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Jian-Bin Chen, Ding Lei, Min He, Hong Sun, Yi Liu, Heng Zhang, Chao You and Liang-Xue Zhou

OBJECT

The present study aimed to clarify the incidence and clinical features of disease progression in adult moyamoya disease (MMD) patients with Graves disease (GD) for better management of these patients.

METHODS

During the past 18 years, 320 adult Chinese patients at West China Hospital were diagnosed with MMD, and 29 were also diagnosed with GD. A total of 170 patients (25 with GD; 145 without GD) were included in this study and were followed up. The mean follow-up was 106.4 ± 48.6 months (range 6–216 months). The progression of the occlusive lesions in the major intracranial arteries was measured using cerebral angiography and was evaluated according to Suzuki's angiographic staging. Information about cerebrovascular strokes was obtained from the records of patients' recent clinical visits. Both angiographic progression and strokes were analyzed to estimate the incidences of angiographic progression and strokes using Kaplan-Meier analysis. A multivariate logistic regression model was used to test the effects of sex, age at MMD onset, disease type, strokes, and GD on the onset of MMD progression during follow-up.

RESULTS

During follow-up, the incidence of disease progression in MMD patients with GD was significantly higher than in patients without GD (40.0% vs 20.7%, respectively; p = 0.036). The interval between initial diagnosis and disease progression was significantly shorter in MMD patients with GD than in patients without GD (p = 0.041). Disease progression occurred in both unilateral MMD and bilateral MMD, but the interval before disease progression in patients with unilateral disease was significantly longer than in patients with bilateral disease (p = 0.021). The incidence of strokes in MMD patients with GD was significantly higher than in patients without GD (48% vs 26.2%, respectively; p = 0.027). The Kaplan-Meier survival curve showed significant differences in the incidence of disease progression (p = 0.038, log-rank test) and strokes (p = 0.031, log-rank test) between MMD patients with GD and those without GD. Multivariate analysis suggested that GD may contribute to disease progression in MMD (OR 5.97, 95% CI 1.24–33.76, p = 0.043).

CONCLUSIONS

The incidence of disease progression in MMD patients with GD was significantly higher than that in MMD patients without GD, and GD may contribute to disease progression in MMD patients. The incidence of strokes was significantly higher in MMD patients with GD than in patients without GD. Management guidelines for MMD patients with GD should be developed.

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Jian-Bin Chen, Yi Liu, Liang-Xue Zhou, Hong Sun, Min He and Chao You

OBJECT

This study explored whether there were differences between the autoimmune disease prevalence rates in unilateral and bilateral moyamoya disease (MMD).

METHODS

The authors performed a retrospective review of data obtained from the medical records of their hospital, analyzing and comparing the clinical characteristics and prevalence rates of all autoimmune diseases that were associated with unilateral and bilateral MMD in their hospital from January 1995 to October 2014.

RESULTS

Three hundred sixteen patients with bilateral MMD and 68 with unilateral MMD were identified. The results indicated that patients with unilateral MMD were more likely to be female than were patients with bilateral MMD (67.6% vs 51.3%, p = 0.014, odds ratio [OR] 1.99). Overall, non-autoimmune comorbidities tended to be more prevalent in the unilateral MMD cases than in the bilateral MMD cases (17.6% vs 9.8%, p = 0.063, OR 1.97, chi-square test). Autoimmune thyroid disease and other autoimmune diseases also tended to be more prevalent in the unilateral MMD cases than in the bilateral MMD cases (19.1% vs 10.8%, p = 0.056, OR 1.96 and 8.8% vs 3.5%, p = 0.092, OR 2.77, respectively, chi-square test). The overall autoimmune disease prevalence in the unilateral MMD cases was significantly higher than in the bilateral MMD cases (26.5% vs 13.6%, p = 0.008, OR 2.29, 95% CI 1.22–4.28, chi-square test). Multiple logistic regression analysis showed that autoimmune disease was more likely to be associated with unilateral than with bilateral MMD (p = 0.039, OR 10.91, 95% CI 1.13–105.25).

CONCLUSIONS

This study indicated a higher overall autoimmune disease prevalence in unilateral than in bilateral MMD. Unilateral MMD may be more associated with autoimmune disease than bilateral MMD. Different pathogenetic mechanisms may underlie moyamoya vessel formation in unilateral and bilateral MMD.

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Hong-Qi Zhang, Tong Chen, Shao-Shuai Wu, Liang-Hong Teng, Yong-Zhong Li, Li-Yong Sun, Zhi-Ping Zhang, De-Yu Guo, De-Hong Lu and Feng Ling

Object

The authors undertook this study to establish an animal model to investigate the pathophysiological changes of venous hypertensive myelopathy (VHM).

Methods

This study was a randomized control animal study with blinded evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by means of renal artery and vein anastomosis and trapping of the posterior vena cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by spinal function evaluation, abdominal aortic angiography, spinal MRI, and pathological examination of the spinal cord at different follow-up stages.

Results

Twenty-two (91.67%) of 24 model rabbits survived the surgery and postoperative period. The patency rate of the arteriovenous fistula was 95.45% in these 22 animals. The model rabbits had significantly decreased motor and sensory hindlimb function as well as abnormalities at the corresponding segments of the spinal cord. Pathological examination showed dilation and hyalinization of the small blood vessels, perivascular and intraparenchymal lymphocyte infiltration, proliferation of glial cells, and neuronal degeneration. Electron microscopic examination showed loose lamellar structure of the myelin sheath, increased numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons.

Conclusions

This model of VHM is stable and repeatable. Exploration of the sequential changes in spinal cord and blood vessels has provided improved understanding of this pathology, and the model may have potential for improving therapeutic results.

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Min He, Heng Zhang, Ding Lei, Bo-Yong Mao, Chao You, Xiao-Dong Xie, Hong Sun, Yan Ju and Jia-Ming Zhang

Object

Utilization of covered stent grafts in treating neurovascular disorders has been reported, but their efficacy and safety in vertebral artery (VA) dissecting aneurysms needs further investigation.

Methods

Six cases are presented involving VA dissecting aneurysms that were treated by positioning a covered stent graft. Two aneurysms were located distal to the posterior inferior cerebellar artery, and 4 were located proximal to the posterior inferior cerebellar artery. Aspirin as well as ticlopidine or clopidogrel were administered after the procedure to prevent stent-related thrombosis. All patients were followed up both angiographically and clinically.

Results

Five of the 6 patients underwent successful placement of a covered stent graft. The covered stent could not reach the level of the aneurysm in 1 patient with serious vasospasm who died secondary to severe subarachnoid hemorrhage that occurred 3 days later. Patient follow-up ranged from 6 to 14 months (mean 10.4 months), and demonstrated complete stabilization of the obliterated aneurysms, and no obvious intimal hyperplasia. No procedure-related complications such as stenosis or embolization occurred in the 5 patients with successful stent graft placement.

Conclusions

Although long-term follow-up studies using a greater number of patients is required for further validation of this technique, this preliminary assessment shows that covered stent graft placement is an efficient, safe, and microinvasive technique, and is a promising tool in treating intracranial VA dissecting aneurysms.

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Yu Shuang Tian, Di Zhong, Qing Qing Liu, Xiu Li Zhao, Hong Xue Sun, Jing Jin, Hai Ning Wang and Guo Zhong Li

OBJECTIVE

Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke–related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke.

METHODS

The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)–treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)–induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3′ untranslated region (3′UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase–9 [MMP-9], tumor necrosis factor–α [TNF-α], and interleukin-1β [IL-1β]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V–FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits.

RESULTS

JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3′UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1β). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit.

CONCLUSIONS

These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.

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Moo Seong Kim, Se Young Pyo, Young Gyun Jeong, Sun Il Lee, Yong Tae Jung and Jae Hong Sim

Object. The purpose of this study was to assess the benefits of radiosurgery for cavernous hemangioma.

Methods. Sixty-five cavernous hemangiomas were treated with gamma knife surgery (GKS) between October 1994 and December 2002. Forty-two patients attended follow up. The mean patient age was 37.6 years (range 7–60 years). The lesions were located in the frontal lobe in 12 cases, deep in the parietal lobe in five, in the basal ganglia in five, in the temporal in three, in the cerebellum in three, in the pons/midbrain in six, and in multiple locations in eight cases. The presenting symptoms were seizure in 12, hemorrhage in 11, and other in 19. The maximum dose was 26.78 Gy, and the mean margin dose was 14.55 Gy.

The mean follow-up period after radiosurgery was 29.6 months (range 5–93 months). The tumor decreased in size in 29 cases, was unchanged in 12, and increased in size in one. In the seizure group, seizures were controlled without anticonvulsant medication in nine cases (81.8%) after 31.3 months (range 12–80 months). After 93 months, one patient developed a cyst, which was resected. Rebleeding occurred in one case (2.3%). On T2-weighted imaging changes were seen in 11 cases (26.2%), in three (7.1%) of which neurological deterioration was correlated with imaging changes. In other cases these deficits were temporary.

Conclusions. The authors found that GKS was an effective treatment modality for cavernous hemangiomas, especially for those located within the brainstem, basal ganglia, or deep portions of the brain. It can reduce seizure frequency significantly although this takes time. In the group receiving a marginal dose below 15 Gy the patients fared better than when the dose exceeded 15 Gy.

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Sook Young Sim, Yong Sam Shin, Kyung Gi Cho, Sun Yong Kim, Se Hyuk Kim, Young Hwan Ahn, Soo Han Yoon and Ki Hong Cho

Object

The clinical features of blood blister–like aneurysms (BBAs) that arise at nonbranching sites of the internal carotid artery (ICA) differ from those of saccular aneurysms. In this study, the authors attempt to describe optimal treatments for BBAs, which have yet to be clearly established.

Methods

Ten of 483 patients with aneurysmal subarachnoid hemorrhage who had been seen at the authors’ institution between March 2001 and June 2005 had intraoperatively confirmed BBAs at nonbranching sites of the ICA. All ten patients were women between the ages of 37 and 64 years (mean age 49.3 years); five had a history of hypertension. The BBAs were localized to the right side of the ICA in seven cases. All patients were successfully treated; clipping was undertaken in six, clipping combined with wrapping in three, and trapping in one. These methods were used in conjunction with various other surgical techniques such as brain relaxation by draining cerebrospinal fluid, anterior clinoidectomy, exposing the cervical ICA, gentle subpial dissection (for aneurysms that adhered to the frontal lobe), complete trapping of the ICA before clipping, and protecting the brain. Clip slippage occurred at the end of dural closing in two cases; the aneurysm was completely obliterated using multiple clips combined with ICA stenosis in one of these cases and ICA trapping with good collateral flow in the other. An excellent clinical outcome was achieved in eight patients, whereas two patients were disabled from massive vasospasm. The authors retrospectively reviewed radiological and surgical data in all cases to determine which treatment methods produced a favorable outcome.

Conclusions

Blood blister–like aneurysms located at nonbranching sites of the ICA are difficult to treat. Preoperative awareness and careful consideration of these lesions during surgery can prevent poor clinical outcomes.

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David A. Sun, Hong Yu, John Spooner, Armanda D. Tatsas, Thomas Davis, Ty W. Abel, Chris Kao and Peter E. Konrad

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for ~ 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.

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Zang-Hee Cho, Hoon-Ki Min, Se-Hong Oh, Jae-Yong Han, Chan-Woong Park, Je-Geun Chi, Young-Bo Kim, Sun Ha Paek, Andres M. Lozano and Kendall H. Lee

Object

A challenge associated with deep brain stimulation (DBS) in treating advanced Parkinson disease (PD) is the direct visualization of brain nuclei, which often involves indirect approximations of stereotactic targets. In the present study, the authors compared T2*-weighted images obtained using 7-T MR imaging with those obtained using 1.5- and 3-T MR imaging to ascertain whether 7-T imaging enables better visualization of targets for DBS in PD.

Methods

The authors compared 1.5-, 3-, and 7-T MR images obtained in 11 healthy volunteers and 1 patient with PD.

Results

With 7-T imaging, distinct images of the brain were obtained, including the subthalamic nucleus (STN) and internal globus pallidus (GPi). Compared with the 1.5- and 3-T MR images of the STN and GPi, the 7-T MR images showed marked improvements in spatial resolution, tissue contrast, and signal-to-noise ratio.

Conclusions

Data in this study reveal the superiority of 7-T MR imaging for visualizing structures targeted for DBS in the management of PD. This finding suggests that by enabling the direct visualization of neural structures of interest, 7-T MR imaging could be a valuable aid in neurosurgical procedures.

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Roh-Eul Yoo, Tae Jin Yun, Young Dae Cho, Jung Hyo Rhim, Koung Mi Kang, Seung Hong Choi, Ji-hoon Kim, Jeong Eun Kim, Hyun-Seung Kang, Chul-Ho Sohn, Sun-Won Park and Moon Hee Han

OBJECTIVE

Arterial spin labeling perfusion-weighted imaging (ASL-PWI) enables quantification of tissue perfusion without contrast media administration. The aim of this study was to explore whether cerebral blood flow (CBF) from ASL-PWI can reliably predict angiographic vascularity of meningiomas.

METHODS

Twenty-seven patients with intracranial meningiomas, who had undergone preoperative ASL-PWI and digital subtraction angiography prior to resection, were included. Angiographic vascularity was assessed using a 4-point grading scale and meningiomas were classified into 2 groups: low vascularity (Grades 0 and 1; n = 11) and high vascularity (Grades 2 and 3; n = 16). Absolute CBF, measured at the largest section of the tumor, was normalized to the contralateral gray matter. Correlation between the mean normalized CBF (nCBF) and angiographic vascularity was determined and the mean nCBF values of the 2 groups were compared. Diagnostic performance of the nCBF for differentiating between the 2 groups was assessed.

RESULTS

The nCBF had a significant positive correlation with angiographic vascularity (ρ = 0.718; p < 0.001). The high-vascularity group had a significantly higher nCBF than the low-vascularity group (3.334 ± 2.768 and 0.909 ± 0.468, respectively; p = 0.003). At the optimal nCBF cutoff value of 1.733, sensitivity and specificity for the differential diagnosis of the 2 groups were 69% (95% CI 41%–89%) and 100% (95% CI 72%–100%), respectively. The area under the receiver operating characteristic curve was 0.875 (p < 0.001).

CONCLUSIONS

ASL-PWI may provide a reliable and noninvasive means of predicting angiographic vascularity of meningiomas. It may thus assist in selecting potential candidates for preoperative digital subtraction angiography and embolization in clinical practice.