By Vincent Musser

Moyamoya disease is a rare cerebrovascular condition characterized by progressive stenosis of the internal carotid artery. The stenosis and resulting hypoplasia of the internal carotid artery lead to the dilation of proximal blood vessels as a consequence of the body's attempt to compensate for the reduced blood flow. The enlargement of the minor vasculature can be seen on   an   angiogram and   is   often   compared   toもやもや (moyamoya), which is Japanese for a "puff of smoke" (see Fig. 1).

There are six stages of Moyamoya Disease progression. These stages are referred to as the Suzuki Grading system (see Table 1). Note that the characteristic "puff of smoke" is not present in all stages. For example, the characteristic disappears in stage VI. This is largely due to a re-routing of the vasculature. Though the collateral vessels may initially expand due to the stenosis of the internal carotid artery, it must be noted that the vessels are ultimately supplied by the internal carotid artery. Thus, after severe progression of the disease, complete blockage of the internal carotid artery may occur, leading to a lack of blood supply from these collateral vessels as well. The "puff of smoke" thus disappears, and blood supply is often derived from the basilar and posterior arteries instead (see Fig. 2).

Disease etiology of Moyamoya is still largely unknown, even though the disease was first discovered nearly seven decades ago. Cellular analyses have proposed some potential aggravating genes and genetic analyses have determined that around 10% of Moyamoya cases are familial, but due to the lack of an animal model, the decreasing number of autopsies performed on Moyamoya patients since the 1990s, and other miscellaneous factors, the cause behind Moyamoya disease remains shrouded in a puff of smoke, so to speak. 

Despite the lack of knowledge of the exact cause behind Moyamoya, certain patterns have arisen thus far. For example, it is known that Moyamoya is bimodal with respect to age, affecting primarily children around the age of 5 and adults in their mid-40s. Females are also around twice as likely to develop the disease. Japan exhibits a significantly higher incidence rate compared to the rest of the world. For reference, Japan's incidence rate is around 0.35 cases per 100,000 children, which is around ten times higher than that of Europe's. This higher incidence rate in Japan may be the reason behind the Japanese name of the disease. 

Symptoms of Moyamoya disease are often not consistent across patients due to the large variability in potential stenosis and variability in how the vasculature responds. Nonetheless, symptoms can often be grouped into two categories: symptoms due to stenosis (such as stroke) and symptoms due to the new apportionment of blood supply (such as a hemorrhage, which is likely caused by the increased blood flow through fragile, minor vessels). Patients usually present with symptoms in the former category, with 50-75% of patients presenting with stroke and 10-40% of patients presenting with hemorrhages. 

Diagnosis of Moyamoya is often difficult, not only because the symptoms described above can be characteristic of multiple other diseases, but also because the disease is especially rare, so it is often at the bottom of a physician's list of differential diagnoses. CTs, MRIs, and/or angiograms are often required to support/refute the diagnosis of Moyamoya. Specialists in Moyamoya are also often consulted to confirm a diagnosis.  

Non-surgical treatments—such as anticoagulants and antiplatelet agents—have largely proved unsuccessful in treating Moyamoya. Those that originally opt for non-surgical options usually ultimately end up undergoing surgery anyway due to the progression of the disease. Surgical treatment typically involves the re-direction of other arteries—especially the external carotid artery—to revascularize the area.

Surgical processes can be direct or indirect. Direct surgical intervention involves bypass surgery in which nearby arteries are anastomosed (connected) to a cortical artery. Indirect surgery involves placing vascular tissue in direct contact with the brain in the hopes that the development of new blood vessels will vascularize the underlying cortex. Direct treatment is often recommended for adults, as the direct approach often leads to a greater increase in blood flow. However, indirect treatment is often recommended for children, as the small size of blood vessels makes bypass surgery difficult. 

Indirect surgical techniques include encephaloduroarteriosynangiosis (EDAS), multiple burr hole procedure, and encephalomyosynangiosis (EMS). In EDAS, which is the most common procedure, the scalp near an artery is dissected and the bone flap is replaced such that the artery dives beneath the scalp onto the level of the brain (see Fig. 3). The proximity of the artery to blood-deficient tissue is thought to encourage branching of the artery, thereby restoring blood flow (see Figs. 4, 5). In a study of 143 patients treated with EDAS, patients displayed a remarkable decrease in the number of presented strokes, with 67% of patients having strokes before treatment and 7.7% having strokes in the perioperative period. Stroke presentation decreased further with increasing time after the surgery. The multiple burr holes procedure is similar to EDAS, except that there is no vessel synangiosis. It is thought that, given the openings to the brain via the burr holes, the vasculature will extend into the level of the brain by itself. 

In total, Moyamoya is a rare and puzzling disease whose etiology has largely eluded professionals. Despite the shortcomings of some of the research, the disease has managed to earn a fascinating title (and history!), and the surgical techniques used to resolve the disease are certainly one-of-a-kind.

References

Houkin, Kiyohiro; Ito, Masaki; Sugiyama, Taku; Shichinohe, Hideo; Nakayama, Naoki; Kazumata, Ken; Kuroda, Satoshi. "Review of Past Research and Current Concepts on the Etiology of Moyamoya Disease". Neurologia medico-chirurgica, vol. 52, no. 5, 2012,pp. 267-277. doi: 10.2176/nmc.52.267. 

"Moyamoya Disease Surgery for Children: Pial Synangiosis." YouTube, uploaded by The Children's Hospital of Philadelphia, 11 Sept. 2015, www.chop.edu/video/moyamoya-disease-coordinated-approach-care.

Scott, R. Michael; Smith, Edward R. "Moyamoya Disease and Moyamoya Syndrome". New England Journal of Medicine, vol. 360, no. 12, 2009, pp. 1226–1237. doi: 10.1056/NEJMra0804622.

Scott, R. Michael; Smith, Edward R. “Surgical management of Moyamoya syndrome.” Skull Base, vol. 15, no. 1, 2005, pp. 15-26. doi: 10.1055/s-2005-868160.

Suzuki J, Takaku A. “Cerebrovascular ‘Moyamoya’ Disease: Disease Showing Abnormal Net-Like Vessels in Base of Brain.” Arch Neurol., vol. 20, no. 3, 1969, pp. 288–299. doi: 10.1001/archneur.1969.00480090076012