5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

The Safety and Feasibility of Image-Guided BrainPath-Mediated Transsulcul Hematoma Evacuation: A Multicenter Study.

BACKGROUND: Subcortical injury resulting from conventional surgical management of intracranial hemorrhage may counteract the potential benefits of hematoma evacuation. OBJECTIVE: To evaluate the safety and potential benefits of a novel, minimally invasive approach for clot evacuation in a multicenter study. METHODS: The integrated approach incorporates 5 competencies: (1) image interpretation and trajectory planning, (2) dynamic navigation, (3) atraumatic access system (BrainPath, NICO Corp, Indianapolis, Indiana), (4) extracorporeal optics, and (5) automated atraumatic resection. Twelve neurosurgeons from 11 centers were trained to use this approach through a continuing medical education-accredited course. Demographical, clinical, and radiological data of patients treated over 2 years were analyzed retrospectively. RESULTS: Thirty-nine consecutive patients were identified. The median Glasgow Coma Scale (GCS) score at presentation was 10 (range, 5-15). The thalamus/basal ganglion regions were involved in 46% of the cases. The median hematoma volume and depth were 36 mL (interquartile range [IQR], 27-65 mL) and 1.4 cm (IQR, 0.3-2.9 cm), respectively. The median time from ictus to surgery was 24.5 hours (IQR, 16-66 hours). The degree of hematoma evacuation was ≥90%, 75% to 89%, and 50% to 74% in 72%, 23%, and 5.0% of the patients, respectively. The median GCS score at discharge was 14 (range, 8-15). The improvement in GCS score was statistically significant ( P < .001). Modified Rankin Scale data were available for 35 patients. Fifty-two percent of those patients had a modified Rankin Scale score of ≤2. There were no mortalities. CONCLUSION: The approach was safely performed in all patients with a relatively high rate of clot evacuation and functional independence.

More fateful than fruitful? Intracranial pressure monitoring in elderly patients with traumatic brain injury is associated with worse outcomes.

BACKGROUND: In an expanding elderly population, traumatic brain injury (TBI) remains a significant cause of death and disability. Guidelines for management of TBI, according to the Brain Trauma Foundation (BTF), include intracranial pressure (ICP) monitoring. Whether ICP monitoring contributes to outcomes in the elderly patients with TBI has not been explored. METHODS: This is a retrospective study extracted from the National Trauma Database 2007-2008 research datasets. Patients were included if aged >55 y and they met BTF indications for ICP monitoring. Patients that had nonsurvivable injuries (any body region, abbreviated injury score = 6), were dead on arrival, had withdrawal of care, or length of stay <48 h were excluded. Outcomes were then stratified based on ICP monitoring. The primary outcomes were inhospital mortality and favorable discharge. Logistic regression was used to analyze the effect of ICP monitoring on outcomes. RESULTS: A total of 4437 patients were included with 11.2% having an ICP monitor placed. Patients requiring an ICP monitor were younger overall, more likely to present hypertensive, had higher injury severity, and more likely to require operative intervention. Median initial Glasgow coma scale (3) was similar between groups. Of those patients with ICP monitoring, overall mortality was significantly higher, and they were less likely to have favorable discharge status. Craniotomy itself was not associated with increased mortality (P = 0.450). CONCLUSIONS: Our findings suggest that the use of ICP monitoring according to BTF guidelines in elderly TBI patients does not provide outcomes superior to treatment without monitoring. The ideal group to benefit from ICP monitor placement remains to be elucidated.

Dabigatran bleed risk with closed head injuries: are we prepared?

OBJECT: The direct thrombin inhibitor dabigatran has recently been approved in the US as an alternative to warfarin. The lack of guidelines, protocols, and an established specific antidote to reverse the anticoagulation effect of dabigatran potentially increases the rates of morbidity and mortality in patients with closed head injury (CHI). Confronted with this new problem, the authors reviewed their initial clinical experience. METHODS: The authors retrospectively reviewed all cases of adult patients (age ≥ 18 years) who sustained CHI secondary to ground-level falls and who presented to the authors' provisional regional Level I trauma center between February 2011 and May 2011. The authors divided these patients into 3 groups based on anticoagulant therapy: dabigatran, warfarin, and no anticoagulants. RESULTS: Between February 2011 and May 2011, CHIs from ground-level falls were sustained by 5 patients while on dabigatran, by 15 patients on warfarin, and by 25 patients who were not on anticoagulants. The treatment of the patients on dabigatran at the authors' institution had great diversity. Repeat CT scans obtained during reversal showed 4 of 5 patients with new or expanded hemorrhages in the dabigatran group, whereas the warfarin group had 3 of 15 (p = 0.03). The overall mortality rate for patients sustaining CHI on dabigatran was 2 (40%) of 5, whereas that of the warfarin group was 0 (0%) of 15 (p = 0.05). CONCLUSIONS: It is critical for physicians involved in the care of patients with CHI on dabigatran to be aware of an elevated mortality rate if no treatment protocol or guideline is in place. The authors will soon implement a reversal management protocol for patients with CHI on dabigatran at their institution in an attempt to improve efficacy and safety in their treatment approach.