pathophysiology compared to patients from Japan. Moyamoya disease can be either congenital or acquired. Patients with Down syndrome, sickle cell anemia, neurofibromatosis type 1, congenital heart disease, fibromuscular dysplasia, activated protein C resistance, or head trauma can develop moyamoya malformations. It is more common in women than in men, although about a third of those affected are male. Pathophysiology The disease moyamoya, which is a Japanese mimetic word, gets its characteristic name due to the appearance of smoke on relevant angiographs resultant from the tangle of tiny vessels in response to stenosis. This makes the blood leak out of the arteries, causing pressure to the brain and subsequent headaches. Over the last six decades since the disease was first described, pathogenesis of moyamoya disease remained elusive, although the gene ring finger protein 213 (RNF213) has been implicated. In September 2021, a south Indian researcher has proposed a pathbreaking theory on moyamoya pathogenesis. Coined the "Mechano-biological theory", the disease has a multifactorial pathogenesis. The authors provide a tangible explanation of the occurrence of moyamoya phenomenon in the idiopathic and syndromic variants of the disease. In short, the authors report that moyamoya disease likely occurs due to a number of factors (e.g., differences in vascular anatomy) that ultimately contribute to broad cerebral blood vessel occlusion and consequent shifts in vessel connections to try to provide blood for the compromised brain. Once it begins, the vascular occlusion tends to continue despite any known medical management. In some people this leads to transient ischemic attacks or repeated strokes with severe functional impairment or even death. In others, the blockage may not cause any symptoms. The disease causes constrictions primarily in the internal carotid artery, and often extends to the middle and anterior cerebral arteries, branches of the internal carotid artery inside the skull. When the internal carotid artery becomes completely blocked, the fine collateral circulation that it supplies is obliterated. Patients often survive on the collateral circulation from the back (posterior) of the circle of Willis, arising from the basilar artery. The arterial constrictions in moyamoya disease are unlike the constrictions in atherosclerosis. In atherosclerosis, the walls of arteries are damaged, leading to the deposition of fat and immune cells, and ultimately the accumulation of immune cells laden with fat. In moyamoya, the inner layer of the carotid artery proliferates within the arterial lumen. The artery also fills with blood clots, which may cause