bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of an effective implantable pump-infusion system for chronic convection-enhanced delivery of intracerebral topotecan in a large animal model
Authors: D’Amico Randy S. , Neira Justin A. , Yun Jonathan , Alexiades Nikita G. , Banu Matei , Englander Zachary K. , Kennedy Benjamin C. , Ung Timothy H. , Rothrock Robert J. , Romanov Alexander , Guo Xiaotao , Zhao Binsheng , Sonabend Adam M. , Canoll Peter , Bruce Jeffrey N. 
Published: August 2019

OBJECTIVEIntracerebral convection-enhanced delivery (CED) has been limited to short durations due to a reliance on externalized catheters. Preclinical studies investigating topotecan (TPT) CED for glioma have suggested that prolonged infusion improves survival. Internalized pump-catheter systems may facilitate chronic infusion. The authors describe the safety and utility of long-term TPT CED in a porcine model and correlation of drug distribution through coinfusion of gadolinium.METHODSFully internalized CED pump-catheter systems were implanted in 12 pigs. Infusion algorithms featuring variable infusion schedules, flow rates, and concentrations of a mixture of TPT and gadolinium were characterized over increasing intervals from 4 to 32 days. Therapy distribution was measured using gadolinium signal on MRI as a surrogate. A 9-point neurobehavioral scale (NBS) was used to identify side effects.RESULTSAll animals tolerated infusion without serious adverse events. The average NBS score was 8.99. The average maximum volume of distribution (Vdmax) in chronically infused animals was 11.30 mL and represented 32.73% of the ipsilateral cerebral hemispheric volume. Vdmax was achieved early during infusions and remained relatively stable despite a slight decline as the infusion reached steady state. Novel tissue TPT concentrations measured by liquid chromatography mass spectroscopy correlated with gadolinium signal intensity on MRI (p = 0.0078).CONCLUSIONSProlonged TPT-gadolinium CED via an internalized system is safe and well tolerated and can achieve a large Vdmax, as well as maintain a stable Vd for up to 32 days. Gadolinium provides an identifiable surrogate for measuring drug distribution. Extended CED is potentially a broadly applicable and safe therapeutic option in select patients.
Association of APOE ε4 with progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage
Authors: Wan Xueyan , Gan Chao , You Chao , Fan Ting , Zhang Suojun , Zhang Huaqiu , Wang Sheng , Shu Kai , Wang Xiong , Lei Ting 
Published: August 2019

OBJECTIVEThe intracranial hematoma volume in patients with traumatic brain injury is a key parameter for the determination of the management approach and outcome. Apolipoprotein E (APOE) ε4 is reported to be a risk factor for larger hematoma volume, which might contribute to a poor outcome. However, whether APOE ε4 is related to progressive hemorrhagic injury (PHI), a common occurrence in the clinical setting, remains unclear. In this study, the authors aimed to investigate the association between the APOE genotype and occurrence of PHI.METHODSThis prospective study included a cohort of 123 patients with traumatic intracerebral hemorrhage who initially underwent conservative treatment. These patients were assigned to the PHI or non-PHI group according to the follow-up CT scan. A polymerase chain reaction and sequencing method were carried out to determine the APOE genotype. Multivariate logistic regression analysis was applied to identify predictors of PHI.RESULTSThe overall frequency of the alleles was as follows: E2/2, 0%; E2/3, 14.6%; E3/3, 57.8%; E2/4, 2.4%; E3/4, 22.8%; and E4/4, 2.4%. Thirty-four patients carried at least one allele of ε4. In this study 60 patients (48.8%) experienced PHI, and the distribution of the alleles was as follows: E2/2, 0%; E2/3, 5.7%; E3/3, 22.8%; E2/4, 2.4%; E3/4, 16.3%; and E4/4, 1.6%, which was significantly different from that in the non-PHI group (p = 0.008). Additionally, the late operation rate in the PHI group was significantly higher than that in the non-PHI group (24.4% vs 11.4%, p = 0.002). Multivariate logistic regression identified APOE ε4 (OR 5.14, 95% CI 2.40–11.62), an elevated international normalized ratio (OR 3.57, 95% CI 1.61–8.26), and higher glucose level (≥ 10 mmol/L) (OR 3.88, 95% CI 1.54–10.77) as independent risk factors for PHI. Moreover, APOE ε4 was not a risk factor for the coagulopathy and outcome of the patients with traumatic intracerebral hemorrhage.CONCLUSIONSThe presence of APOE ε4, an elevated international normalized ratio, and a higher glucose level (≥ 10 mmol/L) are predictors of PHI. Additionally, APOE ε4 is not associated with traumatic coagulopathy and patient outcome.
BIO alleviates inflammation through inhibition of GSK-3β in a rat model of intracerebral hemorrhage
Authors: Zhao Sha , Liu Zhen , Yu Zihan , Wu Xinran , Li Rui , Tang Xiaobo 
Published: August 2019

OBJECTIVEInflammation plays a key role in secondary brain damage following intracerebral hemorrhage (ICH). Glycogen synthase kinase–3β (GSK-3β) plays a strong proinflammatory role in many CNS diseases, including stroke. The present study was undertaken to examine the effects of 6-bromoindirubin-3ʹ-oxime (BIO), a specific inhibitor of GSK-3β, on inflammation in ICH rats.METHODSAn ICH rat model was induced by autologous whole-blood injection into the striatum. First, 10, 20, 40, 60, 80, or 100 μg/kg BIO was applied to ICH animals to determine an optimal dosage for producing sufficient GSK-3β inhibition in rat ipsilateral hippocampus by Western blotting. Second, 40 μg/kg BIO was applied to ICH rats for 1, 3, 7, or 14 days, respectively, to determine a suitable intervention time course of BIO by Western blotting analysis on GSK-3β. Third, Western blotting and enzyme-linked immunosorbent assay were used for quantification of inflammation-related factors upstream or downstream of GSK-3β in rat ipsilateral hippocampus. Then, immunohistochemical staining was applied to detect activated microglia and apoptotic cells in rat ipsilateral hippocampus. Last, neurobehavioral tests were performed to assess the sensorimotor impairments in the ICH rats.RESULTSThe results show that BIO 1) blocked GSK-3βTyr216 phosphorylation/activation, thus stabilizing β-catenin, increasing upstream brain-derived neurotrophic factor and downstream heat shock protein 70 levels, and decreasing the levels of nuclear factor–κB p65 and cyclooxygenase 2; 2) decreased the levels of the proinflammatory cytokines tumor necrosis factor–α and interleukin (IL)–1β and IL-6 and elevated the level of antiinflammatory cytokine IL-10; 3) inhibited microglia activation and cell apoptosis; and 4) improved the sensorimotor deficits of ICH rats.CONCLUSIONSBIO posttreatment inhibited microglia activation, prevented inflammation and hippocampal cell death, and ameliorated functional and morphological outcomes in a rat ICH model through inactivation of GSK-3β.
Surgical treatment of falcotentorial meningiomas: a retrospective review of a single-institution experience
Authors: Zhao Xiaochun , Belykh Evgenii , Przybylowski Colin J. , Borba Moreira Leandro , Gandhi Sirin , Tayebi Meybodi Ali , Cavallo Claudio , Valli Daniel , Wicks Robert T. , Nakaji Peter 
Published: August 2019

OBJECTIVEMeningiomas at the falcotentorial junction represent a rare subgroup of complex meningiomas. Debate remains regarding the appropriate treatment strategy for and optimal surgical approach to these tumors, and surgical outcomes have not been well described in the literature. The authors reviewed their single-institution experience in the management, approach selection, and outcomes for patients with falcotentorial meningiomas.METHODSFrom the medical records, the authors identified all patients with falcotentorial meningiomas treated with resection at the Barrow Neurological Institute between January 2007 and October 2017. Perioperative clinical, surgical, and radiographic data were retrospectively collected. For patients who underwent the supracerebellar infratentorial approach, the tentorial angle was defined as the angle between the line joining the nasion with the tuberculum sellae and the tentorium in the midsagittal plane.RESULTSFalcotentorial meningiomas occurred in 0.97% (14/1441) of the patients with meningiomas. Most of the patients (13/14) were female, and the mean patient age was 59.8 ± 11.3 years. Of 17 total surgeries (20 procedures), 11 were single-stage primary surgeries, 3 were two-stage primary surgeries (6 procedures), 2 were reoperations for recurrence, and 1 was a reoperation after surgery had been aborted because of brain edema. Hydrocephalus was present in 5 of 17 cases, 4 of which required additional treatment. Various approaches were used, including the supracerebellar infratentorial (4/17), occipital transtentorial/transfalcine (4/17), anterior interhemispheric transsplenial (3/17), parietal transventricular (1/17), torcular (2/17), and staged supracerebellar infratentorial and occipital transtentorial/transfalcine (3/17) approaches. Of the 17 surgeries, 9 resulted in Simpson grade IV resection, and 3, 1, and 4 surgeries resulted in Simpson grades III, II, and I resection, respectively. The tentorial angle in cases with Simpson grade I resection was significantly smaller than in those with an unfavorable resection grade (43.3° ± 4.67° vs 54.0° ± 3.67°, p = 0.04). Complications occurred in 10 of 22 approaches (17 surgeries) and included visual field defects (6 cases, 2 permanent and 4 transient), hemiparesis (2 cases), hemidysesthesia (1 case), and cerebellar hematoma (1 case).CONCLUSIONSFalcotentorial meningiomas are challenging lesions. A steep tentorial angle is an unfavorable preoperative radiographic factor for achieving maximal resection with the supracerebellar infratentorial approach. Collectively, the study findings show that versatility is required to treat patients with falcotentorial meningiomas and that treatment goals and surgical approach must be individualized to obtain optimal surgical results.
Quantitative analysis of ipsilateral and contralateral supracerebellar infratentorial and occipital transtentorial approaches to the cisternal pulvinar: laboratory anatomical investigation
Authors: Sun Qing , Zhao Xiaochun , Gandhi Sirin , Tayebi Meybodi Ali , Belykh Evgenii , Valli Daniel , Cavallo Claudio , Borba Moreira Leandro , Nakaji Peter , Lawton Michael T. , Preul Mark C. 
Published: August 2019

OBJECTIVEThe cisternal pulvinar is a challenging location for neurosurgery. Four approaches for reaching the pulvinar without cortical transgression are the ipsilateral supracerebellar infratentorial (iSCIT), contralateral supracerebellar infratentorial (cSCIT), ipsilateral occipital transtentorial (iOCTT), and contralateral occipital transtentorial/falcine (cOCTF) approaches. This study quantitatively compared these approaches in terms of surgical exposure and maneuverability.METHODSEach of the 4 approaches was performed in 4 cadaveric heads (8 specimens in total). A 6-sided anatomical polygonal region was configured over the cisternal pulvinar, defined by 6 reachable anatomical points in different vectors. Multiple polygons were subsequently formed to calculate the areas of exposure. The surgical freedom of each approach was calculated as the maximum allowable working area at the proximal end of a probe, with the distal end fixed at the posterior pole of the pulvinar. Areas of exposure, surgical freedom, and the working distance (surgical depth) of all approaches were compared.RESULTSNo significant difference was found among the 4 different approaches with regard to the surgical depth, surgical freedom, or medial exposure area of the pulvinar. In the pairwise comparison, the cSCIT approach provided a significantly larger lateral exposure (39 ± 9.8 mm2) than iSCIT (19 ± 10.3 mm2, p < 0.01), iOCTT (19 ± 8.2 mm2, p < 0.01), and cOCTF (28 ± 7.3 mm2, p = 0.02) approaches. The total exposure area with a cSCIT approach (75 ± 23.1 mm2) was significantly larger than with iOCTT (43 ± 16.4 mm2, p < 0.01) and iSCIT (40 ± 20.2 mm2, p = 0.01) approaches (pairwise, p ≤ 0.01).CONCLUSIONSThe cSCIT approach is preferable among the 4 compared approaches, demonstrating better exposure to the cisternal pulvinar than ipsilateral approaches and a larger lateral exposure than the cOCTF approach. Both contralateral approaches described (cSCIT and cOCTF) provided enhanced lateral exposure to the pulvinar, while the cOCTF provided a larger exposure to the lateral portion of the pulvinar than the iOCTT. Medial exposure and maneuverability did not differ among the approaches. A short tentorium may negatively impact an ipsilateral approach because the cingulate isthmus and parahippocampal gyrus tend to protrude, in which case they can obstruct access to the cisternal pulvinar ipsilaterally.
Decrease of blood flow velocity in the middle cerebral artery after stellate ganglion block following aneurysmal subarachnoid hemorrhage: a potential vasospasm treatment?
Authors: Wendel Christopher , Scheibe Ricardo , Wagner Sören , Tangemann Wiebke , Henkes Hans , Ganslandt Oliver , Schiff Jan-Henrik 
Published: August 2019

OBJECTIVECerebral vasospasm (CV) is a delayed, sustained contraction of the cerebral arteries that tends to occur 3–14 days after aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured aneurysm. Vasospasm potentially leads to delayed cerebral ischemia, and despite medical treatment, 1 of 3 patients suffer a persistent neurological deficit. Bedside transcranial Doppler (TCD) ultrasonography is used to indirectly detect CV through recognition of an increase in cerebral blood flow velocity (CBFV). The present study aimed to use TCD ultrasonography to monitor how CBFV changes on both the ipsi- and contralateral sides of the brain in the first 24 hours after patients have received a stellate ganglion block (SGB) to treat CV that persists despite maximum standard therapy.METHODSThe data were culled from records of patients treated between 2013 and 2017. Patients were included if an SGB was administered following aSAH, whose CBFV was ≥ 120 cm/sec and who had either a focal neurological deficit or reduced consciousness despite having received medical treatment and blood pressure management. The SGB was performed on the side where the highest CBFV had been recorded with 8–10 ml ropivacaine 0.2%. The patient’s CBFV was reassessed after 2 and 24 hours.RESULTSThirty-seven patients (male/female ratio 18:19), age 17–70 years (mean age 49.9 ± 11.1), who harbored 13 clipped and 22 coiled aneurysms (1 patient received both a coil and a clip, and 3 patients had 3 untreated aneurysms) had at least one SGB. Patients received up to 4 SGBs, and thus the study comprised a total of 76 SGBs.After the first SGB, CBFV decreased in 80.5% of patients after 2 hours, from a mean of 160.3 ± 28.2 cm/sec to 127.5 ± 34.3 cm/sec (p < 0.001), and it further decreased in 63.4% after 24 hours to 137.2 ± 38.2 cm/sec (p = 0.007). A similar significant effect was found for the subsequent SGB. Adding clonidine showed no significant effect on either the onset or the duration of the SGB. Contralateral middle cerebral artery (MCA) blood flow was not reduced by the SGB.CONCLUSIONSTo the authors’ knowledge, this is the largest study on the effects of administering an SGB to aSAH patients after aneurysm rupture. The data showed a significant reduction in ipsilateral CBFV (MCA 20.5%) after SGB, lasting in about two-thirds of cases for over 24 hours with no major complications resulting from the SGB.
Stimulation of endothelial progenitor cells by microRNA-31a-5p to induce endothelialization in an aneurysm neck after coil embolization by modulating the Axin1-mediated β-catenin/vascular endothelial growth factor pathway
Authors: Yu Guo , Liu Peixi , Shi Yuan , Li Sichen , Liu Yingjun , Fan Zhiyuan , Zhu Wei 
Published: August 2019

OBJECTIVEEmerging evidence shows that frequent recurrence of intracranial aneurysms (IAs) after endovascular coiling is attributable to the lack of endothelialization across the aneurysm neck. Recently, much attention has been given to the role of microRNAs (miRs) in vascular disease, although their contributory role to IA is poorly understood.METHODSAdult male Sprague-Dawley rats were subjected to microsurgery to create a coiled embolization aneurysm model, and were injected with miR-31a-5p agomir or a negative control agomir via the tail vein at a dose of 10 mg/kg per week for 4 weeks after IA induction. H & E staining, scanning electron microscopy, and flow cytometry were performed to evaluate the effects of miR-31a-5p agomir on endothelialization and the number of circulating endothelial progenitor cells (EPCs). The effects of miR-31a-5p on the viability and functioning of EPCs were also determined using Cell Counting Kit–8, wound-healing assay, and tube formation assays.RESULTSThe authors tested the ability of miR-31a-5p to promote EPC-induced endothelialization in a model of coiled embolization aneurysm. miR-31a-5p agomir improved endothelialization and elevated the number of circulating EPCs in the peripheral blood compared to a negative control agomir–treated group. In addition, the number of vWF- and KDR-positive cells in the aneurysm neck was increased in the miR-31a-5p agomir–treated group. Furthermore, upregulation of miR-31a-5p promoted EPC proliferation, migration, and tube formation and enhanced the expression of the proangiogenic factor vascular endothelial growth factor in vitro. Mechanistically, miR-31a-5p directly targeted the 3′ untranslated region (3′UTR) of Axin1 messenger RNA and repressed its expression. Besides, miR-31a-5p exerted its effect on EPCs by regulating the Axin1-mediated Wnt/β-catenin pathway.CONCLUSIONSCollectively, these results indicate that miR-31a-5p is an important regulator of EPC mobilization and endothelialization and may have a positive effect on aneurysm repair.
Is 3 years adequate for tracking completely occluded coiled aneurysms?
Authors: Yeon Eung Koo , Cho Young Dae , Yoo Dong Hyun , Lee Su Hwan , Kang Hyun-Seung , Kim Jeong Eun , Cho Won-Sang , Choi Hyun Ho , Han Moon Hee 
Published: August 2019

OBJECTIVEThe authors conducted a study to ascertain the long-term durability of coiled aneurysms completely occluded at 36 months’ follow-up given the potential for delayed recanalization.METHODSIn this retrospective review, the authors examined 299 patients with 339 aneurysms, all shown to be completely occluded at 36 months on follow-up images obtained between 2011 and 2013. Medical records and radiological data acquired during the extended monitoring period (mean 74.3 ± 22.5 months) were retrieved, and the authors analyzed the incidence of (including mean annual risk) and risk factors for delayed recanalization.RESULTSA total of 5 coiled aneurysms (1.5%) occluded completely at 36 months showed recanalization (0.46% per aneurysm-year) during the long-term surveillance period (1081.9 aneurysm-years), 2 surfacing within 60 months and 3 developing thereafter. Four showed minor recanalization, with only one instance of major recanalization. The latter involved the posterior communicating artery as an apparent de novo lesion, arising at the neck of a firmly coiled sac, and was unrelated to coil compaction or growth. Additional embolization was undertaken. In a multivariate analysis, a second embolization for a recurrent aneurysm (HR = 22.088, p = 0.003) independently correlated with delayed recanalization.CONCLUSIONSAlmost all coiled aneurysms (98.5%) showing complete occlusion at 36 months postembolization proved to be stable during extended observation. However, recurrent aneurysms were predisposed to delayed recanalization. Given the low probability yet seriousness of delayed recanalization and the possibility of de novo aneurysm formation, careful monitoring may be still considered in this setting but at less frequent intervals beyond 36 months.
Solutions to the technical challenges embedded in the current methods for intraoperative peripheral nerve action potential recordings
Authors: Wu Gang , Belzberg Allan , Nance Jessica , Gutierrez-Hernandez Sergio , Ritzl Eva K. , Ringkamp Matthias 
Published: August 2019

OBJECTIVEIntraoperative nerve action potential (NAP) recording is a useful tool for surgeons to guide decisions on surgical approaches during nerve repair surgeries. However, current methods remain technically challenging. In particular, stimulus artifacts that contaminate or mask the NAP and therefore impair the interpretation of the recording are a common problem. The authors’ goal was to improve intraoperative NAP recording techniques by revisiting the methods in an experimental setting.METHODSFirst, NAPs were recorded from surgically exposed peripheral nerves in monkeys. For the authors to test their assumptions about observed artifacts, they then employed a simple model system. Finally, they applied their insights to clinical cases in the operating room.RESULTSIn monkey peripheral nerve recordings, large stimulus artifacts obscured NAPs every time the nerve segment (length 3–5 cm) was lifted up from the surrounding tissue, and NAPs could not be recorded. Artifacts were suppressed, and NAPs emerged when “bridge grounding” was applied, and this allowed the NAPs to be recorded easily and reliably. Tests in a model system suggested that exaggerated stimulus artifacts and unmasking of NAPs by bridge grounding are related to a loop effect that is created by lifting the nerve. Consequently, clean NAPs were acquired in “nonlifting” recordings from monkey peripheral nerves. In clinical cases, bridge grounding efficiently unmasked intraoperative NAP recordings, validating the authors’ principal concept in the clinical setting and allowing effective neurophysiological testing in the operating room.CONCLUSIONSTechnical challenges of intraoperative NAP recording are embedded in the current methods that recommend lifting the nerve from the tissue bed, thereby exaggerating stimulus artifacts by a loop effect. Better results can be achieved by performing nonlifting nerve recording or by applying bridge grounding. The authors not only tested their findings in an animal model but also applied them successfully in clinical practice.