesis in the posterior position as compared to the middle position did not significantly affect the ROM, motion coupling, or stiffness of the reconstructed segment; however, the COR location better approximated intact controls with the prosthesis midline located within ±1 mm of the disc-space midline. Overall, the kinematic response after reconstruction with the compressible, six-degree-offreedom prosthesis within ±1 mm of the disc-space midline approximated the intact response in flexion-extension. Clinical studies are needed to understand and interpret the effects of limited restoration of lateral bending and axial rotation motions and motion coupling on clinical outcome.

Bone quality is an important factor that influences stability of posterior thoracic implants. Fixation strength in the osteopenic group was one-fourth of the value measured in vertebrae with good bone quality, irrespective of the instrumentation used. However, in normal bone quality vertebrae, the lamina hook claw system dislocated with significantly less force when compared with other spinal implants. Further studies are needed to investigate the impact of different transpedicular screw designs on the pullout strength in normal and osteopenic thoracic spines.