Glioblastoma multiforme (GBM) are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs). We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA), a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain) slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion). Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

Lymphocytic hypophysitis is an uncommon autoimmune condition that often results in significant morbidity. Although most cases resolve spontaneously or after a short course of steroids, rarely, refractory cases can cause persistent neurological deficits despite aggressive medical and surgical management. A 41-year-old woman presented with progressive visual loss in the left eye and was found to have a sellar mass. She underwent transsphenoidal surgery because of lesion enlargement. Histopathology was consistent with adenohypophysitis with B-cell predominance. Despite steroid treatment, her neurological condition worsened and she experienced loss of vision in the right eye. Craniotomy with decompression of the right optic nerve was performed. Her condition improved initially, but she continued to have progressive visual compromise over the following months. She was therefore treated with rituximab, a monoclonal antibody against B cells. Her vision improved significantly within a few weeks. There was no clinical or radiographic exacerbation 2 years after starting immunotherapy. Rituximab, an anti-CD20 antibody that specifically depletes B lymphocytes, can be an effective treatment strategy for patients with steroid-refractory, B cell-predominant lymphocytic hypophysitis.

Object Single-level anterior cervical discectomy and fusion (ACDF) is an established surgical treatment for cervical myelopathy. Within 10 years of undergoing ACDF, 19.2% of patients develop symptomatic adjacent-level degeneration. Performing ACDF adjacent to prior fusion requires exposure and removal of previously placed hardware, which may increase the risk of adverse outcomes. Zero-profile cervical implants combine an interbody spacer with an anterior plate into a single device that does not extend beyond the intervertebral disc space, potentially obviating the need to remove prior hardware. This study compared the biomechanical stability and adjacent-level range of motion (ROM) following placement of a zero-profile device (ZPD) adjacent to a single-level ACDF against a standard 2-level ACDF. Methods In this in vitro biomechanical cadaveric study, multidirectional flexibility testing was performed by a robotic spine system that simulates flexion-extension, lateral bending, and axial rotation by applying a continuous pure moment load. Testing conditions were as follows: 1) intact, 2) C5–6 ACDF, 3) C4–5 ZPD supraadjacent to simulated fusion at C5–6, and 4) 2-level ACDF (C4–6). The sequence of the latter 2 test conditions was randomized. An unconstrained pure moment of 1.5 Nm with a 40-N simulated head weight load was applied to the intact condition first in all 3 planes of motion and then using the hybrid test protocol, overall intact kinematics were replicated subsequently for each surgical test condition. Intersegmental rotations were measured optoelectronically. Mean segmental ROM for operated levels and adjacent levels was recorded and normalized to the intact condition and expressed as a percent change from intact. A repeated-measures ANOVA was used to analyze the ROM between test conditions with a 95% level of significance. Results No statistically significant differences in immediate construct stability were found between construct Patterns 3 and 4, in all planes of motion (p > 0.05). At the operated level, C4–5, the zero-profile construct showed greater decreases in axial rotation (–45% vs –36%) and lateral bending (–55% vs –38%), whereas the 2-level ACDF showed greater decreases in flexion-extension (–40% vs –34%). These differences were marginal and not statistically significant. Adjacent-level motion was nearly equivalent, with minor differences in flexion-extension. Conclusions When treating degeneration adjacent to a single-level ACDF, a zero-profile implant showed stabilizing potential at the operated level statistically similar to that of the standard revision with a 2-level plate. Revision for adjacent-level disease is common, and using a ZPD in this setting should be investigated clinically because it may be a faster, safer alternative.

Object Classic biomechanical models have used thoracic spines disarticulated from the rib cage, but the biomechanical influence of the rib cage on fracture biomechanics has not been investigated. The well-accepted construct for stabilizing midthoracic fractures is posterior instrumentation 3 levels above and 2 levels below the injury. Short-segment fixation failure in thoracolumbar burst fractures has led to kyphosis and implant failure when anterior column support is lacking. Whether shorter constructs are viable in the midthoracic spine is a point of controversy. The objective of this study was the biomechanical evaluation of a burst fracture at T-9 with an intact rib cage using different fixation constructs for stabilizing the spine. Methods A total of 8 human cadaveric spines (C7–L1) with intact rib cages were used in this study. The range of motion (ROM) between T-8 and T-10 was the outcome measure. A robotic spine testing system was programmed to apply pure moment loads (± 5 Nm) in lateral bending, flexion-extension, and axial rotation to whole thoracic specimens. Intersegmental rotations were measured using an optoelectronic system. Flexibility tests were conducted on intact specimens, then sequentially after surgically induced fracture at T-9, and after each of 4 fixation construct patterns. The 4 construct patterns were sequentially tested in a nondestructive protocol, as follows: 1) 3 above/2 below (3A/2B); 2) 1 above/1 below (1A/1B); 3) 1 above/1 below with vertebral body augmentation (1A/1B w/VA); and 4) vertebral body augmentation with no posterior instrumentation (VA). A repeated-measures ANOVA was used to compare the segmental motion between T-8 and T-10 vertebrae. Results Mean ROM increased by 86%, 151%, and 31% after fracture in lateral bending, flexion-extension, and axial rotation, respectively. In lateral bending, there was significant reduction compared with intact controls for all 3 instrumented constructs: 3A/2B (−92%, p = 0.0004), 1A/1B (−63%, p = 0.0132), and 1A/1B w/VA (−66%, p = 0.0150). In flexion-extension, only the 3A/2B pattern showed a significant reduction (−90%, p = 0.011). In axial rotation, motion was significantly reduced for the 3 instrumented constructs: 3A/2B (−66%, p = 0.0001), 1A/1B (−53%, p = 0.0001), and 1A/1B w/VA (−51%, p = 0.0002). Between the 4 construct patterns, the 3 instrumented constructs (3A/2B, 1A/1B, and 1A/1B w/VA) showed comparable stability in all 3 motion planes. Conclusions This study showed no significant difference in the stability of the 3 instrumented constructs tested when the rib cage is intact. Fractures that might appear more grossly unstable when tested in the disarticulated spine may be bolstered by the ribs. This may affect the extent of segmental spinal instrumentation needed to restore stability in some spine injuries. While these initial findings suggest that shorter constructs may adequately stabilize the spine in this fracture model, further study is needed before these results can be extrapolated to clinical application.