Moyamoya disease and moyamoya syndrome: Treatment and prognosis

INTRODUCTION AND TERMINOLOGY — Moyamoya is an uncommon cerebrovascular condition characterized by progressive narrowing of large intracranial arteries and the secondary development of prominent small vessel collaterals. These collateral vessels produce a characteristic smoky appearance on angiography, which was first called "moyamoya," a Japanese word meaning puffy, obscure, or hazy like a puff of smoke in the air.

Moyamoya, or moyamoya vasculopathy, refers to the characteristic vascular findings. The term moyamoya disease (MMD) is used when the condition is idiopathic and not associated with another disease or due to a genetic susceptibility; moyamoya syndrome (MMS) is used when vascular findings occur in the presence of an associated condition, such as sickle cell disease. MMD or MMS may lead to ischemic stroke or intracranial hemorrhage in children and adults.

This topic will review the treatment and prognosis of moyamoya. The etiologies, clinical features, and diagnosis of MMD and MMS are discussed separately. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis".)

SUPPORTIVE MANAGEMENT FOR ALL PATIENTS — Moyamoya is a progressive intracranial vasculopathy that can lead to neurologic complications due to impaired cerebral circulation, including ischemic stroke and intracranial hemorrhage. There is no curative treatment for moyamoya. However, supportive management may reduce the risk of complications, and imaging surveillance can help to identify patients who are at highest risk for future ischemic and hemorrhagic complications and would benefit from surgical revascularization.

Identify patients with an indication for surgical referral — Surgical revascularization for moyamoya is typically indicated both for patients who are symptomatic and for asymptomatic patients with neuroimaging findings suggestive of severe impairment of resting blood flow or impaired hemodynamic perfusion reserve (algorithm 1). These patients are at high risk for future complications, and surgical revascularization may reduce the risk of subsequent morbidity [1-3]. However, the final decision to pursue surgical revascularization for moyamoya depends on individual risks and benefits with surgery and patient values and preferences. (See 'Preoperative evaluation' below.)

Medical management with follow-up surveillance imaging is continued for other patients who are asymptomatic and have preserved cerebral blood flow. (See 'Management of antithrombotic medications' below and 'Additional management for specific groups' below and 'Follow-up surveillance' below.)

Symptomatic presentations — We suggest surgical revascularization for children and adults with moyamoya who develop symptoms related to cerebral ischemia (including transient ischemic attack [TIA], ischemic stroke, or cognitive decline) or hemorrhage and who have no contraindication to surgery, in agreement with guidelines from the American College of Chest Physicians (ACCP) and the American Heart Association (AHA) [4-6]. Surgical referral may also be appropriate for patients with less common clinical symptoms associated with moyamoya such as dystonia or seizures.

The clinical features of moyamoya are discussed in greater detail separately. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Clinical presentations'.)

Hemodynamic compromise on blood flow studies — We also suggest surgical revascularization for asymptomatic children and adults with decreased regional cerebral blood flow or inadequate hemodynamic perfusion reserve as measured by cerebral blood flow studies, in agreement with ACCP and AHA guidelines [4-6]. Similarly, guidelines from Japan and others support surgical revascularization for patients with progressive ischemic symptoms or evidence of reduced cerebral perfusion reserve or inadequate cerebral blood flow [7-9].

Imaging studies to assess cerebral blood flow for patients with moyamoya include transcranial Doppler (TCD) ultrasound, perfusion computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission CT (SPECT). Indirect information on the status of cerebral blood flow may be attained with vascular studies including multiphase CT angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography. (See 'Neuroimaging' below.)

Management of antithrombotic medications — The use of antithrombotic medications in moyamoya is complex because the vasculopathy is associated with the risk of both ischemic and hemorrhagic cerebrovascular complications.

●Use of antiplatelet therapy – We suggest long-term aspirin for children (2 to 5 mg/kg daily) and adults (50 to 100 mg daily) with asymptomatic or symptomatic ischemic-type moyamoya. Cilostazol may be used as an alternative.

For most patients who present with hemorrhagic-type moyamoya, we avoid antiplatelet therapy acutely and during recovery. We typically start antiplatelet therapy postoperatively for patients with ischemic or hemorrhagic moyamoya who undergo surgical revascularization to help maintain bypass graft patency.

Antiplatelet agents are used to reduce the risk of ischemic symptoms in moyamoya [5,6]. Ischemic events in patients with moyamoya are most frequently due to hypoperfusion, but thromboembolism may also occur [10]. In a retrospective study of patients undergoing revascularization surgery, there was a trend toward fewer postoperative major strokes in patients who took aspirin compared with those who did not (1 of 59 versus 9 of 138 patients) [11]. The rate of hemorrhagic complications was similar for both groups. In another observational study, aspirin use was associated with a lower rate of postoperative hemorrhage complications, possibly due to improved hemodynamic parameters or reduced risk of infarction with hemorrhagic transformation [12]. Guidelines from the ACCP also recommend aspirin over no treatment as initial therapy for children with acute arterial ischemic stroke secondary to moyamoya [4].

Another antiplatelet option is cilostazol, a phosphodiesterase inhibitor that has been associated with improved imaging parameters in small studies of patients with moyamoya. An observational study from Japan found that adults with moyamoya treated with cilostazol (if <50 years of age) had an improvement in cerebral blood flow on a two-year follow-up PET scan while other patients treated with clopidogrel (if ≥50 years of age) showed no change [13]. Moreover, neuropsychologic testing suggested that patients in the cilostazol group, but not the clopidogrel group, had improved cognition [14]. An obvious limitation of these findings is that the benefits associated with cilostazol could also be attributed to the younger age of those in the cilostazol group.

●Avoidance of anticoagulation – Long-term anticoagulation is generally contraindicated for children or adults with moyamoya. High-quality data to suggest benefit of anticoagulation in moyamoya are unavailable. Long-term oral anticoagulation in children is associated with the risk of hemorrhage due to incidental trauma and difficulty maintaining therapeutic levels [15]. In adults, long-term anticoagulation is also avoided because hemorrhage is the predominant manifestation of moyamoya.

The safety of short-term anticoagulation (eg, treatment of deep venous thrombosis) has not been established in moyamoya. The decision to use short-term anticoagulation for patients with a transient thromboembolic risk when alternative options are unavailable should be individualized.

Additional management for specific groups

Patients with moyamoya syndrome — Some patients with moyamoya vasculopathy due to an underlying associated condition (MMS) may also require treatment for the underlying condition. As an example, patients with sickle cell disease who develop MMS typically require transfusion therapy both for primary and secondary stroke prevention. (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease".)

The treatment of underlying causes for MMS is generally the same as the treatment for such patients without MMS. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Associated conditions'.)

Pregnant patients — Pregnant patients with moyamoya should be instructed to maintain adequate oral hydration. Low-dose aspirin is typically used for patients with moyamoya for primary or secondary stroke prevention. (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Aspirin (low dose)'.)

Plans for childbirth for patients with moyamoya should be made by assessment of the individual risks and benefits of birthing options in consultation with the patient's obstetrician. Cesarean delivery is commonly selected for pregnant patients with moyamoya to reduce the risk of morbidity associated with cerebral ischemia due to hypocapnia from hyperventilation [16]. However, Cesarean delivery may expose patients to additional risks of cerebral ischemia due to blood loss or perioperative blood pressure fluctuations. A 2018 systematic review of available case series and reports of pregnant patients with moyamoya failed to find an outcome benefit with Cesarean delivery [17]. In a single-center review of 27 pregnancies of patients with moyamoya, 20 patients had good outcomes with vaginal delivery and epidural anesthesia [18]. For patients with moyamoya undergoing Cesarean delivery, anesthesia management is geared to minimizing ischemic risks as well as pain. Some observational reports have found patients with moyamoya given spinal anesthesia during Cesarean delivery had better blood pressure control and less postoperative pain compared with those managed with general anesthesia [19].

Surgical revascularization for selected patients is typically delayed until after delivery and recovery. (See 'Preoperative evaluation' below.)

Follow-up surveillance — Asymptomatic patients with moyamoya with favorable hemodynamic imaging who are not referred for surgical revascularization should undergo serial surveillance testing to evaluate for evidence of disease progression (algorithm 1).

Patients with clinical symptoms or progression on imaging are typically referred for surgical revascularization. (See 'Surgical revascularization' below.)

Clinical examination — We monitor patients with periodic clinical examinations to assess for the development of symptoms or neurologic examination findings attributable to vascular stenosis in moyamoya. We assess for abnormalities on neurologic examination and the presence of TIA or stroke symptoms or other symptoms including transient episodes of weakness that may be provoked by crying, laughing, or hyperventilating. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Clinical presentations'.)

Neuroimaging — We perform surveillance imaging studies for patients with moyamoya because progressive changes in stenosis or impairment of cerebral perfusion may precede clinical symptoms. Asymptomatic patients are typically referred for surgical revascularization if surveillance imaging shows evidence of impaired resting blood flow or hemodynamic compromise. (See 'Surgical revascularization' below.)

An imaging study may be performed yearly for asymptomatic patients, but the timing of imaging studies varies by the severity of baseline and subsequent surveillance imaging findings. As examples, a shorter follow-up study at six months may be performed for a patient who has not yet had follow-up surveillance imaging when severe stenosis was found at initial diagnosis. The interval for follow-up imaging may be extended to every other year or longer for other asymptomatic adult patients with less severe vascular findings and follow-up surveillance imaging that has been stable for at least three years.

The selection of neuroimaging modality varies by availability and institutional practice. Our practice is as follows:

●Vascular imaging – We perform noninvasive vascular studies to monitor all patients for progressive stenosis or occlusion. Vascular studies may also provide indirect evidence of the status of cerebral blood flow.

For most patients, we prefer surveillance MRA of the brain to minimize exposure to radiation and intravenous contrast and because MRA has comparable resolution to CTA. CTA of the head may be used as an alternative study or for patients unable to obtain MRA. Digital subtraction angiography is typically reserved for instances when noninvasive testing is nondiagnostic or for presurgical planning. (See 'Preoperative evaluation' below.)

TCD ultrasonography is a noninvasive study that may be performed at the bedside to evaluate intracranial hemodynamics by measuring blood flow velocity in large intracranial vessels at the circle of Willis [5]. Since the velocity of blood flow is inversely related to arterial diameter, TCD can detect arterial occlusive disease; a focal increase in velocity usually suggests large artery stenosis. Diagnostic evaluation with TCD avoids exposure to radiation or the use of contrast. However, the study is unable to assess stenosis in smaller arteries, the adequacy of tissue perfusion, or the status of collaterals. Results can be operator dependent, so it should be performed by an experienced operator, but poor acoustic windows still preclude effective insonation in up to 15 percent of patients.

●Cerebral blood flow imaging – For patients with moderate to severe stenosis on vascular imaging, we also use hemodynamic studies to assess for impaired baseline blood flow or hemodynamic perfusion reserve within the tissue distal to the area of stenosis. Regional hypoperfusion may be found on hemodynamic studies before progressive stenosis becomes apparent on vascular studies. Hemodynamic studies may also be performed to evaluate cerebrovascular reserve before and after induced vasodilation using acetazolamide or CO₂. Provocative testing using vasodilation may increase diagnostic sensitivity to detect impairment of perfusion.

Several modalities may be used to determine the extent of inadequate resting blood flow or cerebral perfusion reserve in patients with moyamoya. We typically use perfusion CT or perfusion-weighted MRI. Other methods include Xenon-enhanced CT, MRI with arterial spin labeling techniques, PET, and SPECT [5,20-25]. The selection of modality depends on institutional availability and experience.

●Other brain imaging – Brain MRI can be obtained to identify evidence of ischemia when clinical signs or symptoms are of uncertain relationship to moyamoya. Head CT may be performed as a less sensitive alternative imaging test.

SURGICAL REVASCULARIZATION — Surgical revascularization for moyamoya is the treatment used to improve cerebral blood flow and perfusion reserve, and to reduce the risk of cerebrovascular complications. Revascularization is based on the principle that ischemic and hemorrhagic cerebrovascular complications can be prevented by augmenting cerebral blood flow to the ischemic hemisphere and secondarily reducing pressure in the moyamoya collaterals [26]. Surgery involves one of several techniques typically using a craniotomy to permit connecting a branch of the external carotid artery to the ischemic hemisphere.

Preoperative evaluation — The selection of patients who may benefit from surgical revascularization is guided by a preoperative evaluation that includes clinical examination and imaging testing.

●Clinical evaluation – The benefits of surgery to prevent neurologic damage may be diminished for patients with moyamoya who have chronic neurologic deficits and tissue loss following ischemic stroke or intracerebral hemorrhage. Some patients with severe, irreversible deficits may not benefit from surgery; however, others with milder deficits may pursue surgery after recovery.

Adults with moyamoya and cardiovascular risk factors should undergo a cardiac evaluation prior to surgery to manage and mitigate these risks. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

●Angiographic evaluation – Preoperative cerebral angiography with bilateral injections of the internal and external carotid arteries and vertebral arteries is generally recommended to evaluate the sites of stenosis or occlusion, the status of the collateral circulation, and the identification of donor vessels. At select centers, high-resolution 3-Tesla MRI with magnetic resonance angiography (MRA) has been used for preoperative planning to identify the recipient artery.

Patients with recent neurologic symptoms should be evaluated with brain MRI to identify ischemic and hemorrhagic brain lesions and to assess the overall stroke burden. Head CT is a less sensitive alternative test for patients unable to undergo brain MRI. Patients with recent or acute stroke have an elevated risk of perioperative stroke and hyperperfusion syndrome.

●Timing of surgery – For patients who present with ischemic stroke or intracerebral hemorrhage, revascularization surgery is typically delayed until recovery both to reduce the risk of surgical complications and to permit optimal recovery from the cerebrovascular event. The specific timing varies by the severity of cerebrovascular injury and the duration of recovery, as well as assessment of risks associated with the selected surgical technique and patient-level factors. However, patients with moyamoya who present with intracerebral hemorrhage or subarachnoid hemorrhage due to an associated ruptured aneurysm are typically referred for urgent aneurysm treatment, similar to other patients with a ruptured cerebral aneurysm. (See "Treatment of cerebral aneurysms", section on 'Timing and choice of therapy'.)

For asymptomatic patients, revascularization surgery is typically performed when imaging studies show hemodynamic compromise or progressive vascular changes. However, earlier referral for surgery may be appropriate for selected asymptomatic patients with an expected high risk of future progression, such as for some patients with sickle cell disease [27]. By contrast, surgery may be delayed for other patients such as those who are pregnant and for patients without severe imaging findings who smoke tobacco products to allow time to quit.

Surgical techniques — Surgical techniques for moyamoya can be divided into direct and indirect revascularization procedures and their combinations [2,5,28,29].

The use of specific revascularization procedures for moyamoya varies by institutional protocol and surgical training and experience. There are no convincing data that one method of revascularization surgery is more effective than another. However, indirect revascularization is generally preferred in younger children [5]. (See 'Efficacy of surgery' below.)

●Direct techniques – Direct revascularization refers to procedures where the superficial temporal artery (or middle meningeal artery, occipital artery, or other donor branch) from the external carotid artery is directly connected to a cortical artery within the ischemic hemisphere [30]. Retrograde and anterograde blood flow from the bypass graft improves perfusion to the ischemic territory. Direct revascularization has been associated with improved long-term prognosis in patients with moyamoya [20,31].

Direct revascularization is used by many centers, most commonly in adult patients. Direct methods are technically difficult to perform in children because of the small size of donor and/or recipient vessels.

●Indirect techniques – Indirect revascularization refers to one of the several procedures where tissue perfused by a branch of the external carotid artery is applied to the surface of the ischemic hemisphere to encourage revascularization with underlying cortical vessels over time. The tissue may include dura, muscle, branch of an artery, or omentum.

Indirect revascularization is frequently used for children with moyamoya. In addition, it may be selected when a suitable recipient artery is not available for anastomosis [1]. In general, indirect revascularization requires less operation time and may have lower procedure-related complications than direct revascularization.

•Encephaloduroarteriosynangiosis – Artery and dura

•Encephaloarteriosynangiosis – Artery

•Pial synangiosis – Artery applied to the pial surface

•Encephalomyosynangiosis – Temporalis muscle

•Encephaloduroarteriomyosynangiosis – Artery, dura, and muscle

•Encephalodurogaleosynangiosis – Dura and galeal tissue

•Encephaloperiocranialsynangiosis – Pericranium

Other indirect techniques include [32,33]:

•Craniotomy with inversion of the dura – Revascularization occurs from repositioned dura.

•Multiple burr holes without vessel synangiosis – Revascularization into burr hole sites develops from the overlying scalp.

•Omentum transplantation – Highly vascularized omental tissue is applied to the cortical surface.

●Other procedures – Combined revascularization involves direct revascularization (to augment cerebral blood flow rapidly) plus indirect revascularization (to promote improved cerebral blood flow over time) [9,34,35]. This procedure is a more complex surgery than either direct or indirect procedures alone as it requires a suitable donor and recipient vessel for direct revascularization as well as placement of perfused tissue along the surface of the ischemic hemisphere for indirect revascularization. However, combination procedures may promote both rapid and delayed revascularization. In one small study, the use of a combination revascularization procedure was also associated with regression of dilated lenticulostriate vessels, a major source of hemorrhagic morbidity in moyamoya [36].

Endovascular embolization has been evaluated in small uncontrolled studies to obliterate ruptured intracranial aneurysms or pseudoaneurysms associated with moyamoya disease [37,38].

Efficacy of surgery — Limited data support the effectiveness of surgical treatment for moyamoya. Two meta-analyses compared data of patients who had surgical revascularization with those who received conservative treatment [39,40]. Overall, patients in the surgical group had a reduced risk of stroke compared with the conservative group. In a meta-analysis of 10 studies that included nearly 2500 patients with MMD, the subsequent stroke rate over a mean follow-up of 2.2 to 7.1 years was lower for patients treated with surgery than those who received conservative management (14 versus 30 percent) [39]. In addition, surgery was associated with a reduced rate of hemorrhage during follow-up (5 versus 19 percent) and a trend toward reduction in the rate of ischemic stroke (10 versus 14 percent; pooled odds ratio [OR] 0.71, 95% CI 0.5-1.1). In a separate meta-analysis of nearly 2300 patients from 20 studies of patients who presented with symptomatic MMD, those who underwent surgery had a lower risk of future stroke than patients managed conservatively (OR 0.26, 95% CI 0.2-0.3) [40]. Additionally, the risk of death due to bleeding was lower in the five studies (624 patients) reporting hemorrhagic complications for those treated with surgery (OR 0.27, 95% CI 0.1-0.7). However, the conclusions of these analyses are limited by differences in baseline characteristics, selection and publication bias, and potential variability of outcome measures.

●MMD versus MMS – Most studies reporting the efficacy of surgery included patients with MMD. MMS is also regarded to be a progressive condition, similar to MMD, and is also associated with the risk of cerebrovascular complications due to shared underlying moyamoya vasculopathy, but data to support these similarities are limited [1]. The rate of vascular progression in MMS may vary according to the underlying etiology and epidemiologic differences. In an observational study that included 881 patients with MMD and 292 patients with MMS attributed to atherosclerosis, the incidence of cerebrovascular events was higher over a mean follow-up of 46 months for those with MMD than MMS (14 versus 7 percent) [41]. MMD is more common than MMS in several East Asian countries than elsewhere and frequently presents in children, where the course can be aggressive [42,43]. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Epidemiology'.)

Observational data show that revascularization surgery for MMS appears to be effective. A systematic review of 13 case reports and series for patients with MMS attributed to sickle cell disease found that direct surgical revascularization was feasible and associated with a lower risk of subsequent stroke compared with natural history [27]. In an Irish cohort study of 21 patients with moyamoya including 5 patients with MMS, postoperative complications were uncommon (median follow-up of 52 months) and only one patient had a stroke [44]. In a retrospective study of 141 children with MMS and sickle cell disease, the addition of revascularization to medical therapy (chronic transfusions and/or hydroxyurea) was associated with a reduced risk of subsequent cerebrovascular events (OR 0.3, 95% CI 0.1-0.9) [45]. Successful surgical revascularization with a stable postoperative course has also been reported in case reports and series of patients with MMS from other conditions such as thyroiditis, neurofibromatosis, and Down syndrome [46-48].

●Direct versus indirect techniques – The selection of surgical procedure is based on several factors, including size and availability of suitable donor and recipient arterial vessels, as well as local protocol and experience. Direct procedures are typically more complex surgeries sometimes requiring a larger operative field, longer surgical time to perform a direct anastomosis, and longer hospitalization and recovery [29]. Indirect revascularization surgery is frequently performed for children who have smaller vessels, less suitable to direct anastomosis [1,29].

Direct procedures provide more immediate revascularization for patients with suitable donor and recipient vasculature. In a 2022 pooled analysis of 143 studies involving more than 11,000 adults undergoing surgery for moyamoya, favorable outcome rates were higher for those undergoing direct or combined bypass versus indirect bypass surgery (93 and 94 percent versus 81 percent, respectively) [49]. A 2019 meta-analysis of 15 studies that included patients treated with surgery for moyamoya similarly reported that stroke prevention appeared to be more effective in patients treated with direct surgery (OR 2.0, 95% CI 1.3-3.1) [40]. These results may be driven by lower rates of late (>30 days after surgery) ischemic or hemorrhage stroke in patients treated with direct techniques [49]. However, these data are mostly from observational studies and are limited by differences in baseline characteristics, potential for selection bias, and limited follow-up.

●Hemorrhagic presentations – The use of surgery for hemorrhagic moyamoya has been controversial because of concern that revascularization might increase the risk of recurrent hemorrhage by increasing cerebral perfusion pressure in dilated collateral vessels [50,51]. However, the available data suggest that revascularization surgery reduces the risk of recurrent hemorrhage, at least for adults [52-54]. In a network meta-analysis of nine studies evaluating hemorrhagic moyamoya, with data for 557 patients treated with surgery and 493 patients managed conservatively, surgical revascularization was associated with a lower rate of total recurrent stroke, ischemic stroke, and hemorrhagic stroke [53].

The Japan adult moyamoya trial evaluated 88 patients who presented with intracranial hemorrhage who were assigned to bilateral direct surgery or conservative care [54]. By five-year follow-up, patients in the surgery group had numerically fewer events for the combined end point of recurrent bleeding or stroke (14 versus 34 percent for conservative care; hazard ratio [HR] 0.39, 95% CI 0.15-1.03), a finding that just missed statistical significance. The difference between the surgery and conservative groups for the annual event rate of recurrent bleeding or stroke (8.2 versus 3.2 percent) just achieved statistical significance (p = 0.048).

●Pediatric surgery – Limited indirect evidence suggests that revascularization surgery is more effective in children than in adults [26]. In addition, children who present at a very young age may have a higher stroke rate and a more aggressive course than older children. In a cohort of 204 children with moyamoya treated with indirect surgery, the rate of ischemic stroke at initial presentation was higher for children <3 years old than those 3 to 6 years old and those >6 years old (87 versus 58 versus 46 percent) [55]. In addition, after presentation, the subsequent preoperative stroke rate was also highest in the youngest age group (39 versus 6 versus 1 percent). The rate of stroke attributed to surgery was similar between groups.

A systematic review published in 2005 identified 55 studies with data for 1156 children (mainly from Japan) who had surgical revascularization for moyamoya [2]. Most patients were treated with indirect surgical techniques or a combination of direct and indirect methods. The perioperative stroke rate was 4.4 percent. Over a mean postoperative follow-up of 58 months, symptomatic benefit, defined as complete disappearance or reduction in symptomatic cerebral ischemia, was reported in 1003 children (87 percent). In detail, outcomes were asymptomatic, improved, unchanged, or worse in 51, 36, 11, and 3 percent of patients, respectively.

Long-term outcomes in children also appear to be favorable. In a series from the United States of 143 children with symptomatic moyamoya who were treated with pial synangiosis, perioperative stroke occurred in 11 (8 percent) [56]. In addition, among 126 patients followed for more than one year, late-onset stroke occurred in four (3 percent). In 46 patients who were followed for more than five years, late-onset stroke occurred in two patients (4 percent).

Complications of surgery

●Perioperative stroke – Peri- and postoperative stroke is a major complication of surgical revascularization for moyamoya. Ischemic stroke may occur due to baseline impairment of cerebral blood flow and perioperative hypoperfusion or thrombosis. Improved cerebral blood flow with surgery may also expose patients to the risk of postoperative intracerebral hemorrhage or edema from hyperperfusion. Additionally, other sites of intracranial hemorrhage, including subdural hematoma, may occur following revascularization.

Efforts to maintain optimal cerebral perfusion during the perioperative period are important to minimize the risk of complications. Relative hypoperfusion can occur as a result of competing blood flow from the preexisting collateral circulation and the new anastomosis in the setting of impaired cerebral autoregulation [57]. In a single-center series of 1250 pediatric and adult revascularizations performed from 1991 to 2014, the 30-day postoperative rate of major stroke was 6.8 percent [58]. In a meta-analysis of eight studies with over 1600 adult patients with moyamoya disease who had surgery, independent risk factors for postoperative stroke were operative ischemic events, posterior cerebral artery involvement, and diabetes [59].

Maintaining normocapnia is recommended during and after perioperative period to prevent ischemic complications. Both hypercapnia and hypocapnia can alter the regional cerebral blood flow through the mechanisms of vasoconstriction and steal phenomenon via vasodilation [60].

●Delayed transient neurologic deficits – Delayed transient neurologic deficits can occur typically 12 to 24 hours after revascularization surgery. Symptoms may include aphasia, oro-bulbar apraxia, motor weakness, or sensory abnormalities. Imaging shows no evidence of ischemic stroke, hemorrhage, or edema in these cases, and the symptoms usually resolve within several days to weeks. While the pathophysiology of this syndrome is uncertain, it may be due to either hyperperfusion or hypoperfusion [57,61,62].

●Hyperperfusion syndrome – Cerebral hyperperfusion syndrome may occur after surgical revascularization due to abrupt changes in perfusion to the ischemic hemisphere [5,63,64]. Changes in cerebral autoregulation induced by chronic cerebral hemodynamic insufficiency lead to compensatory vasodilation of cerebral vessels. After revascularization, blood flow is restored to a normal or elevated perfusion pressure within the previously hypoperfused hemisphere. The chronically dilated cerebral vessels are unable to vasoconstrict quickly enough to protect the capillary bed because of impaired cerebral blood flow autoregulation. Breakthrough perfusion pressure then causes the clinical manifestations that may include headache, seizures, focal neurologic deficits, cerebral edema, and rarely intracerebral hemorrhage.

The reported incidence of clinically symptomatic cerebral hyperperfusion syndrome following bypass surgery for moyamoya disease ranges from 15 to 47 percent [63,65-67]. In a 2020 meta-analysis that included 2225 patients from 27 cohort studies, the incidence of postoperative hyperperfusion for adults was 20 percent but only 4 percent for children [64]. In nearly all cases, complete resolution occurs over several days to weeks. However, some patients with hyperperfusion syndrome can have persistent deficits when associated with intracerebral hemorrhage.

Prophylactic postoperative blood pressure control may prevent or ameliorate symptomatic cerebral hyperperfusion. In a cohort of 108 adults with moyamoya, immediate postoperative blood pressure control to a target systolic blood pressure of <130 mmHg was associated a lower risk of hyperperfusion complications than expectant management (25 versus 7 percent) [68]. Hyperperfusion syndrome is discussed in greater detail separately. (See "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome'.)

●Other complications – Infection and surgical site bleeding are other uncommon complications of moyamoya surgery [5].

MANAGEMENT OF COMPLICATIONS OF MOYAMOYA — Patients may present with complications due to moyamoya vasculopathy, including ischemic stroke or intracerebral hemorrhage. Management of the presenting complication involves minimizing the risk of further brain injury associated with cerebral stenosis from moyamoya.

Transient ischemic attack and ischemic stroke — For children and adults with moyamoya and ischemic stroke, acute treatment is mainly supportive, directed toward minimizing ischemic injury, reducing cerebral edema, and controlling secondary complications such as seizures [69].

●Acute treatment measures – During hospitalization for acute stroke or surgery, specific management issues should be addressed to minimize ischemic injury, especially in children with moyamoya [5]:

•Precautions to minimize hyperventilation – Hyperventilation occurring with pain, excitement, or crying can lower the carbon dioxide levels in the blood and induce or worsen cerebral ischemia by causing vasoconstriction [5,70]. Strategies to provide a comfortable and calm setting and control pain are recommended.

Pain control may help reduce the risk of hyperventilation and also reduce the risk of stroke and the length of hospitalization [71]. Specific methods include appropriate periprocedural sedation, painless wound-handling techniques (eg, Steri-Strip closure, use of paraffin gauze, avoidance of adhesive tapes), and protocolized pain management.

•Maintaining euvolemia – Oral and intravenous fluids should be given to reduce the risk of cerebral ischemia from hypotension and hypovolemia [56,70]. Intravenous hydration with isotonic fluids may be administered at 1.25 to 1.5 times the normal maintenance rate [1,71]. Other experts keep blood pressure slightly elevated in the acute setting [71]. However, cerebral hyperperfusion syndrome may occur with significant elevations in blood pressure; blood pressure treatment may be helpful to prevent this complication.

•Thrombolysis – The safety of intravenous thrombolytic therapy for acute ischemic stroke in moyamoya patients has not been established. Its use may be considered on an individual basis for selected patients with disabling stroke symptoms and no history of brain hemorrhage after discussing risks and benefits. Because of the risk of hemorrhage in areas of extensive moyamoya collateral vessels, many experts are reluctant to use thrombolytic therapy to treat acute ischemic stroke in patients with moyamoya [72].

●Secondary preventive therapy – Antiplatelet medications are typically prescribed for patients with ischemic stroke due to moyamoya. Antithrombotic therapy is discussed in greater detail separately. (See 'Management of antithrombotic medications' above.)

Patients with moyamoya may have hypertension, and treatment is indicated to reduce the risk of future ischemic and hemorrhagic complications. However, hypotension and hypovolemia should be avoided to minimize the risk of ischemia.

Additional details on the general approach to the evaluation and management of acute ischemic stroke is reviewed separately. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis" and "Initial assessment and management of acute stroke".)

Intracranial hemorrhage — The treatment of acute intracranial hemorrhage is similar for patients with or without moyamoya. Ventricular drainage and/or hematoma removal may be required for some patients with intracerebral hemorrhage. Vascular repair of ruptured aneurysm may be required for patients presenting with subarachnoid hemorrhage.

The acute treatment of forms of intracranial hemorrhage are presented separately. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Subdural hematoma in adults: Management and prognosis".)

Other complications — Patients with moyamoya may also present with other neurologic symptoms such as seizures and headaches. Other neurologic presentations are uncommon. (See "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Clinical presentations'.)

Neuroimaging evaluation should be performed to assess for evidence of associated cerebral ischemia. In some cases, neurologic symptoms such as seizures or movement disorders may be attributed to moyamoya in patients without clinical or radiographic ischemia. The decision to pursue surgery for these symptomatic patients should be individualized, based on severity of symptoms, effectiveness of medical therapy, and patient preferences after clinical and imaging evaluation. (See 'Identify patients with an indication for surgical referral' above and 'Follow-up surveillance' above.)

Symptomatic management of these conditions is typically the same for patients with or without moyamoya. (See "Evaluation and management of the first seizure in adults" and "Seizures and epilepsy in children: Initial treatment and monitoring" and "Evaluation of headache in adults" and "Headache in children: Approach to evaluation and general management strategies".)

PROGNOSIS — The natural history of moyamoya tends to be progressive in children and adults [73-75]. In studies with long-term follow-up of untreated patients, progressive neurologic deficits and poor outcome were reported in 50 to 66 percent [76-78]. Radiographic progression within five years of diagnosis was reported in 36 percent of a cohort of children with moyamoya [79]. The vascular pathology usually worsens with extensive intracranial large artery occlusion and collateral circulation. Patients often suffer cognitive and neurologic decline due to repeated ischemic stroke or hemorrhage [75].

However, the rate and extent of progression varies substantially between populations. Moyamoya may have a more rapid progression and a worse prognosis in younger rather than in older children, as evidenced by a single-center observational study of 204 patients from Korea who had surgical treatment for moyamoya [55]. Ischemic stroke was more frequent at initial presentation in children ≤6 years old compared with children >6 years old, as were subsequent preoperative infarctions. The median interval between the onset of symptoms and preoperative infarction was three months (range 1 to 14). The rate of favorable clinical outcomes was significantly lower in children less than three years old compared with those who were three to six or older than six years, mainly because of preoperative infarctions.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Stroke in children".)

SUMMARY AND RECOMMENDATIONS

●Identify patients with an indication for surgical referral – For patients with symptomatic moyamoya as well as those with impaired resting blood flow or hypoperfusion on neuroimaging, we suggest surgical revascularization (algorithm 1) (Grade 2C). Antiplatelet management with follow-up surveillance imaging is continued for other patients who are asymptomatic and have preserved cerebral blood flow. (See 'Identify patients with an indication for surgical referral' above.)

●Antithrombotic therapy

•Antiplatelets – For patients with asymptomatic or symptomatic ischemic-type moyamoya, we suggest long-term aspirin for children (2 to 5 mg/kg daily) and adults (50 to 100 mg daily) rather than no therapy (Grade 2C). Cilostazol may be used as an alternative. (See 'Management of antithrombotic medications' above.)

For most patients who present with hemorrhagic-type moyamoya, we avoid antiplatelet therapy acutely and during recovery. We typically start antiplatelet therapy postoperatively for patients with ischemic or hemorrhagic moyamoya who undergo surgical revascularization.

•Anticoagulation – Long-term anticoagulation is generally contraindicated for patients with moyamoya. (See 'Management of antithrombotic medications' above.)

●Follow-up surveillance – Patients with moyamoya who are not referred for surgical revascularization should undergo serial surveillance testing to evaluate for evidence of disease progression (algorithm 1). (See 'Follow-up surveillance' above.)

•Clinical examination – We monitor patients with periodic clinical examinations to assess for the development of symptoms or neurologic examination findings attributable to vascular stenosis in moyamoya including transient episodes of weakness that may be provoked by crying, laughing, or hyperventilating. (See 'Clinical examination' above.)

•Neuroimaging – We perform surveillance imaging studies for patients with moyamoya because progressive changes in stenosis or impairment of cerebral perfusion may precede clinical symptoms. The timing of imaging studies varies by the severity of baseline and subsequent surveillance imaging findings. (See 'Neuroimaging' above.)

Patients who develop symptoms or progression on imaging are typically referred for surgical revascularization.

●Surgical management – Surgery for moyamoya involves one of several techniques using a craniotomy to permit connecting a branch of the external carotid artery to the ischemic hemisphere. (See 'Surgical revascularization' above.)

•Preoperative evaluation – The selection of patients who may benefit from surgical revascularization is guided by a preoperative evaluation that includes clinical examination and imaging testing. (See 'Preoperative evaluation' above.)

•Techniques – Direct revascularization refers to procedures where a branch of the external carotid artery is directly connected to a cortical artery within the ischemic hemisphere. Indirect revascularization refers to procedures where tissue perfused by a branch of the external carotid artery is applied to the surface of the ischemic hemisphere to encourage revascularization with underlying cortical vessels over time. (See 'Surgical techniques' above.)

The use of specific revascularization procedures for moyamoya varies by institutional protocol and surgical training and experience. However, indirect revascularization is generally preferred in younger children because of the small size of donor and/or recipient vessels. (See 'Efficacy of surgery' above.)

●Management of complications of moyamoya – For children and adults with moyamoya and acute stroke, acute treatment is mainly supportive, directed toward minimizing brain injury, limiting cerebral edema, and controlling secondary complications such as seizures.

Efforts to minimize cerebral ischemic injury include avoiding or controlling hyperventilation, preventing pain or agitation, and avoiding hypovolemia. (See 'Management of complications of moyamoya' above.)

●Prognosis – The natural history of moyamoya tends to be progressive. However, the rate and extent of progression varies substantially between populations. (See 'Prognosis' above.)