Ramesh Grandhi

Stereotactic radiosurgery using the Leksell Gamma Knife Perfexion unit in the management of patients with 10 or more brain metastases

OBJECT To better establish the role of stereotactic radiosurgery (SRS) in treating patients with 10 or more intracranial metastases, the authors assessed clinical outcomes and identified prognostic factors associated with survival and tumor control in patients who underwent radiosurgery using the Leksell Gamma Knife Perfexion (LGK PFX) unit. METHODS The authors retrospectively reviewed data in all patients who had undergone LGK PFX surgery to treat 10 or more brain metastases in a single session at the University of Pittsburgh. Posttreatment imaging studies were used to assess tumor response, and patient records were reviewed for clinical follow-up data. All data were collected by a neurosurgeon who had not participated in patient care. RESULTS Sixty-one patients with 10 or more brain metastases underwent SRS for the treatment of 806 tumors (mean 13.2 lesions). Seven patients (11.5%) had no previous therapy. Stereotactic radiosurgery was the sole prior treatment modality in 8 patients (13.1%), 22 (36.1%) underwent whole-brain radiation therapy (WBRT) only, and 16 (26.2%) had prior SRS and WBRT. The total treated tumor volume ranged from 0.14 to 40.21 cm(3), and the median radiation dose to the tumor margin was 16 Gy. The median survival following SRS for 10 or more brain metastases was 4 months, with improved survival in patients with fewer than 14 brain metastases, a nonmelanomatous primary tumor, controlled systemic disease, a better Karnofsky Performance Scale score, and a lower recursive partitioning analysis (RPA) class. Prior cerebral treatment did not influence survival. The median survival for a patient with fewer than 14 brain metastases, a nonmelanomatous primary tumor, and controlled systemic disease was 21.0 months. Sustained local tumor control was achieved in 81% of patients. Prior WBRT predicted the development of new adverse radiation effects. CONCLUSIONS Stereotactic radiosurgery safely and effectively treats intracranial disease with a high rate of local control in patients with 10 or more brain metastases. In patients with fewer metastases, a nonmelanomatous primary lesion, controlled systemic disease, and a low RPA class, SRS may be most valuable. In selected patients, it can be considered as first-line treatment.

Stereotactic radiosurgery for the treatment of symptomatic brainstem cavernous malformations.

OBJECT The authors performed a retrospective review of prospectively collected data to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) for the treatment of patients harboring symptomatic solitary cavernous malformations (CMs) of the brainstem that bleed repeatedly and are high risk for resection. METHODS Between 1988 and 2005, 68 patients (34 males and 34 females) with solitary, symptomatic CMs of the brainstem underwent Gamma Knife surgery. The mean patient age was 41.2 years, and all patients had suffered at least 2 symptomatic hemorrhages (range 2-12 events) before radiosurgery. Prior to SRS, 15 patients (22.1%) had undergone attempted resection. The mean volume of the malformation treated was 1.19 ml, and the mean prescribed marginal radiation dose was 16 Gy. RESULTS The mean follow-up period was 5.2 years (range 0.6-12.4 years). The pre-SRS annual hemorrhage rate was 32.38%, or 125 hemorrhages, excluding the first hemorrhage, over a total of 386 patient-years. Following SRS, 11 hemorrhages were observed within the first 2 years of follow-up (8.22% annual hemorrhage rate) and 3 hemorrhages were observed in the period after the first 2 years of follow-up (1.37% annual hemorrhage rate). A significant reduction (p < 0.0001) in the risk of brainstem CM hemorrhages was observed following radiosurgical treatment, as well as in latency period of 2 years after SRS (p < 0.0447). Eight patients (11.8%) experienced new neurological deficits as a result of adverse radiation effects following SRS. CONCLUSIONS The results of this study support a role for the use of SRS for symptomatic CMs of the brainstem, as it is relatively safe and appears to reduce rebleeding rates in this high-surgical-risk location.

Preinjury warfarin, but not antiplatelet medications, increases mortality in elderly traumatic brain injury patients

BACKGROUND Previous studies of traumatic brain injury (TBI) outcomes in elderly patients on oral antithrombotic (OAT) therapies have yielded conflicting results. Our objective was to examine the effect of premorbid OAT medications on outcomes among elderly TBI patients with intracranial hemorrhage. METHODS We performed a retrospective analysis of elderly TBI patients (≥65 years) with closed head injury and evidence of brain hemorrhage on computed tomography scan from 2006 to 2010. Patient demographics, injury severity, clinical course, hospital and intensive care unit length of stay, and disposition were collected. Comparison of patients stratified by premorbid OAT use was performed using nonparametric Kruskal-Wallis and Fisher’s exact tests. Multivariable logistic regression was used to compare groups and identify predictors of primary outcomes, including mortality, neurosurgical intervention, hemorrhage progression, complications, and infection. RESULTS A total of 1,552 patients were identified: 543 on aspirin only, 97 on clopidogrel only, 218 on warfarin only, 193 on clopidogrel and aspirin, and 501 on no antithrombotic agent. Blood products were administered to reverse coagulopathy in 77.3% of patients on antithrombotic medications. After adjusting for covariates, including medication reversal, OAT use was associated with increased mortality (p = 0.04). Warfarin use was identified as a key predictor (odds ratio, 2.27; p = 0.05), in contrast to the preinjury use of antiplatelet medications, which was not associated with increased risk of in-hospital death. Rates of neurosurgical intervention differed between groups, with patients on warfarin undergoing intervention more frequently. Survivor subset analysis demonstrated that hemorrhage progression was not associated with preinjury antithrombotic therapy, nor were rates of complication or infection, hospital and intensive care unit lengths of stay, or ventilator days. CONCLUSION Preinjury use of warfarin, but not antiplatelet medications, influences survival and need for neurosurgical intervention in elderly TBI patients with intracranial hemorrhage; hemorrhage progression and morbidity are not affected. The importance of antithrombotic therapy may lie in its impact on initial injury severity. LEVEL OF EVIDENCE Epidemiologic study, level III.

Primary manual aspiration thrombectomy (MAT) for acute ischemic stroke: safety, feasibility and outcomes in 112 consecutive patients

Aim To describe procedural aspects and clinical outcomes in a consecutive series of patients in whom manual aspiration thrombectomy (MAT) was performed as the first treatment modality with other techniques used only in case MAT did not yield recanalization. Methods A retrospective review of a prospectively acquired acute stroke intervention database was performed. Primary MAT was carried out with a preference for the largest catheter considered to be trackable into the target occlusive lesion. The catheter was wedged into the thrombus followed by manual aspiration with a 20 ml syringe. Results 112 consecutive patients were evaluated. The median age was 66 years and the median NIH Stroke Scale score was 17. Occlusion locations included the M1 (62%), M2 (8%), internal carotid artery terminus (19%) and the vertebrobasilar artery (11%). Patients with anterior occlusions had tandem extracranial/intracranial occlusive lesions in 18.7% Median time from symptom onset to groin puncture was 267 min, and from groin puncture to recanalization was 70 min. Successful recanalization (defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3) with primary MAT was 59% with a median of two passes. 41% of patients required the use of adjunctive therapy yielding an overall recanalization rate of TICI 2b/3 (86%) and TICI 3 (30.6%). Parenchymal hematoma of any type (PH1/PH2) was seen in 9.8% of patients, with symptomatic hemorrhage in 6%. Favorable outcomes (90-day modified Rankin Scale ≤2) were 46%. Mortality at 3 months was 31%. Primary MAT was associated with faster procedural times (mean 63 vs 97 min, p<0.0001) but not with higher rates of favorable outcomes. Conclusions Primary MAT is an alternative endovascular recanalization technique with reasonable first pass efficacy that will likely improve with technology and experience.

Administration of 4-Factor Prothrombin Complex Concentrate as an Antidote for Intracranial Bleeding in Patients Taking Direct Factor Xa Inhibitors

OBJECTIVE Direct factor Xa inhibitors rivaroxaban and apixaban are efficacious alternatives to warfarin and confer a lower risk of spontaneous intracranial hemorrhage (ICH); however, they lack a validated reversal strategy. We evaluated the efficacy and safety of 4-factor prothrombin complex concentrate (PCC) administration on rivaroxaban- and apixaban-mediated coagulopathy in patients with traumatic and spontaneous ICH. METHODS Retrospective review of patients presenting with traumatic and spontaneous ICH and concurrent use of rivaroxaban or apixaban. Demographic factors, reason for anticoagulation, hemorrhage type and location, Glasgow coma scale score, and when appropriate, ICH score, were included. Patient charts were reviewed for in-hospital mortality, thromboembolic events, pulmonary complications, worsening of hemorrhage, hemorrhagic complications after neurosurgical intervention, and 90-day modified Rankin scale score. RESULTS Eighteen patients met inclusion criteria; 16 used rivaroxaban and 2 used apixaban. Eight patients presented with traumatic ICH, 8 with hemorrhagic stroke, 1 with subarachnoid hemorrhage, and 1 patient with tumoral hemorrhage. Mean Glasgow coma scale score was 12.6 (range, 6-15) and mean ICH score was 2.3 (range, 0-4). After reversal with PCC, 1 patient (5.6%) demonstrated worsening of ICH on follow-up head computed tomography. PCCs were administered before emergent placement of an external ventricular drain in 1 individual, with no hemorrhagic complications. Six patients (33.3%) experienced in-hospital mortality: family withdrew care in 4 and 2 died due to pneumonia. There was 1 (5.6%) thromboembolic complication. Favorable outcomes at 90 days were seen in 6 patients (33.3%). CONCLUSIONS Despite no studies demonstrating the efficacy of 4-factor PCC administration for reversal of coagulopathy in patients on direct factor Xa inhibitors, our early experience demonstrates it to be safe, yet potentially reducing hemorrhagic complications and hematoma expansion in this critically ill population.

Transcervical access in acute ischemic stroke

Background Large vessel occlusive disease portends a poor prognosis unless recanalization is rapidly achieved. Endovascular treatment is typically performed via a transfemoral approach, but catheterization of the occluded vessel can be problematic in cases of extensive vessel tortuosity. Methods A retrospective review of a prospectively maintained database identified 7 patients who underwent acute endovascular reperfusion therapy via transcervical approach. Results We identified 7 patients. Admission NIHSS ranged from 8–27 and recanalization occurred between 7–49 min of carotid access. Prior to carotid access, 20–90 min were spent attempting target vessel catheterization via the transfemoral approach. All occlusions were in the left MCA. In 87.5% of patient, TICI2b/3 recanalization was achieved. Neck hematoma formation occurred in one case requiring elective intubation. At 2 months followup, all patients had survived with mRS 0–4 except for one patient who had a large infarct despite recanalization. Conclusions Transcervical access for acute ischemic stroke leads to rapid and high quality recanalization. Future studies will focus on improved hemostasis and early identification of patients who would benefit the most from direct carotid access for acute stroke.

Preoperative prealbumin level as a risk factor for surgical site infection following elective spine surgery

Background: Nutritional status is a critical factor in patient outcomes in a variety of medical contexts. In the surgical fields, there is substantial evidence suggesting that clinical outcomes including infection risk and surgical efficacy may be affected by preoperative nutritional status. The purpose of this study is to evaluate preoperative serum prealbumin levels, the currently preferred serum biomarker of nutritional deficiency, in relation to the risk of developing a surgical site infection. Methods: A retrospective case–control series was conducted comparing prospectively collected preadmission serum prealbumin levels to the risk for surgical site infection following elective spine surgery. The analysis was conducted under an approved institutional quality assurance protocol. Patients were identified by querying the department billing codes for deep wound washouts over a 3-year period. A cohort of 32 patients with preoperative prealbumin levels who underwent spine surgery complicated by postoperative deep tissue infection was identified. This was compared against a case–control cohort of 74 patients who underwent spine surgery and did not experience postoperative infection. Clinical variables included demographic information, body mass index, smoking, diabetes, steroid use, length of the procedure, and length of hospital stay. The data were analyzed using multivariate Cox regression. Results: Two variables: Preoperative prealbumin < 20 and diabetes were both statistically significant predictors for the risk of developing a postoperative infection with hazard ratios of 2.12 (95% confidence interval [CI]: 1.03–4.37) and 2.22 (95% CI: 1.04–4.75), respectively. Conclusions: Our results reinforce the relationship between preoperative nutritional status and outcomes in elective spine surgery. The data indicate that preoperative prealbumin levels may be useful in risk stratification. Further study is needed to determine whether nutritional supplementation may reduce the risk of infection.

Prealbumin as a Serum Biomarker of Impaired Perioperative Nutritional Status and Risk for Surgical Site Infection after Spine Surgery

INTRODUCTION Impaired perioperative nutritional status has been shown to be an important predictor of surgical morbidity and is the earliest marker of nutritional deficiency. No study, however, has examined serum prealbumin as a surrogate marker of nutritional status in patients undergoing spine surgery. METHODS We performed a retrospective review of all patients who developed a postoperative deep wound infection after undergoing spine surgery at the University of Pittsburgh Medical Center from January 2008 through December 2011. Demographics, preoperative diagnosis, type of surgery, perioperative serum prealbumin level, time to infection, number and type of debridement procedures, and length of hospital stay were recorded. RESULTS A total of 83 patients had prealbumin levels available at the time of presentation of infection. Mean patient age was 56 years, and 71% were women. Surgical treatment for the infection required between 1 and 13 debridements, and 21 (25%) of the 83 patients who had instrumentation placed at the time of the initial surgery required removal of their instrumentation. Inpatient hospitalizations were extended by an average of 13 days. Prealbumin levels were below normal in 82 (99%) of the 83 patients; levels were < 7 mg/dL in 24 patients, between 7 and 11 mg/dL in 32 patients, and between 11 and 19 mg/dL in 26 patients. CONCLUSIONS All patients except one who developed postoperative deep wound infection after spine surgery had serum prealbumin levels in the malnutrition range at the time of presentation. The current study suggests serum prealbumin levels may be an inexpensive screening biomarker for nutritional status and risk stratification for postoperative infection after spine surgery.

Extracellular matrices, artificial neural scaffolds and the promise of neural regeneration.

Over last 20 years, extracellular matrices have been shown to be useful in promoting tissue regeneration. Recently, they have been used and have had success in achieving neurogenesis. Recent developments in extracellular matrix design have allowed their successful in vivo incorporation to engender an environment favorable for neural regeneration in animal models. Promising treatments under investigation include manipulation of the intrinsic extracellular matrix and incorporation of engineered naometer-sized scaffolds through which inhibition of molecules serving as barriers to neuroregeneration and delivery of neurotrophic factors and/or cells for successful tissue regeneration can be achieved. Further understanding of the changes incurred within the extracellular matrix following central nervous system injury will undoubtedly help design a clinically efficacious extracellular matrix scaffold that can mitigate or reverse neural degeneration in the clinical setting.

Onyx embolization of infectious intracranial aneurysms

Background Infectious intracranial aneurysms (IIAs) are rare and potentially devastating. First-line management involves intravenous antibiotics, with surgical or endovascular management reserved for cases of failed medical treatment or aneurysmal rupture. Endovascular therapy has become the primary approach for treating these small, distally located aneurysms. Liquid embolic agents are well suited for use because of their ability to fill the aneurysm and parent vessel. We present our experience in treating these aneurysms via Onyx embolization and review the literature. Methods We retrospectively reviewed the endovascular treatment of IIAs at our institution from 2010 to 2012. Eight patients with 16 IIAs ranging in size from 1 to 16 mm underwent treatment. Seven of the patients initially presented after aneurysmal rupture. Onyx was pushed until the aneurysm and parent artery were filled. Confirmation of aneurysmal occlusion was made by repeat cerebral angiography. Results One symptomatic stroke occurred after embolization. Fourteen of the 16 aneurysms have been evaluated with follow-up angiography and remain occluded. Conclusions Treatment of IIAs using an endovascular approach with Onyx is safe and effective.