Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Presurgical Magnetic Resonance Imaging Indicators of Revascularization Response in Adults With Moyamoya Vasculopathy.

BACKGROUND: Moyamoya is a progressive intracranial vasculopathy, primarily affecting distal segments of the internal carotid and middle cerebral arteries. Treatment may comprise angiogenesis-inducing surgical revascularization; however, lack of randomized trials often results in subjective treatment decisions. HYPOTHESIS: Compensatory presurgical posterior vertebrobasilar artery (VBA) flow-territory reactivity, including greater cerebrovascular reactivity (CVR) and reduced vascular delay time, portends greater neoangiogenic response verified on digital subtraction angiography (DSA) at 1-year follow-up. STUDY TYPE: Prospective intervention cohort. SUBJECTS: Thirty-one patients with moyamoya (26 females; age = 45 ± 13 years; 41 revascularized hemispheres). METHODS: Anatomical MRI, hypercapnic CVR MRI, and DSA acquired presurgically in adult moyamoya participants scheduled for clinically indicated surgical revascularization. One-year postsurgery, DSA was repeated to evaluate collateralization. FIELD STRENGTH: 3 T. SEQUENCE: Hypercapnic T 2 * -weighted gradient-echo blood-oxygenation-level-dependent, T2 -weighted turbo-spin-echo fluid-attenuated-inversion-recovery, T1 -weighted magnetization-prepared-rapid-gradient-echo, and T2 -weighted diffusion-weighted-imaging. ASSESSMENT: Presurgical maximum CVR and response times were evaluated in VBA flow-territories. Revascularization success was determined using an ordinal scoring system of neoangiogenic collateralization from postsurgical DSA by two cerebrovascular neurosurgeons (R.V.C. with 8 years of experience; M.R.F. with 9 years of experience) and one neuroradiologist (L.T.D. with 8 years of experience). Stroke risk factors (age, sex, race, vasculopathy, and diabetes) were recorded. STATISTICAL TESTS: Fisher's exact and Wilcoxon rank-sum tests were applied to compare presurgical variables between cohorts with angiographically confirmed good (>1/3 middle cerebral artery [MCA] territory revascularized) vs. poor (<1/3 MCA territory revascularized) outcomes. SIGNIFICANCE: two-sided P < 0.05. Normalized odds ratios (ORs) were calculated. RESULTS: Criteria for good collateralization were met in 25 of the 41 revascularized hemispheres. Presurgical normalized VBA flow-territory CVR was significantly higher in those with good (1.12 ± 0.13 unitless) vs. poor (1.04 ± 0.05 unitless) outcomes. Younger (OR = -0.60 ± 0.67) and White (OR = -1.81 ± 1.40) participants had highest revascularization success (good outcomes: age = 42 ± 14 years, race = 84% White; poor outcomes: age = 49 ± 11 years, race = 44% White). DATA CONCLUSION: Presurgical MRI-measures of VBA flow-territory CVR are highest in moyamoya participants with better angiographic responses to surgical revascularization. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

Successful multiple burr hole openings for limb-shaking transient ischemic attack due to moyamoya disease: illustrative case.

BACKGROUND: Limb-shaking transient ischemic attacks (LS-TIAs) are a rare form of TIAs that present as involuntary movements of the limbs and indicate severe cerebral hypoperfusion. LS-TIAs are often reported in patients with carotid artery stenosis but can also affect patients with intracranial artery stenosis and moyamoya disease (MMD). OBSERVATIONS: A 72-year-old woman presented with repeated episodes of involuntary shaking movements of the right upper limb. Cerebral angiography revealed complete occlusion of the M1 segment of the left middle cerebral artery (MCA), and the left hemisphere was supplied by moyamoya vessels. She was treated with left direct revascularization without complications, and her involuntary movements subsided. However, she demonstrated involuntary shaking movements of the right lower limb 2 months postoperatively. Cerebral angiography revealed complete occlusion of the A1 segment of the left anterior cerebral artery (ACA). The multiple burr hole opening (MBHO) procedure was performed to improve perfusion in the left ACA territory and after 3 months, the patient's symptoms resolved. LESSONS: This case demonstrated that LS-TIAs can also develop as ischemic symptoms due to MMD. Moreover, instances of LS-TIA of the upper and lower limbs developed separately in the same patient. The patient's symptoms improved with direct revascularization and MBHO.

Postoperative Transient Neurologic Dysfunction: A Proposal for Pathophysiology.

BACKGROUND AND PURPOSE: Sudden neurological deterioration which cannot be explained by structural change, ischemia or seizure is often observed among neurosurgical patients. We aimed to provide new insight into the pathophysiology of postoperative transient neurologic dysfunction. METHODS: We describe prolonged but fully reversible focal neurologic dysfunction of unknown origin based on the initial evaluation in 8 patients who had received encephalo-duro-arterio-synangiosis for moyamoya disease. We performed brain imaging, including diffusion weighted imaging and perfusion magnetic resonance imaging or single photon emission computed tomography, and electroencephalography (EEG) during the episodes and after resolution of the symptoms. RESULTS: The symptoms consisted of dysarthria, hemiparesis, or hemiparesthesia of limbs contralateral to the operated side. These symptoms developed between 12 hours and 8 days after surgery and lasted between 12 hours and 17 days. Structural imaging did not show any significant interval change compared with the immediate postoperative images. Perfusion imaging showed increased cerebral blood flow in the symptomatic hemisphere. EEG revealed low amplitude arrhythmic slowing in the corresponding hemisphere. Follow-up imaging and EEG after recovery did not show any abnormalities. CONCLUSIONS: Transient neurologic dysfunction can occur during the postoperative period of brain surgery. Although this may last more than usual transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we propose that this is the manifestation of the transient cortical depression triggered by mechanical stimulation, analogous to migraine aura associated with cortical spreading depression.

Postoperative Transient Neurologic Dysfunction: A Proposal for Pathophysiology

BACKGROUND AND PURPOSE: Sudden neurological deterioration which cannot be explained by structural change, ischemia or seizure is often observed among neurosurgical patients. We aimed to provide new insight into the pathophysiology of postoperative transient neurologic dysfunction. METHODS: We describe prolonged but fully reversible focal neurologic dysfunction of unknown origin based on the initial evaluation in 8 patients who had received encephalo-duro-arterio-synangiosis for moyamoya disease. We performed brain imaging, including diffusion weighted imaging and perfusion magnetic resonance imaging or single photon emission computed tomography, and electroencephalography (EEG) during the episodes and after resolution of the symptoms. RESULTS: The symptoms consisted of dysarthria, hemiparesis, or hemiparesthesia of limbs contralateral to the operated side. These symptoms developed between 12 hours and 8 days after surgery and lasted between 12 hours and 17 days. Structural imaging did not show any significant interval change compared with the immediate postoperative images. Perfusion imaging showed increased cerebral blood flow in the symptomatic hemisphere. EEG revealed low amplitude arrhythmic slowing in the corresponding hemisphere. Follow-up imaging and EEG after recovery did not show any abnormalities. CONCLUSIONS: Transient neurologic dysfunction can occur during the postoperative period of brain surgery. Although this may last more than usual transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we propose that this is the manifestation of the transient cortical depression triggered by mechanical stimulation, analogous to migraine aura associated with cortical spreading depression.

Effectiveness of surgical revascularization for stroke prevention in pediatric patients with sickle cell disease and moyamoya syndrome.

OBJECTIVE Sickle cell disease (SCD) in combination with moyamoya syndrome (MMS) represents a rare complication of SCD, with potentially devastating neurological outcomes. The effectiveness of surgical revascularization in this patient population is currently unclear. The authors' aim was to determine the effectiveness of surgical intervention in their series of SCD-MMS patients by comparing stroke recurrence in those undergoing revascularization and those undergoing conservative transfusion therapy. METHODS The authors performed a retrospective chart review of patients with MMS who were seen at the Johns Hopkins Medical Institution between 1990 and 2013. Pediatric patients (age < 18 years) with confirmed diagnoses of SCD and MMS were included. Intracranial stroke occurrence during the follow-up period was compared between surgically and conservatively managed patients. RESULTS A total of 15 pediatric SCD-MMS patients (28 affected hemispheres) were included in this study, and all were African American. Seven patients (12 hemispheres) were treated with indirect surgical revascularization. The average age at MMS diagnosis was 9.0 ± 4.0 years, and 9 patients (60.0%) were female. Fourteen patients (93.3%) had strokes before diagnosis of MMS, with an average age at first stroke of 6.6 ± 3.9 years. During an average follow-up period of 11.6 years, 4 patients in the conservative treatment group experienced strokes in 5 hemispheres, whereas no patient undergoing the revascularization procedure had any strokes at follow-up (p = 0.029). Three patients experienced immediate postoperative transient ischemic attacks, but all recovered without subsequent strokes. CONCLUSIONS Indirect revascularization is suggested as a safe and effective alternative to the best medical therapy alone in patients with SCD-MMS. High-risk patients managed on a regimen of chronic transfusion should be considered for indirect revascularization to maximize the effect of stroke prevention.

Acceleration of blood flow as an indicator of improved hemodynamics after indirect bypass surgery in Moyamoya disease.

OBJECTIVE: The ultrasonography findings in the superficial temporal artery (STA) in Moyamoya disease patients treated with indirect bypass remain unclear. We evaluated the time-related changes in ultrasonography findings of the STA main trunk and branches in patients with Moyamoya disease who underwent encephalo-duro-arterio-synangiosis (EDAS). PATIENTS AND METHODS: Patients (n=21, 30 sides) with Moyamoya disease who underwent EDAS at Fukuoka University Hospital were prospectively registered between 2008 and 2015. EDAS using the frontal and parietal branches of the STA was adopted in an indirect bypass procedure. Mean velocity (MV) and resistance index (RI) were used as ultrasonography markers, and their changes over time in the STA main trunk and branches were assessed. RESULTS: There was a significant increase in MV in both the STA main trunk (p=0.001) and branches (frontal: p=0.005, parietal: p=0.003) at 3 months after EDAS, whereas there was a decrease in RI at 14days after EDAS (main trunk: p <0.001, frontal: p <0.001, parietal: p=0.014). In subgroup analysis of patients divided by EDAS outcome, compared with before EDAS, there were significant differences at 3 months after EDAS in MV (responders: main trunk: p=0.002, frontal: p=0.001, parietal: p=0.001; non-responders: main trunk: p=0.093, frontal: p=0.24, parietal: p=0.96) and RI (responders: main trunk: p<0.001, frontal: p<0.001, parietal: p=0.006; non-responders: main trunk: p=0.17, frontal: p=0.12, parietal: p=0.17). CONCLUSIONS: Measurement of MV may be useful for predicting outcome at 3 months after EDAS.

Early and noninvasive evaluation using superficial temporal artery duplex ultrasonography after indirect bypass for adult ischemic moyamoya disease.

BACKGROUND: The validity of indirect bypass for adult patients with moyamoya disease is still debatable. Some patients are poor responders to indirect bypass, and additive intervention is occasionally required in these cases. Therefore, it is necessary to evaluate the development of collateral circulation as early as possible postoperatively. METHODS: Fifteen adult patients (>17 years old) with moyamoya disease (22 affected sides) who underwent encephalo-duro-arterio-synangiosis (EDAS) at Fukuoka University Hospital from April 2008 to August 2014 were included. All patients had ischemic symptoms of at least one hemisphere. Superficial temporal artery duplex ultrasonography (STDU) was performed before and 3, 6, and 12 months postoperatively. Digital subtraction angiography was performed 1 year after the operation to evaluate the development of collateral circulation. Hemispheres exhibiting collateral formation of more than one-third of the MCA distribution were defined as good responders, and those with less than one-third were defined as poor responders. RESULTS: EDAS induced the formation of well-developed collaterals in 17 of 22 affected sides (77.3%) of adult patients with ischemic moyamoya disease. Regardless of the degree of collateral formation, the ischemic event subsided eventually with time in all patients. In good responders, the pulsatility index obtained by STDU showed a drastic decrease 3 months after the operation, while it did not change significantly in poor responders. Absence of this decrease in the pulsatility index along with no change in the flow velocity reliably indicated poor responders. CONCLUSIONS: Neovascularization after EDAS can be evaluated noninvasively in early phase using STDU.

Bypass surgery versus medical treatment for symptomatic moyamoya disease in adults.

OBJECTIVE In this study the authors evaluated whether extracranial-intracranial bypass surgery can prevent stroke occurrence and decrease mortality in adult patients with symptomatic moyamoya disease (MMD). METHODS The medical records of 249 consecutive adult patients with symptomatic MMD that was confirmed by digital subtraction angiography between 2002 and 2011 at 8 institutions were retrospectively reviewed. The study outcomes of stroke recurrence as a primary event and death during the 6-year follow-up and perioperative complications within 30 days as secondary events were compared between the bypass and medical treatment groups. RESULTS The bypass group comprised 158 (63.5%) patients, and the medical treatment group comprised 91 (36.5%) patients. For 249 adult patients with MMD, bypass surgery showed an HR of 0.48 (95% CI 0.27-0.86, p = 0.014) for stroke recurrence calculated by Cox regression analysis. However, for the 153 patients with ischemic MMD, the HR of bypass surgery for stroke recurrence was 1.07 (95% CI 0.43-2.66, p = 0.887). For the 96 patients with hemorrhagic MMD, the multivariable adjusted HR of bypass surgery for stroke recurrence was 0.18 (95% CI 0.06-0.49, p = 0.001). For the treatment modality, indirect bypass and direct bypass (or combined bypass) did not show any significant difference for stroke recurrence, perioperative stroke, or mortality (log rank; p = 0.524, p = 0.828, and p = 0.616, respectively). CONCLUSIONS During the treatment of symptomatic MMD in adults, bypass surgery reduces stroke recurrence for the hemorrhagic type, but it does not do so for the ischemic type. The best choice of bypass methods in adult patients with MMD is uncertain. In adult ischemic MMD, a prospective randomized study to evaluate the effectiveness and safety of bypass surgery to prevent recurrent stroke is necessary.

Operative wound-related complications after cranial revascularization surgeries.

OBJECT: Intracranial revascularization surgeries are an effective treatment for moyamoya disease and other intracranial vascular obliterative diseases. However, in some cases, wound-related complications develop after surgery. Although the incidence of wound complication is supposed to be higher than that with a usual craniotomy, this complication has rarely been the focus of studies in the literature that report the outcomes of revascularization surgeries. Here, the relationship between intracranial revascularization surgeries and their complications is statistically assessed. METHODS: Between October 2004 and February 2010, 71 patients were treated using cerebral revascularization surgeries on 98 sides of the head. The relationship between wound complications and operative technique was retrospectively assessed. Multivariate logistic regression analysis was performed to identify the risk factors of wound complication, including operative technique, age, sex, diabetes mellitus (DM), hypertension, hyperlipidemia, and smoking history. RESULTS: In total, there were 21 (21.4%) operative wound complications. Of these 21 complications, there were 14 (66.7%) minor complications and 7 (33.3%) major complications. No statistically significant relationship was found between wound complications and any surgical procedure. A trend toward severer complications was demonstrated for the procedures that used both STA branches ("double" procedures) in comparison with the procedures that used only 1 STA branch ("single" procedures, p=0.016, Cochran-Armitage trend test). Multivariate logistic regression analysis also revealed that double procedures demonstrated a significantly higher incidence of wound complications than single procedures (OR 3.087, p=0.048). DM was found to be a risk factor for wound complication (OR 9.42, p=0.02), but age, sex, hypertension, and hyperlipidemia were not associated with the incidence of complications. Even though the blood supply to the scalp is abundant due to 5 arteriovenous systems, sometimes cutaneous necrosis develops after intracranial revascularization surgeries. The galeal blood supply is thought to be crucial for preventing wound-related complications. Special care is also thought to be required for DM patients. CONCLUSIONS: Revascularization surgeries seemed to demonstrate a higher risk of wound-related complications. Double-type procedures, which use both branches of the STA, and a history of DM were found to be risk factors for wound-related complications. Attention should be paid to the design of the galeal incision and vessel harvest line. Also, special attention should be paid to patients with DM.

Clinical features and surgical efficacy of moyamoya syndrome in children / 中国脑血管病杂志

Objective Toinvestigatetheclinicalfeaturesandsurgicalprognosisofmoyamoya syndromeinchildren.Methods Theclinicaldataof12childrenwithmoyamoyasyndromeadmittedto the 307th Hospital of People′s Liberation Army from December 2002 to October 2013 were analyzed retrospectively. Eleven of them underwent encephalo-duro-arterio-synangiosis (EDAS). A total of 550 children with moyamoya disease in the same period were used as a control group. The clinical characteristics and surgical efficacy of the children with moyamoya syndrome were summarized and concluded by comparing the clinical data of the two groups,including sex,age of onset,initial symptom,progress symptoms, Suzukiinstallments,imagingfeatures,andsurgicalefficacy.Results Themaleandfemaleratioof the children with moyamoya syndrome was 1∶2. Their mean age of onset was 12 ± 5 years old. There were significant differences in the initial symptom (cerebral infarction and cerebral hemorrhage )and disease progress between the children with moyamoya syndrome group and the control group (5/12 vs. 14. 5%[80/550], 3/12 vs. 61. 8%[340/550],and 5/12 vs. 8.7%[48/550],respectively;all P<0. 05). Within the follow-up period,of the 11 children underwent EDAS,7 cases had no further attack,and 4 cases were improved significantly. There was significant difference in the modified Rankin scale (mRS)between the beforeandaftersurgery(0[0,1]vs.2[1,2];P<0.05).Conclusions Theclinicalfeaturesofthe children with moyamoya syndrome have some differences with those with moyamoya disease. Timely and effective EDAS treatment may effectively prevent disease progression and improve the prognosis of patients.

Effective surgical revascularization improves cerebral hemodynamics and resolves headache in pediatric Moyamoya disease.

BACKGROUND: Headache is one of the major clinical presentations in pediatric Moyamoya disease. However, the clinical features and underlying mechanisms are not fully understood. This study aimed to clarify the clinical feature of headache in pediatric Moyamoya disease and the effect of surgical revascularization. METHODS: This study included 29 pediatric patients who underwent superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect bypass for Moyamoya disease. Their medical records were precisely evaluated to identify the clinical features of their headache. The findings on magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography also were analyzed. RESULTS: Preoperative headache was documented in 11 (38%) of 29 patients. The majority of them complained of severe headache in the frontal or temporal region in the morning. Headache was significantly related to more advanced disease stage and to the decreases in cerebral blood flow and its reactivity to acetazolamide. Surgical revascularization completely resolved headache in all 11 patients. CONCLUSIONS: These findings strongly suggest that disturbed cerebral hemodynamics may play key roles in developing severe headache in pediatric Moyamoya disease. STA-MCA anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis may be effective procedures to rapidly resolve headache by widely supplying collateral blood flow to the operated hemispheres.

The Role of Basic Fibroblast Growth Factor in Moyamoya Disease

OBJECTIVES AND OMPORTANCE: The present study investigated the levels of basic fibroblast growth factor(bFGF) in the CSF of patients with moyamoya disease and its clinical significance. METHODS: The levels of bFGF in CSF, taken from 26 hemispheres of 14 moyamoya patients and 20 patients without vascular anomaly(control group), were measured by an enzyme-linked immunosorbent assay. We analyzed the correlation between the level of bFGF and the clinical factors such as age, onset pattern, development of neovascularization, and cerebral circulation. RESULTS: The CSF of moyamoya patients contained a high concentration of bFGF to a significant extent. The bFGF level was apparently elevated in the patients in whom neovascularization from indirect revascularization, such as modified encephalo-duro-arterio-synangiosis(EDAS) was well developed. A linear correlation between the values of bFGF and clinical progression was noted. CONCLUSIONS: The elevation of bFGF in moyamoya disease seems to be specific. Clinically, the bFGF level may be considered a useful indicator to predict the efficacy of indirect revascularization.

Two Operative Cases of Moya Moya Disease in Children

The treatment of moya moya disease, a chronic occlusive cerebrovascular disease of unknown etiology, isn't settled ut various operative methods to maximize cerebral revascularization have been reported. Two cases in children treated surgically are presented, one with cerebroarteriosynangiosis and the other with encephalo-duro-arterio-synangiosis(EDAS). The methods of cerebral revascularization are discussed in detail.

Treatment of Cerebral Rete Mirabile in Children by Encephalo-duro-arterio-synangiosis: Report of Two Operative Cases

Cerebral rete mirabile is a unusual form of chronic cerebrovascular occlusive disease characterized usually by bilateral stenosis of distal internal carotid arteries and their vicinity, by a hazy network of collateral circulation at the base of brain called moyamoya vessels and clinically by recurring hemispheric ischemic attack in children. We have reported here 2 cases of cerebral rete mirabile in children and performed newly developed operative procedure which we think is an ideal surgical method for treatment of this disease in children and is compared with other surgical treatment.