Jared M. Pisapia

Comparison of endoscopic and microscopic removal of pituitary adenomas: single-surgeon experience and the learning curve.

OBJECT The endoscopic endonasal approach for resection of pituitary lesions is an effective surgical option for tumors of the sella turcica. In this study the authors compared outcomes after either purely endoscopic resection or traditional microscope-aided resection. They also attempted to determine the learning curve associated with a surgical team converting to endoscopic techniques. METHODS Retrospective data were collected on patients who were surgically treated for a pituitary lesion at the Hospital of the University of Pennsylvania between July 2003 and May 2008. Age, sex, race, presenting symptoms, length of hospital stay, surgical approach, duration of surgery, tumor pathological features, gross-total resection (GTR) of tumor, recurrence of the lesion, and intraoperative and postoperative complications were noted. All procedures were performed by the same senior neurosurgeon, who was initially unfamiliar with the endoscopic endonasal approach. RESULTS A total of 25 patients underwent microscopic resection and 25 patients underwent endoscopic resection performed by a single skull base team consisting of the same senior neurosurgeon and otorhinolaryngologist (M.S.G. and B.W.O.). In the microscopically treated cohort, there were 8 intra- or postoperative complications, 6 intraoperative CSF leaks, 17 (77%) of 22 patients had GTR on postoperative imaging, 5 patients underwent >or= 2 operations, and 10 (59%) of 17 patients reported total symptom resolution at follow-up. The endoscopically treated group had 7 intraor postoperative complications and 7 intraoperative CSF leaks. Of the patients who had pre- and postoperative imaging studies, 14 (66%) of 21 endoscopically treated patients had GTR; 4 patients had >or= 2 operations, and 10 (66%) of 15 patients reported complete symptom resolution at follow-up. The first 9 patients who were treated endoscopically had a mean surgical time of 3.42 hours and a mean hospital stay of 4.67 days. The next 8 patients treated had a mean surgical time of 3.11 hours and a mean hospital stay of 3.13 days. The final 8 patients treated endoscopically had a mean surgical time of 2.22 hours and a mean hospital stay of 3.88 days. The difference in length of operation between the first 9 and the last 8 patients treated endoscopically was significantly different. There was a trend toward decreased CSF leaks and other complications from the first 2 groups compared with the third group. CONCLUSIONS In this subset of patients, the use of endoscopic endonasal resection results in a similar complication and symptom resolution rate compared with traditional techniques. The authors postulate that the learning curve for endoscopic resection can be </= 17 procedures.

Deep brain stimulation of the nucleus accumbens for the treatment of addiction

Despite novel medications and other therapeutic strategies, addiction to psychotropic substances remains one of the most serious public health problems worldwide. In this review, beginning with an introduction of deep brain stimulation (DBS), we highlight the importance of the nucleus accumbens (NAc) in the context of the reward circuitry and addictive behavior. We will provide a short historic overview of other neurosurgical approaches to treat addiction and describe the experimental and preclinical data on DBS in addiction. Finally, we call attention to key ethical issues related to using DBS to treat addiction that are important for future research and the design of clinical trials.

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

BACKGROUND MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). METHODS One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. RESULTS Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. CONCLUSIONS By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients.

Systematic Review of Outcome After Ischemic Stroke Due to Anterior Circulation Occlusion Treated With Intravenous, Intra-Arterial, or Combined Intravenous+Intra-Arterial Thrombolysis

Background and Purpose— The optimal approach to recanalization in acute ischemic stroke is unknown. We performed a literature review and meta-analysis comparing the relative efficacy of 6 reperfusion strategies: (1) 0.9 mg/kg intravenous tissue-type plasminogen activator; (2) intra-arterial chemical thrombolysis; (3) intra-arterial mechanical thrombolysis; (4) intra-arterial combined chemical/mechanical thrombolysis; (5) 0.6 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis; and (6) 0.9 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis. Methods— A literature search in Medline, Embase, and the Cochrane database identified case series, observational studies, and treatment arms of randomized trials of anterior circulation arterial occlusion treated with thrombolytic therapy. Included studies had ≥10 subjects, mean time to treatment <6 hours, and treatment specific reporting of disability, death, and intracerebral hemorrhage. Multivariable metaregression evaluated the effects of treatment group on outcome at the same time as accounting for differences in baseline covariates. Results— A total of 2986 abstracts were identified from which 54 studies (5019 subjects) were included. There were significant differences across groups in age (P=0.0008), baseline National Institutes of Health Stroke Scale (P=0.0002), and time to treatment initiation (P<0.0001). There were also differences in mean modified Rankin Scale (P<0.0001), mortality (P=0.0024), and symptomatic intracerebral hemorrhage (P=0.0305). Differences in modified Rankin Scale were not significant in the metaregression and likely attributable to differences in baseline covariates between studies. Conclusions— This study found no evidence that one reperfusion strategy is superior with respect to efficacy or safety, supporting clinical equipoise between reperfusion strategies. Intravenous tissue-type plasminogen activator remains the standard of care for acute ischemic stroke. Randomized clinical trials are necessary to determine the efficacy of alternative reperfusion strategies. Participation in such trials is strongly recommended.

Deep brain stimulation compared with methadone maintenance for the treatment of heroin dependence: a threshold and cost-effectiveness analysis

AIMS To determine the success threshold at which a theoretical course of deep brain stimulation (DBS) would provide the same quality of life (QoL) and cost-effectiveness for heroin dependence as methadone maintenance treatment (MMT). DESIGN We constructed a decision analysis model to calculate QoL after 6 months of MMT and compared it to a theoretical course of DBS. We also performed a cost-effectiveness analysis using societal costs of heroin dependence, MMT and DBS. SETTING Systematic literature review and meta-analysis. PARTICIPANTS Patients (n = 1191) from 15 trials administering 6 months of MMT and patients (n = 2937) from 45 trials of DBS for movement disorders. MEASUREMENTS Data on QoL before and after MMT, retention in MMT at 6 months, as well as complications of DBS and their impact on QoL in movement disorders. FINDINGS We found a QoL of 0.633 (perfect health = 1) in heroin addicts initiating MMT. Sixty-six per cent of patients completed MMT, but only 47% of them had opiate-free urine samples, resulting in an average QoL of 0.7148 (0.3574 quality-adjusted life years (QALYs) over 6 months). A trial of DBS is less expensive (

Microthrombosis after experimental subarachnoid hemorrhage: time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan.

81,000) than untreated (or relapsed) heroin dependence (

Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study

100,000), but more expensive than MMT (

Early experience with flow diverting endoluminal stents for the treatment of intracranial aneurysms

58,000). A theoretical course of DBS would need a success rate of 36.5% to match MMT, but a success rate of 49% to be cost-effective. CONCLUSIONS The success rate, defined as the percentage of patients remaining heroin-free after 6 months of treatment, at which deep brain stimulation would be similarly cost-effective in treating opiate addiction to methadone maintenance treatment, is estimated at 49%.

An institutional series and literature review of pial arteriovenous fistulas in the pediatric population: clinical article.

Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality for patients surviving the rupture of an intracranial aneurysm. Despite an association between vasospasm and DCI, thrombosis and thromboembolism may also contribute to DCI. In this study we investigate the time course of intravascular microclot formation after experimental subarachnoid hemorrhage (SAH) and assess the effects of the following two drugs on microclot burden: mutant thrombin-activated urokinase-type plasminogen activator (scFv/uPA-T), which is bound to red blood cells for use as a thromboprophylactic agent, and clazosentan, an endothelin antagonist. In the first study, adult male C57BL/6 mice were sacrificed at 24 (n=5), 48 (n=6), 72 (n=8), and 96 (n=3) hours after SAH induced by filament perforation of the anterior cerebral artery. Sham animals (n=5) underwent filament insertion without puncture. In the second study, animals received scFv/uPA-T (n=5) 3 hours after hemorrhage, clazosentan (n=5) by bolus and subcutaneous pump after SAH just prior to skin closure, or a combination of scFv/uPA-T and clazosentan (n=4). Control (n=6) and sham (n=5) animals received saline alone. All animals were sacrificed at 48 hours and underwent intra-cardiac perfusion with 4% paraformaldehyde. The brains were then extracted and sliced coronally on a cryostat and processed for immunohistochemistry. An antibody recognizing thrombin-anti-thrombin complexes was used to detect microclots on coronal slices. Microclot burden was calculated for each animal and compared among groups. Following SAH, positive anti-thrombin staining was detected bilaterally in the following brain regions, in order of decreasing frequency: cortex; hippocampus; hypothalamus; basal ganglia. Few microclots were found in the shams. Microclot burden peaked at 48 hours and then decreased gradually. Animals receiving scFv/uPA-T and scFv/uPA-T+clazosentan had a lower microclot burden than controls, whereas animals receiving clazosentan alone had a higher microclot burden (p<0.005). The overall mortality rate in the time course study was 40%; mortality was highest among control animals in the second study. Intravascular microclots form in a delayed fashion after experimental SAH. Microclots may be safely reduced using a novel form of thromboprophylaxis provided by RBC-targeted scFv/uPA-T and represent a potential target for therapeutic intervention in the treatment of DCI.

Ethical Considerations in Deep Brain Stimulation for the Treatment of Addiction and Overeating Associated With Obesity

OBJECT Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries. METHODS Medline searches were performed for studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was considered successful if postoperative excess weight loss exceeded 45% at 1-year follow-up. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no surgical treatment. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS Fifteen studies involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies involving 2937 cases treated with DBS were included. The operative successes were 0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB. Sensitivity analysis revealed utility of surgical complications in LRYGB, probability of surgical complications in DBS, and success rate of DBS as having the greatest influence on outcomes. At no values did LAGB result in superior outcomes compared with other treatments. CONCLUSIONS Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity.