Direct Bypass Techniques for the Treatment of Pediatric Moyamoya Disease

Moyamoya is an increasingly recognized cause of stroke in children and adults. Identification of the disease early in its course with prompt institution of therapy is critical to providing the best outcome for patients. Revascularization surgery seems to be effective in preventing stroke in moyamoya, with direct techniques providing durable protection when performed at experienced centers.

Indications

Moyamoya disease (MMD) has been recognized as a devastating condition in adults and in pediatric patients. Large pediatric epidemiologic studies have shown that MMD is a significant contributor to childhood stroke. Independent studies in the American, Asian, and European literature found a pediatric stroke incidence between 2.1 and 13/100,000/y, with MMD accounting for 6% of the ischemic strokes. With an untreated morbidity estimated to be greater than 70%, and with a 5-year risk of recurrent ipsilateral stroke of 65% in medically treated symptomatic hemispheres, surgical intervention has become the standard of treatment of patients with MMD. In children, the most common presentation is cerebral ischemia. In a study by Scott and colleagues of 143 pediatric patients diagnosed with MMD in North America, nearly all patients presented with either symptoms of stroke or transient ischemic attack (TIA). Similarly, in large populations of Asian patients, approximately 40% of those less than 10 years of age presented with a TIA and nearly 30% presented with cerebral infarction, although some presented with headaches and seizures. Similar findings were made in European studies. In our series including 272 adult and 96 pediatric patients with MMD, we found stroke and TIA to be the most common presenting symptoms in the pediatric patients followed by headache, seizures, and rarely intracerebral hemorrhage ( Fig. 1 ).

The diagnostic guidelines for identifying patients with MMD differ in centers around the world. The Research Committee on MMD of the Ministry of Health and Welfare of Japan has identified 4 criteria necessary for the diagnosis of MMD: (1) stenosis or occlusion of the terminal portion of the internal carotid artery (ICA); (2) a coexisting abnormal vascular network in the base of the brain or basal ganglia; (3) bilaterality; and (4) no other identifiable cause. These guidelines have been modified case by case at various institutions around the United States. Although classically bilateral, unilateral MMD can occur. Patients with the characteristic moyamoya vasculopathy who also have well-recognized associated conditions are categorized as having moyamoya syndrome, whereas patients with no known associated risk factors have MMD. In our series 21% of the children had unilateral disease. We have previously reported that 71% of patients with equivocal or mild stenotic changes in the initially unaffected side eventually progressed to bilateral MMD at a mean follow-up time of 12.7 months.

In light of the findings describing a natural history with a devastating disease course, a poor response to medical therapy, and a good response to surgery, we strongly advocate surgical treatment of symptomatic pediatric patients with MMD. There is ongoing debate about the treatment of asymptomatic or incidentally discovered MMD. Because there are only limited data on the natural history of MMD in children, decision-making is complex. However, substantial evidence suggests inevitable disease progression and therefore close follow-up would be recommended. In our experience, careful history taking and physical examination often uncover signs and symptoms suggestive of cerebral hypoperfusion, such as recurrent TIAs. To avoid devastating strokes, early treatment is advocated.

Patient selection

All patients undergo a detailed clinical assessment as part of the evaluation as a potential surgical candidate. In particular subgroups of patients with syndromes known to be associated with moyamoya, such as neurofibromatosis, Down syndrome, and primordial dwarfism, identifying comorbidities is essential. At our institution, we found a higher risk of postsurgical morbidities in patients with moyamoya syndrome compared with the rest of our cohort (odds ratio 4.16, P = .09 ). Diagnosis of MMD is made based on angiography according to published guidelines. All patients are evaluated with magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI) and fluid attenuated inversed recovery imaging to assess the overall stroke burden. Acute strokes, as identified by diffusion-weighted MR imaging, have to be recognized, because they may put patients at a greater risk for perioperative strokes. The preoperative 6-vessel (including both external carotid arteries [ECAs], both ICAs, and 1 or both vertebral arteries) catheter angiography is important to determine the severity of the disease and to evaluate the presence of the superficial temporal artery (STA) ( Fig. 2 ). All patients undergo a cerebral blood flow analysis using MR imaging and single-photon emission computed tomography (SPECT) studies with and without acetazolamide (Diamox) challenge.

Surgical interventions for MMD have been divided into direct and indirect bypass techniques. The principal difference between the 2 strategies lies in the method of cerebral reperfusion. Whereas direct methods are believed to provide immediate flow increase in the affected areas of the brain, indirect methods aim to stimulate the development of a new vascular network over time. The arteriopathy of moyamoya affects the ICA and spares the ECA. Surgical treatment of moyamoya typically uses the ECA as a source of new blood flow to the ischemic hemisphere. Two general methods of revascularization are used: direct and indirect. In direct revascularization, a branch of the ECA (usually the STA) is directly anastomosed to a cortical artery. Indirect techniques involve the placement of vascularized tissue supplied by the ECA such as dura, temporalis muscle, or the STA itself in direct contact with the brain, leading to an ingrowth of new blood vessels to the underlying cortex. The direct bypass techniques that have been proposed include STA to middle cerebral artery (MCA), occipital artery to MCA, and middle meningeal artery to MCA anastomoses. The indirect techniques include encephalomyosynangiosis (EMS), encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis (EDAMS), encephalomyoarteriosynangiosis, multiple cranial bur holes, and omental transposition.

There has not been a controlled randomized trial comparing direct and indirect revascularization techniques. Therefore, there are currently no data to support either direct or indirect revascularization techniques in the pediatric population with MMD. Some investigators advocate that indirect techniques do not result in an immediate revascularization and may carry an increased risk for postoperative stroke. Thus, it has been suggested to combine direct and indirect techniques to take advantage of immediate revascularization with the security of more diffuse neovascularization.

We advocate the use of direct bypass techniques when possible. In our pediatric series of 96 patients 67% received a direct bypass. The strongest predictor of the feasibility of a direct bypass was the age at surgery. The mean age of pediatric patients undergoing indirect surgery was 6.5 years, whereas it was 11.2 years in children undergoing direct surgery ( P <.05) ( Fig. 3 ). The youngest child to receive a direct bypass was 4.3 years old. The presence of the STA has to be confirmed on cerebral angiogram. However, we found that a small STA on angiogram does not necessarily preclude a direct bypass approach. Generally we consider a direct bypass possible if the STA and the MCA are 0.6 mm or greater.

At our institution, it is our practice to operate on the most symptomatic side first. If both hemispheres are symptomatic, we revascularize the right side first. In bilateral MMD, the second side is usually revascularized 1 week after the first surgery if tolerated by the patient.

Patient selection

All patients undergo a detailed clinical assessment as part of the evaluation as a potential surgical candidate. In particular subgroups of patients with syndromes known to be associated with moyamoya, such as neurofibromatosis, Down syndrome, and primordial dwarfism, identifying comorbidities is essential. At our institution, we found a higher risk of postsurgical morbidities in patients with moyamoya syndrome compared with the rest of our cohort (odds ratio 4.16, P = .09 ). Diagnosis of MMD is made based on angiography according to published guidelines. All patients are evaluated with magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI) and fluid attenuated inversed recovery imaging to assess the overall stroke burden. Acute strokes, as identified by diffusion-weighted MR imaging, have to be recognized, because they may put patients at a greater risk for perioperative strokes. The preoperative 6-vessel (including both external carotid arteries [ECAs], both ICAs, and 1 or both vertebral arteries) catheter angiography is important to determine the severity of the disease and to evaluate the presence of the superficial temporal artery (STA) ( Fig. 2 ). All patients undergo a cerebral blood flow analysis using MR imaging and single-photon emission computed tomography (SPECT) studies with and without acetazolamide (Diamox) challenge.

Surgical interventions for MMD have been divided into direct and indirect bypass techniques. The principal difference between the 2 strategies lies in the method of cerebral reperfusion. Whereas direct methods are believed to provide immediate flow increase in the affected areas of the brain, indirect methods aim to stimulate the development of a new vascular network over time. The arteriopathy of moyamoya affects the ICA and spares the ECA. Surgical treatment of moyamoya typically uses the ECA as a source of new blood flow to the ischemic hemisphere. Two general methods of revascularization are used: direct and indirect. In direct revascularization, a branch of the ECA (usually the STA) is directly anastomosed to a cortical artery. Indirect techniques involve the placement of vascularized tissue supplied by the ECA such as dura, temporalis muscle, or the STA itself in direct contact with the brain, leading to an ingrowth of new blood vessels to the underlying cortex. The direct bypass techniques that have been proposed include STA to middle cerebral artery (MCA), occipital artery to MCA, and middle meningeal artery to MCA anastomoses. The indirect techniques include encephalomyosynangiosis (EMS), encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis (EDAMS), encephalomyoarteriosynangiosis, multiple cranial bur holes, and omental transposition.

There has not been a controlled randomized trial comparing direct and indirect revascularization techniques. Therefore, there are currently no data to support either direct or indirect revascularization techniques in the pediatric population with MMD. Some investigators advocate that indirect techniques do not result in an immediate revascularization and may carry an increased risk for postoperative stroke. Thus, it has been suggested to combine direct and indirect techniques to take advantage of immediate revascularization with the security of more diffuse neovascularization.

We advocate the use of direct bypass techniques when possible. In our pediatric series of 96 patients 67% received a direct bypass. The strongest predictor of the feasibility of a direct bypass was the age at surgery. The mean age of pediatric patients undergoing indirect surgery was 6.5 years, whereas it was 11.2 years in children undergoing direct surgery ( P <.05) ( Fig. 3 ). The youngest child to receive a direct bypass was 4.3 years old. The presence of the STA has to be confirmed on cerebral angiogram. However, we found that a small STA on angiogram does not necessarily preclude a direct bypass approach. Generally we consider a direct bypass possible if the STA and the MCA are 0.6 mm or greater.