Faculty Bibliography

Stereotactic radiosurgery is widely used to treat cerebral arteriovenous malformations (AVMs), with the goal of complete angiographic obliteration. A number of case series have challenged the assumption that absence of residual AVM on follow-up angiograms is consistent with elimination of the risk of hemorrhage. The authors describe 3 cases in which patients who had angiographic evidence of AVM occlusion presented with late hemorrhage in the area of their prior lesions. They compare the radiographic, angiographic, and histological features of these patients with those previously described in the literature. Delayed hemorrhage from the tissue of occluded AVMs has been reported as early as 4 and as late as 11 years after initial stereotactic radiosurgery. In all cases for which data are available, hemorrhage occurred in the area of persistent imaging findings despite negative findings on conventional angiography. The hemorrhagic lesions that were resected demonstrated a number of distinct histological findings. While rare, delayed hemorrhage from the tissue of occluded AVMs may occur from a number of distinct, angiographically occult postirradiation changes. The hemorrhages in the authors' 3 cases were symptomatic and localized. The correlation of histological and imaging findings in delayed hemorrhage from occluded AVMs is an area requiring further investigation.

OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

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.

Introduction: The precise threshold differentiating normal and elevated intracranial pressure (ICP) is variable among individuals. In the context of several pathophysiologic conditions, elevated ICP leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (CNs), either or both which may contribute to ocular dysmotility. The purpose of this study is to assess the impact of elevated ICP on eye tracking performed while watching a short film clip. Methods: Awake patients requiring placement of an ICP monitor for clinical purposes were eye tracked while watching a 220-second continuously playing video moving around the perimeter of a viewing monitor. Pupil position was recorded at 500 Hz and metrics associated with each eye individually and both eyes together were calculated. Linear regression with generalized estimating equations was performed to test the association of eye tracking metrics with changes in intracranial pressure. Results: Eye tracking was performed at ICP levels ranging from -3 to 30 mm Hg in twenty-three patients (twelve female, eleven male, mean age 46.8 years) on fifty-five separate occasions. Eye tracking measures correlating with cranial nerve function linearly decreased with increasing ICP (p-value 12 mm Hg was 0.798. Conclusions: Eye tracking abnormalities detected while watching a short film clip correlate with changes in monitored intracranial pressure. Increasingly elevated ICP was associated with increasingly abnormal eye tracking. Our results suggest that eye tracking while watching a short film clip may be used to quantitate the physiologic impact of elevated intracranial pressure. This represents a new non-invasive automatable means for assessing the physiologic impact of elevated ICP

Rupture of isolated posterior spinal artery (PSA) aneurysms is a rare cause of subarachnoid hemorrhage (SAH) that presents unique diagnostic challenges owing to a nuanced clinical presentation. Here, we report on the diagnosis and management of the first known case of an isolated PSA aneurysm in the context of leukocytoclastic vasculitis. A 53-year-old male presented to an outside institution with acute bilateral lower extremity paralysis 9 days after admission for recurrent cellulitis. Early magnetic resonance imaging was read as negative and repeat imaging 15 days after presentation revealed SAH and a compressive spinal subdural hematoma. Angiography identified a PSA aneurysm at T9, as well as other areas suspicious for inflammatory or post-hemorrhagic reactive changes. The patient underwent a multilevel laminectomy for clot evacuation and aneurysm resection to prevent future hemorrhage and to establish a diagnosis. The postoperative course was complicated by medical issues and led to the diagnosis of leukocytoclastic vasculitis that may have predisposed the patient to aneurysm development. Literature review reveals greater mortality for cervical lesions than thoracolumbar lesions and that the presence of meningitic symptoms portents better functional outcome than symptoms of cord compression. The outcome obtained in this case is consistent with outcomes reported in the literature.

Management of non-emergent, non-acute subdural hematomas (SDHs) ranges from observation to burr-hole evacuation or craniotomy, but recurrence rates are high. We evaluated the safety and efficacy of tranexamic acid (TXA) for the treatment of residual SDHs following bedside twist-drill evacuation. We performed a retrospective analysis of a prospectively maintained database from November 2013 to November 2014 for all patients who underwent placement of a bedside Subdural Evacuating Port System (SEPS) followed by treatment with oral TXA (650 mg daily). All demographics, evidence of VTE and volumes of pertinent CTs were obtained. Twenty subdural hematomas in 14 patients met the inclusion criteria for this study. The majority of SDHs were mixed density. Mean SDH volume on presentation was 145.96 cm3 +/- 40.22 with a mean midline shift of 9.44 mm +/- 4.84. Mean volumes decreased to 80.00 cm3 +/- 31.96, and midline shift improved to 4.44 mm +/- 3.29, after SEPS placement (p < 0.0001 and p = 0.0046). All patients were placed on TXA after their procedure. Mean follow-up with CT was 92.1 days +/- 27.5, and mean SDH volume at last follow-up was 7.41 cm3 +/- 15.54 with a mean midline shift of 0.19 mm +/- 0.69 (p < 0.0001 and p = 0.0002). Percent volume reduction was significantly higher after TXA than after SEPS (91.31% versus 40.74%, p < 0.0001). No increase or delayed recurrence of the SDH was noted during TXA treatment. All but one clinical presenting symptom improved at follow-up. No venous thromboembolisms were noted amongst the patients. In our pilot study, chronic SDH volumes were reduced by 40.74% after SEPS drainage. The residual volume was reduced by an additional 91.31% during oral TXA treatment. No patients developed delayed recurrence or expansion of their SDHs. Further prospective studies are needed to evaluate the role of TXA for adjunctive treatment of chronic SDHs.

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)