Hao Jiang, Michael Schiraldi, and Nestor R. Gonzalez
Encephalo-duro-arterio-synangiosis (EDAS) is a form of indirect bypass revascularization that was initially developed for the treatment of pediatric patients with moya- moya disease, but its application has now extended to adults. Although selection bias and lack of equipoise limit side-to-side comparisons with direct bypass, several clinical studies have shown that EDAS is a durable procedure, with excellent outcomes and low complication rates in adults with moyamoya disease. Scrupulous surgical technique is a key contributor for successful EDAS. In addition, judicious perioperative care is also crucial to prevent perioperative ischemia. Here, we systemically describe the EDAS technique, including its indications, surgical steps, operative challenges, surgical pearls of management, complications, and salvage maneuvers. Additionally, we present detailed EDAS-specific anesthesia and postoperative management protocols important in guaranteeing the success of the procedure.
Keywords: encephalo-duro-arterio-synangiosis (EDAS), adults, intracranial arterial steno-occlusive disorders, perioperative management and postoperative care, antiplatelets
Surgical approaches with direct external carotid to internal carotid bypass operations to treat moyamoya patients were introduced in the early 1970s by Kikuchi and Karasawa1 in Japan and Krayenbuhl2 in Europe with the intention of providing additional blood supply to hypo- perfused vascular territories. Despite initial successes with this technique, a direct bypass depends on patency and suitability of both donor and recipient vessels. In moyamoya patients, often the recipient or donor arteries are either small or fragile and pose significant challenges for direct vasculary anastomosis; this is true in pediatric as well as adult patients. In 1964, Tsubokawa et al, reported successful cerebral revascularization in a 6-year- old female patient with use of a dural autograft containing the middle meningeal artery (MMA). Almost a decade later, Ausman et al reported the development of spontaneous anastomotic connections between the scalp and the cortical surface following direct superficial temporal artery (STA) to middle cerebral artery (MCA) bypass. Subsequent attempts at revascularization without a direct anastomosis led to the development of the encephaloduro-arterio-synangiosis (EDAS) technique for the treatment of pediatric patients with moyamoya disease published by Matsushima et al in 1979. In 1980, Spetzler et al3 were the first to report an “alternative method” for revascularization of the MCA, in which the STA was sutured to the cortical arachnoid in adults “in whom no adequate cortical recipient could be found.” Subsequent angiography demonstrated neovascularization and the patient remained neurologically intact postoperatively. Since then, numerous authors4-8 have reported good clinical results with the use of EDAS in adults with moyamoya.
7.1.1 Literature Support for the Use of EDAS in Adults
Although a paucity of literature comparing EDAS with direct bypass surgery exists, this technique has frequently been employed when the conditions do not permit a direct arterial anastomosis.7,9 Thus, selection bias and lack of equipoise remain hurdles when comparing EDAS with direct bypass. Nevertheless, a literature search using the query “moyamoya disease AND surgery AND adult” yielded 646 references published between November 1971 and February 2015. Twenty-two of these references were clinical trials, of which 20 provided clinical outcome information; none were randomized.9-25 A total of 1,862 patients were included in these 20 studies. Of all patients, 603 (32.4%) had a direct bypass, 814 (43.7%) had indirect revascularization, and 445 (23.9%) patients underwent combined procedures. An overview of these 20 studies appears in Table 7.1. Overall, the clinical outcomes indicate that both forms of surgical revascularization produce durable good outcomes, at least when performed in experienced centers. Interestingly, 4 of the 20 studies were performed with the intention of comparing direct bypass with indirect revascularization, but none showed statistically significant differences. The value of other studies is limited by utilization of perfusion imaging as an outcome measure, a diagnostic modality which lacks consistent correlation with clinical results. Until better surrogate markers are found, lack of postoperative ischemic stroke is the most adequate outcome to evaluate.
EDAS surgery is indicated for the management of all adult patients with intracranial arterial steno-occlusive disorders who present with symptoms of transient ischemic attack (TIA) or stroke in the territory of the affected vessel despite optimal medical management with antiplatelet agents. In our institution, and in a large number of centers in the United States, EDAS is the first choice of revascularization for any patient with intracranial arterial steno-occlusive disorders. For patients who have suffered stroke to be eligible for surgery, they need to have either functional independence (modified ranking scale <3) or perfusion studies demonstrating tissue at risk for further ischemic damage in the territory of the stenoses. The diagnoses of the steno-occlusive disorder for which EDAS is indicated include:
• Moyamoya disease defined as bilateral stenoses of the terminal internal carotid artery and proximal anterior cerebral artery (ACA) or MCA, with different degrees of angiographically evident lenticulostriate, leptomeningeal, or dural collaterals, in patients without risk factors for intracranial atherosclerosis, vascular dissection, or vasculitis.
• Probable moyamoya disease defined as unilateral findings suggestive of moyamoya—as described above— in patients without risk factors for intracranial atherosclerosis, vascular dissection, or vasculitis.
• Intracranial atherosclerosis defined as intracranial arterial disease with evidence of vessel wall calcification plus atherosclerotic risk factors, including history of hypertension, dyslipidemia, diabetes mellitus, smoking, and/or coronary or peripheral vascular atherosclerotic disease, failing intensive medical management with antiplatelets, statins, and risk factor reduction may benefit also from indirect EDAS revascularization.5
Table 7.1 Studies on the use of EDAS in adults
Candidate patients for EDAS surgery are at risk for stoke during the perioperative period, both in the vascular territory to be treated and the contralateral hemisphere, if there is bilateral involvement. To reduce the risk of ischemic events associated with artery-to-artery embolisms, we recommend performing the operation under continuous antiplatelet therapy with aspirin. To reduce the risk of ischemia due to hypoperfusion, strict management of the patient’s blood pressure and fluid balance status must be maintained.
A successful EDAS is most dependent on scrupulous surgical technique. As the patients continue antiplatelet therapy throughout the procedure, meticulous hemostasis needs to be achieved while balancing avoidance of excessive cauterization of the arterial cuff, dura mater, or any other tissue that is used as a donor angiogenesis. Fastidious surgical technique can further minimize vasospasm and tissue injury, thus preventing intra- and postoperative complications. Finally, to facilitate the desired intracranial angiogenesis, donor arteries are positioned and fixed in close proximity to the pial surface while avoiding excessive arterial cuffs, tissue injuries, or bleeding.
As patients remain at risk for untoward events during and after surgery, the intraoperative anesthesia and postoperative critical care management are crucial to prevent stroke in adults undergoing EDAS. A detailed description of the anesthesia management is provided elsewhere.29 In brief, the goals of management include strict control of: (1) blood pressure, (2) fluid balance, (3) cerebral vascular reactivity, (4) platelet aggregation, (5) hematocrit, and (6) oxygenation. Some aspects of this management can seem unusual for a standard neurosurgical case; particularly the need to maintain a sufficiently high blood pressure at all times to avoid cerebral hypoperfusion in the territory of the stenosis may be overlooked with devastating consequences. Close coordination between the anesthesiologist and surgeon is therefore indispensable.
It is important to keep in mind that the surgery itself merely provides the starting point for revascularization, which may take several weeks to occur. Consequently, the perioperative care requires as much diligence as the surgical procedure. This includes continued adherence to anesthesia management goals in the immediate postoperative period until a stable and sufficient systolic blood pressure is reached. Thereafter, continued adherence to strict medical management is the key to obtain good clinical outcomes in adult patients undergoing EDAS.
• No ischemia time to perform anastomosis.
• Avoids manipulation of diseased arterial walls.
• Does not induce sudden hyperemia (reducing hemorrhage risk).
• Shorter surgical time than bypass.
• Revascularization occurs where needed.
• Prevents competing flow with stenotic segment (reducing proximal thrombosis).
• There is no immediate improvement in cerebral perfusion.
• The process of neovascularization depends on individual ability to generate new vessels.
• Mainly produces neovascularization in the MCA but not ACA territory.
• Clinical outcomes do not correlate with surrogate current imaging markers.
• Manipulation of the individual angiogenic response may reduce the time necessary for neovascularization.
• The magnitude of neovascularization could also be regulated.
• Similar procedures with equivalent donors could be developed for ACA territory.
• Improvement of imaging tests may be more accurate to define physiologic impact.
• Surgeons may feel that a scrupulous surgical approach is not necessary if they view EDAS as technically simpler than direct bypass.
• EDAS requirements contradict instinctive operative management by most anesthesiologists.
• The success of the technique goes beyond surgeon control into anesthesiology, critical care, nursing, and support staff involvement.
EDAS surgery is contraindicated for patients with completed strokes of the vascular territory of the involved artery, as in those patients no brain tissue can be salvaged or protected, and no expected benefits justify the risk of surgery. The same is true for patients with disabling strokes who do not have tissue at risk for further ischemic damage in the territory of the vascular stenosis. Furthermore, continued intensive medical management including antiplatelet therapy is necessary to prevent strokes due to the delayed revascularization following surgery. A foreseeable discontinuation of such medical management during and/or after surgery should therefore be considered a contraindication, as it acutely increases the risk of stroke and outweighs the potential benefits of the procedure.
In patients that are nonresponders to antiplatelet therapy with acetylsalicylic acid (ASA) and thus require Plavix or other agents, hemostasis is more difficult and the risk to benefit ratio must be considered carefully. A similar increased risk to benefit ratio is true in patients with innate presence of dural or STA collaterals that may be disturbed with the operation. Disruption of those collaterals may not in every case result in hypoperfusion and stroke, but leaves the patient at increased risk for these events before new vessels are formed. As EDAS results in the forming of new vessels with a consequent delay of increased perfusion, a complete occlusion or a lack of forward flow from collaterals into the distal vascular territory may not benefit in time from this procedure. In those cases, a direct bypass should be considered. The role of EDAS for hemorrhagic moyamoya is unknown, but one could argue that while preventing hyperemia which a bypass induces, the need for increased flow through the native collaterals will decrease as well, theoretically reducing the shear stress on those vessels and risk of rupture.18
7.5.3 Not Contraindications
Within sensible limits, advanced age is not a contraindication to EDAS surgery. Compared to direct bypass techniques, EDAS may reduce surgical risk in elderly and sick patients. However, the need for continuous intensive medical therapy, the consistent use of pressures during the operative and postoperative period with associated cardiac demand, the stress of the surgery itself, and the potentially delayed wound healing in the scalp due to the reduced blood supply should be considered when evaluating patients for EDAS.
While EDAS classically includes the intracranial rerouting of the STA, an absence or suboptimal appearance of this vessel on angiography is not a contraindication. That is, the STA might not be visible during angiography due to vasoconstriction but still suitable for EDAS, or the MMA might be used instead.14'18
7.6.1 Care Beyond the Surgical Field
As indicated above, scrupulous intra- and postoperative management are the key to ensure successful outcomes. Such management should adhere to the following 11 specific intra- and postoperative management rules:
1. ASA always: aspirin, 81 to 325 mg the date of the surgery and for at least 3 days before the procedure.
2. Strict blood pressure (BP) goal: established in the clinic prior to surgery and defined as the average of three systolic blood pressure (SBP) measures at which the patient does not have symptoms. BP is managed with intravenous continuous infusions for rapid correction. Avoid pro re nata (prn) orders.
• Minimum operative SBP = baseline (asymptomatic) SBP.
• Maximum SBP goal is set at 200 mm Hg.
3. Strict CO2 goal: avoid hyperventilation. End tidal CO2 is kept between 35 and 45 mm Hg.
4. Seizure prophylaxis: administer 20 mg/kg phenytoin (slow infusion over 60 min).
5. Mannitol should not be administered before or during the procedure.
6. Steroids are not necessary during the procedure with the exception of a small dose of dexamethasone for nausea reduction. Their anti-inflammatory effects may hinder the process of angiogenesis required to form the new vessel connections to the intracranial circulation.
7. Strict hematocrit goal: greater than or equal to 30% and less than or equal to 50%.
8. Strict intra- and immediate postoperative monitoring: arterial catheter placed prior to induction of anesthesia and central venous catheter.
9. Strict fluid management: target euvolemia to 1.5 L hypervolemia. The patient should receive intravenous fluids to replace the calculated preoperative fluid balance deficit before the initiation of the surgery.
10. Systemic hypothermia and/or barbiturates are not routinely used.
11. Target temperature is normothermia.
EDAS surgery has low morbidity and mortality in adults. Based on our own published data, the risks and possible complications are5:
• Failure of the procedure to protect from stroke at 3 years (< 1%).
• Failure of the procedure to protect from persistent TIA at 3 years (< 2%).
• Seizures (3%).
• Wound dehiscence (3%).
• Mortality, intraoperative, or within 30 days from surgery. (We have not had operative deaths in more than 110 operations. In the consent, we include a statement for a general risk of death of less than 1%.)
7.8.1 Specific Consideration with Anticoagulation
The patient is required to be on ASA (81-325 mg daily) as well as has to respond to ASA to be eligible for the treatment. If the patient is receiving other antiplatelet or anticoagulation agents, they are transitioned to ASA 7 to 10 days before the surgery. The EDAS surgery itself is performed while the patient receives full dose of ASA, which is to be continued postoperatively. If the patient cannot tolerate oral medications immediately after the surgery for more than 24 hours, ASA is administered rectally. Similarly, if a patient vomits within 1 hour of an ASA dose, rectal ASA is administered. In addition to ASA, patients receive standard deep venous thrombosis prophylaxis with subcutaneous heparin during and after surgery.
7.9.1 Patient Position with Skin Incision
• Patient is positioned with the operative side of the head up.
• Elevate the ipsilateral shoulder 45 degrees to avoid excessive head rotation.
• The hair on the side of the operation is clipped to allow for at least 2 cm of hair-free area around any surgical incision.
• No local anesthetic injections should be used as this introduces a potential source of damage to the STA.
• The skin of the scalp is cleaned with at least two scrubs of chlorhexidine or iodine before marking the incision. Do not use the brush part of the scrub sponges.
• Using the portable Doppler and a sterile-tip skin marking pen, the STA is marked in short intervals (Fig. 7.1). The artery should be identified for a length of approximately 10 to 15 cm. In practice, several sterile-tip marking pens will be needed due to the required ultrasound gel. This step is the key for successful rapid dissection of the artery, and every effort is made to mark the artery with precision.
• The anesthesia provider will be notified prior to placement of the Mayfield head holder pins to allow for adjustments to anesthetic depth and/or administration of medications to optimize blood pressure. Evaluate the preoperative angiogram to identify potential spontaneous collaterals from the occipital arteries. If present, it is the key to avoid injuring the artery with the frame pins.
• The three-point Mayfield head holder is placed avoiding injury of the STA, the occipital after and avoiding interference with the operative field.
• The head is positioned above the level of the heart, maintaining the STA as parallel as possible to the floor while avoiding excessive head rotation.
• The skin is prepared with iodine using sterile technique.
• The surgical field is draped in sterile fashion. Do not use staples to secure any of the drapes (Fig. 7.2).
7.10.1 STA Dissection
The STA is dissected using the operative microscope. The skin marking obtained during patient preparation indicates exactly the position of the artery, and the skin incision is performed along these markings using sharp dissection (Fig. 7.3). Incision and artery isolation are performed stepwise from proximal to distal, elongating the epidermal cut once the vessel is dissected in the segment currently exposed (Fig. 7.4). Note that from proximal to distal the artery is located increasingly superficial. Bleeding caused by the skin incision is controlled using a bipolar set at less than or equal to 20 W. Excessive cauterization of the skin edges or monopolar cauterization is avoided. After skin incision, the artery can be easily found with blunt dissection using sharp fine tip mosquitos.
During dissection of the STA, excessive coagulation of its branches is avoided and the anterior limb is preserved. Any necessary coagulation is limited to just the tip of the branches (facilitates sprouting). A small cuff of less than or equal to 2 mm is left on each side of the artery (Fig. 7.5). This reduces the length of necessary new vessels, thus optimizing the gradient of pressure necessary for the maturation of the vessels (arteriogenesis) after the neoangiogenic connection with cerebral vessels is established. Once the artery is dissected within its cuff along the length of the planned incision, it can be separated from the galea, pericranium, and temporalis fascia with sharp or low power cautery (< 6 W) through the loose areolar connective tissue.
7.10.4 Middle Meningeal Artery Preservation
The dura is opened in a cruciate fashion with four resultant flaps. Approximately along the long axis of the craniotomy, these flaps provide space for the STA to be opposed to the brain. While opening the dura, take care to protect the MMA and its branches; avoid excessive coagulation of dural bleedings (Fig. 7.8).
7.10.5 Cerebrospinal Fluid Release
After opening the dura and visualizing the arachnoid, opening of the arachnoid and gentle aspiration provides cerebrospinal fluid (CSF) release (Fig. 7.9). This serves to reduce swelling as no mannitol is used during surgery. The use of mannitol may produce a reduction of the intravascular volume, which can affect the hypoperfused territories. The arachnoid opening is carefully extended to all exposed sulci. The goal is to minimize tissue and distance between STA/MMA branches and pial surface, as well as to remove the potential barrier that the arachnoid represents.
7.10.2 STA Care and Preservation
Once the artery is dissected and mobilized, it is particularly vulnerable. Protect the artery by wrapping it in a cuff of muscle and pericranium along one side of the incision (Fig. 7.6). Do not use sharp fish-hooks on the side where the artery is located. It is highly recommended to check vessel patency with Doppler after every manipulation to immediately detect and correct arterial constriction.
Once the STA is secured and the skull exposed, an oval craniotomy is performed (Fig. 7.7). The longitudinal axis of the oval is determined by the length of exposed STA and marked by two burr holes. These two burr holes serve as the entry and exit points of the STA. During the craniotomy, protect the artery and its shielding cuff with vein retractors. Take care to protect the MMA during the elevation of the bone flap.
7.10.6 Dural Flaps Preparation and Superficial Temporal Artery Fixation
The inner layer of the dura is dissected and removed from each flap as it is fibrotic and prevents the spontaneous formation of connections between the meningeal arteries and pial intracranial vessels. Removing the inner layer of the dura increases the surface area for potential new vessels to form between the meningeal arteries and the cerebral vasculature (Fig. 7.10). Thereafter, the STA cuff is attached to the arachnoid or dura with 8 or 9-0 sutures to minimize movement of the STA and dural flaps relative to the pial surface, thus facilitating the growth of new vessels (Fig. 7.11).
7.10.7 Craniotomy Closure
It is recommended to check the blood flow within the STA regularly during the craniotomy and wound closures. Trim the burr hole openings and the inner table of the bone flap to avoid kinking and permit unrestricted passage of the STA, and avoid excessively tight closure of muscle at the STA entry point. Keep all galeal sutures held with clamps before tying them to ensure visualization of proper purchase with every stitch. Once the muscle and galea are reconstructed and the patency of the STA confirmed using Doppler, the scalp is closed (Fig. 7.12).
The success of EDAS is directly dependent on the perioperative management and close communication between surgeon, anesthesia, postoperative care team, and operating room staff. It further requires careful planning and preparation of the procedure and perioperative care. Even in highly experienced and large neurosurgical centers, a lack of such communication and planning before and during each case can result in stroke and catastrophic outcome despite a “perfect” surgery. While EDAS is a relatively safe procedure, a series of misconceptions and pitfalls should be avoided:
• EDAS is not a direct bypass, however, that does not imply it requires less attention to detail.
• Never assume that the anesthesia team knows how to handle these cases. Time communicating with anesthesia is time well spent.
• A quick, not precise skin marking of the STA is not sufficient but can cause unnecessary problems and complications while finding and dissecting the artery in patients on ASA.
• Loupes are not as good as the microscope during the dissection of the STA. A perfectly dissected STA is one key to a successful outcome.
• Leaving a large cuff around the artery is safe and convenient for direct bypass, but not suitable for EDAS as it limits the formation of new functional collaterals.
Solution (tips of management)
Dissecting the artery on the left side for right handed surgeons
Position the patient always with the head toward the right of anesthesia. This allows for a dissection from proximal to distal for right handed surgeons.
Brain swelling after dura is open in absence of Mannitol
Do not hyperventilate the patient.
Perform the arachnoid dissection and aspirate CSF.
Compression of the STA at entry and exit points
Enlarge the burr holes in the bone flap. Do not use excessive amounts of collagen sponge.
Bowing of the STA after bone flap is placed
Trim the inner layer of thick bone flaps. Create a groove on the inner table of the bone flap in the anticipated location of the STA.
Pass each stitch in each side separately and use hemostats keeping them loosely ligated until all sutures are in place.
Wound healing problems
Keep sutures for 2 to 3 weeks.
• Excessive cauterization of the arterial cuff or the dura matter may seem convenient for quick hemostasis but causes injury to the vascular stumps that yield new vessels.
• Skipping steps may save time during surgery, but results in complications or lack of success afterwards. This is particularly true for the meticulous STA dissection, the opening of the arachnoid for CSF release and exposure of the critical vessels, the dissection of the dural layers, or the suturing of the artery to the arachnoid or dura.
• Lack of attention to details during closure of galea and skin can easily result in wound dehiscence and/or compression of the STA with consequent loss of blood flow and a failed procedure.
• Use of PRNs for BP management. Delays in response to hypo- or hypertension increase the risk of bleeding or strokes in these patients.
• Failure to respond immediately to subtle postoperative neurological changes.
Precise, short cauterization with very low power often is sufficient.
Use of topical papaverine.
Take advantage of collateral flow to the STA.
Reconstruct the artery (wall suture or primary reanastomose).
Pial injury during arachnoid dissection
Mild pressure with a micro cottoned patty.
Do not coagulate.
Lack of Dopplerable pulse after closing
Confirm Doppler is functional.
Immediately reopen and correct cause.
It is better to Doppler few times after placing bone flap, closing muscle, and the skin.
Patient develops new symptoms after the surgery
Place head of the bed down, increase SBP lacing bone flap, closing mHct, check fluid balance. If no improvement after 30 minutes, activate “stroke” system.
Evidence of new stroke in imaging or no improvement of symptoms despite medical measures
Consider immediate endovascular interventions:
• Patients may develop vasospasm that responds to intra-arterial pharmacologic treatment.
• If a new occlusion of the previous stenotic vessels is seen, recombinant tissue plasminogen activator or mechanical retrieval is contraindicated after surgery.
7.14.1 Patient Surveillance
As stated, the patient remains at risk for stroke postoperatively until sufficient new blood vessels have formed, and the principles of strict anesthesia management applied intraoperatively continue during the immediate postoperative period. Therefore, without exception, the patient is monitored in the neurocritical care unit after surgery. Due to the continued risk for cerebrovascular events and bleeding, nursing staff capable of identifying subtle neurological symptoms is required. All rules of preoperative management apply as explained before. Once the patient does not require support of BP for symptom control, s/he is ready to be transferred to the regular ward. No routine diagnostic images are performed in the immediate postoperative period.
7.14.2 EDAS Functional Assessment
The primary functional assessment of EDAS is the clinical examination. Often, perfusion studies fail to show resolution of asymmetric blood flow in asymptomatic patients even after years from the surgery. In addition, traditional perfusion measurement techniques using MRI and CT do not allow for actual comparison of cerebral blood flow over time. New techniques that are not dependent on relative measures, such as arterial spin labeling might be more useful, but may not detect local flow changes. Nevertheless, overall the goal of EDAS is to keep patient symptom free.
7.14.3 EDAS Angiographic Assessment
Angiographic assessment of neovascularization after EDAS is currently the gold standard to identify new collaterals. Early angiographic studies reveal Perren Grade 3 (Extensive neovascularization) in 80% of cases, and new vessels seen as early as 1.5 months after surgery. Although neovascularization is detectable early on, we initially follow-up in our practice with clinic visits and perform an angiographic study only at six months after surgery.5
7.14.4 Advanced Imaging
For research purposes, MRI dynamic susceptibility contrast data is optimized using the functional MRI of the brain (FMRIB) tool library, and a probabilistic independent component analysis is performed (multivariate exploratory linear optimized decomposition into independent components [MELODIC], FMRIB), modeling data into three components—categorized as arterial, venous, and capillary. In a first study this approach revealed functional results that matched the anatomy observed in the angiographic assessment after surgery.30
 KJ K. STA-cortical MCA anastomosis for cerebrovascular occlusive disease. No Shinkei Geka. 1973; 1:5-15
 Krayenbuhl HA. The moyamoya syndrome and the neurosurgeon.
Surg Neurol. 1975; 4(4):353-360
 Spetzler RF, Roski RA, Kopaniky DR. Alternative superficial temporal artery to middle cerebral artery revascularization procedure. Neurosurgery. 1980; 7(5):484-487
 Dusick JR, Jr, Gonzalez NR, Martin NA. Clinical and angiographic outcomes from indirect revascularization surgery for Moyamoya disease in adults and children: a review of 63 procedures. Neurosurgery. 2011; 68(1):34-43, discussion43
 Gonzalez NR, Dusick JR, Connolly M, et al. Encephaloduroarteriosy- nangiosis for adult intracranial arterial steno-occlusive disease: longterm single-center experience with 107 operations. J Neurosurg. 2015; 123(3):654-661
 Hanggi D, Mehrkens JH, Schmid-Elsaesser R, Steiger HJ. Results of direct and indirect revascularisation for adult European patients with moyamoya angiopathy. Acta Neurochir Suppl (Wien). 2008; 103: 119-122
 Isono M, Ishii K, Kobayashi H, Kaga A, Kamida T, Fujiki M. Effects of indirect bypass surgery for occlusive cerebrovascular diseases in adults.JClin Neurosci. 2002; 9(6):644-647
 Sakamoto S, Ohba S, Shibukawa M, et al. Angiographic neovascularization after bypass surgery in moyamoya disease: our experience at Hiroshima University Hospital. Hiroshima J Med Sci. 2007; 56(3-4): 29-32
 Abla AA, Gandhoke G, Clark JC, et al. Surgical outcomes for moyamoya angiopathy at barrow neurological institute with comparison of adult indirect encephaloduroarteriosynangiosis bypass, adult direct superficial temporal artery-to-middle cerebral artery bypass, and pediatric bypass: 154 revascularization surgeries in 140 affected hemispheres. Neurosurgery. 2013; 73(3):430-439
 Agarwalla PK, Stapleton CJ, Phillips MT, Walcott BP, Venteicher AS, Ogilvy CS. Surgical outcomes following encephaloduroarteriosynan- giosis in North American adults with moyamoya. J Neurosurg. 2014; 121(6):1394-1400
 Amin-Hanjani S, Singh A, Rifai H, et al. Combined direct and indirect bypass for moyamoya: quantitative assessment of direct bypass flow over time. Neurosurgery. 2013; 73(6):962-967, discussion 967-968
 Baek HJ, Chung SY, Park MS, Kim SM, Park KS, Son HU. Preliminary study of neurocognitive dysfunction in adult moyamoya disease and improvement after superficial temporal artery-middle cerebral artery bypass. J Korean Neurosurg Soc. 2014; 56(3):188-193
 Bao XY, Duan L, Li DS, et al. Clinical features, surgical treatment and long-term outcome in adult patients with Moyamoya disease in China. Cerebrovasc Dis. 2012; 34(4):305-313
 Cho WS, Kim JE, Kim CH, et al. Long-term outcomes after combined revascularization surgery in adult moyamoya disease. Stroke. 2014; 45(10):3025-3031
 Czabanka M, Pena-Tapia P, Scharf J, et al. Characterization of direct and indirect cerebral revascularization for the treatment of European patients with moyamoya disease. Cerebrovasc Dis. 2011; 32(4):361-369
 Fujimura M, Tominaga T. Lessons learned from moyamoya disease: outcome of direct/indirect revascularization surgery for 150 affected hemispheres. Neurol Med Chir (Tokyo). 2012; 52(5):327-332
 Guzman R, Lee M, Achrol A, et al. Clinical outcome after 450 revascularization procedures for moyamoya disease. Clinical article. J Neuro- surg. 2009; 111(5):927-935
 Jiang H, Ni W, Xu B, et al. Outcome in adult patients with hemorrhagic moyamoya disease after combined extracranial-intracranial bypass. J Neurosurg. 2014; 121(5):1048-1055
 Kim DS, Huh PW, Kim HS, et al. Surgical treatment of moyamoya disease in adults: combined direct and indirect vs. indirect bypass surgery. Neurol Med Chir (Tokyo). 2012; 52(5):333-338
 Lee SB, Kim DS, Huh PW, Yoo DS, Lee TG, Cho KS. Long-term follow-up results in 142 adult patients with moyamoya disease according to management modality. Acta Neurochir (Wien). 2012; 154(7):1179-1187
 Liu X, Zhang D, Shuo W, Zhao Y, Wang R, Zhao J. Long term outcome after conservative and surgical treatment of haemorrhagic moya- moya disease. J Neurol Neurosurg Psychiatry. 2013; 84(3):258-265
 Mallory GW, Bower RS, Nwojo ME, et al. Surgical outcomes and predictors of stroke in a North American white and African American moyamoya population. Neurosurgery. 2013; 73(6):984-991, discussion 981-982
 Miyamoto S, Yoshimoto T, Hashimoto N, et al. JAM Trial Investigators. Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya Trial. Stroke. 2014; 45(5):1415-1421
 Narisawa A, Fujimura M, Tominaga T. Efficacy of the revascularization surgery for adult-onset moyamoya disease with the progression of cerebrovascular lesions. Clin Neurol Neurosurg. 2009; 111(2):123-126
 Starke RM, Komotar RJ, Hickman ZL, et al. Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article. J Neurosurg. 2009; 111(5):936-942
 Laiwalla AN, Ooi YC, Van De Wiele B, et al. Rigorous anaesthesia management protocol for patients with intracranial arterial stenosis: a prospective controlled-cohort study. BMJ Open. 2016; 6(1):e009727
 Laiwalla AN, Kurth F, Leu K, et al. Evaluation of encephaloduroarterio- synangiosis efficacy using probabilistic independent component analysis applied to dynamic susceptibility contrast perfusion MRI. AJNR Am J Neuroradiol. 2017; 38(3):507-514
 Lin N, Aronson JP, Manjila S, Smith ER, Scott RM. Treatment of Moya- moya disease in the adult population with pial synangiosis. J Neuro- surg. 2014; 120(3):612-617
 Sundaram S, Sylaja PN, Menon G, et al. Moyamoya disease: a comparison of long term outcome of conservative and surgical treatment in India.J Neurol Sci. 2014; 336(1 -2):99-102
 Mesiwala AH, Sviri G, Fatemi N, Britz GW, Newell DW. Long-term outcome of superficial temporal artery-middle cerebral artery bypass for patients with moyamoya disease in the US. Neurosurg Focus. 2008; 24(2):E15