bluuebunny/crossref_metadata_2025 huggingface dataset:
Dosimetry and Radioenhancement Comparison of Gold Nanoparticles in Kilovoltage and Megavoltage Radiotherapy using MAGAT Polymer Gel Dosimeter
Authors: Farahani S , Riyahi Alam N , Haghgoo S , Khoobi M , Geraily Gh , Gorji E
Published: August 2019

Background: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results.Objective: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (0.380 KeV) using MAGAT gel dosimeter.Material and Methods: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging.Result: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14).Conclusion: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.
An Efficiency Studying of an Ion Chamber Simulation Using Vriance Reduction Techniques with EGSnrc
Authors: Campos L T , Magalhães L A , De Almeida C E V
Published: August 2019

Background: Radiotherapy is an important technique of cancer treatment using ionizing radiation. The determination of total dose in reference conditions is an important contribution to uncertainty that could achieve 2%. The source of this uncertainty comes from cavity theory that relates the in-air cavity dose and the dose to water. These correction factors are determined from Monte Carlo calculations of ionization chambers. The main problem of this type of calculation is the extremely long computation time to achieve reasonable statistics.Objective: The main purpose of this work is to present a combination with variance reduction techniques for the case of an ionization chamber in water.Methods: The egs_chamber code allows for very efficient computation of ionization chamber doses and dose ratios by using various variance reduction techniques, and also permits realistic simulations of the experimental setup due to the use of EGSnrc C++ library. Russian roulette and Photon Cross Section Enhancement were used with egs_chamber code. Tests were performed to obtain the parameters of variance reduction techniques resulting in a maximum efficiency.Results: It can be seen that the parameters which result in improved Monte Carlo calculation of the efficiency values are XCSE 64 and Russian Roulette (RR) 128.Conclusion: This study determines the parameters of variance reduction techniques that result in an optimal computational efficiency.
Manipulation Effect on Lumbar Kinematics in Patients with Unilateral Innominate Rotation and Comparison with Asymptomatic Subjects
Authors: Zamanlou M , Akbari M , Jamshidi A A , Amiri A , Nabiyouni I
Published: August 2019

Background: Lumbar motion analysis is used as a clinical method in the diagnosis and treatment of low back pain (LBP). So far, no studies have shown if manipulating the sacroiliac joint (SIJ) will change spinal kinematics.Objective: The main objectives of this study were to investigate the effects of SIJ manipulation on the lumbar kinematics in subjects with innominate rotation and to compare lumbar kinematics among experiment and control groups.Material and Methods: This study was a quasi-experiment-control trial study. 21 LBP patients with anterior or posterior innominate rotations in experiment group and 22 asymptomatic subjects in control group were evaluated. Lumbar kinematic variables (LKV) include lumbar range of motion (ROM) and speed, lumbar lateral flexion and rotation asymmetry were evaluated using Qualysis Track Manager (QTM) twice within two days in control group, and these parameters with pelvic asymmetry and disability were tested before and after intervention in the experiment group.Results: While pre-intervention experiment group exhibited significantly lower lumbar lateral flexion (p=0.0001), rotation (p=0.008) ROM and lower lateral flexion speed (p=0.014), post-intervention experiment group exhibited significantly lower lumbar lateral flexion (p=0.01) ROM in comparison with control group. Pelvic asymmetry (p=0.049) and disability (p=0.01) significantly decreased in the experiment group after manipulation, but LKV did not change significantly after the intervention (p˃0.05).Conclusion: Experiment groups had different lumbar kinematics in comparison with control group before and after SIJ manipulation. Despite the changes in pelvic asymmetry and disability, intervention had no effect on lumbar kinematics.
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

OBJECTIVE

Intracerebral 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.

METHODS

Fully 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.

RESULTS

All 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).

CONCLUSIONS

Prolonged 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

OBJECTIVE

The 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.

METHODS

This 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.

RESULTS

The 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.

CONCLUSIONS

The 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

OBJECTIVE

Inflammation 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.

METHODS

An 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.

RESULTS

The 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.

CONCLUSIONS

BIO 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

OBJECTIVE

Meningiomas 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.

METHODS

From 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.

RESULTS

Falcotentorial 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).

CONCLUSIONS

Falcotentorial 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

OBJECTIVE

The 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.

METHODS

Each 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.

RESULTS

No 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).

CONCLUSIONS

The 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

OBJECTIVE

Cerebral 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.

METHODS

The 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.

RESULTS

Thirty-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.

CONCLUSIONS

To 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

OBJECTIVE

Emerging 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.

METHODS

Adult 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.

RESULTS

The 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.

CONCLUSIONS

Collectively, 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

OBJECTIVE

The 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.

METHODS

In 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.

RESULTS

A 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.

CONCLUSIONS

Almost 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

OBJECTIVE

Intraoperative 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.

METHODS

First, 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.

RESULTS

In 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.

CONCLUSIONS

Technical 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.
Outcome evaluation of patients treated with fractionated Gamma Knife radiosurgery for large (> 3 cm) brain metastases: a dose-escalation study
Authors: Kim Kyung Hwan , Kong Doo-Sik , Cho Kyung Rae , Lee Min Ho , Choi Jung-Won , Seol Ho Jun , Kim Sung Tae , Nam Do-Hyun , Lee Jung-Il
Published: August 2019

OBJECTIVE

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.

METHODS

The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.

RESULTS

Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.

CONCLUSIONS

In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.
Deep brain stimulation of the posterior limb of the internal capsule in the treatment of central poststroke neuropathic pain of the lower limb: case series with long-term follow-up and literature review
Authors: Franzini Andrea , Messina Giuseppe , Levi Vincenzo , D’Ammando Antonio , Cordella Roberto , Moosa Shayan , Prada Francesco , Franzini Angelo
Published: August 2019

OBJECTIVE

Central poststroke neuropathic pain is a debilitating syndrome that is often resistant to medical therapies. Surgical measures include motor cortex stimulation and deep brain stimulation (DBS), which have been used to relieve pain. The aim of this study was to retrospectively assess the safety and long-term efficacy of DBS of the posterior limb of the internal capsule for relieving central poststroke neuropathic pain and associated spasticity affecting the lower limb.

METHODS

Clinical and surgical data were retrospectively collected and analyzed in all patients who had undergone DBS of the posterior limb of the internal capsule to address central poststroke neuropathic pain refractory to conservative measures. In addition, long-term pain intensity and level of satisfaction gained from stimulation were assessed. Pain was evaluated using the visual analog scale (VAS). Information on gait improvement was obtained from medical records, neurological examination, and interview.

RESULTS

Four patients have undergone the procedure since 2001. No mortality or morbidity related to the surgery was recorded. In three patients, stimulation of the posterior limb of the internal capsule resulted in long-term pain relief; in a fourth patient, the procedure failed to produce any long-lasting positive effect. Two patients obtained a reduction in spasticity and improved motor capability. Before surgery, the mean VAS score was 9 (range 8–10). In the immediate postoperative period and within 1 week after the DBS system had been turned on, the mean VAS score was significantly lower at a mean of 3 (range 0–6). After a mean follow-up of 5.88 years, the mean VAS score was still reduced at 5.5 (range 3–8). The mean percentage of long-term pain reduction was 38.13%.

CONCLUSIONS

This series suggests that stimulation of the posterior limb of the internal capsule is safe and effective in treating patients with chronic neuropathic pain affecting the lower limb. The procedure may be a more targeted treatment method than motor cortex stimulation or other neuromodulation techniques in the subset of patients whose pain and spasticity are referred to the lower limbs.
Volumetric growth rates of untreated vestibular schwannomas
Authors: Schnurman Zane , Nakamura Aya , McQuinn Michelle W. , Golfinos John G. , Roland J. Thomas , Kondziolka Douglas
Published: August 2019

OBJECTIVE

There remains a large discrepancy among surgeons in expectations of vestibular schwannoma (VS) growth. The anticipated growth rate of a VS and its potential clinical impact are important factors when deciding whether to observe the lesion over time or to intervene. Previous studies of VS natural growth remain limited, mostly confined to linear measurements, often without high-resolution, thin-sequence imaging. The present study comprehensively assessed natural tumor growth rates using volumetric measurements.

METHODS

Between 2012 and 2018, 212 treatment-naïve patients diagnosed with a unilateral VS were evaluated. A total of 699 MR images were assessed, with a range of 2–11 MR images per patient. All MR images preceded any intervention, with patients subsequently being observed through completion of data analysis (36%) or treated with stereotactic radiosurgery (32%) or microsurgical resection (32%). To determine precise tumor volumes, the tumor area was outlined on every slice, and the products of the area and slice thickness were summed (99% of scans were ≤ 1-mm slice thickness). A multilevel model with random effects was used to assess the mean volume change over time. Each tumor was categorized as one of the following: growing (volume increase by more than 20% per year), fast growing (volume increase by more than 100% per year), stable (volume change between 20% decrease and 20% increase per year), and shrinking (volume decrease by more than 20% per year).

RESULTS

The mean VS volumetric growth rate was 33.5% per year (95% CI 26.9%–40.5%, p < 0.001). When assessing the frequencies of individual tumor annual growth rates, 66% demonstrated growth (30% fast growing), 33% were stable, and 1% exhibited shrinking over an average interval of 25 months. Larger tumors were associated with increased absolute growth, but there was no relationship between tumor size and proportional growth rate. There was also no relationship between patient age and tumor growth rate.

CONCLUSIONS

This study comprehensively assessed VS volumetric growth rates using high-resolution images and was conducted in a large and diverse patient sample. The majority of the tumors exhibited growth, with about one-third growing at a rate of 100% per year. These findings may contribute to a consensus understanding of tumor behavior and inform clinical decisions regarding whether to intervene or observe.
Use of a near-infrared vein finder to define cortical veins and dural sinuses prior to dural opening
Authors: Goldschmidt Ezequiel , Faraji Amir H. , Jankowitz Brian T. , Gardner Paul , Friedlander Robert M.
Published: August 2019

Near-infrared (NIR) light is commonly used to map venous anatomy in the upper extremities to gain intravenous access for line placement. In this report, the authors describe the use of a common and commercially available NIR vein finder to delineate the cortical venous anatomy prior to dural opening.

During a variety of cranial approaches, the dura was directly visualized using an NIR vein finder. The NIR light source allowed for recognition of the underlying cortical venous anatomy, dural sinuses, and underlying pathology before the dura was opened. This information was considered when tailoring the dural opening. When the dura was illuminated with the NIR vein finder, the underlying cortical and sinus venous anatomy was evident and correlated with the observed cortical anatomy. The vein finder was also accurate in locating superficial lesions and pathological dural veins. A complete accordance in the findings on the pre– and post–dural opening images was observed in all cases.

This simple, inexpensive procedure is readily compatible with operative room workflow, necessitates no head fixation, and offers a real-time image independent of brain shift.
A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation: the Multi Recharge Trial
Authors: Jakobs Martin , Helmers Ann-Kristin , Synowitz Michael , Slotty Philipp J. , Anthofer Judith M. , Schlaier Jürgen R. , Kloss Manja , Unterberg Andreas W. , Kiening Karl L.
Published: August 2019

OBJECTIVE

Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients are sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators.

METHODS

Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from “very hard” (1) to “very easy” (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups.

RESULTS

Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson’s disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as “easy” (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint.

CONCLUSIONS

Overall, patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden.
Costs and predictors of 30-day readmissions after craniotomy for traumatic brain injury: a nationwide analysis
Authors: Hoffman Haydn , Furst Taylor , Jalal Muhammad S. , Chin Lawrence S.
Published: August 2019

OBJECTIVE

There is increasing interest in the use of 30-day readmission (30dRA) as a quality metric to represent hospital and provider performance. Data regarding the incidence and risk factors for 30dRA after traumatic brain injury (TBI) are sparse. The authors sought to characterize these variables using a national database.

METHODS

The Nationwide Readmissions Database was used to identify patients with a primary diagnosis of TBI who underwent craniotomy or craniectomy between 2010 and 2014. Our primary outcome of interest was 30dRA. Binary logistic regression was used to identify variables related to patient demographics, comorbidities, and index hospital admission that were associated with 30dRA.

RESULTS

A total of 25,354 patients met the inclusion criteria. The 30dRA rate during the entire study period was 15.5%. In 2010 the 30dRA rate was 16.8% and in 2014 it decreased to 15.1% (pooled OR 0.90, 95% CI 0.87–0.94). The mean cost associated with a 30dRA increased slightly but significantly, from $9999 in 2010 to $10,114 in 2014 (p = 0.021). Factors associated with increased odds of 30dRA in the binary logistic regression included increased age, greater comorbidity burden, more severe injury, tracheostomy, gastrostomy, sodium abnormality, and venous thromboembolism. In order of decreasing frequency, the most common causes for 30dRA were neurological, injury/iatrogenic, cardiovascular/cerebrovascular, infectious, and respiratory.

CONCLUSIONS

The incidence of 30dRA after craniotomy for TBI decreased slightly from 2010 to 2014. This study identified several variables associated with 30dRA that require confirmation in a prospective study, which could direct attempts to prevent readmissions.
The history of neurosurgery at the House Clinic in Los Angeles
Authors: Mehta Gautam U. , Lekovic Gregory P.
Published: August 2019

Although most widely known as the birthplace of neuro-otology, the House Clinic in Los Angeles has been the site of several major contributions to the field of neurosurgery. From the beginning of the formation of the Otologic Medical Group in 1958 (later renamed the House Ear Clinic), these contributions have been largely due to the innovative and collaborative work of neurosurgeon William E. Hitselberger, MD, and neuro-otologist William F. House, MD, DDS. Together they were responsible for the development and widespread adoption of the team approach to skull-base surgery. Specific neurosurgical advances accomplished at the House Clinic have included the first application of the operative microscope to neurosurgery, the application of middle fossa and translabyrinthine approaches for vestibular schwannoma, and the development of combined petrosal, retrolabyrinthine, and other alternative petrosal approaches and of hearing preservation surgery for vestibular schwannoma. The auditory brainstem implant, invented at the House Clinic in 1979, was the first ever successful application of central nervous system neuromodulation for restoration of function. Technological innovations at the House Clinic have also advanced neurosurgery. These include the first video transmission of microsurgery, the first suction irrigator, the first debulking instrument for tumors, and the House-Urban retractor for middle fossa surgery.
Neural and vascular architecture of the septum pellucidum: an anatomical study and considerations for safe endoscopic septum pellucidotomy
Authors: Barany Laszlo , Meszaros Cintia , Ganslandt Oliver , Buchfelder Michael , Kurucz Peter
Published: August 2019

OBJECTIVE

The septum pellucidum is a bilateral thin membranous structure representing the border between the frontal horns of the lateral ventricles. Its most examined components are the septal veins due to their surgical importance during endoscopic septum pellucidotomy (ESP), which is a well-accepted method for surgical treatment of unilateral hydrocephalus. It is widely accepted that the septum pellucidum contains nerve fibers as well, but interestingly, no anatomical study has been addressed to its neural components before. The aim of the present study was to identify these elements as well as their relations to the septal veins and to define major landmarks within the ventricular system for neurosurgical use.

METHODS

Nine formalin-fixed human cadaveric brains (18 septa pellucida) were involved in this study. A central block containing both septa pellucida was removed and frozen at −30°C for 2 weeks in 7 cases. The fibers of the septum pellucidum and the adjacent areas including the venous elements were dissected under magnification by using homemade wooden spatulas and microsurgical instruments. In 2 cases a histological technique was used to validate the findings of the dissections. The blocks were sliced, embedded in paraffin, cut in 7-µm-thick slices, and then stained as follows: 1) with H & E, 2) with Luxol fast blue combined with cresyl violet, and 3) with Luxol fast blue combined with Sirius red.

RESULTS

The septum pellucidum and the subjacent septum verum form the medial wall of the frontal horn of the lateral ventricle. Both structures contain nerve fibers that were organized in 3 groups: 1) the precommissural fibers of the fornix; 2) the inferior fascicle; and 3) the superior fascicle of the septum pellucidum. The area directly rostral to the postcommissural column of the fornix consisted of macroscopically identifiable gray matter corresponding to the septal nuclei. The histological examinations validated the findings of the authors’ fiber dissections.

CONCLUSIONS

The nerve elements of the septum pellucidum as well as the subjacent septum verum were identified with fiber dissection and verified with histology for the first time. The septal nuclei located just anterior to the fornix and the precommissural fibers of the fornix should be preserved during ESP. Considering the venous anatomy as well as the neural architecture of the septum pellucidum, the fenestration should ideally be placed above the superior edge of the fornix and preferably dorsal to the interventricular foramen.
Inhibition of motility by NEO100 through the calpain-1/RhoA pathway
Authors: Marín-Ramos Nagore I. , Pérez-Hernández Marta , Tam Anson , Swenson Stephen D. , Cho Hee-Yeon , Thein Thu Zan , Hofman Florence M. , Chen Thomas C.
Published: August 2019

OBJECTIVE

Glioblastoma (GBM) is the most aggressive type of brain tumor with a high rate of tumor recurrence, and it often develops resistance over time to current standard of care chemotherapy. Its highly invasive nature plays an essential role in tumor progression and recurrence. Glioma stem cells (GSCs) are a subpopulation of glioma cells highly resistant to treatments and are considered responsible for tumor recurrence.

METHODS

Patient-derived populations of GSCs were analyzed by western blot, MTT, and cytoplasmic calcium labeling to determine the cytotoxicity of NEO100. High-performance liquid chromatography was used to evaluate the levels of NEO100 in the cell culture supernatants. The effects of the compound on GSC motility were studied using Boyden chamber migration, 3D spheroid migration and invasion assays, and an mRNA expression PCR array. A RhoA activation assay, western blot, and immunofluorescence techniques were employed to confirm the signaling pathways involved. Intracranial implantation of GSCs in athymic mice was used to evaluate the effects of NEO100 in vivo on tumor progression and overall survival.

RESULTS

Here, the authors show how NEO100, a highly purified good manufacturing practices–quality form of perillyl alcohol, is cytotoxic for different subtypes of GSCs, regardless of the mechanisms of DNA repair present. At doses similar to the IC50 (half maximal inhibitory concentration) values, NEO100 induces ER stress and activates apoptotic pathways in all GSC populations tested. At subcytotoxic doses in the micromolar range, NEO100 blocks migration and invasion of GSCs. These results correlate with a decrease in calpain-1 expression and an increase in RhoA activation, leading to enhanced contractility of the GSCs. In addition, NEO100 blocks the activation of the kinases Src, p42/44 MAPK, Akt, and Stat3, all related to cell proliferation and migration. Intranasal administration of NEO100 in mice with GSC-derived intracranial tumors led to a decrease in tumor progression and a 32% increase in overall survival. Immunostaining studies showed that NEO100 induces apoptosis and reduces GSC invasion in vivo.

CONCLUSIONS

NEO100 could have significant value targeting GSCs and could be used for GBM therapy as either monotherapy or a coadjuvant therapy during temozolomide rest cycles.