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Ryan Smith, Kris A. Smith, Christopher A. Biggs and Adrienne C. Scheck

Object

The goal of this study was to develop an assay that makes possible the assessment of the glioma cell response to single-fraction high-dose Gamma Knife surgery. In this assay, the isolation of radioresistant cell subpopulations facilitates mechanistic studies of radioresistance.

Methods

A tissue-equivalent paraffin phantom with an aperture capable of holding an Opticell cell culture cassette was developed for treatment with the Leksell Gamma Knife model C. A second apparatus, which the authors also created, uses the manufacturer-supplied polystyrene phantom, thereby allowing this assay to be performed in the Leksell Gamma Knife Perfexion. After treatment, the cells were morphologically assessed to determine their response to radiation treatment. Two specific parameters were used to determine radiosensitivity: 1) the diameter of the clearing zone, defined as the central region of cell death; and 2) the number of surviving colonies within this central high-dose clearing zone.

Results

Radioresistance was compared in 2 different cell lines from glioblastomas. The first cell line, ME, was established from a primary tumor before its treatment, and the second cell line, DIV, was established from a tumor that recurred after treatment with chemotherapy and fractionated radiotherapy. The ME cell line had the most robust response to radiosurgery, as characterized by a consistently larger clearing zone (28.33 ± 1.1 mm). In contrast, the clearing zone produced when the DIV cell line was used was 24.0 ± 1 mm, indicating an approximate response difference of 5 Gy. The mean number of surviving colonies within the clearing zone for the ME cell line was 1.33 ± 1 compared with that for the DIV cell line, which was 66.67 ± 2.

Conclusions

The authors developed a biological dosimeter to model the response of cells from glioblastomas to single-fraction high-dose radiation. This system also allows the identification and isolation of radioresistant cells.

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Ryan A. Gellner, Eamon T. Campolettano, Eric P. Smith and Steven Rowson

OBJECTIVE

Youth football attracts approximately 3.5 million participants every year, but concern has recently arisen about the long-term effects of experiencing repetitive head accelerations from a young age due to participation in football. The objective of this study was to quantify total involvement in high-magnitude impacts among individual players in youth football practices. The authors explored the relationship between the total number of high-magnitude accelerations in which players were involved (experienced either by themselves or by other players) during practices and the number of high-magnitude accelerations players experienced.

METHODS

A local cohort of 94 youth football players (mean age 11.9 ± 1.5, mean body mass 50.3 ± 16.4 kg) from 4 different teams were recruited and outfitted with helmet-mounted accelerometer arrays. The teams were followed for one season each for a total of 128 sessions (practices, games, and scrimmages). All players involved in high-magnitude (greater than 40g) head accelerations were subsequently identified through analysis of practice film.

RESULTS

Players who experienced more high-magnitude accelerations were more likely to be involved in impacts associated with high-magnitude accelerations in other players. A small subset of 6 players (6%) were collectively involved in 230 (53%) high-magnitude impacts during practice, were involved in but did not experience a high-magnitude acceleration 78 times (21% of the 370 one-sided high-magnitude impacts), and experienced 152 (30%) of the 502 high-magnitude accelerations measured. Quarterbacks/running backs/linebackers were involved in the greatest number of high-magnitude impacts in practice and experienced the greatest number of high-magnitude accelerations. Which team a player was on was an important factor, as one team showed much greater head impact exposure than all others.

CONCLUSIONS

This study showed that targeting the most impact-prone players for individualized interventions could reduce high-magnitude acceleration exposure for entire teams. These data will help to further quantify elevated head acceleration exposure and enable data-driven interventions that modify exposure for individual players and entire teams.

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Ryan Brewster, Wenya Linda Bi, Timothy R. Smith, William B. Gormley, Ian F. Dunn and Edward R. Laws Jr.

Baseball maintains one of the highest impact injury rates in all athletics. A principal causative factor is the “beanball,” referring to a pitch thrown directly at a batter’s head. Frequent morbidities elicited demand for the development of protective gear development in the 20th century. In this setting, Dr. Walter Dandy was commissioned to design a “protective cap” in 1941. His invention became widely adopted by professional baseball and inspired subsequent generations of batting helmets. As a baseball aficionado since his youth, Walter Dandy identified a natural partnership between baseball and medical practice for the reduction of beaning-related brain injuries. This history further supports the unique position of neurosurgeons to leverage clinical insights, inform innovation, and expand service to society.

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Eric R. Trumble, Ryan M. Smith, Gary Pearl and Judith Wall

✓The authors describe the first documented case of transplacental transmission of metastatic melanoma to the neuraxis. The patient was a 7-month-old boy who presented with signs and symptoms of elevated intracranial pressure. Magnetic resonance imaging revealed an inhomogeneously enhancing posterior fossa mass measuring 5 × 5 × 6 cm and filling the fourth ventricle. A posterior fossa craniotomy was performed. Pathological studies confirmed the presence of a metastatic melanoma that was pathologically identical to that of his mother. The boy received aggressive chemotherapy and underwent an additional resection. He also required a ventriculoperitoneal shunt for treatment of his hydrocephalus. He lived longer than any other patient with transplacental transmission of metastatic melanoma but ultimately died of the disease, 18 months after his initial presentation.

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Ekamjeet S. Dhillon, Ryan Khanna, Michael Cloney, Helena Roberts, George R. Cybulski, Tyler R. Koski, Zachary A. Smith and Nader S. Dahdaleh

OBJECTIVE

Venous thromboembolism (VTE) after spinal surgery is a major cause of morbidity, but chemoprophylactic anticoagulation can prevent it. However, there is variability in the timing and use of chemoprophylactic anticoagulation after spine surgery, particularly given surgeons’ concerns for spinal epidural hematomas. The goal of this study was to provide insight into the safety, efficacy, and timing of anticoagulation therapy after spinal surgery.

METHODS

The authors retrospectively examined records from 6869 consecutive spinal surgeries performed in their departments at Northwestern University. Data on patient demographics, surgery, hospital course, timing of chemoprophylaxis, and complications, including deep venous thrombosis (DVT), pulmonary embolism (PE), and spinal epidural hematomas requiring evacuation, were collected. Data from the patients who received chemoprophylaxis (n = 1904) were compared with those of patients who did not (n = 4965). The timing of chemoprophylaxis, the rate of VTEs, and the incidence of spinal epidural hematomas were analyzed.

RESULTS

The chemoprophylaxis group had more risk factors, including greater age (59.70 vs 51.86 years, respectively; p < 0.001), longer surgery (278.59 vs 145.66 minutes, respectively; p < 0.001), higher estimated blood loss (995 vs 448 ml, respectively; p < 0.001), more comorbid diagnoses (2.69 vs 1.89, respectively; p < 0.001), history of VTE (5.8% vs 2.1%, respectively; p < 0.001), and a higher number were undergoing fusion surgery (46.1% vs 24.7%, respectively; p < 0.001). The prevalence of VTE was higher in the chemoprophylaxis group (3.62% vs 2.03%, respectively; p < 0.001). The median time to VTE occurrence was shorter in the nonchemoprophylaxis group (3.6 vs 6.8 days, respectively; p = 0.0003, log-rank test; hazard ratio 0.685 [0.505–0.926]), and the peak prevalence of VTE occurred in the first 3 postoperative days in the nonchemoprophylaxis group. The average time of initiation of chemoprophylaxis was 1.46 days after surgery. The rates of epidural hematoma were 0.20% (n = 4) in the chemoprophylaxis group and 0.18% (n = 9) in the nonchemoprophylaxis group (p = 0.622).

CONCLUSIONS

The risks of spinal epidural hematoma among patients who receive chemoprophylaxis and those who do not are low and equivalent. Administering anticoagulation therapy from 1 day before to 3 days after surgery is safe for patients at high risk for VTE.

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Ryan C. Turner, Zachary J. Naser, Julian E. Bailes, David W. Smith, Joseph A. Fisher and Charles L. Rosen

Object

Helmets successfully prevent most cranial fractures and skull traumas, but traumatic brain injury (TBI) and concussions continue to occur with frightening frequency despite the widespread use of helmets on the athletic field and battlefield. Protection against such injury is needed. The object of this study was to determine if slosh mitigation reduces neural degeneration, gliosis, and neuroinflammation.

Methods

Two groups of 10 adult male Sprague-Dawley rats were subjected to impact-acceleration TBI. One group of animals was fitted with a collar inducing internal jugular vein (IJV) compression prior to injury, whereas the second group received no such collar prior to injury. All rats were killed 7 days postinjury, and the brains were fixed and embedded in paraffin. Tissue sections were processed and stained for markers of neural degeneration (Fluoro-Jade B), gliosis (glial fibrillary acidic protein), and neuroinflammation (ionized calcium binding adapter molecule 1).

Results

Compared with the controls, animals that had undergone IJV compression had a 48.7%–59.1% reduction in degenerative neurons, a 36.8%–45.7% decrease in reactive astrocytes, and a 44.1%–65.3% reduction in microglial activation.

Conclusions

The authors concluded that IJV compression, a form of slosh mitigation, markedly reduces markers of neurological injury in a common model of TBI. Based on findings in this and other studies, slosh mitigation may have potential for preventing TBI in the clinical population.

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Juan S. Uribe, William D. Smith, Luiz Pimenta, Roger Härtl, Elias Dakwar, Urvij M. Modhia, Glen A. Pollock, Vamsi Nagineni, Ryan Smith, Ginger Christian, Leonardo Oliveira, Luis Marchi and Vedat Deviren

Object

Symptomatic herniated thoracic discs remain a surgical challenge and historically have been associated with significant complications. While neurological outcomes have improved with the abandonment of decompressive laminectomy, the attempt to minimize surgical complications and associated morbidities continues through less invasive approaches. Many of these techniques, such as thoracoscopy, have not been widely adopted due to technical difficulties. The current study was performed to examine the safety and early results of a minimally invasive lateral approach for symptomatic thoracic herniated intervertebral discs.

Methods

Sixty patients from 5 institutions were treated using a mini-open lateral approach for 75 symptomatic thoracic herniated discs with or without calcification. The mean age was 57.9 years (range 23–80 years), and 53.3% of the patients were male. Treatment levels ranged from T4–5 to T11–12, with 1–3 levels being treated (mean 1.3 levels). The most common levels treated were T11–12 (14 cases [18.7%]), T7–8 (12 cases [16%]), and T8–9 (12 cases [16%]). Symptoms included myelopathy in 70% of cases, radiculopathy in 51.7%, axial back pain in 76.7%, and bladder and/or bowel dysfunction in 26.7%. Instrumentation included an interbody spacer in all but 6 cases (10%). Supplemental internal fixation included anterolateral plating in 33.3% of cases and pedicle screws in 10%; there was no supplemental internal fixation in 56.7% of cases. Follow-up ranged from 0.5 to 24 months (mean 11.0 months).

Results

The median operating time, estimated blood loss, and length of stay were 182 minutes, 290 ml, and 5.0 days, respectively. Four major complications occurred (6.7%): pneumonia in 1 patient (1.7%); extrapleural free air in 1 patient (1.7%), treated with chest tube placement; new lower-extremity weakness in 1 patient (1.7%); and wound infection in posterior instrumentation in 1 patient (1.7%). Reoperations occurred in 3 cases (5%): one for posterior reexploration, one for infection in posterior instrumentation, and one for removal of symptomatic residual disc material. Back pain, measured using the visual analog scale, improved 60% from the preoperative score to the last follow-up, that is, from 7.8 to 3.1. Excellent or good overall outcomes were achieved in 80% of the patients, a fair or unchanged outcome resulted in 15%, and a poor outcome occurred in 5%. Moreover, myelopathy, radiculopathy, axial back pain, and bladder and/or bowel dysfunction improved in 83.3%, 87.0%, 91.1%, and 87.5% of cases, respectively.

Conclusions

The authors' early experience with a large multicenter series suggested that the minimally invasive lateral approach is a safe, reproducible, and efficacious procedure for achieving adequate decompression in thoracic disc herniations in a less invasive manner than conventional surgical techniques and without the use of endoscopes. Symptom resolution was achieved at similar rates using this approach as compared with the most efficacious techniques in the literature, and with fewer complications in most circumstances.

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Christopher M. Duma, Brian S. Kim, Peter V. Chen, Marianne E. Plunkett, Ralph Mackintosh, Marlon S. Mathews, Ryan M. Casserly, Gustavo A. Mendez, Daniel J. Furman, Garrett Smith, Nathan Oh, Chad A. Caraway, Ami R. Sanathara, Robert O. Dillman, Azzurra-Sky Riley, David Weiland, Lian Stemler, Ruslana Cannell, Daniela Alexandru Abrams, Alexa Smith, Christopher M. Owen, Burton Eisenberg and Michael Brant-Zawadzki

OBJECTIVE

Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes.

METHODS

Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed. The LE was defined as a region outside the contrast-enhancing tumor nidus, defined by FLAIR MRI. The median age of patients was 59 years (range 22–87 years). Patients underwent LERS a median of 18 days from original diagnosis. The median target volume of 48.5 cm3 (range 2.5–220.0 cm3) of LE tissue was targeted using a median dose of 8 Gy (range 6–14 Gy) at the 50% isodose line.

RESULTS

The median overall survival was 23 months (mean 43 months) from diagnosis. The 2-, 3-, 5-, 7-, and 10-year actual overall survival rates after LERS were 39%, 26%, 16%, 10%, and 4%, respectively. Nine percent of patients developed treatment-related imaging-documented changes due to LERS. Nineteen percent of patients were hospitalized for management of edema, 22% for resection of a tumor cyst or new tumor bulk, and 2% for shunting to treat hydrocephalus throughout the course of their disease. Of the patients still alive, Karnofsky Performance Scale scores remained stable in 90% of patients and decreased by 1–3 grades in 10% due to symptomatic treatment-related imaging changes.

CONCLUSIONS

LERS is a safe and effective upfront adjunctive therapy for patients with newly diagnosed GBM. Limitations of this study include a single-center experience and single-institution determination of the LE tumor target. Use of a leading-edge calculation algorithm will be described to achieve a consistent approach to defining the LE target for general use. A multicenter trial will further elucidate its value in the treatment of GBM.