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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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Meng Zhao, Xiaofeng Deng, Dong Zhang, Shuo Wang, Yan Zhang, Rong Wang, and Jizong Zhao

OBJECTIVE

The risk factors and clinical significance of postoperative complications in moyamoya disease are still unclear. The aim of this study was to investigate the predictors of postoperative complications in moyamoya disease and examine the impact of complications on outcomes.

METHODS

The authors reviewed consecutive cases involving adult moyamoya disease patients who underwent indirect, direct, or combined bypass surgery in their hospital between 2009 and 2015. Preoperative clinical characteristics and radiographic features were recorded. Postoperative complications within 14 days after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for either postoperative ischemia or postoperative cerebral hyperperfusion. Outcome data, including recurrent strokes and neurological status (modified Rankin Scale [mRS]) during follow-up, were collected. Outcomes were compared between patients who had complications with those without complications, using propensity-score analysis to account for between-group differences in baseline characteristics.

RESULTS

A total of 500 patients (610 hemispheres) were included in this study. Postoperative complications were observed in 74 operations (12.1%), including new postoperative ischemia in 30 cases (4.9%), hyperperfusion in 27 (4.4%), impaired wound healing in 12 (2.0%), and subdural effusion in 6 (1.0%). The complication rates for different surgery types were as follows: 12.6% (n = 25) for indirect bypass, 12.7% (n = 37) for direct bypass, and 10.0% (n = 12) for combined bypass (p = 0.726). Postoperative ischemic complications occurred in 30 hemispheres (4.9%) in 30 different patients, and postoperative symptomatic hyperperfusion occurred after 27 procedures (4.4%). Advanced Suzuki stage (OR 1.669, 95% CI 1.059–2.632, p = 0.027) and preoperative ischemic presentation (OR 5.845, 95% CI 1.654–20.653, p = 0.006) were significantly associated with postoperative ischemia. Preoperative ischemic presentation (OR 5.73, 95% CI 1.27–25.88, p = 0.023) and admission modified Rankin Scale (mRS) score (OR 1.81, 95% CI 1.06–3.10, p = 0.031) were significantly associated with symptomatic postoperative cerebral hyperperfusion syndrome (CHS). Compared with patients without postoperative complications, patients who experienced any postoperative complications had longer hospital stays and worse mRS scores at discharge (both p < 0.0001). At the final follow-up, no significant differences in functional disability (mRS score 3–6, 11.9% vs 4.5%, p = 0.116) and future stroke events (p = 0.513) between the 2 groups were detected.

CONCLUSIONS

Advanced Suzuki stage and preoperative ischemic presentation were independent risk factors for postoperative ischemia; the mRS score on admission and preoperative ischemic presentation were independently associated with postoperative CHS. Although patients with postoperative complications had worse neurological status at discharge, postoperative complications had no associations with future stroke events or functional disability during follow-up.

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Fuxin Lin, Bing Zhao, Jun Wu, Lijun Wang, Zhen Jin, Yong Cao, and Shuo Wang

OBJECT

Case selection for the surgical treatment of arteriovenous malformations (AVMs) of the eloquent motor area remains challenging. The aim of this study was to determine the risk factors for worsened muscle strength after surgery in patients with this disorder.

METHODS

At their hospital the authors retrospectively studied 48 consecutive patients with AVMs involving motor cortex and/or the descending pathway. All patients had undergone preoperative functional MRI (fMRI) and diffusion tensor imaging (DTI), followed by resection. Both functional and angioarchitectural factors were analyzed with respect to the change in muscle strength. Functional factors included lesion-to-corticospinal tract distance (LCD) on DTI and lesion-to-activation area distance (LAD) and cortical reorganization on fMRI. Based on preoperative muscle strength, the changes in muscle strength at 1 week and 6 months after surgery were defined as short-term and long-term surgical outcomes, respectively. Statistical analysis was performed using the statistical package SPSS (version 20.0.0, IBM Corp.).

RESULTS

Twenty-one patients (43.8%) had worsened muscle strength 1 week after surgery. However, only 10 patients (20.8%) suffered from muscle strength worsening 6 months after surgery. The LCD was significantly correlated with short-term (p < 0.001) and long-term (p < 0.001) surgical outcomes. For long-term outcomes, patients in the 5 mm ≥ LCD > 0 mm (p = 0.009) and LCD > 5 mm (p < 0.001) categories were significantly associated with a lower risk of permanent motor worsening in comparison with patients in the LCD = 0 mm group. No significant difference was found between patients in the 5 mm ≥ LCD > 0 mm group and LCD > 5 mm group (p = 0.116). Nidus size was the other significant predictor of short-term (p = 0.021) and long-term (p = 0.016) outcomes. For long-term outcomes, the area under the ROC curve (AUC) was 0.728, and the cutoff point was 3.6 cm. Spetzler-Martin grade was not associated with short-term surgical outcomes (0.143), although it was correlated with long-term outcomes (0.038).

CONCLUSIONS

An AVM with a nidus in contact with tracked eloquent fibers (LCD = 0) and having a large size is more likely to be associated with worsened muscle strength after surgery in patients with eloquent motor area AVMs. Surgical treatment in these patients should be carefully considered. In patients with an LCD > 5 mm, radical resection may be considered to eliminate the risk of hemorrhage.

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Xiaofeng Deng, Yan Zhang, Long Xu, Bo Wang, Shuo Wang, Jun Wu, Dong Zhang, Rong Wang, Jia Wang, and Jizong Zhao

OBJECT

Cerebral arteriovenous malformations (AVMs) are congenital malformations that may grow in the language cortex but usually do not lead to aphasia. In contrast, language dysfunction is a common presentation for patients with a glioma that involves language areas. The authors attempted to demonstrate the difference in patterns of language cortex reorganization between cerebral AVMs and gliomas by blood oxygen level–dependent (BOLD) functional MRI (fMRI) evaluation.

METHODS

The authors retrospectively reviewed clinical and imaging data of 63 patients with an unruptured cerebral AVM (AVM group) and 38 patients with a glioma (glioma group) who underwent fMRI. All the patients were right handed, and all their lesions were located in the left cerebral hemisphere. Patients were further categorized into 1 of the 2 following subgroups according to their lesion location: the BA subgroup (overlying or adjacent to the inferior frontal or the middle frontal gyri [the Broca area]) and the WA subgroup (overlying or adjacent to the supramarginal, angular, or superior temporal gyri [the Wernicke area]). Lateralization indices of BOLD signal activations were calculated separately for the Broca and Wernicke areas. Statistical analysis was performed to identify the difference in patterns of language cortex reorganization between the 2 groups.

RESULTS

In the AVM group, right-sided lateralization of BOLD signal activations was observed in 23 patients (36.5%), including 6 with right-sided lateralization in the Broca area alone, 12 in the Wernicke area alone, and 5 in both areas. More specifically, in the 34 patients in the AVM-BA subgroup, right-sided lateralization of the Broca area was detected in 9 patients (26.5%), and right-sided lateralization of the Wernicke area was detected in 4 (11.8%); in the 29 patients in the AVM-WA subgroup, 2 (6.9%) had right-sided lateralization of the Broca area, and 13 (44.8%) had right-sided lateralization of the Wernicke area. In the glioma group, 6 patients (15.8%) showed right-sided lateralization of the Wernicke area, including 2 patients in the glioma-BA subgroup and 4 patients in the glioma-WA subgroup. No patient showed right-sided lateralization of the Broca area. Moreover, although the incidence of right-sided lateralization was higher in cases of low-grade gliomas (5 in 26 [19.2%]) than in high-grade gliomas (1 in 12 [8.3%]), no significant difference was detected between them (p = 0.643). Compared with the AVM group, the incidence of aphasia was significantly higher (p < 0.001), and right-sided lateralization of language areas was significantly rarer (p = 0.026) in the glioma group.

CONCLUSIONS

Right-sided lateralization of BOLD signal activations was observed in patients with a cerebral AVM and in those with a glioma, suggesting that language cortex reorganization may occur with both diseases. However, the potential of reorganization in patients with gliomas seems to be insufficient compared with patients AVMs, which is suggested by clinical manifestations and the fMRI findings. Moreover, this study seems to indicate that in patients with an AVM, a nidus near the Broca area mainly leads to right-sided lateralization of the Broca area, and a nidus near the Wernicke area mainly leads to right-sided lateralization of the Wernicke area.

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Yuanxiang Lin, Fuxin Lin, Dezhi Kang, Yuming Jiao, Yong Cao, and Shuo Wang

OBJECTIVE

Diffusion tensor imaging (DTI) findings may facilitate clinical decision making in patients with supratentorial cavernous malformations adjacent to the corticospinal tract (CST-CMs). The objective of this study was to determine the predictive value of preoperative DTI findings for surgical outcomes in patients with CST-CMs.

METHODS

A prospectively maintained database of patients with CM referred to the authors' hospital between September 2012 and October 2015 was reviewed to identify all consecutive surgically treated patients with CST-CM. All patients had undergone sagittal T1-weighted anatomical imaging and DTI before surgery. Both DTI findings and clinical characteristics of the patients and lesions were analyzed with respect to surgery-related motor deficits. DTI findings included lesion-to-CST distance (LCD) and the alteration (i.e., deviation, interruption, or degeneration due to the CM) of CST on preoperative DTI images. Surgery-related motor deficits at 1 week and the last clinic visit (≥ 3 months) after surgery were defined as short-term and long-term deficits, respectively. Preoperative and final modified Rankin Scale scores were also analyzed to identify the surgical outcomes in these patients.

RESULTS

A total of 56 patients with 56 CST-CMs were included in this study. The mean LCD was 3.9 ± 3.2 mm, and alterations of the CST were detected in 20 (36.7%) patients. One week after surgery, 21 (37.5%) patients had short-term surgery-related motor deficits, but only 14 (25.0%) patients had long term deficits at the last clinical visit. The mean patient follow-up was 14.7 ± 10.1 months. The difference between preoperative and final modified Rankin Scale scores was not statistically significant (p = 0.490). Multivariate analysis showed that both short-term (p < 0.001) and long-term (p = 0.002) surgery-related motor deficits were significantly associated with LCD. Receiver operating characteristic (ROC) curve results were as follows: for short-term surgery-related motor deficits, the area under the ROC curve (AUC) was 0.860, and the cutoff point was LCD = 2.55 mm; for long-term deficits, the AUC was 0.894, and the cutoff point was LCD = 2.30 mm. Both univariate (p = 0.012) and multivariate (p = 0.049) analyses revealed that CST alteration on preoperative DTI was significantly correlated with short-term surgery-related motor deficits. On univariate analysis, deep location of the CST-CMs was significantly correlated with long-term motor deficits (p = 0.016). Deep location of the CST-CMs had a trend toward significance with long-term motor deficits on the multivariate analysis (p = 0.060).

CONCLUSIONS

To facilitate clinical practice, the authors propose that 3.00 mm (2.55 to ∼3.00 mm) may be the safe LCD for surgery in patients with CST-CMs. A CST alteration on preoperative DTI and a deep location of the CST-CM may be risk factors for short- and long-term surgery-related motor deficits, respectively. A randomized controlled trial is needed to demonstrate the predictive value of preoperative DTI findings on surgical outcomes in patients with CST-CMs in future studies.

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*Qingyuan Liu, Jiangan Li, Yisen Zhang, Xinyi Leng, Mahmud Mossa-Basha, Michael R. Levitt, Shuo Wang, and Chengcheng Zhu

OBJECTIVE

Calcium channel blockers (CCBs) are antihypertensive agents with potential vascular protection effects. This study investigated whether CCB usage was associated with a lower incidence of unruptured intracranial aneurysm (UIA) instability (growth and rupture) in patients with hypertension.

METHODS

UIA patients were included in two prospective, multicenter cohort studies (IARP-CP and 100-Project cohorts). All patients received conservative treatment and were regularly followed up every 6 months by CT angiography for 2 years. Patients taking CCBs at least 5 days per week were considered CCB users; otherwise, they were considered non-CCB users. The primary endpoint was UIA instability (rupture, growth of > 20% and/or 1 mm in any dimension, or appearance of a new dome irregularity on imaging follow-up).

RESULTS

A total of 392 UIA patients with hypertension (191 male, 201 female; median age 57 years) were included with a mean follow-up duration of 21.7 ± 5.2 months. The primary endpoint was met in 81 patients (20.7%) during follow-up, including 68 patients with aneurysms that grew and 13 with aneurysms that ruptured. CCB users had a lower UIA instability rate than non-CCB users (27/237 [11.4%] vs 54/155 [34.8%], p < 0.001). Multivariable Cox analysis demonstrated that CCB use was associated with a lower risk of UIA instability (HR 0.37, 95% CI 0.22–0.61; p < 0.001). The protective effect of CCB use was consistent in patients taking a single antihypertensive agent (HR 0.22, 95% CI 0.12–0.40; p < 0.001) and patients taking > 1 antihypertensive agent (HR 0.42, 95% CI 0.20–0.87; p = 0.021). For patients with controlled hypertension, CCB use was still associated with a lower risk of UIA instability (HR 0.22, 95% CI 0.09–0.52; p = 0.001).

CONCLUSIONS

In UIA patients with hypertension, CCB use was associated with a lower incidence of aneurysm instability.

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Xing-ju Liu, Dong Zhang, Shuo Wang, Yuan-li Zhao, Mario Teo, Rong Wang, Yong Cao, Xun Ye, Shuai Kang, and Ji-Zong Zhao

OBJECT

The aim of this study was to describe the baseline clinical features and long-term outcomes of patients with moyamoya disease (MMD) based on a 25-year period at a single center in China.

METHODS

 Data obtained in 528 consecutive patients with MMD treated at the authors' hospital from 1984 to 2010 were reviewed retrospectively. Events of transient ischemic attack, new infarction, and hemorrhage were included. The Kaplan-Meier risk of stroke was calculated.

RESULTS

 The mean (± SD) patient age was 26 ± 13 years (range 2–67 years), and the female/male ratio was 0.9:1. There were 332 cases of ischemia and 196 hemorrhages. Adults had a higher rate of bleeding than children (50.7% vs 14.0%, respectively; p < 0.001). One hundred twenty-two patients were treated conservatively, and 406 patients underwent revascularization procedures. Of 528 patients, 331 (62.7%) had at least 1 year of follow-up (median 39.5 months) and data from these patients were analyzed. Rebleeding and mortality rates in patients with hemorrhagic MMD (n = 104) were higher than in those with ischemic MMD (n = 227) (26.9% vs 2.2% [p < 0.001] and 4.8% vs 0.4% [p < 0.05], respectively). Twenty-five of 60 (41.7%) conservatively treated patients and 8 of 271 (2.9%) surgically treated patients experienced rebleeding events, a difference that was significant in the Kaplan-Meier curve of rebleeding (p < 0.01). An improvement in perfusion was found in 164 of 224 (73.2%) surgically treated patients 1 month after discharge. However, there was no significant difference in the rate of ischemic events in the surgical and conservative groups (18.8% and 28.3%, respectively; p = 0.09). Among the 104 hemorrhagic cases, rebleeding attacks were observed in 25 patients in the nonsurgical group (n = 60) and 3 patients in the surgical group (n = 44) (41.7% and 6.8%, respectively; OR 9.7 [95% CI 2.7–35.0]; p < 0.01).

CONCLUSIONS

 There was no difference in the sex distribution of Chinese patients with MMD. Patients with hemorrhagic MMD had a much higher rate of rebleeding and poorer prognosis than those with the ischemic type. Surgical revascularization procedures can improve cerebral perfusion and have a positive impact in preventing rebleeding in patients with hemorrhagic MMD.

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Dezhi Hu, Shuo Zhang, Yingjie Zhao, Shiming Wang, Qihan Wang, Xiao Song, Daru Lu, Ying Mao, and Hongyan Chen

Object

The retinoblastoma binding protein 6 (RBBP6) gene plays an important role in the induction of apoptosis and regulation of the cell cycle, and interacts with both p53 and retinoblastoma protein in carcinogenesis. Recently, many studies investigating the function of the RBBP6 gene, including its roles in lung cancer and breast cancer, have been reported. However, the association between RBBP6 variants and glioma was unknown. Therefore, to uncover the association between single nucleotide polymorphisms (SNPs) of RBBP6 and glioma, a hospital-based case-control study was performed in a Chinese Han population.

Methods

Ten common tagging SNPs of the RBBP6 gene (covering 100% of all SNPs) were genotyped with the Sequenom MassARRY iPLEX platform, including 992 cases and 1008 controls, according to the HapMap database based on a pairwise linkage disequilibrium r2 threshold of 0.8, minor allele frequency of 0.05, and Hardy-Weinberg equilibrium of 0.05.

Results

The authors found that 4 SNPs were significantly associated with glioma (rs2033214, p = 0.013, adjusted OR 2.46, 95% CI 1.18–5.14; rs11860248, p = 8.64 × 10−6, adjusted OR 1.59, 95% CI 1.23–2.05; rs9933544, p = 3.65 × 10−4, adjusted OR 1.39, 95% CI 1.13–1.87; rs13332653, p = 0.004, adjusted OR 1.49, 95% CI 1.14–1.95). Stratification analyses revealed that rs2033214 was only significantly associated with low-grade gliomas; rs9933544 and rs13332653 were only significantly associated with glioblastoma multiforme; and rs11860248 was significantly associated with both low-grade gliomas and glioblastoma multiforme, compared with the common wild-type homozygous genotype. Further stratified analysis revealed that rs11860248 was more pronounced in certain subgroups: adults, males, histological types, and family history of cancer. What's more, the haplotype and diplotype analyses consistently revealed that the subjects carrying 1 copy of haplotype CCGCC had a 53% increased glioma risk compared with their corresponding noncarriers (p = 0.018, adjusted OR 1.53, 95% CI 1.08–2.17).

Conclusions

The authors' results suggested that RBBP6 gene variants are associated with glioma and contribute to glioma susceptibility, which was first reported elsewhere. Individuals with the so-called risk alleles might have an increased risk of glioma. These results might provide new insight into the occurrence of glioma.

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Yuming Jiao, Fuxin Lin, Jun Wu, Hao Li, Lijun Wang, Zhen Jin, Shuo Wang, and Yong Cao

OBJECTIVE

Case selection for the surgical treatment of brain arteriovenous malformations (BAVMs) remains challenging. This study aimed to construct a predictive grading system combining lesion-to-eloquence distance (LED) for selecting patients with BAVMs for surgery.

METHODS

Between September 2012 and September 2015, the authors retrospectively studied 201 consecutive patients with BAVMs. All patients had undergone preoperative functional MRI and diffusion tensor imaging (DTI), followed by resection. Both angioarchitectural factors and LED were analyzed with respect to the change between preoperative and final postoperative modified Rankin Scale (mRS) scores. LED refers to the distance between the lesion and the nearest eloquent area (eloquent cortex or eloquent fiber tracts) measured on preoperative fMRI and DTI. Based on logistic regression analysis, the authors constructed 3 new grading systems. The HDVL grading system includes the independent predictors of mRS change (hemorrhagic presentation, diffuseness, deep venous drainage, and LED). Full Score combines the variables in the Spetzler-Martin (S-M) grading system (nidus size, eloquence of adjacent brain, and venous drainage) and the HDVL. For the third grading system, the fS-M grading system, the authors added information regarding eloquent fiber tracts to the S-M grading system. The area under the receiver operating characteristic (ROC) curves was compared with those of the S-M grading system and the supplementary S-M grading system of Lawton et al.

RESULTS

LED was significantly correlated with a change in mRS score (p < 0.001). An LED of 4.95 mm was the cutoff point for the worsened mRS score. Hemorrhagic presentation, diffuseness, deep venous drainage, and LED were independent predictors of a change in mRS score. Predictive accuracy was highest for the HDVL grading system (area under the ROC curve 0.82), followed by the Full Score grading system (0.80), the fS-M grading system (0.79), the supplementary S-M grading system (0.76), and least for the S-M grading system (0.71). Predictive accuracy of the HDVL grading system was significantly better than that of the Spetzler-Martin grade (p = 0.040).

CONCLUSIONS

LED was a significant predictor for the preoperative risk evaluation for surgery. The HDVL system was a good predictor of neurological outcomes after BAVM surgery. Adding the consideration of the involvement of eloquent fiber tracts to preoperative evaluation can effectively improve its predictive accuracy.