The production and aggregation of cerebral amyloid-␤ (A␤) peptide are thought to play a causal role in Alzheimer's disease (AD). Previously, we found that the Nogo-66 receptor (NgR) interacts physically with both A␤ and the amyloid precursor protein (APP). The inverse correlation of A␤ levels with NgR levels within the brain may reflect regulation of A␤ production and/or A␤ clearance. Here, we assess the potential therapeutic benefit of peripheral NgR-mediated A␤ clearance in APPswe/PSEN-1⌬E9 transgenic mice. Through site-directed mutagenesis, we demonstrate that the central 15-28 aa of A␤ associate with specific surface-accessible patches on the leucine-rich repeat concave side of the solenoid structure of NgR. In transgenic mice, subcutaneous NgR(310)ecto-Fc treatment reduces brain A␤ plaque load while increasing the relative levels of serum A␤. These changes in A␤ are correlated with improved spatial memory in the radial arm water maze. The benefits of peripheral NgR administration are evident when therapy is initiated after disease onset. Thus, the peripheral association of NgR(310)ecto-Fc with central A␤ residues provides an effective therapeutic approach for AD.

OBJECT The aging of the population will require that surgeons increasingly consider operating on elderly patients. Performing surgery safely in the elderly will require an understanding of the factors that predict successful outcomes and avoid complications. METHODS Records of patients 85 years and older undergoing elective lumbar spinal surgery were retrospectively reviewed. Microdiscectomies were excluded. Preexisting medical illnesses measured using the Charlson Comorbidity Index (CCI), American Society of Anesthesiologists (ASA) Physical Status class, age, and surgical parameters were analyzed as factors potentially predictive of complications. Ambulatory function was rated on a 4-point scale. RESULTS During the study 26 consecutive patients (mean age 87 years) with a mean ASA class of 2.6 ± 0.65 and CCI of 1.1 ± 1.27 were enrolled. The average number of levels treated was 2.17 ± 1.23, and 73% underwent fusion. The mean follow-up was 41.9 months with a minimum of 24 months, and all patients were alive at last follow-up. Average blood loss was 142 ± 184 ml, and the operative time was 183.3 ± 80.6 minutes. The mean number of levels treated was 2.17 ± 1.13 (range 1–4). Ambulatory function improved significantly by 0.59 ± 1.0 points. Five complications (19.2%) occurred in 4 patients, 2 major and 3 minor. Four complications were temporary and 1 was permanent. Patient age, blood loss, CCI score, ASA class, the number of levels treated, and fusion surgery were not statistically associated with a complication. Operative time of longer than 180 minutes (p = 0.0134) was associated with complications. CONCLUSIONS Lumbar spine surgery in patients 85 years and older can be accomplished safely if careful attention is paid to preoperative selection. Prolonged operative times are associated with a higher risk of complications.

Spondylolysis of the lumbar spine has traditionally been treated using a variety of techniques ranging from conservative care to fusion. Direct repair of the defect may be utilized in young adult patients without significant disc degeneration and lumbar instability. We used minimally invasive techniques to place pars interarticularis screws with the use of an intraoperative CT scanner in three young adults, including two athletes. This technique is a modification of the original procedure in 1970 by Buck, and it offers the advantage of minimal muscle dissection and optimal screw trajectory. There were no intra- or postoperative complications. The detailed operative procedure and the postoperative course along with a brief review of pars interarticularis defect treatment are discussed.

SUMMARYObjective: The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Methods: Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Results: Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R 2 = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Significance: Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy.