*Neuropsychology of Moyamoya Disease DOI: http://dx.doi.org/10.5772/intechopen.96558*

also concluded that the location and severity of the vascular involvement might correlate with various ischemic infarction patterns in MMD and require further study.

In pMMD, a state of chronic ischemia persists in the developing brain, and the possibility of persistent neurologic events and progressive intellectual impairment has been recognized, with no significant correlation detected between age at onset and intellectual quotient (I.Q.) when patients have been monitored from childhood into adulthood [25]. I.Q. begins to decrease after the onset of pMMD, and often stabilizes ten years later [26]. Some studies have reported that 10–30% of patients experience difficulties in school life due to intellectual impairment [27–29]. An analysis of 410 consecutive cases revealed that the overall clinical outcome was excellent in 66%, good in 15%, fair in 15%, and poor in 4% of the patients. According to these results, 81% of the patients had a favorable clinical outcome (excellent or good). Multivariate analyses revealed that infarction on presentation was associated with an unfavorable clinical outcome and decreased vascular reserve only on single-photon emission computerized tomography, with favorable clinical outcome. These results indicate that an early diagnosis and active intervention before irreversible hemodynamic changes take place are essential to achieve a favorable clinical outcome in children with MMD [30]. In 2016 Titsworth, Scott and Smith published a U.S.A. national analysis of 2454 pMMD admissions and the effect of hospital volume on stroke outcome. They concluded that high-volume centres provide significantly improved care and reduced mortality in pediatric moyamoya patients, with the most substantial benefit observed in admissions for surgical revascularization [31].

Tho-Calvi et al. described the characteristics and clinical course of a large UK cohort (eighty-eight) of children with moyamoya attended in multiple centres. When they examined prognostic predictors they concluded that pMMD is associated with multiple recurrences, progressive arteriopathy, and poor outcome in half of patients, especially those who present with arterial ischemic stroke (AIS) and posterior circulation involvement [32]. Cooper et al. evaluated the relationship between neurologic outcome one month after diagnosis of pediatric AIS and motor and adaptive behaviour outcomes at 12 months. Their prospective longitudinal observational cohort study recruited sixty-four children (27 neonates, 19 preschool, and 18 school-aged) from a single children's tertiary hospital who were diagnosed with first AIS between December 2007 and November 2013. Neurologic impairment was evaluated at four time points following AIS diagnosis (at 0 months and 1, 6, and 12 months) using the Pediatric Stroke Outcome Measure (PSOM) or the Recovery and Recurrence Questionnaire. Motor function and adaptive behaviour were assessed at 12 months using standardized measures. Children were grouped for analysis according to age at diagnosis (neonates vs preschool vs school-aged). They concluded that PSOM has value as a predictive tool concerning motor and adaptive behavior when it is used one month after the first AIS has been diagnosed, with variation according to age [33]. In the same line, Funaki, Takahashi and Miyamoto reviewed the long-term outcome of pMMD, focusing on late cerebrovascular events and social outcome of pediatric patients once they reach adulthood. Long-term follow-up data for Asian populations suggested that the incidence of de novo hemorrhage increased at the age of 20 or later, even when 10 years has passed since bypass surgery. According to these authors, social adaptation difficulty, possibly related to cognitive impairment caused by frontal ischemia, continues in 10–20% of patients after they reach adulthood, even though no significant disability is evident in daily life [34].

The pathogenesis of pMMD is unknown. It can result in progressive, irreversible brain function impairment, and an earlier onset corresponds with a worse neuropsychological prognosis. Therefore, evidence-based medical treatment of affected

children at an early stage is highly recommended. These treatments consist of direct (intra and extracranial vascular reconstructions, usually involving superficial temporal artery-middle cerebral artery anastomosis) or indirect (multiple burr-hole surgery, encephalomyosynangiosis, and encephaloduroarteriosynangiosis) neurosurgical procedures. This surgery aims to improve the cognitive prognosis, increase the quality of life and reduce the risk of ischemic diseases thanks to improved cerebral hemodynamics [35]. Therefore, compared to adult patients, children with MMD can enjoy a good prognosis if diagnosis and surgical treatment are achieved as soon as possible [36].

In 2018, Kim et al. studied the neuropsychological impacts of indirect revascularization (pre-postoperative) in fifty-five children with MMD. The study was carried out to show that temporal encephaloduroarteriosynangiosis (EDAS) has a positive neuropsychological impact on pMMD patients [37]. The mean age at preoperative evaluation was 9.5 years and the mean age at postoperative evaluation was 10.4. The average interval between initial and follow-up test was ten months. K-WISC-III, the Rey-Kim memory test, the Children's Color Trails Test (CCTT), the Wisconsin Card Sorting Test (WCST), and the Advanced Test of Attention (ATA) were employed to assess patient's neurocognitive profile. Prior to the operation, patients displayed a 54.2% inattention deficit, but only around a 2.5% deficit in verbal memory recall function. After surgery there was a significant increase in performance I.Q. and an improvement of approximately ten scores in memory quotient (M.Q.). The study also reported parietal activation following surgical treatment, which enhanced the ability to interpret visual materials and, which enchanced the ability to interpret visual materials, record, and retrieve visual information. Interestingly, there was a significant improvement in performance in the WCST and CCTT, wich measured prefrontal executive function. Concerning failure to maintain set, no significant postoperative improvements were evident. However, simple and selective visual attention was significantly improved post-operation. The results of neuropsychological field comparison testifies to the effectiveness of temporal EDAS in pediatric MMD patients. This surgical intervention enhances the blood flow in operative areas and improves general cerebral function, including that in frontoparietal domains, leading to an overall improvement in the cognitive function impaired by MMD.

In a sample of thirty children with MMD, Williams et al. [38] examined intellectual and executive functioning. They evaluated the impact of moyamoya type, stroke (clinical or silent), vasculopathy laterality, and disease duration on neurocognitive abilities. All the subjects completed Wechsler Intelligence Scales before therapeutic revascularization procedures were carried out. Reports of executive function were obtained from parents and teachers using the Behavior Rating Index of Executive Function. The children scored significantly lower than the test standardization samples on all indices of intelligence and ratings of executive functioning. The patients did not differ by type of moyamoya or history of stroke. Those with bilateral disease and stroke scored significantly lower than those with unilateral disease on overall intellectual function and verbal comprehension measures. According to teacher ratings, deficits in metacognitive executive functions were even more pronounced in bilateral patients than unilateral ones. Finally, the authors concluded that children with MMD are at risk of intellectual and executive problems, which are exacerbated by bilateral disease and clinical stroke history [38].

Gutierrez-Martignon et al. analyzed the cognitive, academic, and emotional profile of a pediatric case of MMD at diagnosis, on three occasions during evolution (from 9 to 15 years old), before surgery, and after EDAS. An evident cognitive decline in visual attention, processing speed (PS), memory, and visual perception was detected between the first and second evaluations during evolution, while the
