Attenuation of neuronal ferroptosis in intracerebral hemorrhage by inhibiting HDAC1/2: Microglial heterogenization via the Nrf2/HO1 pathway.

AIM: The class I histone deacetylases (HDACs) implicate in microglial heterogenization and neuroinflammation following Intracerebral hemorrhage (ICH). Ferroptosis has also been reported in the ICH model. However, the relationship between HDAC1/2's role in microglial heterogenization and neuronal ferroptosis remains unclear. METHODS: In both in vivo and in vitro models of ICH, we used Romidepsin (FK228), a selective HDAC1/2 inhibitor, to investigate its effects on microglial heterogenization and neuronal ferroptosis. In the in vitro ICH model using Hemin, a transwell system was utilized to examine how microglia-driven inflammation and ICH-triggered neuronal ferroptosis interact. Immunostaining, Western blotting and RT-qPCR were used to evaluate the microglial heterogenization and neuronal ferroptosis. Microglial heterogenization, neuronal ferroptosis, and neurological dysfunctions were assessed in vivo ICH mice model performed by autologous blood injection. RESULTS: HDAC1/2 inhibition altered microglial heterogenization after ICH, as showing the reducing neuroinflammation and shifting microglia towards an anti-inflammatory phenotype by immunostaining and qPCR results. HDAC1/2 inhibition reduced ferroptosis, characterized by high ROS and low GPx4 expression in HT22 cells, and reduced iron and lipid deposition post-ICH in vivo. Additionally, the Nrf2/HO1 signaling pathway, especially acetyl-Nrf2, activated in the in vivo ICH model due to HDAC1/2 inhibition, plays a role in regulating microglial heterogenization. Furthermore, HDAC1/2 inhibition improved sensorimotor and histological outcomes post-ICH, offering a potential mechanism against ICH. CONCLUSION: Inhibition of HDAC1/2 reduces neuro-ferroptosis by modifying the heterogeneity of microglia via the Nrf2/HO1 pathway, with a particular focus on acetyl-Nrf2. Additionally, this inhibition aids in the faster removal of hematomas and lessens prolonged neurological impairments, indicating novel approach for treating ICH.

Computer-Assisted Microcatheter Shaping for Intracranial Aneurysm Embolization.

BACKGROUND: This study investigates the accuracy, stability, and safety of computer-assisted microcatheter shaping for intracranial aneurysm coiling. METHODS: Using the solid model, a microcatheter was shaped using computer-assisted techniques or manually to investigate the accuracy and delivery of microcatheter-shaping techniques in aneurysm embolization. Then, forty-eight patients were randomly assigned to the computer-assisted microcatheter-shaping (CAMS) group or the manual microcatheter-shaping (MMS) group, and the accuracy, stability, and safety of microcatheter in the patients were compared between the CAMS and MMS groups. RESULTS: The speed of the successful microcatheter position was significantly faster in the CAMS group than in the MMS group (114.4 ± 23.99 s vs. 201.9 ± 24.54 s, p = 0.015) in vitro. In particular for inexperienced operators, the speed of the microcatheter position with the assistance of computer software is much faster than manual microcatheter shaping (93.6 ± 29.23 s vs. 228.9 ± 31.27 s, p = 0.005). In vivo, the time of the microcatheter position in the MMS group was significantly longer than that in the CAMS group (5.16 ± 0.46 min vs. 2.48 ± 0.32 min, p = 0.0001). However, the mRS score at discharge, the 6-month follow-up, and aneurysm regrowth at the 6-month follow-up were all similar between the groups. CONCLUSIONS: Computer-assisted microcatheter shaping is a novel and safe method for microcatheter shaping that introduces higher accuracy in microcatheter shaping during the treatment of intracranial aneurysms. SIGNIFICANT: Endovascular coiling of intracranial aneurysms can be truly revolutionized through computer assistance, which could improve the endovascular treatment of aneurysms.

Safety and efficacy of remote ischemic conditioning in adult moyamoya disease patients undergoing revascularization surgery: a pilot study.

Background and purpose: Revascularization surgery for patients with moyamoya disease (MMD) is very complicated and has a high rate of postoperative complications. This pilot study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) in adult MMD patients undergoing revascularization surgery. Methods: A total of 44 patients with MMD were enrolled in this single-center, open-label, prospective, parallel randomized study, including 22 patients assigned to the sham group and 22 patients assigned to the RIC group. The primary outcome was the incidence of major neurologic complications during the perioperative period. Secondary outcomes were the modified Rankin Scale (mRS) score at discharge, at 90 days post-operation, and at 1 year after the operation. The outcome of safety was the incidence of adverse events associated with RIC. Blood samples were obtained to monitor the serum concentrations of cytokines (VEGF, IL-6). Results: No subjects experienced adverse events during RIC intervention, and all patients could tolerate the RIC intervention in the perioperative period. The incidence of major neurologic complications was significantly lower in the RIC group compared with the control group (18.2% vs. 54.5%, P = 0.027). The mRS score at discharge in the RIC group was also lower than the control group (0.86 ± 0.99 vs. 1.18 ± 1.22, P = 0.035). In addition, the serum IL-6 level increased significantly at 7 days after bypass surgery in the control group and the serum level of VEGF at 7 days post-operation in the RIC group. Conclusion: In conclusion, our study demonstrated the neuroprotective effect of RIC by reducing perioperative complications and improving cerebral blood flow in adult MMD patients undergoing revascularization surgery. Thus, RIC seems to be a potential treatment method for MMD. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05860946.

18F-FDG PET and a classifier algorithm reveal a characteristic glucose metabolic pattern in adult patients with moyamoya disease and vascular cognitive impairment.

Vascular cognitive impairment (VCI) is a critical issue in moyamoya disease (MMD). However, the glucose metabolic pattern in these patients is still unknown. This study aimed to identify the metabolic signature of cognitive impairment in patients with MMD using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) and establish a classifier to identify VCI in patients with MMD. One hundred fifty-two patients with MMD who underwent brain 18F-FDG PET scans before surgery were enrolled and classified into nonvascular cognitive impairment (non-VCI, n = 52) and vascular cognitive impairment (VCI, n = 100) groups according to neuropsychological test results. Additionally, thirty-three health controls (HCs) were also enrolled. Compared to HCs, patients in the VCI group exhibited extensive hypometabolism in the bilateral frontal and cingulate regions and hypermetabolism in the bilateral cerebellum, while patients in the non-VCI group showed hypermetabolism only in the cerebellum and slight hypometabolism in the frontal and temporal regions. In addition, we found that the patients in the VCI group showed hypometabolism mainly in the left basal ganglia compared to those in the non-VCI group. The sparse representation-based classifier algorithm taking the SUVr of 116 Anatomical Automatic Labeling (AAL) areas as features distinguished patients in the VCI and non-VCI groups with an accuracy of 82.4%. This study demonstrated a characteristic metabolic pattern that can distinguish patients with MMD without VCI from those with VCI, namely, hypometabolic lesions in the left hemisphere played a more important role in cognitive decline in patients with MMD.

Long-term outcome of a tailored embolization strategy with Gamma Knife radiosurgery for high-grade brain arteriovenous malformations: a single-center experience.

OBJECTIVE: The safety and efficacy of embolization with Gamma Knife radiosurgery (GKRS) for high-grade brain arteriovenous malformations (bAVMs) are uncertain. The purpose of this study was to elucidate the long-term outcome of a tailored embolization strategy with GKRS and identify the independent factors associated with bAVM obliteration. METHODS: Between January 2014 and January 2017, a consecutive cohort of 159 patients with high-grade bAVMs who underwent embolization with GKRS was enrolled in this prospective single-center cohort study. All patients received a tailored embolization strategy with GKRS. The primary outcome was defined as bAVM obliteration. Secondary outcomes were neurological function and complications. RESULTS: After a mean follow-up of 40.4 months, 5 patients were lost to follow-up. One hundred eighteen of the remaining 154 patients had favorable neurological outcomes with complete bAVM obliteration. A decrease in bAVM nidus size was observed in 36 patients. Five patients developed intracranial hemorrhage during the latency period, and 2 patients died. The Kaplan-Meier analysis showed that the obliteration rate increased each year and reached the peak point at approximately 3 years. The multivariate Cox regression analysis of factors affecting bAVM obliteration revealed that postembolization bAVM volume < 10 cm3 (p = 0.02), supratentorial location (p < 0.01), staged embolization prior to GKRS (p < 0.01), and mean Spetzler-Martin (SM) grade (p < 0.01) were independent factors associated with a high obliteration rate. CONCLUSIONS: These data suggested that high-grade bAVMs treated using a tailored embolization strategy with GKRS were associated with a favorable clinical outcome and obliteration rate. Postembolization bAVM volume < 10 cm3, supratentorial location, staged embolization prior to GKRS, and low mean SM grade were associated with a high obliteration rate.

Combined Microsurgical and Endovascular Treatment of Cavernous Sinus Dural Arteriovenous Fistula in a Hybrid Neurovascular Operating Room.

Cavernous sinus dural arteriovenous fistula (DAVF) was a special type of intracranial vascular malformation, and endovascular treatment was usually the first choice. However, sometimes it might fail for patients without the proper approach. Video 1 illustrates the case of a patient who presented with left exophthalmos and conjunctival hyperemia caused by cavernous sinus DAVF. Transarterial and transvenous embolization have been attempted but unsuccessful due to no pathways to the fistula. The orbital symptoms aggravated gradually. Therefore we performed combined microsurgical and endovascular treatment in a hybrid neurovascular operating room through direct puncture of caverous sinus by craniotomy and subsequent embolization. A zygomatic-pterional approach was used with epidural exposure of anterior clinoid process and cavernous sinus. After precise localization of the cavernous sinus, we directly punctured it until the blood spurted. An Echelon-10 microcatheter was inserted into cavernous sinus assisted by a Synchro microwire without any resistance. Microcathether angiography confirmed that it was in the true cavity of the cavernous sinus. Curative embolization was achieved successfully using coils and Onyx-18, and no procedure-related complications occurred. The orbital signs and symptoms significantly relieved after surgery and did not relapse at 6-month follow-up. Endovascular treatment remained the optimal choice for cavernous sinus DAVF. However, for practical cases without accessible pathways, combined microsurgical and endovascular management in a hybrid neurovascular operating room was feasible, although challenging. The patient gave informed consent for the procedure and video production.

Postoperative cerebral infarction after revascularization in patients with moyamoya disease: Incidence and risk factors.

Objectives: Cerebral infarction is the major complication of revascularization surgery in patients with moyamoya disease (MMD), and we analyzed the possible causes of cerebral infarction after revascularization surgery for MMD. Methods: MMD patients who were admitted and underwent surgical revascularization at Shanghai Huashan Hospital from January 2019 to December 2021 were retrospectively analyzed. Results: A total of 815 patients and 890 revascularization surgeries (677 first revascularization surgeries and 213 second revascularization surgeries) were included in this study; 453 (50.9%) were performed on the left side and 437 (49.1%) on the right side, with 779 (87.5%) combined procedures and 111 (12.5%) indirect bypasses included. The mean patient age at the time of these procedures was 44.6 ± 11.7 years (range 6-72 years). Postoperative cerebral infarctions were observed in 46 (5.17%) surgeries, among which 31 occurred after left hemisphere revascularization surgeries, with an incidence of 6.84%, and 15 occurred after right hemisphere revascularization surgeries, with an incidence of 3.43%. Of these, 30 (65.2%) occurred in the operated hemispheres, 2 (4.3%) in the contralateral hemisphere and 13 (28.3%) in the bilateral hemisphere. There were 11 cases of massive infarction (23.9%). The incidence of postoperative infarction in patients undergoing the first revascularization was 6% (41/677) and 2.3% (5/213) in the second revascularization surgeries. Initial presentation as infarction (P < 0.001), initial presentation as hemorrhage (P < 0.001), hypertension (P = 0.018), diabetes (P = 0.006), 1st or 2nd surgery and surgical side (P = 0.007) were found to be related to postoperative cerebral infarction. Initial presentation as infarction (OR = 2.934, 95% CI 1.453-5.928, P = 0.003), initial presentation as hemorrhage (OR = 0.149, 95% CI 0.035-0.641, P = 0.011), and 1st or 2nd surgery and surgical side (OR = 1.66, 95% CI 1.106-2.491, P = 0.014) were independently associated with cerebral infarction after revascularization surgeries. Conclusions: In patients with MMD undergoing surgical revascularization, initial presentation as infarction and first revascularization surgery performed on the left hemisphere are independent risk factors for postoperative cerebral infarction, whereas initial presentation as hemorrhage is a protective factor.

Preliminary Study on the Application of Ultrahigh Field Magnetic Resonance in Moyamoya Disease.

Magnetic resonance imaging (MRI) is widely used for the evaluation of moyamoya disease (MMD). In this paper, we describe the features of time-of-flight magnetic resonance angiography (TOF-MRA) and susceptibility-weighted imaging (SWI) at 7 T in a series of MMD patients. In this prospective pilot study, 7 patients (median age: 45.6 years; range: 30-52 years) with MMD and no contraindications for MRI underwent T2-weighted, SWI, and TOF-MRA sequences using a research 7 T head-only scanner. We show that such sequences at ultrahigh field (UHF) represent new and valuable approaches to unravel and characterize MMD. While SWI reveals more remarkable imaging signs related to an improved magnitude and phase contrast imaging, the collateral network pathways in MMD could be excellently delineated using 7 T TOF-MRA. In particular, using SWI and MRA fusion images in UHF MRI helps to improve the detection of bleeding points in hemorrhagic MMD. Our findings indicate that ultrahigh field MRI is very promising to access the severity of the disease and may facilitate revascularization surgery of MMD patients.

HDAC inhibition reduces white matter injury after intracerebral hemorrhage.

Inhibition of histone deacetylases (HDACs) has been shown to reduce inflammation and white matter damage after various forms of brain injury via modulation of microglia/macrophage polarization. Previously we showed that the HDAC inhibitor scriptaid could attenuate white matter injury (WMI) after ICH. To access whether modulation of microglia/macrophage polarization might underlie this protection, we investigated the modulatory role of HDAC2 in microglia/macrophage polarization in response to WMI induced by intracerebral hemorrhage (ICH) and in primary microglia and oligodendrocyte co-cultures. HDAC2 activity was inhibited via conditional knockout of the Hdac2 gene in microglia or via administration of scriptaid. Conditional knockout of the Hdac2 gene in microglia and HDAC inhibition with scriptaid both improved neurological functional recovery and reduced WMI after ICH. Additionally, HDAC inhibition shifted microglia/macrophage polarization toward the M2 phenotype and reduced proinflammatory cytokine secretion after ICH in vivo. In vitro, a transwell co-culture model of microglia and oligodendrocytes also demonstrated that the HDAC inhibitor protected oligodendrocytes by modulating microglia polarization and mitigating neuroinflammation. Moreover, we found that scriptaid decreased the expression of pJAK2 and pSTAT1 in cultured microglia when stimulated with hemoglobin. Thus, HDAC inhibition ameliorated ICH-mediated neuroinflammation and WMI by modulating microglia/macrophage polarization.

Pharmacokinetics and Acute Toxicity of a Histone Deacetylase Inhibitor, Scriptaid, and its Neuroprotective Effects in Mice After Intracranial Hemorrhage.

BACKGROUND & OBJECTIVE: The pharmacokinetics and acute toxicity of a histone deacetylase inhibitor, Scriptaid, was unknown in the mouse. The aim of this study was to determine the pharmacokinetics, acute toxicity, and tissue distribution of Scriptaid, a new histone deacetylase inhibitor, in mice, and its neuroprotective efficacy in a mouse intracranial hemorrhage (ICH) model. METHODS: The pharmacokinetics, acute toxicity, and tissue distribution were determined in C57BL/6 male and female mice after the intraperitoneal administration of a single dose. Behavioral tests, as well as investigations of brain atrophy and white matter injury, were used to evaluate the neuroprotective effect of Scriptaid after ICH. Western blotting was used to investigate if Scriptaid could offer antiinflammatory benefits after ICH. RESULTS: No significant differences were observed in body weight or brain histopathology between the group that received Scriptaid at 50 mg/kg and the group that received dimethyl sulfoxide (control). The pharmacokinetics of Scriptaid in mice was nonlinear, and it was cleared rapidly at low doses and slowly at higher doses. Consistent with the pharmacokinetic data, Scriptaid was found to distribute in several tissues, including the spleen and kidneys. In the ICH model, we found that Scriptaid could reduce neurological deficits, brain atrophy, and white matter injury in a dose-dependent manner. Western blotting results demonstrated that Scriptaid could decrease the expression of pro-inflammatory cytokines IL1ß and TNFα, as well as iNOS, after ICH. CONCLUSION: These findings indicate that Scriptaid is safe and can alleviate brain injury after ICH, thereby providing a foundation for the pharmacological action of Scriptaid in the treatment of brain injury after ICH.

Proximal Middle Cerebral Artery Aneurysms: Microsurgical Management and Therapeutic Results.

BACKGROUND: Management of proximal (M1) middle cerebral artery (MCA) aneurysms can be challenging. Because of the diversity of aneurysm morphology and location of M1 aneurysms, the surgical strategy should be tailored to each individual case, especially for complex cases. We assessed the safety and efficacy of an algorithmic strategy for the management of M1 aneurysms. METHODS: A prospective single-center study of M1 aneurysms treated with microsurgery was performed. Our algorithmic strategy was determined by the location and complexity (e.g., size, shape) of the aneurysms. The surgical modalities included neck clipping, aneurysm resection and/or trapping, and proximal occlusion with revascularization. The clinical and radiographic data were analyzed. RESULTS: From January 2007 to March 2017, 92 proximal MCA aneurysms in 92 patients were treated microsurgically. Aneurysm treatment techniques included clipping in 55, proximal occlusion in 21, aneurysm resection in 11, and trapping in 4. Bypass techniques included 2 anterior temporal artery reconstructions, 5 middle cerebral bifurcation reconstructions, 4 parent artery reanastomoses, 2 interpositional bypasses, 25 high-flow bypasses, and 7 medium-flow bypasses. Overall, good outcomes (modified Rankin scale score, 0-2) were seen in 49 of 92 patients (53.3%) at discharge and in 79 of 91 (86.8%) at the last follow-up visit. On the latest angiogram, 78 of 90 aneurysms (86.7%) had been completely occluded without a remnant. Bypass patency was confirmed in 38 of 43 bypass procedures. CONCLUSIONS: Our present treating strategy might provide a benefit for patients with proximal MCA aneurysms.

Histone Deacetylase Inhibitor Scriptaid Alleviated Neurological Dysfunction after Experimental Intracerebral Hemorrhage in Mice.

OBJECTIVES: To investigate the role of Scriptaid in reducing brain injury after intracerebral hemorrhage (ICH) in mice. METHODS: An ICH model was constructed by injecting autologous blood into the right basal ganglia in mice. The animals were administered 3.5 mg/kg of Scriptaid intraperitoneally after ICH. The hematoma volume and hemoglobin level were measured to examine hematoma resolution. A behavior test and brain edema and white matter injury examinations indicated brain injury after ICH. RESULTS: Scriptaid treatment promoted hematoma resolution and reduced the hematoma volume 7 d after ICH compared with the vehicle group (P < 0.05). Scriptaid treatment also alleviated the brain water content in the ipsilateral basal ganglia (P < 0.05) and cortex (P < 0.01) 3 d after ICH. In addition, Scriptaid improved neurological function recovery and alleviated white matter injury 35 d after ICH. CONCLUSIONS: Scriptaid can protect against brain injury after ICH and may be considered a new medical therapy method for ICH.

Long-Term Outcomes After Combined Revascularization Surgery in Adult Hemorrhagic Moyamoya Disease.

OBJECTIVE: Risk factors for rebleeding after revascularization surgery are unclear. We aimed to evaluate long-term outcomes after combined revascularization surgery for adult hemorrhagic moyamoya disease (MMD) and identify risk factors for initial and recurrent hemorrhage. METHODS: A total of 105 adult patients with hemorrhagic MMD from January 2007 to May 2011 were prospectively enrolled in this study. All patients underwent combined revascularization surgery on unilateral hemorrhagic hemispheres and were observed for at least 5 years. RESULTS: After a median follow-up time of 77 months, 12 patients were lost to follow-up. Twelve of the remaining 93 patients developed rebleeding, and 6 patients died. According to rebleeding sites, ipsilateral and contralateral rebleeding occurred in 6 and 6 patients, respectively. There was no significant difference between the 2 groups (P > 0.05). The annual risks of overall, ipsilateral, and contralateral rebleeding were 1.1%, 0.62%, and 0.51%, respectively. A significant correlation was observed between improvement of anterior choroidal artery-posterior communicating artery dilation or extension in the operated hemispheres and low risk of ipsilateral rebleeding (P < 0.05). Progression of Suzuki stage in the nonhemorrhagic hemispheres was significantly associated with contralateral rebleeding (P < 0.05). CONCLUSIONS: Combined revascularization surgery may help prevent ipsilateral rebleeding in adult patients with hemorrhagic MMD by improvement of anterior choroidal artery-posterior communicating artery dilation and extension in the operated hemisphere. Progression of Suzuki stage in the nonhemorrhagic hemispheres was a strong predictor of subsequent contralateral rebleeding.

Treatment of aneurysms in patients with moyamoya disease: a 10-year single-center experience.

OBJECTIVE Moyamoya disease (MMD) is occasionally accompanied by intracranial aneurysms. The purpose of this study was to delineate the efficacy of the authors' current surgical strategy in the management of MMD-associated aneurysms of different types. METHODS Between January 2007 and March 2016, a consecutive cohort of 34 patients with 36 MMD-associated aneurysms was enrolled in this prospective single-center cohort study. The lesions were classified as peripheral (17 aneurysms) or main trunk aneurysms (13 in the anterior circulation and 6 in the posterior circulation). For the peripheral aneurysms, revascularization with or without endovascular treatment was suggested. For the main trunk aneurysms, revascularization alone, revascularization with aneurysm clipping, or revascularization with aneurysm embolization were used, depending on the location of the aneurysms. RESULTS Of the peripheral aneurysms, 4 were treated endovascularly with staged revascularization, and 13 were treated solely with cerebral revascularization. Of the 13 main trunk aneurysms in the anterior circulation, 10 were clipped followed by revascularization, and 3 were coiled followed by staged cerebral revascularization. Of the 6 main trunk aneurysms in the posterior circulation, 4 underwent endovascular coiling and 2 were treated solely with revascularization. One patient died of contralateral intracerebral hemorrhage 6 months after the operation. No other patients suffered recurrent intracranial hemorrhage, cerebral ischemia, or aneurysm rupture. An angiographic follow-up study showed that all the bypass grafts were patent. Complete occlusion was achieved in all 21 aneurysms that were clipped or embolized. Of the remaining 15 aneurysms that were not directly treated, 12 of 13 peripheral aneurysms were obliterated during the follow-up, whereas 1 remained stable; 1 of 2 posterior main trunk aneurysms remained stable, and the other became smaller. CONCLUSIONS The authors' current treatment strategy may benefit patients with MMD-associated aneurysms.

Aberrant regional homogeneity of resting-state executive control, default mode, and salience networks in adult patients with moyamoya disease.

Aberrant local connectivity within cerebral intrinsic connectivity networks (ICNs) at rest has not been reported in adult moyamoya disease (MMD). Our aim was to examine the regional homogeneity (ReHo) of executive control (ECN), default mode (DMN), and salience networks (SN) in patients with executive dysfunction to explore the underlying mechanism. Twenty-six adult patients with MMD and 24 normal control (NC) subjects were recruited. Executive function was evaluated by Trail Making Test Part B (TMT-B) and executive subtests of Memory and Executive Screening (MES-EX). Compared with NC, the case group exhibited ReHo decrease mainly in the frontal and parietal gyrus, and increase only in the left middle temporal gyrus. Subsequent ICNs analysis indicated that compared with NC, patients with MMD exhibited significantly decreased ReHo in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal gyrus (IPG) of left ECN; the IPG, superior frontal gyrus, and DLPFC of the right ECN; the right precuneus, left medial superior frontal gyrus, and right medial orbitofrontal gyrus of the DMN; as well as the left middle frontal gyrus and right supplemental motor area of SN. When referring to the Suzuki's 6-stage classification, a trend of ReHo decrease with disease severity was observed in all of the ICNs examined, but only bilateral ECNs reached statistical significance. Finally, only bilateral ECNs exhibited a significant correlation of averaged ReHo values with executive performance. Our results provide new insight into the pathophysiology of adult MMD.

Postoperative executive function in adult moyamoya disease: a preliminary study of its functional anatomy and behavioral correlates.

OBJECTIVE Chronic frontal hemodynamic disturbances are associated with executive dysfunction in adult patients with moyamoya disease (MMD). However, the impact of surgical revascularization on executive dysfunction and its underlying mechanism remains unclear. The aim of the present study was to examine the postoperative radiological correlates of cognitive improvement and thereby explore its underlying mechanism. METHODS Fourteen patients who met the inclusion criteria were identified at Huashan Hospital, were operated on, and were successfully followed up for 6 months. Postoperative changes in cortical perfusion and regional amplitude of low-frequency fluctuations (ALFF) were examined by SPECT and resting-state functional MRI, respectively. Executive function was evaluated by 2 tests (Trail Making Test Part B and the summation of executive subtests of Memory and Executive Screening [MES-EX]). Follow-up neuropsychological outcomes were then correlated with radiological changes to identify nodes functioning as leading contributors to postoperative executive outcomes. RESULTS All patients underwent successful unilateral bypass procedures, with some operations performed on the left side and some on the right side. At the 6-month follow-up, the baseline and follow-up test scores for the different sides did not differ significantly. The group with good collaterals (Matsushima Grade A, 9 patients) exhibited significantly increased postoperative perfusion (change in [△] hemodynamics) in bilateral frontal (left, p = 0.009; right, p = 0.003) and left parietal lobe (p = 0.014). The Spearman's correlation test suggested that only the right frontal lobe exhibited significant positive postoperative radiological correlates with cognitive performance (△MES-EX vs △hemodynamics, r = 0.620, p = 0.018; △MES-EX vs △ALFF, r = 0.676, p = 0.008; △hemodynamics vs △ALFF, r = 0.547, p = 0.043). Subsequent regional ALFF analysis revealed that the right dorsolateral prefrontal cortex (DLPFC) was the only node in the responsible hemisphere to exhibit significant postoperative changes. CONCLUSIONS The results not only advance our understanding of pathological interactions of postoperative executive performance in adult MMD, but also indicate that the right DLPFC amplitude might be a quantitative predictor of postoperative executive control improvement.

Combined extracranial-intracranial bypass surgery with stent-assisted coil embolization for moyamoya disease with a ruptured wide-necked basilar trunk aneurysm: a case report.

A ruptured wide-necked basilar trunk aneurysm is uncommon in patients with moyamoya disease. The optimal treatment is unclear. We report a safe and beneficial treatment modality for moyamoya disease with aneurysms located in the posterior circulation. A 37-year-old man presenting with subarachnoid hemorrhage was admitted to our hospital. Emergent cerebral angiography demonstrated moyamoya disease associated with a wide-necked basilar trunk aneurysm. We performed bilateral extracranial-intracranial bypass surgeries prior to stent-assisted coil embolization of the aneurysm after the acute phase. No complication occurred and the patient was discharged with no neurological deficit. Follow-up digital subtraction angiography (DSA) performed 6 months after the surgery showed that all the anastomosises were patent and bilateral collateral vascular compensation was fully established with no recanalization of the basilar trunk aneurysm post embolization.We also found that high-flow bypass did not contribute to cerebral revascularization as imagined despite the good patency. Combined extracranial-intracranial bypass surgery with endovascular treatment proved to be an efficient therapeutic modality for moyamoya disease with aneurysms located in the posterior circulation. High-flow bypass surgery was not essential due to the inefficiency and the high risk of postoperative cerebral hyperperfusion syndrome.

Outcome in adult patients with hemorrhagic moyamoya disease after combined extracranial-intracranial bypass.

OBJECT: The outcome of patients with hemorrhagic moyamoya disease (MMD) after cerebral revascularization is uncertain. The purpose of this study was to delineate the efficacy of this surgical method in the treatment of hemorrhagic MMD. METHODS: Between January 2007 and August 2011, a consecutive cohort of 113 patients with hemorrhagic MMD was enrolled into this prospective single-center cohort study. The surgical method was combined direct and indirect bypass. The cumulative probability of the primary end point (all stroke and deaths from surgery through 30 days after surgery and ipsilateral recurrent hemorrhage afterward) was analyzed. The angiographic outcome was measured by the following parameters: bypass patency, reduction of basal MMD vessels, improved degree of dilation, and branch extension of the anterior choroidal and posterior communicating arteries (AChA-PCoA). RESULTS: Of the 113 enrolled cases, CT scans revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases (31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was extremely dilated with extensive branches beyond the choroidal fissure. A total of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5 patients, 4 of whom died of the rebleeding event. The cumulative probability of the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105 unoperated hemispheres (35.2%). CONCLUSIONS: Revascularization may provide a benefit over conservative therapy for hemorrhagic MMD patients. The improvement of dilation and branch extension of AChA-PCoA might be correlated with the low rebleeding rate.

[Characteristics of cognitive impairment in adults with cerebral ischemia].

OBJECTIVE: To explore the characteristics of cognitive impairment of cerebral ischemia in adults to provide rationales for proper diagnosis and targeted treatment. METHODS: A battery of standardized neuropsychological tests including mini-mental state examination (MMSE) and memory and executive screening (MES) was administered in a cohort of consecutive patients with cerebral ischemia. According to the screening results, they were divided into 3 subgroups of vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and non-vascular cognitive impairment (VCI). The general profiles of 3 subgroups were compared and the characteristics of VaMCI subgroup examined. Then the relationship between the composition of cognitive impairment and the type of ischemia (stroke and transient ischemic attack) was analyzed. RESULTS: Fifty-six patients and 48 healthy subjects (normal control group) matched with regards to age, gender and education were recruited. Compared to normal control group, there was a decline in the scores of MMSE [(25.0 ± 5.6) vs (28.0 ± 1.4); t = 2.695, P = 0.007] and MES [(67 ± 21) vs (84 ± 7); z = 3.860, P = 0.000] in case group. There were 33 cases (58.9%) of VCI in case group, including 11 (19.6%) in VaD subgroup, 22 (39.3%) in VaMCI subgroup and 23 (41.1%) in non-VCI subgroup. And the rate of VaD/VaMCI was 1/2. The percentage of males (36.4% vs 78.3%; χ(2) = 5.720, P = 0.017) and education [(8 ± 3) vs (12 ± 4); P = 0.010] of VaD subgroup were significantly lower than that of non-VCI subgroup; the education of VaMCI subgroup was significantly lower than that of non-VCI subgroup [(7 ± 3) vs (12 ± 4); P = 0.001]; a positive correlation existed between scores of MMSE/MES and cognitive impairment. The neuropsychological tests were both sensitive and specific.In VaMCI subgroup, 22 cases (100%) presented with a deficit of at least 1 certain executive function/attention index, 21(95.5%) with at least 1 certain memory index, 17(77.3%) with at least 1 certain language index and 16(72.7%) with at least 1 certain visuospatial function index; all VaMCI cases presented with comprehensive cognitive impairment: 11 (50%) in 4 domains, 10 (45%) in 3 domains and 1 (5%) in 2 domains.No significant difference existed among 3 subgroups with regard to type of ischemia (χ(2) = 1.111, P = 0.574). In the case group, 30 patients suffered stroke and 17 (56.7%) had an onset of VCI with a rate of VaMCI/VCI at 58.8%; transient ischemic attack occurred in 26 patients and 16 (61.5%) suffered VCI with a rate of VaMCI/VCI at 75.0%. CONCLUSION: Our study not only profiles the prevalence and peculiarity of cognitive impairment in patients with cerebral ischemia, but also provides concrete rationales for further diagnosis and classification of VCI.

Spontaneous brain activity in adult patients with moyamoya disease: a resting-state fMRI study.

Adult patients with moyamoya disease (MMD) are reported to suffer from vascular cognitive impairment (VCI), including considerable impairment of executive function/attention. The spatial pattern of functional brain activity in adult MMD patients with VCI has not been studied before and can be measured by examining the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) during rest. Twenty-three adult patients with MMD were recruited to participate in this study, including 11 with VCI and 12 without VCI (NonVCI), as well as 22 healthy young adults (normal control, NC). Widespread differences in ALFF were observed between the VCI/NonVCI and NC groups in such regions as the frontal, parietal and temporal gyri, with parts of the frontal gyrus, such as the anterior cingulate cortex (ACC) and the right supplemental motor area (SMA), showing significant differences in ALFF. It is worth to note that regions such as the parietal gyrus, the right superior frontal gyrus (SFG), the right superior temporal gyrus (STG) and the left caudate nucleus (CN) exhibited significant changes in ALFF during the progressive cognitive decline of MMD. Taken together, our results demonstrate that MMD exhibits a specific intrinsic pattern of ALFF and that this pattern changes with the progression of cognitive decline, providing insight into the pathophysiological nature of this disease.