Massive Biventricular Thrombi in a Patient with Endometrial Adenocarcinoma Diagnosed on Computed Tomography Angiography.

Biventricular thrombi are a rare clinical entity and only reported in several case reports. Given ventricular thrombi are high risk for cardioembolic events, accurate detection and therapeutic management has an important influence on clinical outcomes. We present a case of a patient with biventricular thrombi that was initially diagnosed on computed tomography angiography, emphasizing its clinical utility as a rapid, non-invasive imaging modality for early detection.

Soluble ST2 and Soluble Markers of Fibrosis: Emerging Roles for Prognosis and Guiding Therapy.

PURPOSE OF REVIEW: Biomarkers of cardiac fibrosis closely track the disease state that gives rise to heart failure. The purpose of this review is to highlight recent data on the use of soluble ST2, galectin-3, and procollagen, three markers of cardiac fibrosis, for aiding with prognostication, and to explore the use of these biomarkers for guiding therapy. RECENT FINDINGS: Soluble ST2, galectin-3, and procollagen are prognostic in both acute and chronic heart failure, and data are emerging as to their potential uses for guiding therapies. Mortality benefit from exercise, cardiac resynchronization therapy, statin use, as well as anti-fibrotic therapies such as aldosterone antagonism may vary based upon levels of these fibrosis markers. Soluble ST2, galectin-3, and procollagen provide independent prognostic information for heart failure morbidity and mortality. Markers of cardiac fibrosis may also help identify the subsets of patients who are most likely to benefit from various therapies. However, further studies are needed prior to formalizing individual patient care algorithms guided by fibrosis biomarkers.

An update on the use and discovery of prognostic biomarkers in acute decompensated heart failure.

Introduction: Acute decompensated heart failure (ADHF) remains a significant health care burden as evidenced by high readmission rates and mortality. Over the years, the care of patients with ADHF has been transformed by the use of biomarkers, specifically to aid in the diagnosis and prognosis. Patients with HF follow a variable course given the complex and heterogenous pathophysiological processes, thus it is imperative for clinicians to have tools to predict short and long-term outcomes in order to educate patients and optimize management. Areas Covered: The natriuretic peptides, including B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, are considered the gold standard biomarkers. Yet, other emerging biomarkers such as suppression of tumerogenicity-2, cardiac troponin, galectin-2, mid-regional pro-adrenomedullin, copeptin, cystatin, and neutrophil gelatinase-associated lipocalin have increasingly shown promise in evaluating prognosis in patients with ADHF. This article reviews the pathophysiology and utility of both established and emerging biomarkers for the prognostication of patients with ADHF. Expert Opinion: As of 2019, the most validated biomarkers for use in decompensated heart failure include natriuretic peptides, high sensitivity troponin, and sST2. These biomarkers are involved in the underlying pathophysiology of disease and as such provide added information to that of exam, x-ray, and echocardiography.

Diffusion tractography imaging-guided frameless linear accelerator stereotactic radiosurgical thalamotomy for tremor: case report.

Essential tremor and Parkinson's disease-associated tremor are extremely prevalent within the field of movement disorders. The ventral intermediate (VIM) nucleus of the thalamus has been commonly used as both a neuromodulatory and neuroablative target for the treatment of these forms of tremor. With both deep brain stimulation and Gamma Knife radiosurgery, there is an abundance of literature regarding the surgical planning, targeting, and outcomes of these methodologies. To date, there have been no reports of frameless, linear accelerator (LINAC)-based thalomotomies for tremor. The authors report the case of a patient with tremor-dominant Parkinson's disease, with poor tremor improvement with medication, who was offered LINAC-based thalamotomy. High-resolution 0.9-mm isotropic MR images were obtained, and simulation was performed via CT with 1.5-mm contiguous slices. The VIM thalamic nucleus was determined using diffusion tensor imaging (DTI)-based segmentation on FSL using probabilistic tractography. The supplemental motor and premotor areas were the cortical target masks. The authors centered their isocenter within the region of the DTI-determined target and treated the patient with 140 Gy in a single fraction. The DTI-determined target had coordinates of 14.2 mm lateral and 8.36 mm anterior to the posterior commissure (PC), and 3 mm superior to the anterior commissure (AC)-PC line, which differed by 3.30 mm from the original target determined by anatomical considerations (15.5 mm lateral and 7 mm anterior to the PC, and 0 mm superior to the AC-PC line). There was faint radiographic evidence of lesioning at the 3-month follow-up within the target zone, which continued to consolidate on subsequent scans. The patient experienced continued right upper-extremity resting tremor improvement starting at 10 months until it was completely resolved at 22 months of follow-up. Frameless LINAC-based thalamotomy guided by DTI-based thalamic segmentation is a feasible method for achieving radiosurgical lesions of the VIM thalamus to treat tremor.

Chondrosarcoma of the Osseous Spine: An Analysis of Epidemiology, Patient Outcomes, and Prognostic Factors Using the SEER Registry From 1973 to 2012.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To determine the epidemiology and prognostic indicators in patients with chondrosarcoma of the osseous spine. SUMMARY OF BACKGROUND DATA: Chondrosarcoma of the spine is rare, with limited data on its epidemiology, clinicopathologic features, and treatment outcomes. Therapy centers on complete en bloc resection with radiotherapy reserved for subtotal resection or advanced disease. METHODS: The Surveillance, Epidemiology, and End Results Registry was queried for patients with chondrosarcoma of the osseous spine from 1973 to 2012. Study variables included age, sex, race, year of diagnosis, size, grade, extent of disease, and treatment modality. RESULTS: The search identified 973 cases of spinal chondrosarcoma. Mean age at diagnosis was 51.6 years, and 627% of patients were males. Surgical resection and radiotherapy were performed in 75.2% and 21.3% of cases, respectively. Kaplan-Meier analysis demonstrated overall survival (OS) and disease-specific survival (DSS) of 53% and 64%, respectively, at 5 years. Multivariate Cox regression analysis showed that age (OS, P < 0.001; DSS, P = 0.007), grade (OS, P < 0.001; DSS, P < 0.001), surgical resection (OS, P < 0.001; DSS, P < 0.001), and extent of disease (OS, P < 0.001; DSS, P < 0.001) were independent survival determinants; tumor size was an independent predictor of OS (P = 0.006). For confined disease, age (P = 0.013), decade of diagnosis (P = 0.023), and surgery (P = 0.017) were independent determinants of OS. For locally invasive disease, grade (OS, P < 0.001; DSS, P = 0.003), surgery (OS, P = 0.013; DSS, P = 0.046), and size (OS, P = 0.001, DSS, P = 0.002) were independent determinants of OS and DSS. Radiotherapy was an independent indicator of worse OS for both confined (P = 0.004) and locally invasive disease (P = 0.002). For metastatic disease, grade (OS, P = 0.021; DSS, P = 0.012) and surgery (OS, P = 0.007; DSS, P = 0.004) were survival determinants for both OS and DSS, whereas radiotherapy predicted improved OS (P = 0.039). CONCLUSION: Surgical resection confers survival benefit in patients with chondrosarcoma of the spine independent of extent of disease. Radiotherapy improves survival in patients with metastatic disease and worsens outcomes in patients with confined and locally invasive disease. LEVEL OF EVIDENCE: 4.

Radiosurgical target distance from the root entry zone in the treatment of trigeminal neuralgia.

PURPOSE: Stereotactic radiosurgery (SRS) provides a noninvasive treatment modality for patients with medically refractory trigeminal neuralgia. The root entry zone (REZ) has been proposed to be an ideal stereotactic target because it is partially composed of centrally produced myelin, conferring a theoretical increased sensitivity to irradiation as well as increased susceptibility to neurovascular conflict, making it the site in which nociceptive signals likely arise. The aim of this study is to determine if there is a statistically and clinically significant difference in pain relief or facial hypesthesia following SRS based on distance of the stereotactic isocenter from REZ. METHODS AND MATERIALS: Patients undergoing Novalis radiosurgery for the treatment of trigeminal neuralgia with at least 3 months' follow-up were included in this study. Postoperative outcomes were stratified by Barrow Neurological Institute (BNI) score for pain relief and BNI facial numbness score for facial hypesthesia. RESULTS: Sixty-seven patients met inclusion criteria and were included in this study. BNI score of I-IIIa was attained in 82% of patients at 3 months and 65% at 1 year following SRS. Distance from isocenter to REZ varied from 0 to 8.6 mm, with a mean of 1.94 ± 1.62 mm. Logistic regression of target-REZ distance against pain relief outcome (patients with score I-IIIa and IIIb-V) was insignificant at 3 months (P = .988), 6 months (P = .925), 9 months (P = .845), and 12 months (P = .547) postoperatively. Furthermore, no significant correlation was found with logistic regression of target-REZ distance with pain relief outcome (patients with score I and score II-IV) (P = .544). CONCLUSIONS: The current analysis suggests that distance from REZ does not correlate with degree of postoperative pain relief or facial hypesthesia; thus, targeting specific regions within the trigeminal nerve in relation to these anatomical characteristics may not afford any advantage from this perspective.

Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.

OBJECTIVE: To evaluate the efficacy of postoperative fractionated stereotactic radiosurgery (FSRS) and hypofractionated stereotactic radiotherapy (SRT) to large surgical cavities after gross total resection of brain metastases. METHODS: A retrospective analysis of 41 patients who had received tumor-bed FSRS (5 fractions) or SRT (10 fractions) after resection of brain metastasis between 2005 and 2015 was performed. All resection cavities were treated with a frameless linear accelerator-based system. Patients who underwent subtotal resection, single-dose SRS to the resection cavity, or were treated with a fractionation schedule other than 5 or 10 fractions, were excluded. RESULTS: Twenty-six patients were treated with 5 fractions and 15 patients with 10 fractions. The median planning target volume was 19.78 cm3 (12.3-28 cm3) to the 5-fraction group and 29.79 cm3 (26.3-47.6 cm3) to the 10-fraction group (P = 0.020). The 1-year and 2-year local control rates for all patients were 89.4% and 77.1%, respectively, and 89.6% and 78.6% were free from distant intracranial progression, respectively. No difference was observed in local control or freedom from distant intracranial progression between the 5-fraction or 10-fraction groups. The median overall survival was 28.27 months (95% confidence interval, 19.42-37.12) for all patients. No patient developed necrosis at the resection cavity. CONCLUSIONS: Fractionation offers the potential to exploit the different biological responses between neoplastic and normal tissues to ionizing radiation. The use of 5 daily doses of 5-6 Gy or 10 daily doses of 3 Gy is a good strategy to have a reasonable local control and avoid neurotoxicity.

Prognostic determinants and treatment outcomes analysis of osteosarcoma and Ewing sarcoma of the spine.

BACKGROUND CONTEXT: Osteosarcoma (OGS) and Ewing sarcoma (EWS) are the two classic primary malignant bone tumors. Due to the rarity of these tumors, evidence on demographics, survival determinants, and treatment outcomes for primary disease of the spine are limited and derived from small case series. PURPOSE: To use population-level data to determine the epidemiology and prognostic indicators in patients with OGS and EWS of the osseous spine. STUDY DESIGN/SETTING: Large-scale retrospective study. PATIENT SAMPLE: Patients diagnosed with OGS and EWS of the spine in the Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2012. OUTCOME MEASURES: Overall survival (OS) and disease-specific survival (DSS). METHODS: Two separate queries of the SEER registry were performed to identify patients with OGS and EWS of the osseous spine from 1973-2012. Study variables included age, sex, race, year of diagnosis, tumor size, extent of disease (EOD), and treatment with surgery and/or radiation therapy. Primary outcome was defined as OS and DSS in months. Univariate survival analysis was performed using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed using Cox proportional hazards regression models. RESULTS: The search identified 648 patients with primary OGS and 736 patients with primary EWS of the spine from 1973 to 2012. Mean age at diagnosis was 48.1 and 19.9 years for OGS and EWS, respectively, with OGS showing a bimodal distribution. The median OS and DSS were 1.3 and 1.7 years, respectively, for OGS, with OGS in Paget's disease having worse OS (0.7 years) relative to the mean (log-rank p=.006). The median OS and DSS for EWS were 3.9 and 4.3 years, respectively. Multivariate cox regression analysis showed that age (OS p<.001, DSS p<.001), decade of diagnosis (OS p=.049), surgical resection (OS p<.001, DSS p<.001), and EOD (OS p<.001, DSS p<.001) were independent positive prognostic indicators for spinal OGS; radiation therapy predicted worse OS (hazard ratio [HR] 1.48, confidence interval [CI] 1.05-2.10, p=.027) and DSS (HR 1.74, CI 1.13-2.66, p=.012) for OGS. For EWS, age (OS p<.001, DSS p<.001), surgical resection (OS p=.030, DSS p=.046), tumor size (OS p<.001, DSS p<.001), and EOD (OS p<.001, DSS p<.001) were independent determinants of improved survival; radiation therapy trended toward improved survival but did not achieve statistical significance for both OS (HR 0.76, CI 0.54-1.07, p=.113) and DSS (0.76, CI 0.54, 1.08, p=.126). CONCLUSIONS: Age, surgical resection, and EOD are key survival determinants for both OGS and EWS of the spine. Radiation therapy may be associated with worse outcomes in patients with OGS, and is of potential benefit in EWS. Overall prognosis has improved in patients with OGS of the spine over the last four decades.

Pulmonary hypertension secondary to pulmonary veno-occlusive disease complicated by right heart failure, hypotension and acute kidney injury.

Pulmonary veno-occlusive disease (PVOD) is rare condition which can lead to severe pulmonary hypertension, right ventricular dysfunction, and cardiopulmonary failure. The diagnosis of PVOD can be challenging due to its nonspecific symptoms and its similarity to idiopathic pulmonary arterial hypertension and interstitial lung disease in terms of diagnostic findings. This case describes a 57 year old female patient who presented with a 5-month history of progressive dyspnea on exertion and nonproductive cough. Workup at another hospital was nonspecific and the patient underwent surgical lung biopsy due to concern for interstitial lung disease. She subsequently became hemodynamically unstable and was transferred to our hospital where she presented with severe hypoxemia, hypotension, and suprasystemic pulmonary artery pressures. Preliminary lung biopsy results suggested idiopathic pulmonary arterial hypertension and the patient was started on vasodilating agents, including continuous epoprostenol infusion. Pulmonary artery pressures decreased but remained suprasystemic and the patient did not improve. Final review of the biopsy by a specialized laboratory revealed a diagnosis of PVOD after which vasodilating therapy was immediately weaned off. Evaluation for dual heart-lung transplantation was begun. The patient's hospital course was complicated by hypotension requiring vasopressors, worsening right ventricular dysfunction, and acute kidney injury. During the transplantation evaluation, the patient decided that she did not want to undergo continued attempts at stabilization of her progressive multi-organ dysfunction and she was transitioned to comfort care. She expired hours after removing inotropic support.

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

OBJECTIVE: Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. MATERIALS AND METHODS: The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. RESULTS: Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. CONCLUSION: This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization.

Anterior Cingulotomy for the Treatment of Chronic Intractable Pain: A Systematic Review.

BACKGROUND: Anterior cingulotomy for chronic pain aims to modulate patients' attention or emotional reaction to pain rather than to modulate pain intensity. OBJECTIVES: To evaluate the clinical efficacy, both short- and long-term, of anterior cingulotomy in the treatment of chronic pain. STUDY DESIGN: Systematic review. SETTING: This systematic review assessed studies reporting anterior cingulotomy for the treatment of chronic pain. METHODS: A systematic search of Web of Science, Scopus, PubMed, and PsychINFO was performed using both key words and controlled vocabulary. Articles included in this review included peer-reviewed articles describing clinical outcomes or efficacy of cingulotomy in the treatment of chronic pain with minimum follow-up of 3 months for non-malignant and 2 weeks for malignant pain. Articles reporting cingulectomies or cingulotomy only as combined with other ablative procedures were excluded, as were individual case reports. RESULTS: A total of 11 articles encompassing 224 patients are included in the review, with age ranging 22 to 85 (mean: 56) years at the time of the operation, 59% of which were men. Greater than 60% of patients across all studies were reported to have significant pain relief post-operatively as well as at one year after surgery. Common transient adverse effects included urinary incontinence and confusion/disorientation, subsiding within days postoperatively. Serious/permanent adverse effects included seizure in less than 5%, hemiparesis in less than 1%, and personality change in less than 1% of operations reported across all studies, all of which occurred primarily in operations where magnetic resonance (MR)-guidance was not used. LIMITATIONS: The limitations of this systematic review include the lack of studies other than observational reports and the inevitable heterogeneity between included studies. CONCLUSIONS: Despite decreased utilization in recent years, anterior cingulotomy is an effective neurosurgical intervention in the treatment of pain and carries little risk of permanent or serious adverse effects.Key words: Anterior cingulotomy, chronic pain, stereotaxis, systematic review, pain, cingulate gyrus, cingulotomy, intractable pain.

Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis.

Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.

Lateralization of the Subthalamic Nucleus with Age in Parkinson's Disease.

Age-related changes in subthalamic nucleus (STN) position have not been well characterized in patients with Parkinson's disease (PD). We report a systematic retrospective analysis of age-related changes in radiographic and final deep brain stimulator (DBS) STN coordinates in PD patients. The charts of 134 PD patients (97 males, 28-84 years) representing 255 STN were reviewed. Multiple linear regression, stepwise regression, and relative importance of regressors analysis was performed to determine the significance of the relationship between STN position and age. Across all subjects, both radiographic STN localization and final DBS position within the STN showed a lateralization of the STN target with age (R2=0.1096,p=6.9×10-8 and R2=0.0433,p=8.7×10-4, respectively). Lateralization with age was observed regardless of MR field strength (1.5T and 3.0T) (R2=0.0946,p=7.6×10-6 and R2=0.2687,p=9.2×10-5, respectively). No other consistent or clinically significant age-related changes were identified. Multiple linear regression revealed that the third ventricle width and age are statistically significant predictors of radiographic STN lateralization (R2 = 0.2404, p = 1.51×10-5 and p = .00784 respectively). Step-wise regression demonstrated that age is a non-redundant predictor of STN lateralization relative to third ventricle width. Similar to healthy controls, STN position appears to shift laterally with age in PD. This highlights limitations of indirect targeting and atlas-based stereotactic surgery and argues for reliance on patient specific anatomy since factors such as age and 3rd ventricular width can contribute to patient-specific variability in STN localization.

Feature visualization and classification for the discrimination between individuals with Parkinson's disease under levodopa and DBS treatments.

BACKGROUND: Over the years, a number of distinct treatments have been adopted for the management of the motor symptoms of Parkinson's disease (PD), including pharmacologic therapies and deep brain stimulation (DBS). Efficacy is most often evaluated by subjective assessments, which are prone to error and dependent on the experience of the examiner. Our goal was to identify an objective means of assessing response to therapy. METHODS: In this study, we employed objective analyses in order to visualize and identify differences between three groups: healthy control (N = 10), subjects with PD treated with DBS (N = 12), and subjects with PD treated with levodopa (N = 16). Subjects were assessed during execution of three dynamic tasks (finger taps, finger to nose, supination and pronation) and a static task (extended arm with no active movement). Measurements were acquired with two pairs of inertial and electromyographic sensors. Feature extraction was applied to estimate the relevant information from the data after which the high-dimensional feature space was reduced to a two-dimensional space using the nonlinear Sammon's map. Non-parametric analysis of variance was employed for the verification of relevant statistical differences among the groups (p < 0.05). In addition, K-fold cross-validation for discriminant analysis based on Gaussian Finite Mixture Modeling was employed for data classification. RESULTS: The results showed visual and statistical differences for all groups and conditions (i.e., static and dynamic tasks). The employed methods were successful for the discrimination of the groups. Classification accuracy was 81 ± 6% (mean ± standard deviation) and 71 ± 8%, for training and test groups respectively. CONCLUSIONS: This research showed the discrimination between healthy and diseased groups conditions. The methods were also able to discriminate individuals with PD treated with DBS and levodopa. These methods enable objective characterization and visualization of features extracted from inertial and electromyographic sensors for different groups.

Effect of Cranial Window Diameter During Deep Brain Stimulation Surgery on Volume of Pneumocephalus.

OBJECTIVE: Successful deep brain stimulation (DBS) surgery necessitates high accuracy in targeting specific intracranial nuclei. Brain shift due to pneumocephalus can contribute to decreased accuracy. Larger burr holes and dural openings may increase pneumocephalus volume due to a greater degree of communication between the subdural space and extracranial air. The aim of this study is to determine if there is a statistically and clinically significant difference in postoperative pneumocephalus volume related to burr hole and durotomy size. MATERIALS AND METHODS: DBS electrodes were surgically implanted through either large (14 mm) burr holes or small (4 mm) twist drill holes. Immediate postoperative computerized tomography (CT) scans of 165 electrode implantations in 85 patients from 2010 to 2013 were retrospectively analyzed. Student's t-test and Mann-Whitney U-test were employed with a threshold of significance set at p ≤ 0.05. RESULTS: No significant difference in pneumocephalus was identified between patients who had implantation of DBS electrodes through 4 mm twist drill holes (N = 71 hemispheres, 12.84 ± 9.79 cm(3) ) and those with large 14 mm burr holes (N = 87, 11.70 ± 7.46 cm(3) , p = 0.42). Volume of pneumocephalus did not correlate with duration of surgery or patient age. The groups did not differ significantly with respect to other aspects of surgical implantation technique or surgical duration. CONCLUSION: While identifying factors that may reduce pneumocephalus volume may be critical to improving stereotactic accuracy and targeting, the current results suggest that burr hole size may not alter the degree of brain shift.