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Jin Guo-Xin and Wang Huan

OBJECT

Atlantoaxial instability often requires surgery, and the current methods for fixation pose some risk to vascular and neurological tissues. Thus, new effective and safer methods are needed for salvage operations. This study sought to assess unilateral C-1 posterior arch screws (PASs) and C-2 laminar screws (LSs) combined with 1-side C1–2 pedicle screws (PSs) for posterior C1–2 fixation using biomechanical testing with bilateral C1–2 PSs in a cadaveric model.

METHODS

Six fresh ligamentous human cervical spines were evaluated for their biomechanics. The cadaveric specimens were tested in their intact condition, stabilization after injury, and after injury at 1.5 Nm of pure moment in 6 directions. The 3 groups tested were bilateral C1–2 PSs (Group A); left side C1–2 PSs with an ipsilateral C-1 PAS + C-2 laminar screw (Group B); and left side C1–2 PSs with a contralateral C-1 PAS + C-2 LS (Group C). During the testing, angular motion was measured using a motion capture platform. Data were recorded, and statistical analyses were performed.

RESULTS

Biomechanical testing showed that there was no significant difference among the stabilities of these fixation systems in flexion-extension and rotation control. In left lateral bending, the bilateral C1–2 PS group decreased flexibility by 71.9% compared with the intact condition, the unilateral C1–2 PS and ipsilateral PAS+LS group decreased flexibility by 77.6%, and the unilateral C1–2 PS and contralateral PAS+LS group by 70.0%. Each method significantly decreased C1–2 movements in right lateral bending compared with the intact condition, and the bilateral C1–2 PS system was more stable than the C1–2 PS and contralateral PAS+LS system (p = 0.036).

CONCLUSIONS

A unilateral C-1 PAS + C-2 LS combined with 1-side C-1 PSs provided the same acute stability as the PS, and no statistically significant difference in acute stability was found between the 2 screw techniques. These methods may constitute an alternative method for posterior atlantoaxial fixation.

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Yu Sun, Li-Xin Wang, Lei Wang, Si-Xin Sun, Xiao-Jian Cao, Peng Wang and Li Feng

Object

The effectiveness of the topical application of mitomycin C (MMC) or 5-fluorouracil (5FU) in preventing peridural adhesion after laminectomy was compared in this study.

Methods

Laminectomies were performed at L-1 in 30 rats. Cotton pads soaked with 0.1 mg/ml MMC, 25 mg/ml 5FU, or 9 mg/ml saline (control) were applied to the operative sites. To evaluate neurological deficits pre- and postoperatively, somatosensory evoked potentials were monitored and the Basso-Beattie-Bresnahan locomotion test was performed. Four weeks postlaminectomy the rats were killed, and peridural scar adhesion was evaluated histologically. The level of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts were determined. The degree of peridural adhesion was classified according to the Rydell standard.

Results

No obvious adhesion formed in the rats in the MMC group, but severe peridural adhesions were found in those in the 5FU and control groups. The content of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts in the MMC group were significantly lower than those in the 5FU and control groups.

Conclusions

The topical application of MMC rather than 5FU may be a successful method of preventing post-laminectomy peridural adhesions.

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Ming Luo, Wengang Wang, Mingkui Shen, Xin Luo and Lei Xia

OBJECTIVE

The radiographic and clinical outcomes of low-density (LD) versus high-density (HD) screw constructs in patients with adolescent idiopathic scoliosis (AIS) treated with all–pedicle screw constructs are still controversial. A systematic review and pooled analysis were performed to compare radiographic, perioperative, and quality-of-life (QOL) outcomes and complications in patients with moderate AIS treated with LD or HD screw constructs.

METHODS

The MEDLINE, Embase, and Web of Science databases were searched for English-language articles addressing LD versus HD screw constructs in AIS patients treated with all–pedicle screw constructs. The division of LD and HD groups was based on relative screw density and screw techniques. This systematic analysis strictly followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and all articles included in the analysis met the criteria specified in the guidelines. Two reviewers independently assessed the quality of the studies using the Newcastle-Ottawa Scale. Date on radiographic, perioperative, and QOL outcomes and complications were extracted from the included studies.

RESULTS

Twelve studies, involving a total of 827 patients (480 treated with LD constructs, 347 with HD), were analyzed—1 randomized controlled trial, 1 quasi-randomized controlled trial, and 10 retrospective studies. The patients' age at surgery, preoperative Cobb angle of the major curve, amount of thoracic kyphosis, and major curve flexibility were reasonably distributed, and no statistically significant differences were found. Regarding the outcomes at most recent follow-up, there were no significant differences in the Cobb angle of the major curve (mean difference 0.96°, 95% CI −0.06° to 1.98°, p = 0.06, I2 = 1%), major curve correction (mean difference −0.72%, 95% CI −2.96% to 1.52%, p = 0.53, I2 = 0%), thoracic kyphosis (mean difference −1.67°, 95% CI −4.59° to 1.25°, p = 0.26, I2 = 79%), complications (odds ratio [OR] 0.66, 95% CI 0.31–1.42, p = 0.29, I2 = 0%), and QOL outcomes. Reduced operative time (mean difference −48.56 minutes, 95% CI −82.69 to −14.43 minutes, p = 0.005, I2 = 87%), blood loss (mean difference −77.85 ml, 95% CI −153.10 to −2.60 ml, p = 0.04, I2 = 0%), and hospital charges (mean difference −$5.92K, 95% CI −$6.59K to −$5.26K, p < 0.00001, I2 = 0%) were found in the LD group, compared with the HD group.

CONCLUSIONS

LD and HD screw constructs are both associated with satisfactory radiographic and QOL outcomes with few complications. This study supports the use of LD screw constructs for the treatment of moderate AIS, because they resulted in reduced operative time, blood loss, and hospital charges while maintaining radiographic and QOL outcomes and complication rates similar to those achieved with HD screw constructs.

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Da Li, Yu-Ming Jiao, Liang Wang, Fu-Xin Lin, Jun Wu, Xian-Zeng Tong, Shuo Wang and Yong Cao

OBJECTIVE

Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs).

METHODS

A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent). The study enrolled 23 patients who underwent preoperative DTI/DTT and 24 patients who did not (the control group). The pre- and postoperative muscle strength of both limbs and modified Rankin Scale (mRS) scores were evaluated. Muscle strength of any limb at 12 months after surgery at the clinic visit was the primary outcome; worsened muscle strength was considered to be a poor outcome. Outcome assessors were blinded to patient management. This study reports the preliminary results of the interim analysis.

RESULTS

The cohort included 47 patients (22 women) with a mean age of 35.7 years. The clinical baselines between these 2 groups were not significantly different. In the DTI/DTT group, the corticospinal tract was affected in 17 patients (73.9%): it was displaced, deformed/partially interrupted, or completely interrupted in 6, 7, and 4 patients, respectively. The surgical approach and brainstem entry point were adjusted in 3 patients (13.0%) based on DTI/DTT data. The surgical morbidity of the DTI/DTT group (7/23, 30.4%) was significantly lower than that of the control group (19/24, 79.2%, p = 0.001). At 12 months, the mean mRS score (1.1, p = 0.034) and percentage of patients with worsened motor deficits (4.3%, p = 0.006) were significantly lower in the DTI/DTT group than in the control group (1.7% and 37.5%). Multivariate logistic regression identified the absence of preoperative DTI/DTT (OR 0.06, 95% CI 0.01–0.73, p = 0.028) and use of the 2-point method (OR 4.15, 95% CI 1.38–12.49, p = 0.011) as independent adverse factors for a worsened motor deficit. The multivariate model found a significant correlation between poor mRS score and both an increased preoperative mRS score (t = 3.559, p = 0.001) and absence of preoperative DTI/DTT (t = −2.747, p = 0.009).

CONCLUSIONS

DTI/DTT noninvasively allowed for visualization of the anatomical relationship between vital tracts and pathologies as well as facilitated the brainstem surgical approach and entry-point decision making. The technique was valuable for complex neurosurgical planning to reduce morbidity. Nonetheless, DTI/DTT data should be interpreted cautiously.

■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: class I.

Clinical trial registration no.: NCT01758211 (ClinicalTrials.gov)

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Eun Young Han, He Wang, Dershan Luo, Jing Li and Xin Wang

OBJECTIVE

For patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.

METHODS

Ten patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.

RESULTS

Plans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.

CONCLUSIONS

All 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

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Xin Wang, Zhiqi Mao, Zhiqiang Cui, Xin Xu, Longsheng Pan, Shuli Liang, Zhipei Ling and Xinguang Yu

OBJECTIVE

Primary Meige syndrome is characterized by blepharospasm and orofacial–cervical dystonia. Deep brain stimulation (DBS) is recognized as an effective therapy for patients with this condition, but previous studies have focused on clinical effects. This study explored the predictors of clinical outcome in patients with Meige syndrome who underwent DBS.

METHODS

Twenty patients who underwent DBS targeting the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) at the Chinese People’s Liberation Army General Hospital from August 2013 to February 2018 were enrolled in the study. Their clinical outcomes were evaluated using the Burke–Fahn–Marsden Dystonia Rating Scale at baseline and at the follow-up visits; patients were accordingly divided into a good-outcome group and a poor-outcome group. Putative influential factors, such as age and course of disease, were examined separately, and the factors that reached statistical significance were subjected to logistic regression analysis to identify predictors of clinical outcomes.

RESULTS

Four factors showed significant differences between the good- and poor-outcome groups: 1) the DBS target (STN vs GPi); 2) whether symptoms first appeared at multiple sites or at a single site; 3) the sub-item scores of the mouth at baseline; and 4) the follow-up period (p < 0.05). Binary logistic regression analysis revealed that initial involvement of multiple sites and the mouth score were the only significant predictors of clinical outcome.

CONCLUSIONS

The severity of the disease in the initial stage and presurgical period was the only independent predictive factor of the clinical outcomes of DBS for the treatment of patients with Meige syndrome.

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Xin Yu, Jianning Zhang, Rui Liu, Yaming Wang, Hongwei Wang, Peng Wang, Jinhui Chen and Song Liu

OBJECT

The treatment for giant posterior fossa cystic craniopharyngiomas remains an important challenge in neurosurgery. The authors evaluated the effects of treating 20 patients with giant posterior fossa cystic craniopharyngiomas using phosphorus-32 (P-32) interstitial radiotherapy at their hospital.

METHODS

The patients included 11 boys and 9 girls with an age range of 3 to 168 months. Before treatment, the tumor volumes ranged from 65 to 215 ml. The intracranial pressure was increased in 16 patients, and optic nerve damage had occurred in 18. The patients received P-32 interstitial radiotherapy following stereotactic cyst-fluid aspiration or drainage and were followed up for 7–138 months.

RESULTS

The treatment immediately relieved the intracranial hypertension symptoms in all patients. At the end of follow-up, imaging examinations revealed that the cystic tumors had disappeared, but some residual calcification remained in 12 patients, and had decreased by more than 75% of the initial volume in 8 patients. The damaged optic nerve recovered in 3 cases, improved in 12 cases, remained unchanged in 1 case, and was aggravated in 2 cases. No other severe complications related to surgery or interstitial radiation occurred. During the follow-up period, 7 new cysts appeared in 5 patients who had received additional interstitial radiotherapies with a dose of P-32 that was calculated using the same formula as for the initial treatment. The new tumors then disappeared in 2 patients, significantly shrank in 2 patients, and progressed in 1 patient.

CONCLUSIONS

For treating giant posterior fossa cystic craniopharyngiomas, P-32 interstitial radiation after stereotactic cyst-fluid aspiration or drainage can achieve a high tumor control rate and has relatively satisfactory clinical effects and quality of life outcomes with few complications.

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Jorgen Kjaergaard, Li-Xin Wang, Hideyuki Kuriyama, Suyu Shu and Gregory E. Plautz

Object

Immunotherapy for malignant brain tumors by active immunization or adoptive transfer of tumor antigen-specific T lymphocytes has the potential to make up for some of the limitations of current clinical therapy. In this study, the authors tested whether active immunotherapy is curative in mice bearing advanced, rapidly progressive intracranial tumors.

Methods

Tumor vaccines were created through electrofusion of dendritic cells (DCs) and irradiated tumor cells to form multinucleated heterokaryons that retained the potent antigen processing and costimulatory function of DCs as well as the entire complement of tumor antigens. Murine hosts bearing intracranial GL261 glioma or MCA 205 fibrosarcoma were treated with a combination of local cranial radiotherapy, intrasplenic vaccination with DC/tumor fusion cells, and anti-OX40R (CD134) monoclonal antibody (mAb) 7 days after tumor inoculation.

Whereas control mice had a median survival of approximately 20 days, the treated mice underwent complete tumor regression that was immunologically specific. Seven days after vaccination treated mice demonstrated robust infiltration of CD4+ and CD8+ T cells, which was exclusively confined to the tumor without apparent neurological toxicity. Cured mice survived longer than 120 days with no evidence of tumor recurrence and resisted intracranial tumor challenge.

Conclusions

These data indicate a strategy to achieve an antitumor response against tumors in the central nervous system that is highly focused from both immunological and anatomical perspectives.

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Haitao Ju, Xin Li, Hong Li, Xiaojuan Wang, Hongwei Wang, Yang Li, Changwu Dou and Gang Zhao

Object

Signal transducer and activator of transcription 1 (STAT1) is thought to be a tumor suppressor protein. The authors investigated the expression and role of STAT1 in glioblastoma.

Methods

Immunohistochemistry was used to detect the expression of STAT1 in glioblastoma and normal brain tissues. Reverse transcription–polymerase chain reaction and Western blot analysis were used to detect mRNA and protein expression levels of STAT1. Cell growth, proliferation, migration, apoptosis, and the expression of related genes and proteins (Bcl-2, Bax, cleaved caspase-3, caspase-9, p21, and proliferating cell nuclear antigen) were examined in vitro via cell counting kit-8, wound-healing, flow cytometry, Rhodamine B, TUNEL, and Western blot assays.

Results

Human glioblastoma had decreased expression of STAT1 proteins. Transfection of the U87MG cells with STAT1 plasmid in vitro demonstrated significant inhibition of cell growth and an increase in apoptotic cell death compared with cells transfected with vector or mock plasmids. These effects were associated with the upregulation of cleaved caspase-3, Bax, and p21 and the downregulation of Bcl-2 expression.

Conclusions

The results of this study suggest that increased expression of STAT1 by transfection with STAT1 plasmid synergistically inhibits human U87MG glioblastoma cell growth in vitro.

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Feizhou Lu, Hongli Wang, Jianyuan Jiang, Wenjun Chen, Xin Ma, Xiaosheng Ma, Xinlei Xia and Lixun Wang

Object

Monomelic amyotrophy (MMA) is a benign, self-limiting lower motor neuron disease. Optimal surgical strategies—discectomy decompression and fusion (DDF) or corpectomy decompression and fusion (CDF)—for patients with aggravated symptoms (within 6 months of presentation) are controversial, particularly in those who are ineligible for conventional treatment. These 2 methods of anterior cervical decompression and fusion for MMA in patients unwilling or unable to wear a conventional cervical collar long term were evaluated.

Methods

Anterior cervical decompression and fusion were performed in 48 male patients with MMA between September 2007 and September 2010. Patients were randomly treated with anterior cervical discectomy decompression with autologous iliac crest bone grafting and internal plate fixation (DDF group: 24 patients) or anterior cervical corpectomy, posterior longitudinal ligament resection, autologous iliac crest bone grafting, and internal plate fixation (CDF group: 24 patients). Subjective symptom assessments and electromyography (EMG) examinations were conducted both preoperatively and postoperatively.

Results

Subjective assessments and EMG studies (mean follow-up duration 25.9 months) indicated improvement in 64.6% and 60% of patients, respectively. No significant correlations between the effectiveness of surgery and age at symptom onset, preoperative symptom duration, or postoperative follow-up time were found.

Conclusions

The lack of a significant difference in effectiveness between DDF and CDF favors DDF as more clinically applicable because of its lower procedural risks. As a second-line alternative to cervical collar treatment, surgical anterior cervical decompression and fusion via DDF or CDF may prevent further deterioration and produce good short-term therapeutic effects in patients with MMA; however, cervical collar treatment is recommended for eligible patients because of its lower associated risks.