**2. Pediatric Moyamoya disease (pMMD)**

During the onset of Pediatric Moyamoya disease (pMMD), progressive occlusion occurs at the end of the intracranial internal carotid artery, and compensatory net-like abnormal vessels develop in the skull base, generating several clinical symptoms. These collateral vessels mimic a "puff of smoke" when revealed by and angiogram [11]. pMMD can affect both children and adults, but pediatric patients exhibit distinct clinical features, and treatment and prognosies differ from those in adult patients [12].

The distinctive clinical profile of pMMD includes headache, cognitive impairment, hypertension, temporary or permanent blindness, hemiplegia, general paresis of the insane, loss of sensation, aphasia, and mechanisms related to ischemia in the frontal, parietal, and temporal lobes [13, 14]. Children are at a higher risk of suffering Moyamoya Disease (MMD) and the condition is more severe in young children, especially those under four years, in whom the prognosis is often poor [15]. In children, the disease mainly manifests as ischemia, while bleeding is the primary symptom in adults [16]. Despite normal general intellectual functioning, some children with moyamoya disease exhibit cognitive deterioration, primarily learning disability, attention deficit, episodic memory, slow processing speed and neurological abnormalities [17]. Cognitive impairment is not generalized in all children, since some show neuropsychological alterations and others do not. The worst prognosis tends to be seen in children who have had a stroke or cerebral infarction. In contrast, Transient Ischemic Attack (TIA) usually has a better cognitive prognosis [18, 19], with only 15% of patients exhibiting single-domain impairment and 23% showing multiple cognitive domains to be affected after a TIA [20]. The affected area usually includes the terminal portions of the Internal Carotid Arteries (ICAs) and the proximal areas of the anterior or middle cerebral arteries, although Posterior Cerebral Arteries (PCAs) can be affected in some cases [21]. The pattern of cognitive dysfunction is often associated with lesions in frontotemporal areas, with young age [22] and young onset of the disease [23] proving to be the main risk factors for poor neuropsychological outcomes.

Moyamoya disease is characterized by progressive cerebrovascular stenosis with recurrent cerebral ischemic events. TIA attacks are often associated with hyperventilation in children with moyamoya, pointing to hypoperfusion rather than thrombotic vaso-occlusion as a prominent mechanism. The patterns of ischemia and severity of steno-occlusive disease in such children may hold clues to these mechanisms. In this sense, Rafay et al. studied twenty children (between 1 month to 18 years) with MMD in a neuroradiological MRI and angiography [24]. The initial clinical presentation revealed neurological deficits in 17, recurrent TIA in 7, headache in 8, seizures in 8, and alteration in consciousness in 4 children. Infarcts were bilateral in 13 (65%) children (ischemia alone was observed in 14, ischemic stroke with hemorrhagic transformation in two, and primary hemorrhage in two). Infarcts were cortical and/or subcortical in 13 (65%), both deep and cortical watershed in 11 (55%), and cortical watershed alone in 5 (25%) children. The predominant vascular territory involved was the middle cerebral artery. The internal carotid arterial system was involved in all cases, with stage IV being the most frequent angiographic stage. The authors concluded that ischemic injury in deep watershed zones is common in pMMD and may reflect non–vaso-occlusive ischemic mechanisms. They
