Search Results

OBJECTIVE

A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques.

开云体育世界杯赔率

The MRI contrast agent gadopentetate dimeglumine (Magnevist, 5 mM) was used to noninvasively evaluate catheter patency and infusion volume associated with 2 flow rates sequentially tested in each of 3 animals: 0.1 µl/min for 14 days into the right substantia nigra and 0.1 µl/min for 7 days plus 0.2 µl/min for an additional 7 days into the left substantia nigra. Flow rate tolerability was assessed via clinical observations and a microscopic examination of the striatum and midbrain regions.

RESULTS

Evaluation of postsurgical MRI indicated that all 6 catheters remained patent throughout the study and that the volume of distribution achieved in the left midbrain region at a rate of up to 0.2 µl/min (2052 ± 168 mm³) was greater than that achieved in the right midbrain region at a constant rate of 0.1 µl/min (1225 ± 273 mm³) by nearly 2-fold. Both flow rates provided sufficient infusate coverage of the rhesus (and possibly the human) midbrain region. There were no indications of observable deficits in behavior. Histopathological evaluations confirmed that all catheter tips were placed in or near the pars compacta region of the substantia nigra in all animals. There was no evidence of infection at any of the 6 catheter sites. Mild to moderate microglial reactions were observed at most catheter track sites and were comparable between the 2 infusion rates. Finally, there was neither observable decrease of tyrosine hydroxylase staining in the striatum nor detectable necrosis of neurons in the pars compacta region of the substantia nigra in any of the animals.

CONCLUSIONS

The data from this study support the feasibility of using a pump-and-catheter system for chronic intranigral infusion and lay the foundation for using this approach to treat Parkinson's disease or other related degenerative diseases that would benefit from targeted drug delivery to the substantia nigra or to other brainstem regions.

OBJECTIVE

To characterize the clinical outcomes when stereotactic body radiation therapy (SBRT) alone is used to treat high-grade epidural disease without prior surgical decompression, the authors conducted a retrospective cohort study of patients treated at the Memorial Sloan Kettering Cancer Center between 2014 and 2018. The authors report locoregional failure (LRF) for a cohort of 31 cases treated with hypofractionated SBRT alone for grade 2 epidural spinal cord compression (ESCC) with radioresistant primary cancer histology.

开云体育世界杯赔率

High-grade epidural disease was defined as grade 2 ESCC, which is notable for radiographic deformation of the spinal cord by metastatic disease. Kaplan-Meier survival curves and cumulative incidence functions were generated to examine the survival and incidence experiences of the sample level with respect to overall survival, LRF, and subsequent requirement of vertebral same-level surgery (SLS) due to tumor progression or fracture. Associations with dosimetric analysis were also examined.

RESULTS

Twenty-nine patients undergoing 31 episodes of hypofractionated SBRT alone for grade 2 ESCC between 2014 and 2018 were identified. The 1-year and 2-year cumulative incidences of LRF were 10.4% (95% CI 0–21.9) and 22.0% (95% CI 5.5–38.4), respectively. The median survival was 9.81 months (95% CI 8.12–18.54). The 1-year cumulative incidence of SLS was 6.8% (95% CI 0–16.0) and the 2-year incidence of SLS was 14.5% (95% CI 0.6–28.4). All patients who progressed to requiring surgery had index lesions at the thoracic apex (T5–7).

CONCLUSIONS

In carefully selected patients, treatment of grade 2 ESCC disease with hypofractionated SBRT alone offers a 1-year cumulative incidence of LRF similar to that in low-grade ESCC and postseparation surgery adjuvant hypofractionated SBRT. Use of SBRT alone has a favorable safety profile and a low cumulative incidence of progressive disease requiring open surgical intervention (14.5%).

OBJECTIVE

The authors compared the contemporary perioperative procedure-related complications between coiling with stent placement and coiling without stent placement for acutely ruptured aneurysms treated in a single center after improvement of interventional skills and strategy.

开云体育世界杯赔率

In an institutional review board–approved protocol, 133 patients who underwent coiling with stent placement and 289 patients who underwent coiling without stent placement from January 2012 to December 2014 were consecutively reviewed retrospectively. Baseline characteristics, procedure-related complications and mortality rate, angiographic follow-up results, and clinical outcomes were compared between the two groups. Univariate analysis and logistic regression analysis were performed to determine the association of procedure-related complications of coiling with stent placement with potential risk factors.

RESULTS

The coiling/stent group and coiling/no-stent group were statistically comparable with respect to all baseline characteristics except for aneurysm location (p < 0.001) and parent artery configuration (p = 0.024). The immediate embolization results and clinical outcomes between the two groups showed no significant differences (p = 0.807 and p = 0.611, respectively). The angiographic follow-up results of the coiling in stent group showed a significant higher occlusion rate and lower recurrence rate compared with the coiling/no-stent group (82.5% vs 66.7%, 3.5% vs 14.5%, p = 0.007). Procedure-related intraoperative rupture and thrombosis, postoperative early rebleeding and thrombosis, and external ventricular drainage–related hemorrhagic event occurred in 3.0% (4 of 133), 2.3% (3 of 133), 1.5% (2 of 133), 0.7% (1 of 133), and 0.8% (1 of 133) of the coiling/stent group compared with 1.0% (3 of 289), 1.4% (4 of 289), 1.4% (4 of 289), and 0.7% (2 of 289) of the coiling/no-stent group, respectively (p = 0.288, p = 0.810, p = 1.000, p = 0.315, and p = 1.000, respectively). One patient presented with coil protrusion in the group of coiling without stent. The procedure-related mortality was 1.5% (2 of 133) in the coiling/stent group and 0.7% in the coiling/no-stent group (p = 0.796). Multivariable analysis showed no significant predictors for the total perioperative procedure-related complications, hemorrhagic complications, or ischemic complications.

CONCLUSIONS

The perioperative procedure-related complications and mortality rate did not differ significantly between the coiling/stent group and the coiling/no-stent group for patients with acutely ruptured aneurysms. Considering the better angiographic follow-up results, coiling with stent placement might be a feasible, safe, and promising option for treatment in the acute phase of selected wide-necked ruptured intracranial aneurysms.

BACKGROUND

Ependymomas are the most frequent tumors of the adult spinal cord, representing 1.9% of all central nervous system tumors and 60% of spinal cord tumors. Spinal ependymomas are usually solitary, intramedullary lesions. While intradural extramedullary (IDEM) ependymomas are infrequent, multifocal IDEM ependymomas are exceptionally rare.

OBSERVATIONS

在文学作者报道第一例ure of a patient diagnosed with multifocal IDEM ependymomas who was treated with tumor resection and brain and spinal radiotherapy. The patient presented with a 10-day history of bilateral leg numbness extending to the umbilicus and gait instability. Magnetic resonance imaging (MRI) studies revealed multiple enhancing nodular nodules throughout the entire spinal canal. Brain MRI revealed no abnormal lesions. A World Health Organization grade II ependymoma was confirmed histologically. At 31 months postoperatively, the patient remained clinically asymptomatic. Although cervical and thoracic MRI revealed stable intradural nodules and several areas of leptomeningeal enhancement, no malignant cells were seen in the cerebrospinal fluid (CSF). He underwent genetic testing to determine the appropriate chemotherapeutic agent if activation of the tumor should arise.

LESSONS

Because complete resection of multifocal IDEM ependymomas is not feasible, continued monitoring with brain and spine MRI is warranted to detect potential tumor dissemination in the CSF.

OBJECTIVE

Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features.

开云体育世界杯赔率

单中心,这种前瞻性纵向银rt study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors’ institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission.

RESULTS

A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524–5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522–6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006–1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224–3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified.

CONCLUSIONS

海绵窦侵袭、诊断年龄和sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.

OBJECTIVE

The authors sought to test the hypothesis that adding dexamethasone (DXM) to atorvastatin (ATO) potentiates the effects of ATO on chronic subdural hematoma (CSDH).

开云体育世界杯赔率

Sixty patients with CSDH underwent 5 weeks of treatment with an additional 7-week follow-up. Patients were randomized to receive a 5-week regimen of ATO 20 mg daily or ATO 20 mg daily plus a DXM regimen (ATO+DXM). The 5-week DXM regimen was 2.25 mg daily for 2 consecutive weeks, followed by 0.75 mg twice daily for 2 weeks and 0.75 mg once daily for 1 week. The primary endpoint was hematoma reduction assessed by neuroimaging at baseline and at 5 weeks of follow-up. Secondary outcomes included neurological improvement assessed by using the Markwalder’s Grading Scale and Glasgow Coma Scale (MGS-GCS).

RESULTS

The mean patient age was 66.6 years, and 25% of patients were women. The patients who were treated with ATO+DXM had more obvious hematoma reduction at the 5th week (between-groups difference 18.37 ml; 95% CI 8.17–28.57; p = 0.0005). This reduction started from the 2nd week (14.51 ml; 95% CI 4.31–24.71; p = 0.0056) of treatment and persisted until the 12th week (17.50 ml; 95% CI 7.30–27.70; p = 0.0009). Complete recovery of neurological function (MGS-GCS grade 0) at 5 weeks was achieved in 83.33% and 32.14% of patients in the ATO+DXM and ATO groups, respectively. At the 5th week, patients receiving ATO+DXM had significantly lower levels of T cells and higher levels of regulatory T cells and endothelial progenitor cells in their peripheral blood.

CONCLUSIONS

ATO + DXM比独自ATO在增加更有效ing hematoma and improving neurological function in patients with CSDH. These results require further confirmation in a randomized placebo-controlled trial.

Clinical trial registration no.: ChiCTR-IPR-14005573 (http://www.chictr.org.cn/index.aspx)

OBJECTIVE

It has been reported that microRNA-195 (miR-195) protects against chronic brain injury induced by chronic brain hypoperfusion. However, neither the expression profile of miR-195 nor its potential role during acute ischemic stroke has been investigated. In this study, the authors’ aim was to verify the mechanism of miR-195 in acute ischemic stroke.

开云体育世界杯赔率

The plasma levels of miR-195 expression were assessed using real-time PCR in 96 patients with acute ischemic stroke, and the correlation with the National Institutes of Health Stroke Scale score was evaluated. In addition, cerebral infarct volume, neurological score, and levels of miR-195 and CX3CL1/CX3CR1 mRNA and protein expression were assessed in mice subjected to middle cerebral artery occlusion (MCAO) with or without intra-cerebroventricular infusion of lentiviral vector. The inflammatory cytokines tumor necrosis factor–α (TNFα), interleukin (IL)–1β, and IL-6 of mouse brains after MCAO and BV2 cells treated with oxygen-glucose deprivation were measured using enzyme-linked immunosorbent assay, and apoptotic proteins were examined by Western blotting. Direct targeting of CX3CL1/CX3CR1 by miR-195 was determined by immunoblotting and dual luciferase assay.

RESULTS

In ischemic stroke patients, miR-195 was significantly downregulated and expression levels of miR-195 in these patients negatively correlated with the National Institutes of Health Stroke Scale score. In mice after MCAO, miR-195 overexpression decreased infarct volume, alleviated neurological deficits, and most importantly, suppressed an inflammatory response. Meanwhile, miR-195 suppressed the expression of the inflammatory cytokines TNFα, IL-1β, and IL-6 in vitro and in vivo. The authors further discovered that both CX3CL1 and CX3CR1 are direct targets of miR-195, but miR-195 exerts neuroprotective roles mainly through inhibiting CX3CR1-mediated neuroinflammation and subsequent neuronal cell apoptosis.

CONCLUSIONS

Taken together, these findings suggest that miR-195 promotes neuronal cell survival against chronic cerebral ischemic damage by inhibiting CX3CR1-mediated neuroinflammation. This indicates that miR-195 may represent a novel target that regulates neuroinflammation and brain injury, thus offering a new treatment strategy for cerebral ischemic disorders.