Pediatric patients with moyamoya disease (MMD) tend to show cognitive impairment, learning disability, and attention deficits as well as neurological abnormalities. The affected area mainly includes the terminal portions of the ICAs and the proximal areas of the anterior or the middle cerebral arteries (ACAs, MCAs)27), although posterior cerebral arteries (PCAs) might be affected in some cases12). Surgical revascularization such as superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and indirect bypass improves their cerebral hemodynamics and prevents further ischemic attacks27). With regard to stroke recurrence and activity of daily living (ADL), postoperative long-term outcome is favorable in both pediatric and adult patients10162036). However, it is also known that intellectual development is impaired in a certain subgroup of pediatric patients429). Even after surgical revascularization, intellectual impairment has been reported to disturb an independent social life in more than 20% of the patients14163436).

The natural course of intellectual outcome is poor in pediatric patients with MMD. Cognitive function is reported to decline within 5-10 years after the onset13). The older patients have a more marked reduction of intelligence quotient (IQ). Lower IQ is closely associated with cerebral blood flow reduction15). More than one-third of them were poorly educated429). Kurokawa et al.29) evaluated the natural course of pediatric patients with MMD and reported that mild intellectual and/or motor impairment was observed in 26% of them, with special school enrollment or care by parents/institutions in teenage years in 11%, and total 24-h care in 7%. Early onset, younger age or longer duration of disease24343541), non-transient ischemic attack (TIA) type or completed stroke patients1435), major preoperative stroke202441), PCA involvement5) have been reported as factors associated with unfavorable social or functional outcomes. However, social outcomes vary in terms of education and employment at adulthood, and a substantial portion of the patients suffer from social adaptation difficulties even after3741).

In pediatric moyamoya disease, in particular, a state of chronic ischemia persists in the developing brain, and the possibility of persistent neurologic findings and progressive intellectual impairment has been recognized. Thus, previous studies have clarified that about 10-30% of the patients had difficulties in social or school life because of intellectual impairment16203436). However, Imaizumi et al.14) found no significant correlation between age of onset and IQ when the patients were monitored into adulthood. In their later work, Imaizumi et al.13) further indicated that the intellectual function begins to decrease after the onset of symptoms but eventually stabilize about 10 years later.

Most of the literatures about cognitive ability in pediatric MMD have focused on intellectual function, yet the results have been inconclusive. Neuropsychological impairments are not infrequent in children with MMD despite normal general intellectual functioning. Some revealed a decline in the intellectual functions947), while others found normal results1530). The pattern of cognitive dysfunction is often associated with lesions in frontotemporal areas. Some risk factors of poor intellectual function have been reported, such as younger age15), younger onset34), and longer symptom duration13). Some also found completed stroke27) and infarction2830) were poor prognostic while the TIA type of symptom presentation usually linked to a better cognitive outcome1314). Hsu et al.11) reported that single-domain cognitive impairment in 15% of patients and multiple-domain cognitive impairments in 23% of TIA type patients. Selective impairments of episodic memory and processing speed were especially noted in those with younger age of onset and prolonged symptom duration1128).

Neuropsychological assessments were preoperatively done on 76 children (boys 31, girls 45, mean of age=8.04 years) with pediatric MMD patients in authors institute. In addition, children with attention-deficit hyperactivity disorder (ADHD) (boys 36, girls 10, mean of age=8.43 years) were selected in clinical control group and thirty-four children (boys 19, girls 10, mean of age=7.85 years) in non-clinical normal control group, who were participating in separate studies that were conducted at the department of clinical psychology, completed the same battery of neuropsychological assessments. On neurocognitive functions, even though the mean of the group on intelligence, memory, executive functions were included within the level of average range, the ratio of belonging to below the average range were 25 to 50%, suggesting declined neurocognitive functions. Among those functions, the decline of performance IQ and memory quotient, and the increased attention and impulsivity problems were remarkable. On emotion and behavioral problems, about 22-25% of children with moyamoya demonstrated significantly increased depression and anxiety, and internalizing problems were reported comparatively much more increased, particularly on social and attention problem. On parenting stress and negative emotion of their mothers, above 30% of mothers of children with moyamoya disease were shown to be experiencing significantly increased parenting stress and depressed mood. On quality of life, children with moyamoya and their mothers reported comparatively low satisfaction on physical, emotion, and academic function (unpublished data).

It is not surprising that the patients of the TIA type showed better intellectual outcome1114). The pattern of functional difficulty seen in MMD patients may result from vasculopathy due to insufficient blood supply of the ICAs in frontal-temporal circuits under moyamoya pathology43). Furthermore these areas are the least revascularized region with either indirect or combined procedures, even though with 'large craniotomy surgery'. There are several features of cognitive functions of MMD patients related to a pathological picture that is consistent to lesions of the frontotemporal regions. First, only free recall but not recognition performances were found defective during memory tests. This contrast of normal acquisition and retention but impaired retrieval ability is commonly seen in patients with subcortical or frontal dysfunction840). Second, memory impairment combined with a deficit of executive function that could be seen in our patients are usually associated with dysfunction in frontotemporal network8). Third, poor performance on the test of psychomotor speed was observed. The slowed processing speed may reflect reduced structural integrity of the white matter associated with frontoparietotemporal systems46). This is worthy of educational attention since learning, memory and goal-directed behaviors are important for daily adaptation and essential for academic accomplishment11). In authors study (unpublished data) learning ability as well as attention were critically impaired. These are critical factor for school life of pediatric MMD patients. However, fortunately the FSIQ were relatively preserved. A direct survey of real life performance level combined with standardized neuropsychological testing will be still valuable in subsequent studies. Recurrent ischemic strokes may result in neurocognitive dysfunction to be a crucial handicap in learning and social adaptation. School absences and the lack of normal classes during the illness and treatment course can exacerbate this situation41). Phi et al.41) surveyed and reported that compared with the general population, the patients showed a similar rate of attaining a higher education. 80% of patients had entered college or university. Phi et al.41) also stressed that the presence of neurological deficits on preoperative examination was a negative predictor of entrance into a college or university, as well as employment. Those children with MMD did not have any problems with acquired knowledge, long-term memory, verbal concept formation ability, mathematical ability, vocabulary, social comprehension, or attention span before surgery, and that those abilities were maintained well after surgery. This maintained ability resulted that 48% of patients showed no change of school performance, 15% showed improvement, and 28% reported worsened school performance after surgical treatment41). Definitely the cognitive function is an important factor in determining social outcome, especially after school age. Most of the papers about the surgical outcomes for these patient population insisted that appropriate surgical intervention could reduce further ischemic insults and neurological deteriorations23132343537). Conservatively treated pediatric patients showed poor long-term intellectual outcome131429). Hence, a role for early active surgery to save the intellectual abilities of children with MMD should be stressed again to reduce the development of neurological deficits, major lobar infarction or hemorrhage30).

The prediction of the long term outcome of MMD patients is extremely difficult because of the progressiveness of natural course and bilateral discrepancy of this disease. It is reasonable assumption that less neurological insult will lead to better cognitive outcomes. However, the impact of MMD on cognition is still unclear. Even if the surgical treatment may result in good neurological outcomes the relationship between surgical treatment and cognitive outcome need to be investigated. Further clinical studies should be focused on a wide range of neuropsychological testing and cerebral blood flow and metabolism measurements in large series.