Faculty Bibliography

Object/UNASSIGNED:The purpose of the current study is to determine the sensitivity and specificity of an eye tracking method as a classifier for identifying concussion. Methods/UNASSIGNED:Brain injured and control subjects prospectively underwent both eye tracking and Sport Concussion Assessment Tool 3. The results of eye tracking biomarker based classifier models were then validated against a dataset of individuals not used in building a model. The area under the curve (AUC) of receiver operating characteristics was examined. Results/UNASSIGNED:An optimal classifier based on best subset had an AUC of 0.878, and a cross-validated AUC of 0.852 in CT- subjects and an AUC of 0.831 in a validation dataset. The optimal misclassification rate in an external dataset (n = 254) was 13%. Conclusion/UNASSIGNED:If one defines concussion based on history, examination, radiographic and Sport Concussion Assessment Tool 3 criteria, it is possible to generate an eye tracking based biomarker that enables detection of concussion with reasonably high sensitivity and specificity.

BACKGROUND AND PURPOSE: The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. METHODS: We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with >/=12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. RESULTS: The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. CONCLUSIONS: Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.

Intracranial hypotension (IH) can occur following lumbar drainage for clipping of an intracranial aneurysm. We observed 3 cases of IH, which were all successfully treated by epidural blood patch (EBP). Herein, the authors report our cases.

RATIONALE: Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and non-ischemic heart failure (HF). OBJECTIVE: To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million [M] cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial. METHODS AND RESULTS: We sequentially allocated 60 patients to a dosing cohort (20 per dose-group) and randomized them to transendocardial MPC injections (n=15) or mock procedures (n=5). The primary objective was safety, including antibody testing. Secondary efficacy endpoints included major adverse cardiac events (MACE; cardiac death, myocardial infarction, or revascularization), left ventricular imaging, and other clinical-event surrogates. Safety and MACE were evaluated for up to 3 years. MPC injections were feasible and safe. Adverse events were similar across groups. No clinically symptomatic immune responses were noted. MACE was seen in 15 patients: 10/45 (22%) MPC-treated and 5/15 (33%) control patients. We found no differences between MPC-treated and control patients in survival probability, MACE-free probability, and all-cause mortality. We conducted a post-hoc analysis of HF-related MACE (HF hospitalization, successfully resuscitated cardiac death, or cardiac death); events were significantly reduced in the 150M group (0/15) versus control (5/15;33%), 25M (3/15;20%), and 75M (6/15;40%); the 150M group differed significantly from all groups according to Kaplan-Meyer statistics over 3 years (P=0.025 for 150M vs control). CONCLUSIONS: Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients. High-dose allogeneic MPCs may provide benefits in this population.

Background: Mild traumatic brain injuries are frequently evaluated in EDs. Standardized concussion surveillance tools such as the SCAT 3 have been proposed. Developed as a post-injury tool for athletes, SCAT3 is routinely used in pre-injury, baseline assessment. Population-based normative data can aid in interpretation of individual variability or when baseline data are unavailable. To date, all SCAT3 data have been collected in the athlete population with an absence of data on non-athlete (N-A) controls or acutely injured nonathletes. Objectives: We investigate SCAT3 subcomponents in N-A healthy controls, corpus (non head-injured) trauma, and acutely head-injured patients presenting to the ED to derive reference values for novel populations. We hypothesize that trauma patients with suspected head injury will have worse SCAT3 metrics than uninjured controls. Methods: Target groups were extracted from a database of prospectively recruited patients. SCAT3/SAC (Standardized Assessment of Concussion) was administered at time of ED presentation or recruitment. Multi-sample comparisons were evaluated by the Kruskal- Wallis test; pairwise comparisons were analyzed by the Steel-Dwass procedure. Results: A comparison of SCAT3 subcomponents by patient group is seen in Table 732a. One hundred eleven N-A healthy controls, 121 bodily trauma not warranting head CT in ED, 242 head trauma with negative head CT findings, and 67 head trauma patients with positive head CT were evaluated. Control group comparison seen in Table 732b. In number of symptoms, symptom severity score, and SAC, there was a significant difference between control, corpus and - CT/+CT groups. In immediate memory and Balance Error Scoring System (BESS), there was a significant difference between control, corpus, and -CT/+CT, with corpus statistically similar to -CT/ +CT. In concentration, there was a significant difference between control, corpus, and -CT/+CT, with corpus similar to -CT. In orientation, there was a significant difference between control/corpus and -CT/+CT. Conclusion: In healthy, N-A controls, all SCAT3 values were significantly different from all trauma groups'. In -CT/+CT groups, all SCAT3 values were similar to each other. A graded effect was seen from control to corpus to head trauma. Diagnostic ranges of SCAT3 subcomponents vary in the N-A and bodily trauma population. (Table presented)

Introduction: Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. Methods: We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 seconds and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy non-injured control subjects and compared findings to 75 trauma subjects with either a positive head CT (n=13), negative head CT (n=39) or non-head injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure SCAT3 in trauma patients. Results: Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to non-injured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion (SAC) score. Abnormal eye tracking metrics improved over time towards baseline in brain injured subjects seen in follow-up. Conclusions: Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury.

OBJECT Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. METHODS The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. RESULTS In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value +/- SD of 1.0117 +/- 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 +/- 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. CONCLUSIONS This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

OBJECT Physicians are often solicited by patients or colleagues for clinical recommendations they would make for themselves if faced by a clinical situation. The act of making a recommendation can alter the clinical course being taken. The authors sought to understand this dynamic across different neurosurgical scenarios by examining how neurosurgeons value the procedures that they offer. METHODS The authors conducted an online survey using the Congress of Neurological Surgeons listserv in May 2013. Respondents were randomized to answer either as the surgeon or as the patient. Questions encompassed an array of distinct neurosurgical scenarios. Data on practice parameters and experience levels were also collected. RESULTS Of the 534 survey responses, 279 responded as the "neurosurgeon" and 255 as the "patient." For both vestibular schwannoma and arteriovenous malformation management, more respondents chose resection for their patient but radiosurgery for themselves (p = 0.002 and p = 0.001, respectively). Aneurysm coiling was chosen more often than clipping, but those whose practice was >/= 30% open cerebrovascular neurosurgery were less likely to choose coiling. Overall, neurosurgeons who focus predominantly on tumors were more aggressive in managing the glioma, vestibular schwannoma, arteriovenous malformation, and trauma. Neurosurgeons more than 10 years out of residency were less likely to recommend surgery for management of spinal pain, aneurysm, arteriovenous malformation, and trauma scenarios. CONCLUSIONS In the majority of cases, altering the role of the surgeon did not change the decision to pursue treatment. In certain clinical scenarios, however, neurosurgeons chose treatment options for themselves that were different from what they would have chosen for (or recommended to) their patients. For the management of vestibular schwannomas, arteriovenous malformations, intracranial aneurysms, and hypertensive hemorrhages, responses favored less invasive interventions when the surgeon was the patient. These findings are likely a result of cognitive biases, previous training, experience, areas of expertise, and personal values.

BACKGROUND: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a major neurosurgical emergency associated with significant morbidity and mortality. Rapid aneurysm growth is associated with rupture. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder whose complications can include cerebral vasculitis and vasculopathy. Intracranial aneurysms are not known to occur more frequently in SLE patients than the general population; however, aneurysm growth rates have not been studied in SLE. CASE DESCRIPTION: We present a 43-year-old female with SLE on prednisone, hydroxychloroquine, and azathioprine with moderate disease activity who presented with severe, acute-onset headache and was found to have Hunt and Hess grade II SAH due to rupture of an 8 mm saccular anterior communicating artery (ACoA) aneurysm. The patient developed severe vasospasm, re-ruptured, and was taken for angiography and embolization, which was challenging due to a high degree of vasospasm and arterial stenosis. Review of imaging from less than 2 years prior demonstrated a normal ACoA complex without evidence of an aneurysm. CONCLUSION: We review the literature and discuss the risk factors and pathophysiology of rapid aneurysm growth and rupture, as well as the pathologic vascular changes associated with SLE. Although SLE patients do not develop intracranial aneurysm at an increased rate, these changes may predispose them to higher incidence of growth and rupture. This possibility-coupled with increased morbidity and mortality of SAH in SLE-suggests that SAH should be considered in SLE patients presenting with headache, and advocates for more aggressive treatment of SLE patients with unruptured aneurysms.

BACKGROUND AND PURPOSE: Although there is generally thought to be a 2% to 4% per annum rupture risk for brain arteriovenous malformations (bAVMs), there is no way to estimate risk for an individual patient. METHODS: In this retrospective study, patients were eligible who had nidiform bAVMs and underwent detailed pretreatment diagnostic cerebral angiography at our medical center from 1996 to 2006. All patients had superselective microcatheter angiography, and films were reviewed for the purpose of this project. Patient demographics, clinical presentation, and angioarchitectural characteristics were analyzed. A univariate analysis was performed, and angioarchitectural features with potential physiological significance that showed at least a trend toward significance were added to a multivariate logistic regression model. RESULTS: One hundred twenty-two bAVMs met criteria for study entry. bAVMs with single venous drainage anatomy were more likely to present with hemorrhage. In addition, patients with multiple draining veins and a venous stenosis reverted to a risk similar to those with 1 draining vein, whereas those with multiple draining veins and without stenosis had diminished association with hemorrhage presentation. Those bAVMs with associated aneurysms were more likely to present with hemorrhage. These findings were robust in both univariate and multivariate models. CONCLUSIONS: The results of this article lead to the first physiological, internally consistent model of individual bAVM hemorrhage risk, where 1 draining vein, venous stenosis, and associated aneurysms increase risk.