Indirect Revascularization Procedures Research Articles

The Potential Role of Preoperative Posterior Cerebral Artery Involvement in Predicting Postoperative Transient Neurological Deficits and Ischemic Stroke After Indirect Revascularization in Patients With Moyamoya Disease

ObjectiveTransient neurological deficits (TNDs) are known to develop after direct bypass for moyamoya disease (MMD) and may be risk factors for subsequent stroke. However, the factors involved in the development of TNDs and stroke after indirect revascularization alone, including their association with subsequent stroke, remain unclear. The purpose of this study was to investigate this issue. MethodsThe subjects of the study were 30 patients with MMD who underwent a total of 40 indirect revascularization procedures at our institution. Clinical and radiological data were collected retrospectively. To examine factors associated with the development of postoperative TND/stroke/asymptomatic disease, the clinical characteristics of each group were statistically compared. ResultsThe mean age at surgery was 7 years (range 1-63). TNDs developed after surgery in 9 out of 40 patients (22.5%). Stroke in the acute postoperative period occurred in 3 patients (7.5%), all of whom experienced cerebral infarctions. Demographic data and preoperative clinical information were not different between the groups. However, posterior cerebral artery (PCA) involvement on preoperative imaging was significantly associated with the development of TNDs and stroke (p=0.006). Furthermore, postoperative stroke was associated with unfavorable outcomes (p=0.025). ConclusionsPCA involvement is significantly associated with the occurrence of TNDs. In contrast, TNDs after indirect revascularization have little relationship with the subsequent development of stroke. TNDs usually resolve without new strokes, and a better understanding of this particular pathology could help establish an optimal treatment regimen.

A novel system for evaluating collateralization of the external carotid artery after cerebral revascularization in moyamoya disease.

The objective of this retrospective study was to establish a novel system for evaluating collateralization of the external carotid artery in patients with moyamoya disease (MMD) following direct and indirect revascularization surgeries. The authors conducted a retrospective analysis of 456 patients diagnosed with MMD who underwent direct and indirect revascularization procedures at Beijing Tiantan Hospital, Capital Medical University, between January 2015 and May 2023. Using a newly proposed digital subtraction angiography (DSA)-based evaluation system, the authors assessed collateralization angiogenesis objectively and in a standardized manner. The authors' findings indicated that there was no significant difference in collateralization angiogenesis between patients undergoing direct or indirect cerebral revascularization (p = 0.702). However, after cerebral revascularization, patients with ischemic MMD exhibited significantly higher collateralization angiogenesis compared with those with hemorrhagic MMD (p = 0.007). Children with MMD demonstrated higher angiogenesis levels than adults (p < 0.001), but subgroup analysis showed age-specific variations. In adults, collateralization angiogenesis was significantly greater in those with ischemic MMD (p = 0.006), whereas in children, no significant difference was noted between ischemic and hemorrhagic MMD (p = 0.962). Furthermore, regardless of MMD type, direct and indirect revascularization methods yielded similar collateralization angiogenesis (p = 0.962 and p = 0.963, respectively). Importantly, the Matsushima grading system revealed significant differences in angiogenesis in patients with ischemic MMD (p < 0.001). The newly introduced DSA-based evaluation system offers an objective and standardized method for assessing collateralization angiogenesis in MMD. This study supports the efficacy of both direct and indirect revascularization surgical procedures and highlights distinct pathophysiological processes of ischemic and hemorrhagic disease subtypes. These findings contribute to a better understanding of surgical outcomes and aid in the selection of appropriate treatment strategies for patients with MMD.

Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using minimally invasive encephalodurosynangiosis in patients with moyamoya angiopathy

Moyamoya angiopathy (MMA) can be treated using direct, indirect, or combined revascularization procedures. We perform combined revascularization using the STA-MCA bypass and minimally invasive encephalodurosynangiosis (MIS-EDS). Due to lack of systematic analyses to date it remains unclear whether and to which extent this limited EDS serves as a growth source for extracerebral blood vessels into the brain. The objective of the current study is to characterize the extent of angiographic filling of MIS-EDS and STA-MCA bypass development over time and to determine possible predictors of EDS development in adult MMA patients. Single-center retrospective analysis of 81 MMA patients (139 hemispheres) treated with a MIS-EDS and STA-MCA bypass was performed. Angiographic images and clinical/operative data were reviewed and scored. Uni-/ and multivariate Cox regression analyses identified preoperative predictors of good EDS vascularization. At 3–6 months after surgery EDS showed moderate and high angiographic filling in 40% and 5% of hemispheres, respectively. After 12 months moderate and high filling was found in 57% and 4% of hemispheres, respectively. STA-MCA bypass filling was moderate in 47% and high in 7% of hemispheres at 3–6 months and 45% moderate and 9% high after 12 months. High STA-MCA bypass filling on angiography was a negative predictor of EDS development. MIS-EDS is a simple technique and serves as a source of vessel growth into the brain. EDS development lags behind that of STA-MCA bypass and can be recommended as an additive revascularization source when combined with a direct bypass.

Indirect Revascularization Surgery for Chronic Ischemia in Moyamoya Disease

Indirect revascularization is a surgical procedure to reduce cerebral ischemia, using subcutaneous tissues or dura mater supplied by extracranial arteries as grafts. The perfusion pressure gradient between the cortex and the graft, if present, induces arteriogenesis and develops extracranial-intracranial anastomoses to supply blood flow to the cerebral cortex underneath the graft. Therefore, it is essential to perform the craniotomy over the site of the cerebral ischemia to induce functional anastomoses. The details of the indirect revascularization procedure vary among institutes in terms of the grafts used(skin arteries, such as the superficial temporal artery; temporal muscle, galea, or pericranium), dura mater incisions(removal and replacement with the grafts, linear incision, or multiple small incisions), and the location and size of the craniotomy. Indirect revascularization is especially effective in patients with moyamoya disease because the pathophysiology of the disease itself is related to intracranial to extracranial carotid system conversion. Generally, indirect revascularization was considered ineffective in patients with atherosclerotic steno-occlusive cerebrovascular disease; however, recent clinical trials suggested that it may also be effective in these patients. If a future clinical trial demonstrates a positive outcome, indirect revascularization may become a possible treatment for atherosclerotic patients.

A RARE CASE OF SICKEL CELL DISEASE (SCD) MOYA MOYA SYNDROME : CASE REPORT

BACKGROUND: Moyamoya syndrome (MMS) is a relatively uncommon vascular complication of sickle cell disease (SCD) characterized by progressive stenosis of the supraclinoid carotid arteries and development of typical collaterals. MMS confers a signicant lifetime risk of ischemic stroke, and frequently results in multiple cerebrovascular events leading to poor outcomes. Management of MMS in this population is challenging. Ischemic stroke develops in 7% to 11% of children with homozygous sickle cell anemia (HbSS) CLINICAL DESCRIPTION: We present a case of Moyamoya syndrome disease that was detected in a 7-year-old female who presented with transient altered mental status &amp;leftsided hemiparesis. On MR angiography and further investigation, the child was diagnosed to have Moyamoya diseases with sickle cell disease. MANAGEMENT: Although there is no denitive medicaltreatment, numerous direct and indirect revascularization procedures have been used to improve the compromisedcerebral circulation, with outcomes varying according to procedure type, the treatment goal is toimprove blood ow to hypoperfused cerebral regions bysurgery. Our patient was treated conservatively and referred to a higher Centre for specic neurosurgery. Neurosurgical revascularization process leads to favorable outcome. CONCLUSION: Moyamoya disease can be diagnosed if history, physical exam and brain imaging is highly suspicious. Conventional angiography remains the gold standard for diagnosis and aids in surgical planning for patients with suspected Moyamoya disease

Value of Burr‐Hole Surgery as an Adjunct to Encephaloduroarteriosynangiosis in Treatment of Adult Moyamoya Disease: A Case Series

Background Using a single indirect revascularization technique in adult patients with moyamoya disease has been associated with inconsistent outcomes. Herein, we aimed to describe treatment outcomes following combined encephaloduroarteriosynangiosis plus burr‐hole surgery (BHS) in adult moyamoya disease. Methods Encephaloduroarteriosynangiosis combined with 1 anterior and 1 posterior burr hole per hemisphere was performed in 16 adults with moyamoya disease who presented to our center between 2013 and 2019. Patients were followed with clinical reassessments and cerebral angiograms to evaluate for neovascularization. Results Combined encephaloduroarteriosynangiosis and BHS procedures were performed on 24 hemispheres in 16 patients. Follow‐up ranged from 9 to 57 months, during which no new ischemic or hemorrhagic events, perioperative or long‐term complications, or deterioration of symptoms was observed. Follow‐up angiography showed evidence of additional neovascularization provided by the burr holes in 18 of the 24 hemispheres. Of 9 hemispheres with poor revascularization response to encephaloduroarteriosynangiosis, 5 achieved neovascularization at the burr‐hole sites. Older age, smoking, and cerebral infarction or hemorrhage on preoperative magnetic resonance imaging tended to correlate with absence of neovascularization following BHS. Conclusions BHS is a simple and safe procedure that can be done simultaneously with other indirect or direct revascularization procedures. It can provide additional neovascularization even in patients unresponsive to encephaloduroarteriosynangiosis (EDAS) and can be tailored to improve the blood flow in any vascular territory that may not be properly covered by standard revascularization procedures. We find value in adding BHS as an adjunct to other indirect or direct revascularization techniques such as encephaloduroarteriosynangiosis for treatment of adult moyamoya disease.

Long-term clinical and radiographic outcomes after pial pericranial dural revascularization: a hybrid surgical technique for treatment of anterior cerebral territory ischemia in pediatric moyamoya disease.

Isolated anterior cerebral artery (ACA) territory ischemia in pediatric moyamoya disease (MMD) is rare but has been increasingly recognized, particularly in children manifesting progression of disease in a delayed fashion after middle cerebral artery revascularization surgery. Surgical treatment is complicated by limited graft choices, with the small number of case series largely focused on complex, higher-risk operations (omental flap transfers, large interhemispheric rotational grafts); direct bypass (often untenable in children due to vessel size); or, alternatively, the technically simpler method of multiple burr holes (of limited efficacy outside of infants). Faced with the problem of a growing cohort of pediatric patients with MMD that could benefit from anterior cerebral revascularization, the authors sought to develop a solution that was specifically designed for children and that would be lower risk than the more complex approaches adapted from adult populations but more effective than simple burr holes. In this study, the authors aimed to describe the long-term clinical and radiographic outcomes of a novel approach of pial pericranial dural (PiPeD) revascularization, building on the principles of pial synangiosis but unique in using the pericranium and the dura mater as the primary vascular supply, and employing a larger craniotomy with arachnoid dissection to provide robust full-territory revascularization in all ages with reduced risk relative to more complex procedures. The medical records of all pediatric patients with MMD who presented at a single center between July 2009 and August 2019 were retrospectively reviewed to identify patients with MMD with anterior cerebral territory ischemia. Clinical characteristics, surgical indications, operative techniques, and long-term clinical and radiographic follow-up data were collected and analyzed. A total of 25 operations (5.6% of total procedures) were performed in 21 patients (mean age 9.4 years [range 1-16.5 years]; 12 female and 9 male). Almost one-third of the patients had syndromic associations, with no familial cases. Complications included 1 patient (4.7%) with a superficial infection, with no postoperative strokes, hemorrhage, seizures, or deaths. Long-term follow-up was available in 18 of 21 patients (mean 24.9 months [range 4-60 months]). Radiographic engraftment was present in 90.9% (20/22 hemispheres), and no new strokes were evident on MRI on long-term follow-up, despite radiographic progression of the disease. The use of the pericranium and the dura mater for indirect revascularization provided robust vascularized graft with great flexibility in location and high potential for engraftment, which may obviate more complex and higher-risk operations for ACA territory ischemia. Long-term follow-up demonstrated that PiPeD revascularization conferred durable, long-term radiographic and clinical protection from stroke in pediatric patients with MMD. Based on the results of the current study, the PiPeD technique can be considered an additional tool to the armamentarium of indirect revascularization procedures in select pediatric patients with MMD.

Postoperative neovascularization, cerebral hemodynamics, and clinical prognosis between combined and indirect bypass revascularization procedures in hemorrhagic moyamoya disease

ObjectiveWe evaluated what few studies emphasized the postoperative collateral formation and cerebral hemodynamics of hemorrhagic moyamoya disease (MMD). MethodsHemorrhagic MMD patients treated surgically were retrospectively collected and dichotomized into combined bypass (CB) and indirect bypass (IB) groups. CB used superficial temporal artery-to-middle cerebral artery anastomosis combined with encephaloduroarteriomyosynangiosis (STA-MCA+EDAMS), and IB used encephaloduroarteriomyosynangiosis (EDAMS) for revascularization. Postoperative complications and clinical prognosis, as well as pre- and post-operative Modified Rankin Scale (mRS), collateral circulation status, and cerebral hemodynamics were observed and compared between the CB and IB groups. ResultsA total of 37 patients with hemorrhagic MMD were identified. Of the 68 cerebral hemispheres, 47(69.1%) were combined revascularization, and the rest were indirect. During an average follow-up of 16.5 ± 8.7 months, the recurrent stroke events were significantly lower, as well as having a postoperative mRS scores≤ 2. A satisfactory postoperative collateral formation, and an improved dilation or extension of the anterior choroidal/posterior communication artery (AchA/PcoA) were significantly higher in the CB group than in the IB group (all P < .05). Compared with preoperative cerebral hemodynamics, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and relative time to peak (rTTP) in the CB group; rCBF, rCBV, and MTT in the IB group were significantly improved (all P < .001). The CB group’s postoperative rCBF was significantly improved compared with the IB group (P < .001). ConclusionsSTA-MCA bypass combined with EDAMS can obtain better postoperative collateral formation, cerebral hemodynamics, and clinical prognosis than EDAMS alone.

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate. To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations. We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere. A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P=.24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P=.007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P=.12). There was no difference in outcome (modified Rankin Scale [mRS]≥3) between the 2 cohorts (P=.92). There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.

Moyamoya Syndrome in Children with Sickle Cell Disease: A 10-Year Single-Center Experience

▪Background: Moyamoya syndrome (MMS) is a relatively uncommon vascular complication of sickle cell disease (SCD) characterized by progressive stenosis of the supraclinoid carotid arteries and development of typical collaterals. MMS confers a significant lifetime risk of ischemic stroke, and frequently results in multiple cerebrovascular events leading to poor outcomes. Management of MMS in this population is challenging, and to date no clinical trials have evaluated the long-term neurologic outcome of treatment with chronic transfusion versus surgical intervention [Encephaloduroarteriosynangiosis (EDAS) or Encephalomyoarteriosynangiosis (EMAS)]. Determination of efficacy and safety of various interventions and information about long-term progression could guide treatment decisions and potentially support the establishment of treatment guidelines. We report clinical and radiographic characteristics and neurological outcomes in children with SCD and MMS treated at our center over the last 10 years.Methods: We conducted a retrospective chart review of all patients with SCD who were diagnosed with MMS at our center from 2006 to 2016. Cases were identified utilizing radiology data mining software (MONTAGETM Search and Analytics). The radiological images and reports of potential MMS cases were independently reviewed by a hematologist, a radiologist and a neurologist to confirm the diagnosis of MMS. Relevant clinical data were collected and summarized using descriptive statistics.Results: During the study period, 542 unique patients with SCD required neuroimaging at our institution. Indications for neuroimaging included concerns for stroke, abnormal TCD, headaches or follow up imaging. Out of the 542 patients, 23 patients (4%) [18 males] were diagnosed with MMS. The median age at time of diagnosis of MMS was 6 years [Interquartile range (IQR) 4-8]. The genotype was SS in 20 patients, S-beta0 thalassemia in 2, and SC in 1. Of the 23 patients with MMS, 16 patients (70%) were diagnosed with MMS after initially presenting with a clinically overt ischemic stroke, while 7 patients (30%) were diagnosed following an abnormal or conditional surveillance Transcranial Doppler (TCD) study. MMS was bilateral in 16 patients (70%) and unilateral in the remaining 7 patients (30%). Prior to diagnosis, baseline laboratory values were (median and IQR): hemoglobin (Hb) 7.5 g/dL [IQR 6.7-8]; absolute reticulocyte count 333 k/mL [IQR 227-414]; white blood cell count 14.6 k/mL [IQR 12-18]; platelet count 371 k/mL [IQR 282-424]; total bilirubin 3.25 mg/dL [ IQR 2-4.45]; lactate dehydrogenase 522 u/L [IQR 426-862]; and HbF 6.6% [IQR 3.4-17.1]. Of the 16 patients who presented with clinically overt ischemic stroke, 11 patients (69%) experienced recurrent ischemic events (mean 2 strokes/patient). After diagnosis of MMS, 19/23 patients (82%) were started on chronic monthly transfusions aimed at maintaining HbS level below 30%. Nine patients (39%) were treated with indirect surgical revascularization procedure performed at a median of 17 months [IQR3.5-36] after MMS diagnosis. Two patients received matched sibling bone marrow transplantation. Two patients died after suffering a massive stroke.Conclusion: Children with SCD who develop MMS are at significant risk of recurrent strokes and poor neurologic outcomes. Optimal management remains unclear but should include consideration for urgent surgical revascularization procedures. The most effective treatment as well as the optimal time for revascularization procedure should be addressed by a large multi-center trial. Future studies should also evaluate mechanisms underlying MMS. DisclosuresNo relevant conflicts of interest to declare.

Encephaloduroarteriosynangiosis with Dural Inversion for Moyamoya Disease in a Pediatric and Adult Population—a Single-Center 20-Year Experience

Moyamoya disease refers to a progressive vasostenotic or vaso-occlusive disease that puts patients at risk for ischemic and/or hemorrhagic events. Surgical revascularization procedures aim to restore cerebral blood flow to mitigate stroke risk and functional decline. Direct and indirect bypass procedures have been proposed. Encephaloduroarteriosynangiosis (EDAS) with dural inversion is a well-accepted indirect procedure. Patients with moyamoya disease undergoing EDAS with dural inversion between 2000 and 2019 were retrospectively reviewed. Clinical data including short-term and long-term outcome were measured using the modified Rankin Scale. Patient satisfaction was assessed in patients with a minimum of 3 years of clinical follow-up. Over a 20-year period, 54 patients underwent 88 EDAS with dural inversion procedures. Most patients underwent bilateral surgery (34/54 patients, 63.0%). Median age at surgery was 19 years (range, 1-63 years) with a median follow-up of 6 years (range, 1-20 years). Periprocedural complications occurred in 4 of 54 patients (7.4%). Periprocedural infarction occurred in 3 of 88 operations (3.4%). Functional outcome at 90 days was favorable (modified Rankin Scale score 0-2) in 92.6% of cases. On long-term follow-up, 3 patients experienced ischemic infarction (5.6%), and 1 patient (1.9%) experienced hemorrhagic infarction. Patients' overall satisfaction with the surgical procedure at last follow-up was determined in 36 of 45 patients with at least 3 years of follow-up (response rate 80.0%). Median satisfaction was very good (score 5; range, 3-5). EDAS with dural inversion is a safe and effective indirect revascularization procedure for pediatric and adult moyamoya disease that is associated with favorable long-term outcomes and high patient satisfaction.

Surgical Outcome of Encephaloduroarteriomyosynangiosis for Moyamoya Disease.

Indirect bypass surgeries for moyamoya disease have included modifications of procedures involving placement of the superficial temporal artery on the brain pial surface. We evaluate the functional and angiographic outcomes of patients treated with encephaloduroarteriomyosynangiosis (indirect) revascularization and examine the outcome in relation to demographic and radiological factors. Patients treated surgically for moyamoya disease over a 14-year period were identified. Demographics, clinical presentation, and radiology were analyzed to assign a stage for the disease (Suzuki staging) and the extent of revascularization (Matsushima grade) at the last follow-up. A modified Rankin score was used to assess the clinical status at presentation and the functional outcome at follow-up. There were 46 patients operated on by a single surgeon over a 14-year period. A higher incidence of motor deficits, seizures, and speech deficits was seen in the pediatric population. Age, sex, preoperative Suzuki disease stage, and hemispheric involvement had no bearing on angiographic outcome at last follow-up. Three of 46 patients (6.5%) developed immediate postoperative complications. Among 43 patients on follow-up, 39 had stable disease or showed improvement in clinical symptoms with 90% event-free status at last follow-up. Indirect revascularization procedures are an effective alternative to direct cerebral revascularizations in the early or advanced stages of moyamoya disease. This is effective in a predominant ischemic presentation as noted in our series.

Moyamoya Disease: A Review of Current Literature.

Moyamoya disease (MMD) is an infrequent disease of cerebral vasculature characterized by long-standing and progressive occlusion of large intracranial arteries. It is seen predominantly in the East Asian population. Most of the cases of MMD are sporadic, but there is a small percentage that is familial. The mode of inheritance is reported to be autosomal dominant with incomplete penetrance. Studies show that the susceptibility gene of MMD is located on chromosome 17. The clinical presentation is variable and is influenced by the age and geographic region of the patient. Children mainly present with ischemia-related neurologic episodes whereas MMD in adults can manifest as either an ischemic event or an intracranial hemorrhage (ICH). The gold standard investigation for diagnosis is cerebral angiography which reveals a smoky appearance of arteries at the base of the skull, thus granting the disease its name. The treatment is mostly surgical and includes direct and indirect revascularization procedures, which prevent the recurrence of both ischemic and hemorrhagic strokes. However, combination revascularization procedures are now on the rise due to studies showing better long-term outcomes. The aim of the article is to critically analyze the current literature and updates on various aspects of MMD including, but not limited to, etiology, diagnosis, and treatment.

Abstract TP487: Comprehensive Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients

Background: Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive occlusion of the internal carotid arteries leading to ischemic and hemorrhagic events. The underlying pathogenesis of MMD remains unclear. In this study we investigated key secreted molecules in the cerebrospinal fluid (CSF) of MMD patients including relation to the extent of neovascularization and eventual functional outcomes. Methods: This study included intraoperative CSF collected from 32 controls (Chiari malformation and cranial nerve hyperactive syndromes) and 73 MMD patients (ischemic: 39; hemorrhagic: 34) that underwent combined direct and indirect superficial temporal artery-middle cerebral artery revascularization procedure. 62 factors were analyzed using multiplex luminex assay, including angiogenic growth factors, cytokines, and chemokines. Cellular retinoic acid binding protein (CRBP1) was also measured using ELISA. Functional outcome was assessed using the modified Rankin scale score (mRS). Matsushima criteria was used for grading the neovascularization. Results: Forty molecules were significantly elevated in both MMD subtypes in comparison with controls. The common top highly secreted CSF proteins included platelet-derived growth factor bb, chemokine ligand 5 and plasminogen activator inhibitor 1 (p&lt;0.001). CRBP1 and other growth factors such as brain-derived nerve growth factor and basic fibroblast growth factor were also elevated in both MMD subtypes (p&lt;0.01). Our results also revealed a number of proteins not previously reported in MMD. Ingenuity pathway analysis indicated that the ischemic and hemorrhagic MMD subtypes exhibited similar cellular/molecular functions and pathways including cellular activation, migration and inflammatory response. Interestingly, while neuro-inflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors PPAR and LXR/RXR signaling were inhibited. Conclusions: CSF analysis revealed that a number of cytokines, chemokines and growth factors are elevated in both MMD subtypes. These molecules potentially contribute to the pathogenesis of MMD and could be potential future therapeutic targets.

Clinical and Imaging Outcomes After Combined Direct and Indirect Bypass for Pediatric Moyamoya Disease: A Single Center Retrospective Series

Abstract INTRODUCTION Moyamoya disease is a progressive cerebrovascular arteriopathy of unknown etiology, causing narrowing and eventual occlusion of the internal carotid arteries and their branches. Surgical revascularization is a key component of the overall treatment strategy. The goal of this study was to determine outcomes and complications related to direct vascular bypass in a pediatric cohort with Moyamoya disease. METHODS All pediatric patients (&lt;18 yr of age) treated with direct bypass combined with encephalomyosynangiosis between 2006 and 2017 at the authors’ institution were included in the cohort. Demographic features, treatment, and outcomes were determined retrospectively from clinical reports available through the electronic medical record. RESULTS A total of 18 patients (11 females and 7 males) underwent 32 bypass procedures with a median follow-up of 2.2 yr (range 22 d 8.6 yr). Mean age at operation was 8.3 yr (range 1.4-16.9 yr). Preoperative Suzuki stage 1, 2, 3, 4, and 5 were seen in 2, 7, 7, 12, and 4 hemispheres, respectively. By last follow-up, 3 patients had evidence of new clinical ischemic stroke, all occurring within 30 d of surgery. Favorable outcomes (pediatric modified Rankin scores 0-2) at last follow-up were seen in 15 patients (83.3%). There was 1 death in the cohort due to gastrointestinal bleeding related to underlying medical comorbidities. On review of imaging at last follow-up for surviving patients, 29 of 30 direct arterial bypasses were patent; 12 and 5 patients had stable and worse imaging findings, respectively, when compared to immediate postoperative scans. CONCLUSION Combined direct and indirect revascularization procedures may be successfully applied to pediatric patients with Moyamoya disease of all age groups. The direct bypass component provides immediate revascularization and is associated with high rates of patency on follow-up imaging.

Improving Indirect Revascularization for Effective Treatment of Adult Moyamoya Disease: A Prospective Clinical, Cerebral Angiographic, and Perfusion Study

Indirect revascularization is simple and safe, but it is not commonly used in adult moyamoya disease owing to its unreliable effect. This prospective study aimed to evaluate the effectiveness of indirect revascularization in treating adult moyamoya disease after refinement of the surgical technique and perioperative care. Adult patients who underwent indirect revascularization as the primary treatment for moyamoya disease between November 2013 and January 2017 were studied. The indirect revascularization procedures included encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis in the temporal region and encephalo-pericranio-synangiosis in other hypoperfusion areas. The preoperative and postoperative clinical conditions, cerebral angiography findings, and time-to-peak prolongation areas on magnetic resonance perfusion studies were assessed to evaluate the revascularization effect. Refinements of the surgical technique included the selection of surgical area based on perfusion imaging, craniotomy size, and number of affected hemispheres, along with the inclusion of a dural flap in every procedure. Nineteen patients (17 females and 2 males), and a total of 31 cerebral hemispheres, were included. The mean patient age was 32.7 ± 11.4 years. After a mean follow-up of 38.6 ± 11.5 months, all patients showed clinical improvement or stabilization. Available postoperative angiography demonstrated Matsushima grade A or B in 19 of 21 hemispheres. The mean time-to-peak prolongation index of all 31 hemispheres improved from 24.09 ± 9.83% preoperatively to 12.82 ± 6.75% at 3-6 months after surgery (P < 0.001). The complication rate was 12.9%, and all complications were transient. With refinements of surgical techniques and perioperative care, indirect revascularization is more reliable and can be a viable alternative treatment for adult moyamoya disease. In our cohort, outcomes were satisfactory, with mean 38.6-month follow-up.

Risk Factors Associated with Neurologic Deterioration After Combined Direct and Indirect Revascularization in Patients with Moyamoya Disease on the East Coast of China

Neurologic deterioration is the primary distinctive complication after revascularization surgery in patients with moyamoya disease (MMD). The present study investigated the risk factors for neurologic deterioration after combined direct and indirect revascularization in patients with MMD. A retrospective review of 123 patients with MMD undergoing 138 combined direct and indirect revascularization procedures was performed. Demographics, clinical manifestation, medical history, neurologic deterioration complications, and relevant information of the operation were recorded. There were 25 (18.12%) postoperative neurologic deterioration complications (13 reversible neurologic deficits, 9 infarctions with neurologic sequelae, and 3 hemorrhages). Preoperative multiple symptom episodes and one-staged bilateral revascularization were significantly correlated with postoperative neurologic deterioration complications (P < 0.05 and P < 0.01, respectively). The incidence rate (26.39%) of postoperative neurologic deterioration in ischemic MMDs was significantly greater than hemorrhagic MMDs (7.69%; P < 0.01) In total, 34.78% of patients with transient ischemic attack onset and 22.45% of patients with infarction onset suffered from postoperative neurologic deterioration, and there was no significant difference between them (P > 0.05). Postoperative neurologic deterioration complications had no significant correlation with sex, age at the time of surgery, type of surgical procedure, unilateral MMD or not, interval between the last attack and operation, and history of thyroid disease, hypertension, and autoimmune disease. Preoperative multiple symptom episodes and one-staged bilateral revascularization are risk factors associated with postoperative neurologic deterioration in patients with MMD. Therefore, 2 unilateral revascularization procedures performed successively rather than one-staged bilateral revascularization procedures should be performed in patients with bilateral MMD.

Color Doppler ultrasonography as an alternative tool for postoperative evaluation of collaterals after indirect revascularization surgery in Moyamoya disease.

The cerebral hypoperfusion caused by chronic progressive stenosis or occlusion of intracranial arteries in moyamoya disease can be treated by direct bypass or indirect revascularization procedures. The extent of collaterals from the external carotid artery (ECA) after indirect revascularization surgery is the key point of angiographic follow-up, and the invasiveness of angiography impelled us to investigate the role of ultrasonography in the evaluation of collaterals. We hypothesized that the collaterals shown on angiography might produce corresponding hemodynamic changes in color Doppler ultrasonography. We prospectively recruited moyamoya patients who underwent indirect revascularization surgery and received both preoperative and postoperative angiography and color Doppler ultrasound studies. The collaterals on angiography were graded according to Matsushima method. A total of 21 patients (age, 17 ± 10.2 years) with 24 operated hemispheres were enrolled. Patients who showed better collateral establishment by angiography had higher end-diastolic velocity (EDV), lower resistance index (RI), and larger flow volume in the superficial temporal artery (STA) and ECA (all p < 0.05). In STA, increase of EDV greater than 13.5 cm/sec or reduction of RI greater than 0.19 after operation corresponded to 94% of Matsushima grade A+B. In ECA, post-operative EDV greater than 22 cm/sec or increase of EDV greater than 6.4 cm/sec also corresponded to 94% of Matsushima grade A+B. Our findings revealed potential roles of color Doppler ultrasonography in identifying patients with poor collaterals after indirect revascularization procedures.

Clinical presentation, progression, and treatment outcomes of moyamoya disease in the elderly.

Moyamoya disease is a vascular disorder characterized by progressive stenosis of the internal carotid artery. The presentation, progression, treatment options, and post-operative clinical outcomes for elderly (60 and older) Moyamoya patients have never been reported. A retrospective analysis of all patients who were diagnosed with Moyamoya disease by the senior authors between 1991 and 2016 was performed. Patients who were 60years or older at the time of surgery or last follow-up were further evaluated. Seventy patients were diagnosed with probable or definite Moyamoya disease during the study period (1991-2016). Eight patients (11.4 %; six females: two males; median age 63; range, 60-71 years) were found to be 60years or older at the time of surgery or last follow-up and were included in the study. All patients had a modified Rankin scale (mRS) of either one or two (median 1) pre-operatively. Six patients (75%) underwent surgical treatment on a total on seven hemispheres. Post-surgery, one patient had an improved mRS score, three had no changes, and two had worsening in their mRS scores. Both patients who did not undergo surgical interventions suffered from intra-parenchymal hemorrhages post-diagnosis. Moyamoya disease is most commonly seen in young and middle-aged patients. Presentation in the elderly (defined as 60years and older in this study) is rare, and has never been reported in the literature. In this study, both direct and indirect revascularization procedures demonstrated potential benefit in some of these patients, with stabilization of progressive symptoms.

Long-term follow-up of pediatric moyamoya disease treated by combined direct-indirect revascularization surgery: single institute experience with surgical and perioperative management.

Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that mainly presents in children as cerebral ischemia. Prompt treatment with either a direct or indirect revascularization procedure is necessary for children with MMD in order to prevent repeated ischemic events. We herein present our experience with combined direct and indirect bypass surgery for the treatment of pediatric MMD as well as our uniquely designed perioperative protocol. Twenty-three patients with MMD, aged between 2 and 16years old (mean 9.36), underwent 38 combined bypass procedures between 2008 and 2015. All patients underwent single superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis combined with encephalo-duro-myo-synangiosis (EDMS). The perioperative management protocol was stratified into two unique eras: the first era with normotensive care and the second era with strict blood pressure control (systolic 100-130mmHg) and routine aspirin administration. Patients were followed after surgery for a period ranging between 3 and 131months (mean 77months) in yearly clinical and radiological follow-ups. Three postoperative complications were observed: two cases of cerebral hyperperfusion (2/38, 5.3%) and one case of perioperative minor stroke (1/38, 2.6%), two of which were in the first era. No strokes, either ischemic or hemorrhagic, were observed in the follow-up period, and the activity of daily living as shown by the modified Rankin Scale improved in 20 patients, with no deterioration being observed in any of our patients. STA-MCA bypass with EDMS is safe and effective for the management of pediatric MMD and provides long-term favorable outcomes. Perioperative care with blood pressure control combined with the administration of aspirin may reduce the potential risk of surgical complications.