**4. Clinical presentation**

Patients affected by MMD present with ischemia like transient ischemic attack (TIA) and stroke and seizures or with intraparenchymal bleeds due to the rupture of fragile collateral vessels formed to compensate for the ischemia. They may also present with headache due to dilated transdural collateral blood vessels. A 2012 systematic review of population-based studies by Kleinloog et al. found that the predominant mode of presentation was ischemia, especially in children [18]. Ninety percent of children present with stroke and 7.5% present with TIA as per International Pediatric Stroke Study published in 2017 [19]. In children, exercise, crying, coughing, straining, fever, or hyperventilation can trigger symptomatic episodes of ischemia.

Adult patients in Japan with MMS mostly present with hemorrhagic stroke in some old reports [20] in contrast to patients from the United States in whom the ischemic stroke was found to be more common [21]. In a study done on 88 Korean patients, 45% of them had only a single ischemic or hemorrhagic stroke, 55% recurrent attacks mostly ischemic, and 64% of them presented with hemiplegia [22].

Ischemic symptoms of MMD are typically associated with the anterior circulation regions like frontal, parietal, and temporal lobes supplied by internal carotid

(ICA) and middle cerebral artery (MCA). Commonly the symptoms are hemiparesis, dysarthria, aphasia, and cognitive impairment [23]. Some patients may present with seizures, defective vision, syncopal attacks, or personality changes and can mimic psychiatric disorders [24]. Surgical patients undergoing minor procedures under anesthesia may present with perioperative stroke due to hyperventilationinduced cerebral vasoconstriction of the already compromised cerebral vasculature of the ischemic penumbra [25]. Patients with MMD can develop cerebral aneurysms at the tip of the basilar artery and the posterior communicating artery and present with subarachnoid hemorrhage [26].

Choreiform movements are another group of symptoms with which children can present due to the moyamoya-associated dilated collateral vessels in the basal ganglia [27]. Occasionally a characteristic ophthalmologic finding is seen in association with MMD identified as "morning glory disk," an optic disk enlargement with concomitant retinovascular anomalies [28].
