Jizong Zhao

Long term outcome after conservative and surgical treatment of haemorrhagic moyamoya disease

Objective To investigate the long term outcomes after conservative and surgical treatment for haemorrhagic moyamoya disease. Methods 97 consecutive patients with haemorrhagic moyamoya disease from 1997 to 2009 were enrolled in this study (mean age 31±10 years; range 5–56 years). We reviewed the clinical charts and radiographs of patients at the first bleeding episode. Follow-up was obtained prospectively by questionnaires and radiographic examinations. Outcomes were compared based on initial treatment (conservative vs surgical). Results After a median follow-up of 7.1 years, 21 of the 97 (21.7%) patients developed a second episode of bleeding, and six patients (6.2%) died of intracranial rebleeding. The median interval from initial episode to subsequent rebleeding was 9.1 years (0.1–23.2 years). 17 of 43 (37.1%) conservatively treated patients and four of 54 (7.4%) surgically treated patients experienced a rebleeding event (OR 8.1; 95% CI 2.4 to 26.8; p<0.001). There was a difference in the Kaplan–Meier curve of rebleeding between the two groups (Breslow test p=0.047; log rank test p=0.05). The rebleeding ratio in patients who underwent direct bypass was lower than that in patients treated with indirect bypass alone (0% vs 28.5%, 95% CI 1.0 to 1.9; p=0.002). No significant correlation was found between rebleeding and the patients age, sex, location of haemorrhage, hypertension status or presence of cerebral aneurysm (p>0.05). Conclusions There is a high risk of rebleeding after the first haemorrhagic episode in Chinese patients with haemorrhagic moyamoya disease. Revascularisation surgery can improve regional blood flow and have greater efficacy at preventing rebleeding than conservative treatment.

Noncontrast dynamic MRA in intracranial arteriovenous malformation (AVM), comparison with time of flight (TOF) and digital subtraction angiography (DSA).

Digital subtraction angiography (DSA) remains the gold standard to diagnose intracranial arteriovenous malformations (AVMs) but is invasive. Existing magnetic resonance angiography (MRA) is suboptimal for assessing the hemodynamics of AVMs. The objective of this study was to evaluate the clinical utility of a novel noncontrast four-dimensional (4D) dynamic MRA (dMRA) in the evaluation of intracranial AVMs through comparison with DSA and time-of-flight (TOF) MRA. Nineteen patients (12 women, mean age 26.2±10.7 years) with intracranial AVMs were examined with 4D dMRA, TOF and DSA. Spetzler-Martin grading scale was evaluated using each of the above three methods independently by two raters. Diagnostic confidence scores for three components of AVMs (feeding artery, nidus and draining vein) were also rated. Kendalls coefficient of concordance was calculated to evaluate the reliability between two raters within each modality (dMRA, TOF, TOF plus dMRA). The Wilcoxon signed-rank test was applied to compare the diagnostic confidence scores between each pair of the three modalities. dMRA was able to detect 16 out of 19 AVMs, and the ratings of AVM size and location matched those of DSA. The diagnostic confidence scores by dMRA were adequate for nidus (3.5/5), moderate for feeding arteries (2.5/5) and poor for draining veins (1.5/5). The hemodynamic information provided by dMRA improved diagnostic confidence scores by TOF MRA. As a completely noninvasive method, 4D dMRA offers hemodynamic information with a temporal resolution of 50-100 ms for the evaluation of AVMs and can complement existing methods such as DSA and TOF MRA.

Risk of cerebral arteriovenous malformation rupture during pregnancy and puerperium

Objective: To determine whether the risk of arteriovenous malformation (AVM) rupture is increased during pregnancy and puerperium. Methods: Participants included 979 female patients with intracranial AVM admitted to Beijing Tiantan Hospital between 1960 and 2010. Two neurosurgery residents reviewed medical records for each case. Of them, 393 patients with ruptured AVM between 18 and 40 years of age were used for case-crossover analysis. Number of children born and clinical information during pregnancy and puerperium were retrieved to identify whether AVM rupture occurred during this period. Results: Of the 979 women, 797 hemorrhages occurred during 25,578 patient-years of follow-up, yielding an annual hemorrhage rate of 3.11%. The annual AVM hemorrhage rate in patients aged 18 to 40 years (n = 579) was 2.78%, lower than the rate in other age groups (odds ratio = 0.75, 95% confidence interval 0.65–0.86, p < 0.05). Of the 393 patients with rupture of AVM aged 18 to 40 years, 12 hemorrhages occurred in 12 patients over 452 pregnancies, yielding a hemorrhage rate of 2.65% per pregnancy or 3.32% per year. Among the remaining 381 patients, 441 hemorrhages occurred during 10,627 patient-years of follow-up, yielding an annual hemorrhage rate of 4.14%. The odds ratio for rupture of AVM during pregnancy and puerperium, compared with the control period, was 0.71 (95% confidence interval 0.61–0.82). Conclusions: No increased risk of hemorrhage was found in patients with cerebral AVM during pregnancy and the puerperium. We therefore would not advise against pregnancy in women with intracranial AVM.

Evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery

The primary aim of this study is to assess the value of intraoperative near-infrared indocyanine green videoangiography (ICGA) during intracranial aneurysm surgery. Altogether, 129 patients harboring 152 intracranial aneurysms were recruited in this study between March 2007 and December 2008 and the clinical data were retrospectively analyzed. Intraoperative ICGA was performed to examine the completeness of the aneurysm clipping and the patency of the parent arteries in all cases. The intraoperative findings were compared with that of postoperative digital subtraction angiography (DSA). On all of the patients, 276 successful ICGA investigations were performed intraoperatively. The image quality and resolution were excellent, allowing real-time assessment of the cerebral circulation. Indocyanine green (ICG) angiographic results could be divided into arterial, capillary, and venous phases, comparable to those observed with postoperative DSA. In all cases, the postoperative angiographic results corresponded to the intraoperative ICGA findings. In three cases, the information provided by intraoperative ICG angiography significantly changed the surgical procedure. Intraoperative ICG videoangiography may be a useful tool in real-time evaluation of the aneurysm clipping. Its simplicity and easy reproducibility all suggest it to be carried out as a routine procedure during aneurysm surgery.

Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway.

Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression.

The Effect of Age, Sex, and Lesion Location on Initial Presentation in Patients with Brain Arteriovenous Malformations

OBJECTIVE To identify whether age, sex, and lesion location are associated with initial presentation in patients with brain arteriovenous malformations (AVMs). METHODS Collected data of 3299 consecutive patients with AVM treated at Beijing Tiantan Hosptial from January 1980 to January 2015 were analyzed. The variables assessed were age at diagnosis, sex, AVM location, and mode of initial presentation. RESULTS Initial presentation was AVM hemorrhage in 57.9%, seizure in 20.9%, chronic headache in 14.9%, focal neurologic deficit in 5.2%, and incidental in 1.2%. Younger age and female sex were associated with initial hemorrhage (all P < 0.05). Hemorrhage was more likely to occur in patients with AVMs in the basal ganglia, the corpus callosum, the ventricles, the cerebellum, and the brainstem (all P < 0.05). Male sex was associated with initial seizure (P < 0.05). Initial seizure was more likely to occur in patients with AVMs in the frontal, temporal, parietal, frontotemporal, and frontoparietal lobe (all P < 0.05). Compared with frontal AVMs, temporal AVMs were more likely to present with hemorrhage (P < 0.05) and less likely to present with seizure (P < 0.05). AVMs involving the occipital lobe were more likely to present with chronic headaches (P < 0.05). CONCLUSIONS Initial AVM presentation varied with patient age, sex, and AVM locations. Younger age, female sex, and deep and infratentorial locations may be associated with initial hemorrhage. Male sex and frontal, temporal, and parietal AVM locations may be predictors of initial seizure. Chronic headache was more likely to occur in patients with AVMs involving the occipital lobe.

Surgical treatment of giant intracranial arteriovenous malformations.

BACKGROUND:The treatment of giant arteriovenous malformations (AVMs) remains a challenge in the neurosurgical field. Microsurgery is one of the most effective ways for eliminating giant cerebral AVMs. OBJECTIVE:To review surgical outcomes in treating the disease, and form conclusions regarding the indications for and outcomes of surgical treatment in giant intracranial AVMs. METHODS:We studied 40 consecutive cases of giant AVMs treated in Beijing Tiantan Hospital between 2000 and 2008. The radiologic and clinical features were analyzed. The Spetzler-Martin grading system was used to classify the patients. All patients were surgically treated, and the final outcomes of the patients were gathered for analysis. RESULTS:The major presenting symptoms were seizures, headaches, hemorrhage, and neurological deficits. The mean AVM diameter was 6.3 cm. According to the Spetzler-Martin grading system, 5 patients had grade III lesions, 21 had grade IV lesions, and 14 had grade V lesions. Out of the total 40 patients, 31 (77.5%) demonstrated excellent or good outcome. Complications included hemiparalysis, aphasia, hemianopia, cranial nerve dysfunction, and seizures. After follow-up, 27 of 30 (90%) surviving patients presented normal function or minimal symptoms. CONCLUSION:Presurgical evaluation of every candidate and treatment choice is the determining factor in therapy for giant AVMs. For giant cerebral AVMs located superficially or not involving critical components, a good outcome can be expected through surgical resection. The obliteration and recurrence rates were satisfying, and the complication rate was acceptable.

Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study

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.

Reversion effects of curcumin on multidrug resistance of MNNG/HOS human osteosarcoma cells in vitro and in vivo through regulation of P-glycoprotein.

Background P‐glycoprotein (P‐gp) encoded by ATP‐binding cassette sub‐family B member 1 (ABCB1) gene is a kind of ATP‐dependent drug transporter, which plays important roles in multidrug resistance (MDR) of human cancers, such as osteosarcoma. Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma longa, which is proved to possess antitumor biological activities including reversion of MDR. However, the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear. Methods We established a human osteosarcoma drug‐resistant cell line MNNG/HOS/MTX by pulse exposure to methotrexate (MTX) and verified that the new cell lines were cross‐resistant to other anticancer agents. Then, according to the cytotoxicity assay, we reversed MDR of MNNG/HOS/MTX by 30 &mgr;mol/L curcumin, and detected the mechanisms of curcumin reversing MDR through Real‐time PCR, Western blotting assay, and Rhodamine123 (Rh123) transport test. Finally, we evaluated the effect of curcumin reversing MDR in vivo by MNNG/HOS/MTX cells xenograft‐nude mice model. Results MNNG/HOS/MTX was proved to be a human osteosarcoma MDR cell line. MTT tumor chemosensitivity test indicates that 30 &mgr;mol/L curcumin attenuates the half maximal inhibitory concentration (IC50) and resistance index (RI) to MTX, diamminedichloroplatinum (DDP), adriamycin (ADM), ifosfamide (IFO), and epirubicin (EPI) in MNNG/HOS/MTX cells (P<0.05). Real‐time PCR and Western blotting assays demonstrated that curcumin down‐regulated P‐gp expression of MNNG/HOS/MTX cells. Rh123 transport test showed that curcumin inhibited the transport function of P‐gp in vitro. In vivo studies showed that curcumin displayed the features of sensitizing antitumor drugs and inhibiting the proliferation, invasion, and metastasis of osteosarcoma MDR cells. Conclusion Down‐regulation of P‐gp and inhibition of the function of P‐gp efflux pump may contribute to MDR reversion induced by curcumin in vitro and in vivo.

Cortical electrical stimulation promotes neuronal plasticity in the peri-ischemic cortex and contralesional anterior horn of cervical spinal cord in a rat model of focal cerebral ischemia

PURPOSE This study evaluated the effect of cortical electrical stimulation (CES) on function recovery, dendritic plasticity, astrogliosis, and neuron recruitment in the peri-ischemic cortex (PIC) and contralesional anterior horn of cervical spinal cord (CSC) in a rat model of focal cerebral ischemia. MATERIALS AND METHODS Rats were pre-trained on single pellet retrieval task, then received focal ischemic lesions and electrodes implantation. Seven days after surgery, rats received CES (CES group) or no stimulation (NS group) during 18 days of training. Behavior data on stimulation days 2, 4, 6, 8, 10, 12, 14, 16 and 18 were pooled for use. Immunohistochemical investigations for microtubule-associated protein 2 (MAP-2), glial fibrillary acidic protein (GFAP) and neuronal nuclei antigen (NeuN) were performed. RESULTS Rats in CES group showed greater functional recovery of the impaired forelimb compared to the NS group. Moreover, the functional improvement coincided with a significant increase in MAP-2-immunoreactive dendritic surface density in PIC and CSC (P=0.011; P=0.005, respectively). CES group had a significant decrease in GFAP-immunoreactive astrocytic surface density in PIC and CSC (P=0.039; P=0.013, respectively). In the immunoassaying of NeuN, there was no significant difference between the two groups in PIC and CSC (P=0.834, P=0.782, respectively). CONCLUSION CES can promote dendritic plasticity and reduce astrogliosis in the PIC and CSC in a rat model of focal cerebral ischemia. CES is still an appealing method for post-stroke rehabilitation provided that viability of pathways is evaluated presurgically.