Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.
Tej D. Azad, Anand Veeravagu and Gary K. Steinberg
Anand Veeravagu, Tyler S. Cole, Tej D. Azad and John K. Ratliff
The significant medical and economic tolls of spinal disorders, increasing volume of spine surgeries, and focus on quality metrics have made it imperative to understand postoperative complications. This study demonstrates the utility of a longitudinal administrative database for capturing overall and procedure-specific complication rates after various spine surgery procedures.
The Thomson Reuters MarketScan Commercial Claims and Encounters and the Medicare Supplemental and Coordination of Benefits database was used to conduct a retrospective analysis of longitudinal administrative data from a sample of approximately 189,000 patients. Overall and procedure-specific complication rates at 5 time points ranging from immediately postoperatively (index) to 30 days postoperatively were computed.
The results indicated that the frequency of individual complication types increased at different rates. The overall complication rate including all spine surgeries was 13.6% at the index time point and increased to 22.8% at 30 days postoperatively. The frequencies of wound dehiscence, infection, and other wound complications exhibited large increases between 10 and 20 days postoperatively, while complication rates for new chronic pain, delirium, and dysrhythmia increased more gradually over the 30-day period studied. When specific surgical procedures were considered, 30-day complication rates ranged from 8.6% in single-level anterior cervical fusions to 27.3% in multilevel combined anterior and posterior lumbar spine fusions.
This study demonstrates the usefulness of a longitudinal administrative database in assessing postoperative complication rates after spine surgery. Use of this database gave results that were comparable to those in prospective studies and superior to those obtained with nonlongitudinal administrative databases. Longitudinal administrative data may improve the understanding of overall and procedure-specific complication rates after spine surgery.
Michael Zhang, Yi-Ren Chen, Steven D. Chang and Anand Veeravagu
Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making.
A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS.
Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%–40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated.
SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.
Michael C. Jin, Zachary A. Medress, Tej D. Azad, Vanessa M. Doulames and Anand Veeravagu
Recent advances in stem cell biology present significant opportunities to advance clinical applications of stem cell–based therapies for spinal cord injury (SCI). In this review, the authors critically analyze the basic science and translational evidence that supports the use of various stem cell sources, including induced pluripotent stem cells, oligodendrocyte precursor cells, and mesenchymal stem cells. They subsequently explore recent advances in stem cell biology and discuss ongoing clinical translation efforts, including combinatorial strategies utilizing scaffolds, biogels, and growth factors to augment stem cell survival, function, and engraftment. Finally, the authors discuss the evolution of stem cell therapies for SCI by providing an overview of completed (n = 18) and ongoing (n = 9) clinical trials.
Michael Y. Wang, Tetsuya Goto, Enrico Tessitore and Anand Veeravagu
Tae Sung Park
Lewis C. Hou, Anand Veeravagu, Andrew R. Hsu and Victor C. K. Tse
✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.
Albert E. Telfeian, Anand Veeravagu, Adetokunbo A. Oyelese and Ziya L. Gokaslan
Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development.
Kunal Varshneya, Adrian J. Rodrigues, Zachary A. Medress, Martin N. Stienen, Gerald A. Grant, John K. Ratliff and Anand Veeravagu
Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes.
The authors queried the MarketScan database (2007–2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs.
The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non–CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6–13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2–44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7–5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5–4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001).
The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.
Anand Veeravagu, Marco Lee, Bowen Jiang and Steven D. Chang
The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.