**3. Asymptomatic moyamoya disease**

It has been described as moyamoya features in the absence of any ischemic or haemorrhagic stroke [12]. The number of these patients has increased progressively over the years with improved diagnostic capacities [5, 24, 29–32] and the introduction of regular medical brain check-ups [12, 33]. In the Japan brain check-ups, the percentage of positive asymptomatic moyamoya patients was 0.07% (0.05% for males and 0.10% for females) with a female to male ratio of 3.3:1, mean age of 54 years [33]. Most of these asymptomatic patients were adults [34–37]. In children, the diagnosis can be unduly delayed due to their inability to communicate adequately, particularly at a very young ages [38].

But clinically asymptomatic patients do not mean that they have no pathological findings. In Japan, 20-30% of them harboured a cerebral infarction in watershed brain areas [24, 31] while the incidence of asymptomatic brain infarction in the general Japanese population in their fifth decade of life was 4.4% [39]. Additionally, 15-44% of adult moyamoya asymptomatic patients have clinically silent microbleeds [40–42] in the basal ganglia, thalamus and periventricular areas [43]. In a multicenter study in Japan, 34.3% of asymptomatic moyamoya patients with a normal cerebral blood flow had reduced cerebral vascular reserve [43]. In the follow-up, 12.5% [30] to 30% [12] of these patients suffered transitory ischemic attacks, ischemic or haemorrhagic stroke [12, 24, 31, 32], with a 3.2% annual stroke risk [12, 30, 31]. The female gender was associated with a greater risk of disease progression [31].

In Korea, the symptomatic progression in asymptomatic moyamoya patients was radiological in 12% and clinical in 5.3% with a reduced cerebral reserve capacity in 9.3% [30]. Clinical progression has been the rule worldwide for paediatric asymptomatic moyamoya patients [44]. As asymptomatic moyamoya disease is not a stable situation [12, 45, 46] close surveillance is mandatory, notably if there is a reduced cerebral vascular reserve [12, 30], ivy sign on MRI flair imaging [47, 48] or smoking habit [12]. The ivy sign is associated with an impaired cerebrovascular hemodynamic status [47]. It has been reported in 31.3% of asymptomatic moyamoya patients [47] that rises to 66% in those that already have ischemic stroke-related symptoms [48–50].

Moreover, these patients are not entirely asymptomatic but suffer from a steady cognitive decline in intelligence, spatial imagination, working memory, working memory-backwards digit span, computational ability, complex subtraction, complex arithmetic and word short-term memory [8, 51], particularly in children [45, 52, 53]. This cognitive decay precedes the onset of clinical symptoms due to brain infarction, or haemorrhage [8] and inevitable worsens when these cerebrovascular insults happen [51, 54]. Additionally, asymptomatic moyamoya patients can suffer from ischemic or haemorrhagic strokes [31]. Another critical aspect is that 20% of moyamoya children who undergo ischemic strokes are handicapped to undergo an independent social life [45, 53, 55].

Some have recommended performing surgical revascularization on asymptomatic moyamoya patients, particularly children, to prevent this unpleasant progressive neurological and cognitive deterioration [30, 44, 54]. Some have suggested undertaking surgical treatment if the ivy sign is seen in MRI flair imaging [47]. In any case, symptomatic progression in previously asymptomatic patients should be addressed with aggressive surgical revascularization in adults and children [30] as it halts disease progression [31].
