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Alex Kharazi, Michael L. Levy, Maria Cristina Visperas and Chih-Min Lin

Object

The multipotency of neural stem cells (NSCs) can be assessed in vitro by detection of stage-specific markers in response to a suitable differentiation signal. This test is frequently used because it is fast and affordable. However, it is not clear how the in vitro potential for multilineage differentiation and stem cell marker expression would reflect the ability of NSCs to engraft into the brain following transplantation. The authors undertook this study to directly compare the in vitro potency and in vivo migration of human NSCs (hNSCs) expanded under conditions of gradually increased concentration of fetal bovine serum (FBS) as a maturation factor.

Methods

Human NSCs isolated from fetal brain were propagated in serum free media (SF-hNSCs) and in media containing 0.1% and 0.2% serum. At Passage 4 in tissue culture the NSCs were harvested and either differentiated in vitro or transplanted into the lateral ventricle of chicken embryonic brain at the late stage of its development (Hamburger and Hamilton Stage 26). The in vitro differentiation was evaluated by immunostaining with neural or glial specific markers, and the in vivo migration was assessed using immunohistology.

Results

The authors found that SF-hNSCs successfully engrafted into the chicken embryonic brain, which correlated with their ability to differentiate in vitro. NSCs grown at as low as 0.1% concentration of FBS failed to demonstrate the robust in vivo migration pattern but still preserved the capability to differentiate in vitro. Furthermore, NSCs generated in media containing a higher concentration of FBS (0.2%) lost both the in vivo engraftment and in vitro differentiation potential.

Conclusions

The present study suggests that marker expression and in vitro differentiation assays might not provide adequate information regarding the behavior of NSCs following their transplantation. The in vivo migration following injection into chicken embryonic brain may provide an important assay of the potency of NSCs.

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Chun-Pi Chang, Yu-Min Chang, Chuang-Yen Huang, Hung-Shiang Fang, Chia-Hua Lin and Dueng-Yuan Hueng

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Yu-Shu Yen, Li-Min Sun, Cheng-Li Lin, Shih-Ni Chang, Fung-Chang Sung and Chia-Hung Kao

Object

Evidence suggests that hormones play a role in modifying both uterine myoma (UM) and meningioma. A number of studies have observed the positive association between these diseases. The aim of the current population-based study was to determine if women with UM are at a higher risk for meningioma.

Methods

The authors used data from the National Health Insurance system of Taiwan for the study. The UM cohort contained 281,244 women. Each woman was randomly frequency-matched with 4 women without UM, based on age, index year of diagnosis, occupation, urbanization (urbanization level was categorized by the population density of the residential area into 4 levels, with Level 1 as the most urbanized and Level 4 as the least urbanized), and comorbidity, to form the control cohort. Cox's proportional hazard regression analysis was conducted to estimate the influence of UM on the meningioma risk.

Results

Among women with UM, the risk of developing meningioma was significantly higher (45%) than among women without UM (95% CI 1.23–1.70). The same phenomenon was observed among most age groups, but a significant difference was only seen in the middle-age range. For women with UM, further analysis did not show a significant change after myomectomy. The cumulative incidence of meningioma between groups with and without UM differed over time.

Conclusions

The nationwide population-based cohort study found that Taiwanese women with UM are at higher risk for developing meningioma.

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Chung-Ching Chio, Li Wei, Tyng Guey Chen, Chien-Min Lin, Ja-Ping Shieh, Poh-Shiow Yeh and Ruei-Ming Chen

OBJECT

Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults.

METHODS

Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, cas-pase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding (CREB), and cellular inhibitor of apoptosis protein 2 (cIAP2) genes. Translations of these gene expressions were knocked down using RNA interference. Mice subjected to traumatic brain injury (TBI) and NOR-1 was immunodetected.

RESULTS

Exposure of neuro-2a cells to OGD decreased cell viability in a time-dependent manner. Additionally, OGD led to cell shrinkage, DNA fragmentation, and cell apoptosis. In parallel, treatment of neuro-2a cells with OGD time dependently increased cellular NOR-1 mRNA and protein expressions. Interestingly, administration of TBI also augmented NOR-1 levels in the impacted regions of mice. As to the mechanism, exposure to OGD increased nuclear levels of the transcription factor CREB protein. Downregulating CREB expression using RNA interference simultaneously inhibited OGD-induced NOR-1 mRNA expression. Also, levels of cIAP2 mRNA and protein in neuro-2a cells were augmented by OGD. After reducing cIAP2 translation, OGD-induced cell death was reduced. Sequentially, application of NOR-1 small interfering RNA to neuro-2a cells significantly inhibited OGD-induced cIAP2 mRNA expression and concurrently alleviated hypoxia-induced alterations in cell viability, caspase-3 activation, DNA damage, and cell apoptosis.

CONCLUSIONS

This study shows that NOR-1 can transduce survival signals in neuronal cells responsible for hypoxiainduced apoptotic insults through activation of a CREB/cIAP2-dependent mechanism.

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Chih-Hsiang Liao, Chun-Fu Lin, Sanford PC. Hsu, Min-Hsiung Chen and Yang-Hsin Shih

Symptomatic intracavernous aneurysm is rare. Cranial nerves in the cavernous sinus are subjected to the mass effect of an expanding aneurysm. Microsurgical clipping is the treatment of choice to relieve compressive cranial neuropathy. In this video, the authors present a case of intracavernous aneurysm causing diplopia, ptosis, and facial numbness. The patient was operated on via a pretemporal transclinoid-transcavernous approach. The aneurysm was completely obliterated through direct clipping. There were no new-onset neurologic deficits and complications after the operation. Complete recovery of the diplopia, ptosis, and facial numbness was observed at the 6-month postoperative follow up.

The video can be found here: http://youtu.be/4w5QUoNIAQM.

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Yong-Jian Zhu, Guang-Yu Ying, Ai-Qin Chen, Lin-Lin Wang, Dan-Feng Yu, Liang-Liang Zhu, Yu-Cheng Ren, Chen Wang, Peng-Cheng Wu, Ying Yao, Fang Shen and Jian-Min Zhang

OBJECT

Posterior midline laminectomy or hemilaminectomy has been successfully applied as the standard microsurgical technique for the treatment of spinal intradural pathologies. However, the associated risks of postoperative spinal instability increase the need for subsequent fusion surgery to prevent potential long-term spinal deformity. Continuous efforts have been made to minimize injuries to the surrounding tissue resulting from surgical manipulations. The authors report here their experiences with a novel minimally invasive surgical approach, namely the interlaminar approach, for the treatment of lumbar intraspinal tumors.

METHODS

A retrospective review was conducted of patients at the Second Affiliated Hospital of Zhejiang University School of Medicine who underwent minimally invasive resection of lumbar intradural-extramedullary tumors. By using an operative microscope, in addition to an endoscope when necessary, the authors were able to treat all patients with a unilateral, paramedian, bone-sparing interlaminar technique. Data including preoperative neurological status, tumor location, size, pathological diagnosis, extension of resections, intraoperative blood loss, length of hospital stay, and clinical outcomes were obtained through clinical and radiological examinations.

RESULTS

Eighteen patients diagnosed with lumbar intradural-extramedullary tumors were treated from October 2013 to March 2015 by this interlaminar technique. A microscope was used in 15 cases, and the remaining 3 cases were treated using a microscope as well as an endoscope. There were 14 schwannomas, 2 ependymomas, 1 epidermoid cyst, and 1 enterogenous cyst. Postoperative radiological follow-up revealed complete removal of all the lesions and no signs of bone defects in the lamina. At clinical follow-up, 14 of the 18 patients had less pain, and patients' motor/sensory functions improved or remained normal in all cases except 1.

CONClUSIONS

When meeting certain selection criteria, intradural-extramedullary lumbar tumors, especially schwannomas, can be completely and safely resected through a less-invasive interlaminar approach using a microscope, or a microscope in addition to an endoscope when necessary. This approach was advantageous because it caused even less bone destruction, resulting in better postoperative spinal stability, no need for facetectomy and fusion, and quicker functional recovery for the patients. Individualized surgical planning according to preoperative radiological findings is key to a successful microsurgical resection of these lesions through the interlaminar space.

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Chih-Hsiang Liao, Jui-To Wang, Chun-Fu Lin, Shao-Ching Chen, Chung-Jung Lin, Sanford P. C. Hsu and Min-Hsiung Chen

OBJECTIVE

Despite the advances in skull base techniques, large petroclival meningiomas (PCMs) still pose a challenge to neurosurgeons. The authors’ objective of this study was to describe a pretemporal trans–Meckel’s cave transtentorial approach for large PCMs and to report the surgical outcomes.

METHODS

From 2014 to 2017, patients harboring large PCMs (> 3 cm) and undergoing their first resection via this procedure at the authors’ institute were included. In combination with pretemporal transcavernous and anterior transpetrosal approaches, the trans–Meckel’s cave transtentorial route was created. Surgical details are described and a video demonstrating the procedure is included. Retrospective review of the medical records and imaging studies was performed.

RESULTS

A total of 18 patients (6 men and 12 women) were included in this study, with mean age of 53 years. The mean sizes of the preoperative and postoperative PCMs were 4.36 cm × 4.09 cm × 4.13 cm (length × width × height) and 0.83 cm × 1.08 cm × 0.75 cm, respectively. Gross-total removal was performed in 7 patients, near-total removal (> 95%) in 7 patients, and subtotal removal in 4 patients (> 90% in 3 patients and > 85% in 1 patient). There were no surgical deaths or patients with postoperative hemiplegia. Surgical complications included transient cranial nerve (CN) III palsy (all patients, resolved in 3 months), transient CN VI palsy (2 patients), CN IV palsy (3 patients, partial recovery), hydrocephalus (3 patients), and CSF otorrhea (1 patient). Temporal lobe retraction–related neurological deficits were not observed.

CONCLUSIONS

A pretemporal trans–Meckel’s cave transtentorial approach offers large surgical exposure and multiple trajectories to the suprasellar, interpeduncular, prepontine, and upper-half clival regions without overt traction, which is mandatory to remove large PCMs. To unlock Meckel’s cave where a large PCM lies abutting the cave, pretemporal transcavernous and anterior transpetrosal approaches are prerequisites to create adequate exposure for the final trans–Meckel’s cave step.

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Jie Cao, Hang Lin, Min Lin, Kaifu Ke, Yunfeng Zhang, Yong Zhang, Weihong Zheng, Xingyu Chen, Wei Wang, Meng Zhang, Jinggang Xuan, Ya Peng and for the REDIRECT Trial Investigators

OBJECTIVE

The RECO flow restoration (FR) device is a new stent retriever designed for rapid flow restoration in acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Here, the authors compared the efficacy and safety of the RECO device with the predicate Solitaire FR stent retriever.

METHODS

The RECO Flow Restoration Device Versus Solitaire FR With the Intention for Thrombectomy Study (REDIRECT) was a multicenter, prospective, open randomized controlled trial. Patients with acute LVO at 7 Chinese stroke centers participated in the study. The primary efficacy endpoint was defined as a modified thrombolysis in cerebral infarction (mTICI) reperfusion grade ≥ 2 within three passes. The primary safety endpoint comprised any serious adverse device effect, symptomatic intracerebral hemorrhage (sICH), and any serious adverse event (SAE; defined as cerebral palsy or death) within 24 hours after the procedure. The secondary efficacy endpoints consisted of functional independence (modified Rankin Scale score 0–2), procedure duration, and 90-day all-cause mortality.

RESULTS

Between January 2014 and August 2016, 67 patients were randomly allocated to the RECO group and 69 patients to the Solitaire FR group. The primary efficacy endpoint (mTICI grade ≥ 2 within three passes) was similar in the two treatment groups (91% vs 87%, respectively, p = 0.5861), and the rate of reperfusion with an mTICI grade 2b/3 was 87% versus 75% (p = 0.1272). There were no serious adverse device effects in any patient. The rates of sICH (1.5% vs 7.2%, p = 0.1027) and SAEs (6.0% vs 1.4%, p = 0.2050) within 24 hours after the procedure were similar in the two treatment groups. There was no significant difference in the rate of functional independence (63% vs 46%, p = 0.0609) or 90-day all-cause mortality (13% vs 23%, p = 0.1848) or in procedure duration (85.39 ± 47.01 vs 89.94 ± 53.34 minutes, p = 0.5986) between the two groups.

CONCLUSIONS

The RECO stent retriever is effective and safe as a mechanical thrombectomy device for AIS due to LVO.

Clinical trial registration no.: NCT01983644 (clinicaltrials.gov)

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Chih-Hsiang Liao, Chung-Jung Lin, Chun-Fu Lin, Hsin-Yi Huang, Min-Hsiung Chen, Sanford P. C. Hsu and Yang-Hsin Shih

OBJECTIVE

The treatment of paraclinoid aneurysms remains challenging. It is important to determine the exact location of the paraclinoid aneurysm when considering treatment options. The authors herein evaluated the effectiveness of using the optic strut (OS) and tuberculum sellae (TS) as radiographic landmarks for distinguishing between intradural and extradural paraclinoid aneurysms on source images from CT angiography (CTA).

METHODS

Between January 2010 and September 2013, a total of 49 surgical patients with the preoperative diagnoses of paraclinoid aneurysm and 1 symptomatic cavernous-clinoid aneurysm were retrospectively identified. With the source images from CTA, the OS and the TS were used as landmarks to predict the location of the paraclinoid aneurysm and its relation to the distal dural ring (DDR). The operative findings were examined to confirm the definitive location of the paraclinoid aneurysm. Statistical analysis was performed to determine the diagnostic effectiveness of the landmarks.

RESULTS

Nineteen patients without preoperative CTA were excluded. The remaining 30 patients comprised the current study. The intraoperative findings confirmed 12 intradural, 12 transitional, and 6 extradural paraclinoid aneurysms, the diagnoses of which were significantly related to the type of aneurysm (p < 0.05) but not factors like sex, age, laterality of aneurysm, or relation of the aneurysm to the ophthalmic artery on digital subtraction angiography. To measure agreement with the correct diagnosis, the OS as a reference point was far superior to the TS (Cohen's kappa coefficients 0.462 and 0.138 for the OS and the TS, respectively). For paraclinoid aneurysms of the medial or posterior type, using the base of the OS as a reference point tended to overestimate intradural paraclinoid aneurysms. The receiver operating characteristic curve indicated that if the aneurysmal neck traverses the axial plane 2 mm above the base of the OS, the aneurysm is most likely to grow across the DDR and present as a transitional aneurysm (sensitivity 0.806; specificity 0.792).

CONCLUSIONS

High-resolution thin-cut CTA is a fast and crucial tool for diagnosing paraclinoid aneurysms. The OS serves as an effective landmark in CTA source images for distinguishing between intradural and extradural paraclinoid aneurysms. The DDR is supposed to be located 2 mm above the base of the OS in axial planes.