Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease.

Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100-nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.

Lumbar Spine Surgery in Patients with Parkinson Disease.

BACKGROUND: Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. METHODS: All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. RESULTS: Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was <2 in thirteen patients, 2 in thirty patients, 2.5 in twenty-three patients, and ≥3 in thirty patients. The primary indication for surgery was spinal stenosis in seventy-two patients, spondylolisthesis in seventeen patients, and coronal and/or sagittal deformity in seven patients. There were nineteen early complications, including postoperative infections requiring surgical irrigation and debridement and long-term antibiotics in ten patients. The visual analog scale for back pain improved from 7.4 cm preoperatively to 1.8 cm postoperatively (p < 0.001). The visual analog scale for lower-limb pain improved from 7.7 cm preoperatively to 2.3 cm postoperatively (p < 0.001). The Oswestry Disability Index score dropped from 54.1 points to 17.7 points at the time of the latest follow-up (p < 0.001). The Short Form-12 Physical Component Summary score improved from 26.6 points preoperatively to 30.5 points postoperatively (p < 0.05). Twenty patients required revision surgery. Risks for further surgery included a Parkinson disease severity stage of ≥3 (p < 0.05), a history of diabetes mellitus, treatment for osteoporosis, and a combined anterior and posterior approach. CONCLUSIONS: Despite a higher rate of complications than in the general population, the overall outcome of spine surgery in patients with mild to moderate Parkinson disease is good, with improvement of spine-related pain. A larger prospective study is warranted.

Spinal subdural hematoma following lumbar decompressive surgery: a report of two cases.

Spinal subdural hematoma (SSDH) following spine surgery is an extremely rare condition, with only three cases being reported in the literature. Unintended durotomy has been associated with SSDH due to alterations of pressures in the dural compartments. The objective of the present report was to report two rare cases of acute SSDH developed after lumbar decompressive surgery. In one of the patients, the diagnosis of SSDH was followed by urgent hematoma evacuation via durotomy due to the patient's worsening neurological symptoms. In the second patient, the SSDH was treated conservatively due to the absence of severe or progressive motor or sensory deficits. In conclusion, emergency evacuation via durotomy is the treatment of choice for patients with SSDH and neurologic impairment. Conservative management may be indicated in selected cases with absent motor and sensory deficits.

Medical students' and interns' interest in orthopedic surgery: the gender factor.

OBJECTIVE: There is an extremely small proportion of female medical students choosing to specialize in orthopedic surgery. The aim of the study was to assess medical students' and interns' interests and perceptions of orthopedic surgery and explore why women are not interested in orthopedic surgery. SETTING: Questionnaires were distributed to final-year medical students and interns assessing their interests and perception of orthopedic surgery. PARTICIPANTS: Final-year medical students and interns. RESULTS: Responses were obtained from 317 students and 199 interns. Among the medical students, 15% were interested in orthopedic surgery, but only 2% were women. Both male and female students perceived orthopedics as an "action"-packed, procedure-based profession, providing instant gratification, time in the operating room, high income, and the option for private practice. Female medical students considered it boring. Among interns, 11% were interested in orthopedic surgery; however, only 2% were women. When compared with the interns who were not interested in orthopedic surgery, a greater number of the interns interested in orthopedic surgery rated time with family and a procedure-intensive profession as important. Female students and interns were also interested in other surgical fields. CONCLUSIONS: The increasing majority of women among medical students will reshape the future of physician workforce by dictating changes in workforce participation, working conditions, and intercollegial relationships. Orthopedic surgery will need to adapt to these realities.

The Utility of 3-Dimensional-Navigation in the Surgical Treatment of Children With Idiopathic Scoliosis.

STUDY DESIGN: Ambispective study of patients undergoing surgical correction of adolescent idiopathic scoliosis. OBJECTIVE: To evaluate the accuracy of screw placement using preoperative 3-dimensional (3D) computed tomography (CT)-based navigation with intraoperative fluoroscopic guidance compared with freehand placement. SUMMARY OF BACKGROUND DATA: Pedicle screws placed in deformed vertebrae have a high malposition rate. The use of navigation-based systems has increased placement accuracy. METHODS: Intraoperative registration of patient anatomy to preoperative 3D-CT was performed using anatomic landmarks. When registration accuracy was high (mean square error, <1.0 mm), screw tracts were drilled under navigation guidance; when the error was >1.0 mm, re-registration was performed. The researchers documented times for registration, navigation, and screw placement, and the number of passes. Results were compared with outcomes in cases operated on with freehand screw placement. RESULTS: A total of 62 patients were included (54 females and 8 males; mean age was 15.1 years [range, 12-18 years]). Mean deformity was 67° (range, 52° to 80°). Mean follow-up was 35 months (range, 42-19 months). In the navigation group, 710 pedicle screws were placed. Mean times were 55 seconds for tracker placement, 94.5 seconds per vertebra for patient registration, 131.1 seconds for screw tract formation on the concave side of the deformity, and 129.5 seconds on the convex side. Average total procedure time was 3.5 hours (range, 2-7 hours). Mean overall registration accuracy was 0.7 mm. Pedicle integrity was breached in 1.6% trajectories. In the freehand group, 470 pedicle screws were placed. Average time for screw placement was 135.2 seconds (p < .001 vs. navigation). Pedicle integrity was breached in 5.1% of trajectories (p < .0001 vs. navigation). No patient developed neurological or other complications. There was no destabilization of the instrumented spine during short- or long-term follow-up. CONCLUSIONS: Intraoperative optic fluoroscopic navigation based on anatomic landmark registration to preoperative 3D-CT spine images enables precise pedicle screw placement with only a minor increase in pedicle preparation time in patients with adolescent idiopathic scoliosis.