Pediatric moyamoya is typically treated with surgical revascularization. In this chapter, we review variations of surgical treatments of this disease, with a specific focus on methods of encephalo-duro-arterio-synangiosis. This approach employs vascularized tissue supplied by the external carotid artery to serve as a graft to ischemic territories of the brain. Surgical indications, preoperative evaluation, perioperative management, and technical nuances—with relevant illustrations—will be discussed.
Keywords: encephalo-duro-arterio-synangiosis, pial synangiosis, moyamoya, indirect, pediatric, revascularization, stroke
Indirect procedures for moyamoya syndrome tend to be reserved for pediatric patients where there is more successful collateralization, when compared with direct revascularization and where direct procedures are difficult due to the small size of the arteries. Indirect procedures include encephalo-myo-synangiosis, encephalogaleo-myo-synangiosis, encephalo-duro-arterio-synangiosis, pial synangiosis, omental transplant (encephalo- omental synangiosis), and multiple burr holes. All are based on the observation that vascularized tissue placed on the brain induces vascular collateralization from the graft to the brain. Encephalo-duro-arterio-synangiosis (EDAS) involves the use of the dura and a branch of the superficial temporal artery (STA) to revascularize the brain. Originally described by Matsushima, the technique uses a branch of the STA to revascularize the brain by suturing the vessel in between two leaves of dura. A variant of this procedure, pial synangiosis, was developed by R. Michael Scott and differs by (1) affixing the STA to the brain surface with pial sutures and (2) widely opening the arachnoid to facilitate ingrowth of new vessels in response to growth factors elaborated by the ischemic brain. Pial synangiosis has become widely used in the pediatric population in the United States.
With caveats, the analysis from American Heart Association (AHA) concluded that “the data from the medical literature suggest that surgical revascularization is a safe intervention for pediatric moyamoya syndrome and most treated patients derive some symptomatic benefit.” The authors offer revascularization for patients with radiographic evidence of moyamoya, as defined by Suzuki grade II-VI on angiogram (or comparable findings on magnetic resonance angiogram/computed tomography angiogram [MRA/CTA] in the rare cases when catheter angiography is not possible), typically coupled with evidence of diminished or limited brain perfusion (most commonly the presence of “ivy sign”—hyperintense sulcal signal on axial fluid-attenuated inversion recovery (FLAIR) MRI, but also with evidence from other perfusion studies when necessary). This radiographic evidence is paramount, but clinical examination is important for decision making. Symptomatic patients are usually offered surgical treatment, but asymptomatic children are also operated if the imaging findings indicate severe perfusion deficits or progression of disease over time. In contrast, contraindications to surgery include evidence of preexisting neurologic devastation or very early disease (Suzuki I or II without perfusion problems) in an asymptomatic patient.
Surgical procedure selection is predicated on the symptom presentation, patient age, and anatomy. In most cases, there is a predilection to choose pial synangiosis over direct bypass, because of the data supporting the long-term durability of these grafts, and the ability to offer this operation to any age group. In patients without suitable vessels, myosyangiosis (using temporalis muscle) or pericranium with dura are suitable alternatives. Direct bypass is typically reserved for patients with vessels large enough for anastomosis (often teens or older), coupled with acute presentation of rapidly progressive strokes.
Regarding timing, the general principle of minimizing the time between diagnosis and revascularization is supported.
• Delays may be reasonable to schedule experienced anesthetic/intensive care unit (ICU).
• Medical contraindications may mandate delays (such as recent infarction, infection, or hemorrhage) (Class IIb C).
The surgical technique of EDAS is unique in the focus on creating a direct connection between the recipient brain and donor tissue. This principle is best exemplified by the most common subtype of EDAS used in the United States for children, pial synangiosis. In this procedure, an indirect anastomosis of the parietal branch of the superficial temporal artery is made to the cerebral cortex. Like other indirect operations, it also benefits from the recruitment of collateral vasculature from adjacent tissue, such as the dura and middle meningeal vessels. It differs from other EDAS procedures because pial sutures and the aggressive approach of a wide arachnoidal opening are used. The principle of the pial sutures rests on the concept that the normal pulsatile nature of the brain and donor vessel might inhibit growth of new vasculature, but suturing them together reduces relative motion and facilitates better growth.
The wide arachnoidal opening is perhaps the biologically most important aspect of the surgery, as recent data have revealed the significant role of angiogenic growth factors in the spinal fluid and embedded in the extracellular matrix of the pia as contributors to new vessel growth. Opening the arachnoid offers the double benefit of removing a mechanical barrier to ingrowth while also facilitating improved contact between nascent vasculature and growth factors.
Assessment of EDAS using SWOT analysis is summarized below.
• EDAS can be applied with any age group and any size artery.
• No concerns with proximal vessel stenoses that might limit retrograde filling with direct bypass.
• It is technically less challenging than a direct bypass, with no clamping time or potential ischemic period.
• It can be used in any vascular territory and can be expanded to cover as much cortex as wanted, with a broader area of revascularization.
• It takes time for the donor vessels to grow in, thereby not providing immediate protection.
• Preexisting spontaneous transdural collaterals may limit surgical exposure.
• Indirect bypasses can sometimes be combined with direct procedures (although committing donor vessels to direct bypass necessarily limits distal revascularization).
• Laboratory data suggest that angiogenesis can be accelerated with biological agents, offering opportunities to enhance the speed and effectiveness of this approach in the future.
• Donor vessels may not grow if there is no underlying brain ischemia to drive angiogenesis.
• Patient selection needs to be tailored to surgical approach.
There are a number of contraindications to EDAS. These can be divided into general contraindications for revascularization surgery of any sort with moyamoya and specific contraindications to EDAS.
6.5.1 General Contraindications to Revascularization Surgery
• Unclear angiographic (or MRI) evidence of moyamoya.
• Medically unstable for operating room (OR).
• Recent stroke (may increase risk of general anesthesia and might consider 4-6 week delay).
6.5.2 Specific Contraindications to EDAS
• May not produce robust collateral growth if poor ischemic drive, so EDAS may not be suitable for early- stage, asymptomatic moyamoya (Suzuki I/II).
• Rapid, repeated strokes in a short period of time may suggest a role for direct bypass if a proper vessel and anatomy is favorable, given the delay inherent to EDAS revascularization.
Several special considerations are worth reviewing while performing EDAS. Given the importance of underlying ischemia to drive surgical collateral vessel growth, the presence of radiographic evidence of ischemia (such as ivy sign on axial FLAIR imaging in MRI) is important. In some cases, arterial spin labeling (ASL) may be a useful adjunct to document ischemia if other studies, such as single-photon emission computed tomography (SPECT), are not available or practical in a pediatric population.
Aspirin is generally used in all cases, typically with doses adjusted for weight. For practical purposes, 41 mg/ day is given to children 3 years of age and younger, 81 mg/day is given to all others (including adults), but some obese patients (100 kg or more in weight) or those with limited aspirin resistance may require higher doses (up to 325 mg twice a day). Some patients may exhibit varying degrees of innate aspirin resistance, in which case some institutions perform specific testing to assess the degree of impairment. In other cases, children may experience side effects from the aspirin, such as bruising or stomach upset. In these cases, adjusting the dose of aspirin often solves the problems, but alternatives exist in the use of low-molecular-weight heparin or other antiplatelet agents, if necessary. Consultation with hematology may be helpful in these circumstances.
Lastly, pediatric moyamoya has a high percentage of children who have arteriopathy in association with other systemic disorders (neurofibromatosis, sickle cell disease, Down’s syndrome, etc.). In these complex medical cases, multidisciplinary consultation is often important to coordinate care and reduce risk of surgical intervention.
The overall perioperative stroke rate is reported at about 4.5% per hemisphere (during the operation and subsequent 30 days postoperatively). This rate varies in different populations, with higher risk associated with younger age (under 3 years of age), syndromic cases (Down’s syndrome and sickle cell disease in particular), and history of recent stroke (within 1 month prior to surgery). Another known risk factor for perioperative stroke is the presence of transdural collateral vessels. It is particularly important to consider a full catheter angiogram (including the selective injection of the internal carotids, external carotids, and vertebrobasilar system) to fully detail the extracranial circulation. This allows identification of any preexisting, spontaneous transdural collateral vessels that may be supplying the cortex, thereby reducing the risk of inadvertently interrupting these vessels during surgery. This is particularly important in children who have already undergone any cranial operations (ventricular shunt, tumor, etc.).
The technical aspects of the surgery include several unique steps. Preoperatively, the patient is admitted the day before surgery for overnight intravenous hydration and aspirin therapy is continued right up to, and including, the day before surgery.
On the day of surgery, intraoperative electroencephalographic (EEG) monitoring may be used to help identify real-time changes in cerebral blood flow, as indicated by EEG slowing, allowing anesthesia to adjust blood pressure, carbon dioxide (CO2) levels, and medications. Positioning is important, keeping the neck as neutral as possible with the use of a shoulder roll and bed turning, in order to prevent kinking of vessels in the neck and concomitant reductions in cerebral blood flow. Keeping the STA course flat relative to the floor and seating on opposite sides of the vessel with the microscope will aid an easy dissection for both the surgeon and assistant.
During the initial dissection of the STA, the risk of vessel injury can be minimized by exposing the vessel in small segments. Arachnoidal opening is critical and spending time to widely open as much area as possible is important. Use of an arachnoid knife, linear openings along cortical vessels, and sharp dissection with microscissors are helpful techniques. At closure, the risk of cerebrospinal fluid (CSF) leak can occur if there is inadequate galea closure. Careful inspection of the wound prior to skin suture placement can reveal areas that may need additional sutures.
Immediate postoperative care should be administered in the ICU, with the goals of avoiding hypotension and hypocarbia. Generally patients are extubated, awake and have an arterial line (for blood pressure management) and a bladder catheter (for monitoring volume status). Antibiotics are used for 24 hours. Aspirin is administered on postoperative day #1. Antiepileptics are not routinely prescribed. Intravenous fluids are run at 1 to 1.5 times maintenance and slowly decreased as the ability to take oral fluids recovers. Pain control is important and frequent neurological examinations are critical to detect any changes in examination. The patient is encouraged to ambulate as soon as possible and children are managed to minimize pain and anxiety (as crying can cause vasoconstriction and potentially increase the risk of stroke).
• The patient is placed supine in the Mayfield head holder or on a headrest with a roll placed under the ipsilateral shoulder. The head is turned to the contralateral side (Fig. 6.1).
• The STA is marked by Doppler ultrasonography, and a linear incision is made over it. The artery is skeletonized with perivascular tissue using the microscope (Fig. 6.2).
• The temporalis muscle is incised in a cruciate fashion and the craniotomy performed based on burr holes placed at either end of the arterial segment. The dura is incised along the artery and in flaps so as to allow retraction of the dura (Fig. 6.3).
• The arachnoid is incised widely under the microscope. The superficial temporal artery is then placed on the pial surface and sutured to the pia using 10-0 monofilament sutures (Fig. 6.4).
• Several sutures are placed to encourage tight approximation of the artery to the brain surface.
• When replacing the bone flap, care must be taken to prevent stretching the artery. The artery must enter and exit the burr holes in a gentle curve without tension (Fig. 6.5).
• The temporalis muscle is loosely approximated so as not to kink or occlude the artery. The galea and skin are closed in the standard fashion, taking care not to injure the artery.
There are general problems that can occur at any time during a moyamoya procedure.
• EEG slowing can herald reduced cerebral blood flow (possibly from spasm or blood pressure changes) and bolus administration of propofol may serve to reduce metabolic demand of the brain and thereby provide a neuroprotective effect.
• Bleeding is particularly troublesome and may be more pronounced if aspirin is used. Meticulous hemostasis is crucial, although “over-cautery” will only serve to deprive the brain from potential additional sources of blood supply.
• Brain swelling (unrelated to direct bypass) can create a cycle of reduced venous outflow—feeding more swelling. Elevation of the head of the bed, opening of arachnoid to drain CSF, and increased sedation are all tools to help. Hyperventilation and driving down pCO2 should be avoided in moyamoya patients, as this may precipitate vasoconstriction and stroke in a brain with a tenuous blood supply.
The major risk of this surgery is perioperative stroke. Steps to mitigate this risk include:
• Preoperative hydration (admitting patients one day before surgery for intravenous fluids).
• Ongoing use of aspirin, including the day before and the day after surgery.
• Good pain control to minimize crying/hyperventilation (in order to avoid hypocarbic-related vasoconstriction).
Despite these measures (in addition to careful operative and anesthetic technique) a number of children will still experience strokes. Limitations of this technique include:
• Operator-independent capacity for stroke.
• Delayed ingrowth of collateral vessels, leaving a period of relative vulnerability to ischemia (for indirect procedures).
• Arterial injury: Can employ frontal branch, posterior auricular.
• No artery: Can use muscle, galea, dura as an alternative source of blood supply.
• EEG slowing/swelling: Anesthetic changes, including administration of propofol.
In bilateral cases, the dominant or most symptomatic side is generally done first, so that if there are intraoperative events that preclude continuing with the second side, the most important hemisphere has been treated. If the EEG and vital signs are stable, the patient is repositioned and the same operation is performed on the contralateral side in the same anesthesia.
• The most important aspects of this procedure may be nontechnical, including preoperative hydration and experienced anesthesia.
• Mapping as much STA as possible will increase potential collateral development.
• Wide opening of the arachnoid facilitates exposure of the donor vessel to growth factors present in the CSF, increasing the likelihood of better collateralization.
• Hemostasis at all stages of the operation is critical.
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