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Sung-Min Kim, T. Jesse Lim, Josemaria Paterno, Tae-Jin Hwang, Kun-Woo Lee, Raju S. V. Balabhadra, and Daniel H. Kim

Object. The authors compared the biomechanical stability of two anterior fixation procedures—anterior C1–2 Harms plate/screw (AHPS) fixation and the anterior C1–2 transarticular screw (ATS) fixation; and two posterior fixation procedures—the posterior C-1 lateral mass combined with C-2 pedicle screw/rod (PLM/APSR) fixation and the posterior C1–2 transarticular screw (PTS) fixation after destabilization.

Methods. Sixteen human cervical spine specimens (Oc—C3) were tested in three-dimensional flexion—extension, axial rotation, and lateral bending motions after destabilization by using an atlantoaxial C1–2 instability model. In each loading mode, moments were applied to a maximum of 1.5 Nm, and the range of motion (ROM), neutral zone (NZ), and elastic zone (EZ) were determined and values compared using the intact spine, the destabilized spine, and the postfixation spine.

The AHPS method produced inferior biomechanical results in flexion—extension and lateral bending modes compared with the intact spine. The lateral bending NZ and ROM for this method differed significantly from the other three fixation techniques (p < 0.05), although statistically significant differences were not obtained for all other values of ROM and NZ for the other three procedures. The remaining three methods restored biomechanical stability and improved it over that of the intact spine.

Conclusions. The PLM/APSR fixation method was found to have the highest biomechanical stiffness followed by PTS, ATS, and AHPS fixation. The PLM/APSR fixation and AATS methods can be considered good procedures for stabilizing the atlantoaxial joints, although specific fixation methods are determined by the proper clinical and radiological characteristics in each patient.

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Joong-Uhn Choi, Kook-Hee Yang, Tae-Gon Kim, Jong Hee Chang, Jin Woo Chang, Byung-In Lee, and Dong-Seok Kim

✓ Although intractable epilepsy associated with hypothalamic hamartoma (HH) can be controlled by microsurgical resection of the lesion, excision of deep-seated lesions is often associated with morbidity and mortality. Endoscopic disconnection is less invasive and seems to be well suited for this indication. The authors discuss the role of endoscopic-assisted surgery in the management of HH-induced seizures.

Four patients with HH-related intractable gelastic seizure underwent endoscopic disconnection surgery. Postoperatively, all patients exhibited improvement. Two patients became seizure free immediately after endoscopic disconnection surgery, one patient with a widespread seizure focus involving the motor strip continued to experience rare complex partial seizures but gelastic seizures ceased, and one experienced a reduced frequency of seizures but persistence of some generalized seizures. Three patients suffered postoperative disconnection-like syndrome, which continued 3 to 7 days and spontaneously disappeared.

The authors advocate the endoscopic disconnection surgery as a safe and effective treatment for HH-related epilepsy by blocking the spread of epileptic discharges from the lesion.

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Tae-Wan Kim, Hyang-Hwa Ryu, Song-Yuan Li, Chun-Hao Li, Sa-Hoe Lim, Woo-Youl Jang, and Shin Jung

OBJECTIVE

In patients with glioblastoma, local invasion of tumor cells causes recurrence and shortens survival. The goal of this study was to determine whether protein disulfide isomerase (PDI) A6 regulates migration and invasion of glioblastoma cells and the associated factors.

METHODS

U87MG cells were treated with either PDIA6 or ADAM17 small interfering RNA (siRNA) fragments or with both types of siRNA fragments, and expression was confirmed by reverse transcription–polymerase chain reaction and Western blot. Migration and invasion were assessed using a wound-healing assay, a Matrigel assay, and an organotypic culture system. After the U87MG cells were treated with siRNAs and epidermal growth factor receptor (EGFR) inhibitors, the expression of matrix metalloproteinase–2 (MMP-2), membrane Type 1-matrix metalloproteinase (MT1-MMP), integrin, phosphorylated focal adhesion kinase (pFAK), and phosphorylated EGFR (pEGFR) was detected by Western blotting and zymography.

RESULTS

U87MG cell migration and invasion increased significantly after inhibition of PDIA6. The MMP-2 activation ratio and ADAM17 activity (as a sheddase of the proligand) increased, and expression of pEGFR, pFAK, integrin α5β3, and MT1-MMP was induced, compared with control levels. Furthermore, heparin-binding epidermal growth factor (EGFR signaling ligand) was highly expressed in PDIA6-knockdown cells. After siPDIA6-transfected U87MG cells were treated with EGFR signaling inhibitors, expression of pFAK, MMP-2, and MT1-MMP decreased and invasion decreased significantly. Simultaneous double-knockdown of PDIA6 and ADAM17 reduced pEGFR and pFAK expression, compared with control levels.

CONCLUSIONS

The authors propose that inhibiting PDIA6 could transduce EGFR signaling by activating and inducing ADAM17 during migration and invasion of U87MG glioblastoma cells. The results of this study suggest that PDIA6 is an important component of EGFR-mediated migration and invasion of U87MG cells. This is the first report of the effects of PDIA6 on migration and invasion in glioblastoma.

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Young Mi Yoo, Yong Jung Kim, Uhn Lee, Doo Jin Paik, Hyun Tae Yoo, Cheol Wan Park, Young Bo Kim, Sang Goo Lee, Woo Kyung Kim, and Chan Jong Yoo

Object

Parkinson disease (PD) is a well-known degenerative disease resulting in the depletion of dopamine-producing neurons in the pars compacta of the substantia nigra. Adenoviral vector delivery of neurotrophic factors may provide a potential therapy for PD. The authors examined whether glial cell line–derived neurotrophic factor (GDNF) delivered via adenoviral vector (Ad-GDNF) could promote functional recovery in a rat model of PD. Additionally, they examined whether neural precursor cells (NPCs) provide the therapeutic potential of cultured neural cells for cell regeneration and replacement in PD.

Methods

All animals underwent stereotactic injection of 6-hydroxydopamine into the right substantia nigra. Eight weeks later, the rats were tested for apomorphine-induced rotational asymmetry and evaluation of explanted grafts infected with the complementary DNA for GDNF containing NPCs and NPCs alone. In the NPC cultures of embryonic rat striata, the authors found that basic fibroblast growth factor induced the proliferation of stem cells, which give rise to spheres of undifferentiated cells that generate neurons and glia.

Conclusions

In this study the authors found that the reduction of apomorphine-induced rotation was more prominent in parkinsonian rats that received Ad-GDNF-treated grafts containing NPCs (61%) than in those that received grafts of NPCs alone (16%).

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Eun-Hee Kim, Mi-Sun Yum, Young-Shin Ra, Jun Bum Park, Jae Sung Ahn, Gu-Hwan Kim, Hyun Woo Goo, Tae-Sung Ko, and Han-Wook Yoo

OBJECT

Moyamoya disease (MMD) is an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. In the pathogenesis of MMD, the important role of genetic factors is being elucidated, and RNF213 has recently been identified as a susceptibility gene for MMD. The aim of this retrospective study was to investigate the RNF213 genotype in patients with MMD and to determine their genotype-phenotype associations.

METHODS

The study involved 165 Korean MMD patients from 155 unrelated families who were diagnosed with MMD at a single center from 1995 to 2013. Their demographic, radiological, and clinical findings were evaluated. Direct sequencing of the major RNF213 single nucleotide polymorphisms was performed. The association of the common RNF213 variant with MMD risk was evaluated using historical controls for comparison. Correlations between RNF213 genotype and phenotype were statistically analyzed.

RESULTS

The c.14429G>A (p.R4810K) variant was identified in 125 (75.8%) of 165 MMD patients. Most patients (112) were heterozygous, and 13 patients had 2 copies of the c.14429G>A variant. A novel heterozygous variant, c.12086A>G (p.Q4029R), was found in 1 additional patient. The minor allele frequency of the c.14429G>A variant was significantly higher in the MMD group (138 [41.8%] of 330 patients) than in the control group (8 [1.36%] of 588 subjects; p < 0.001). The c.14429G>A (p.R4810K) variant significantly increased the risk of MMD in Korean patients, with an OR of 52.11 (p < 0.001) compared with controls. Moreover, c.14429G>A (p.R4810K) genotypes occurred more frequently in patients with a family history of MMD. The homozygous variant was highly associated with early-onset MMD (age at onset < 5 years), cerebral infarction at diagnosis, and cognitive impairment in long-term outcome.

CONCLUSIONS

The findings indicate that the c.14429G>A (p.R4810K) allele of RNF213 is strongly associated with Korean patients with MMD. The homozygous c.14429G>A (p.R4810K) variant is particularly related to early-onset MMD, severe symptomatic manifestations at diagnosis, and poor prognosis. This genotypic variant may be a useful biomarker for early-onset MMD or unstable MMD with cerebral infarction, which requires early diagnosis and revascularization treatment.

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Ju-Hwi Kim, Kyung-Sub Moon, Ji-Ho Jung, Woo-Youl Jang, Tae-Young Jung, In-Young Kim, Kyung-Hwa Lee, and Shin Jung

OBJECTIVE

Indocyanine green videoangiography (ICGVA) has been used in many neurosurgical operations, including vascular and brain tumor fields. In this study, the authors applied ICGVA to intracranial meningioma surgery and evaluated it usefulness with attention to collateral venous flow.

METHODS

Forty-two patients with intracranial meningioma who underwent ICGVA during microsurgical resection were retrospectively analyzed. For ICGVA, the ICG was injected intravenously at the standard dose of 12.5 mg before and/or after tumor resection. Intravascular fluorescence from blood vessels was imaged through a microscope with a special filter and infrared excitation light to illuminate the operating field. The authors assessed the benefits of ICGVA and analyzed its findings with preoperative radiological findings on MRI.

RESULTS

ICGVA allowed real-time assessment of the patency and flow direction in very small peritumoral vessels in all cases. A safe dural incision could also be done based on information from ICGVA. The collateral venous channel due to venous obstruction of tumoral compression was found in 10 cases, and venous flow restoration after tumor resection was observed promptly after tumor resection in 4 cases. Peritumoral brain edema (PTBE) was observed on preoperative T2-weighted MRI in 19 patients. The presence of collateral venous circulation or flow restoration was significantly related to PTBE formation in multivariate analysis (p = 0.001; HR 0.027, 95% CI 0.003–0.242).

CONCLUSIONS

ICGVA, an excellent method for monitoring blood flow during meningioma resection, provides valuable information as to the presence of venous collaterals and flow restoration. Furthermore, the fact that the presence of venous collaterals was found to be associated with PTBE may directly support the venous theory as the pathogenesis of PTBE formation.

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Woo-Jin Lee, Keun-Hwa Jung, Keon-Joo Lee, Jeong-Min Kim, Soon-Tae Lee, Kon Chu, Sang Kun Lee, and Jae-Kyu Roh

OBJECT

The progression of arterial stenosis in patients with moyamoya disease (MMD) has variable courses and an unclear mechanism. The authors hypothesized that elevated wall shear stress (WSS) at the terminal internal carotid artery (ICA) and proximal middle cerebral artery (MCA) may facilitate MMD progression. They indirectly evaluated the relative magnitude of WSS (WSS value [WSSV]) with MR angiography (MRA) and transcranial Doppler to determine its predictive value for stenosis progression (SP) and the development of vascular complications.

METHODS

Thirty-one medically treated patients (58 hemispheres and 95 nonoccluded vessels) were analyzed with serial MRA (median follow-up 23 months). The parameters studied were SP, SP rates (SPRs) for individual ICAs/MCAs, and their mean values from the ipsilateral hemispheres as mean SP (MSP) and MSP rates (MSPRs). Significant progression was defined as decrements of ≥ 20% for SP and MSP and ≥ 10%/year for SPR and MSPR. The development of vascular complications in relevant hemispheres was also recorded. The WSSV (dyne/cm2) was defined as the shear rate multiplied by blood viscosity.

RESULTS

After adjusting the initial stenosis degree and MRA stage of MMD, an SP of ≥ 20% and an SPR of ≥ 10%/year were associated with the highest-quartile WSSVs for all individual vessels and for MCAs and ICAs separately. For each hemisphere, an MSP of ≥ 20% and an MSPR of ≥ 10%/year were associated with the highest-quartile mean WSSVs. Furthermore, significant SP was highly correlated with vascular complications, and the highest-quartile mean WSSV was independently associated with vascular complications in relevant hemispheres.

CONCLUSIONS

An elevated WSSV is an independent predictor for SP and vascular complications in nonoccluded MMD.

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Ji Hoon Phi, Jung Won Choi, Moon-Woo Seong, Tackeun Kim, Youn Joo Moon, Joongyub Lee, Eun Jung Koh, Seul Ki Ryu, Tae Hee Kang, Jae Seung Bang, Chang Wan Oh, Sung Sup Park, Ji Yeoun Lee, Kyu-Chang Wang, and Seung-Ki Kim

OBJECTIVE

In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not.

METHODS

The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing.

RESULTS

In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57–1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement.

CONCLUSIONS

The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1–moyamoya connection.

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Jun Jae Shin, Hyeongseok Jeon, Jong Joo Lee, Hyung Cheol Kim, Tae Woo Kim, Sung Bae An, Dong Ah Shin, Seong Yi, Keung-Nyun Kim, Do-Heum Yoon, Narihito Nagoshi, Kota Watanabe, Masaya Nakamura, Morio Matsumoto, Nan Li, Sai Ma, Da He, Wei Tian, Kenny Yat Hong Kwan, Kenneth Man Chee Cheung, K. Daniel Riew, Daniel J. Hoh, Yoon Ha, and the Asia Pacific Spine Study Group (APSSG)

OBJECTIVE

The purpose of this retrospective multicenter study was to compare prognostic factors for neurological recovery in patients undergoing surgery for cervical ossification of the posterior longitudinal ligament (OPLL) based on their presenting mild, moderate, or severe myelopathy.

METHODS

The study included 372 consecutive patients with OPLL who underwent surgery for cervical myelopathy between 2006 and 2016 in East Asian countries with a high OPLL prevalence. Baseline and postoperative clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) myelopathy score and recovery ratio. Radiographic assessment included occupying ratio, cervical range of motion, and sagittal alignment parameters. Patient myelopathy was classified as mild, moderate, or severe based on the preoperative JOA score. Linear and multivariate regression analyses were performed to identify patient and surgical factors associated with neurological recovery stratified by baseline myelopathy severity.

RESULTS

The mean follow-up period was 45.4 months (range 25–140 months). The mean preoperative and postoperative JOA scores and recovery ratios for the total cohort were 11.7 ± 3.0, 14.5 ± 2.7, and 55.2% ± 39.3%, respectively. In patients with mild myelopathy, only age and diabetes correlated with recovery. In patients with moderate to severe myelopathy, older age and preoperative increased signal intensity on T2-weighted imaging were significantly correlated with a lower likelihood of recovery, while female sex and anterior decompression with fusion (ADF) were associated with better recovery.

CONCLUSIONS

Various patient and surgical factors are correlated with likelihood of neurological recovery after surgical treatment for cervical OPLL, depending on the severity of presenting myelopathy. Older age, male sex, intramedullary high signal intensity, and posterior decompression are associated with less myelopathy improvement in patients with worse baseline function. Therefore, myelopathy-specific preoperative counseling regarding prognosis for postoperative long-term neurological improvement should include consideration of these individual and surgical factors.