Moyamoya Disease

Definitions

• MMD is a progressive idiopathic stenosis of proximal intracranial arteries feeding the circle of Willis that leads to small vessel angiogenesis and collateralization. “Moyamoya” is a Japanese term meaning a hazy puff of smoke, which is the characteristic angiographic finding in patients with this condition (Figure 1).

• Moyamoya syndrome (MMS) describes patients with characteristic angiographic findings of arterial stenosis and small-vessel collateralization, with an additional associated medical condition, most commonly neurofibromatosis 1, Down syndrome, or sickle cell disease.
• Other associated conditions include thalassemias, congenital heart diseases, vasculopathies, polycystic kidney disease, Wilms tumor, Marfan syndrome, Alagille syndrome, Noonan syndrome, Prader-Willi syndrome, Sturge-Weber syndrome, Turner syndrome, Williams syndrome, tuberous sclerosis, and type 1 diabetes.¹
• In the United States, an annual incidence of moyamoya was reported at 0.57 per 100,000 individuals with a female-to-male ratio of 2.6.¹
• MMD and MMS have a bimodal age distribution, with peaks at approximately 10 years and 40 years.
• While both ischemic and hemorrhagic infarctions can be seen in either age group, the younger group shows a predominance of ischemic insults. In contrast, the older group shows a predominance of hemorrhagic infarctions.²
• Seizure is not as common as an initial presentation, and is often attributed to prior or concurrent stroke.¹

Pathophysiology

• A genetic susceptibility to MMD has been linked to mutations in RNF213 gene on chromosome 17q25.3. Additional chromosomal mutations have also been identified, suggesting that familial moyamoya is an autosomal dominant disease with incomplete penetrance.¹
• Upregulation of various pro-angiogenic factors has been implicated in the pathogenesis of MMD, such as vascular endothelial growth factor, transforming growth factor beta-1, and fibroblast growth factor.¹
• Classically, moyamoya vessels branch from the circle of Willis adjacent to areas of vessel stenosis, but collateral vessels can form elsewhere in the brain, and, rarely, extracranial involvement has been seen. Aneurysms can also develop at vessel branching points or along collateral vessels, and most patients with this symptom present with intracranial hemorrhage.¹
• Stenosis of the intracranial arteries can lead to focal cerebral ischemia. Children and young adults commonly present with headaches, transient ischemic attacks, and strokes. A subset of pediatric patients has a more aggressive course with repeated ischemic events and become candidates for surgical intervention.
• MMS has been associated with numerous medical conditions, and it is unclear whether these associations are causative or syndromic.

Anesthetic Considerations

• The incidence of perioperative ischemic events with moyamoya undergoing revascularization surgery ranges from 4% to 18%.³
• The goal of surgery is to increase collateral blood flow by promoting neoangiogenesis and inducing collateral vessel formation. This can be accomplished directly via direct bypass from the superficial temporal artery to the middle cerebral artery, or indirectly via an encephaloduroarteriosynangiosis, encephalomyosynangiosis, or pial synangiosis. These indirect procedures use a segment of the superficial temporal artery or temporalis muscle to promote collateral vessel formation.
• Children are usually treated by indirect revascularization. Adults are treated by direct revascularization or a combination of techniques.
• A thorough preoperative assessment is key, as medical conditions associated with MMD can influence anesthetic management. Prior strokes and transient ischemic attacks are risk factors for perioperative complications.
• Patients may also have pre-existing neurologic deficits from chronic ischemia and be taking chronic anti-seizure medications or anticoagulants, such as low-dose aspirin.³
• Preoperative hydration is recommended. MMD patients should be admitted the evening prior to surgery for aggressive intravenous (IV) hydration. Some protocols recommend 1.5x maintenance IV fluids for a goal urine output of 4 ml/kg/h.⁴
• Premedication with anxiolysis is beneficial in pediatric MMD patients because crying can cause hyperventilation and subsequent hypocapnia with possible cerebral vasoconstriction, decreased CBF, and cerebral ischemia.
• The main anesthetic goals for these patients are to minimize perturbations to CBF (Table 1). This can be achieved by avoiding hypotension and hypoxia, maintaining normocarbia and normothermia, and ensuring adequate anesthesia and analgesia.
• Either inhalational or intravenous induction can be used with careful attention to avoid hyperventilation, hypotension, or stimulation with laryngoscopy.
• Induction and intubation should be smooth to avoid increases in intracranial pressure (ICP) and decreases in cerebral perfusion pressure.
• Normocarbia (goal PaCO₂ of 35-40 mmHg) avoids both vasodilation, which can result in cerebral steal, and vasoconstriction, which can cause ischemia.⁴
• Blood pressure should be maintained at or 15% above the preoperative level. Hypotension refractory to IV fluids may require vasopressors. Intentional hypotension is generally avoided unless there is concern for hyperperfusion or intracranial hemorrhage.⁴
• Some centers use cerebral monitors, such as intraoperative EEG, cerebral near-infrared spectroscopy, and transcranial Doppler. However, these have not been shown to reliably decrease the incidence of perioperative ischemic stroke.^3,4
• Finally, emergence from anesthesia should be smooth to minimize acute increases in ICP and blood pressure. For the same reasons, adequate analgesia throughout emergence and the postop period should be ensured to prevent postoperative agitation and crying, which can lead to hyperventilation, hypertension, and increases in ICP.