Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

Moyamoya disease is a progressive intracranial arteriopathy characterized by bilateral stenosis of the distal portion of the internal carotid artery and the proximal anterior and middle cerebral arteries, resulting in transient ischemic attacks or strokes. The pathogenesis of moyamoya disease remains unresolved, but recent advances have suggested exciting new insights into a genetic contribution as well as into other pathophysiological mechanisms. Treatment that may halt progression of the disease or even reverse the intracranial arteriopathy is yet to be found. There are strong indications that neurosurgical intervention, through direct, indirect, or combined revascularization surgery, can reduce the risk of ischemic stroke and possibly also cognitive dysfunction by improving cerebral perfusion, although randomized clinical trials have not been performed. Many questions regarding the indication for and timing of surgery remain unanswered. In this review, we discuss recent developments in the pathogenesis and treatment of moyamoya disease.

Background and PurposePatients with moyamoya vasculopathy (MMV) may experience cognitive impairment, but its reported frequency, severity, and nature vary. In a systematic review and metaanalysis, we aimed to assess the presence, severity, and nature of cognitive impairments in children and adults with MMV. MethodsWe followed the MOOSE guidelines for meta-analysis and systematic reviews of observational studies. We searched Ovid Medline and Embase for studies published between January 1, 1969 and October 4, 2016. Independent reviewers extracted data for mean intelligence quotient (IQ) and standardized z-scores for cognitive tests, and determined percentages of children and adults with cognitive deficits, before and after conservative or surgical treatment. We explored associations between summary measures of study characteristics and cognitive impairments by linear regression analysis. ResultsWe included 17 studies (11 studies reporting on 281 children, six on 153 adults). In children, the median percentage with impaired cognition was 30% (range, 13% to 67%); median IQ was 98 (range, 71 to 107). Median z-score was –0.39 for memory, and –0.43 for processing speed. In adults, the median percentage with impaired cognition was 31% (range, 0% to 69%); median IQ was 95 (range, 94 to 99). Median z-scores of cognitive domains were between –0.9 and –0.4, with multiple domains being affected. We could not identify determinants of cognitive impairment. ConclusionsA large proportion of children and adults with MMV have cognitive impairment, with modest to large deficits across various cognitive domains. Further studies should investigate determinants of cognitive deficits and deterioration, and the influence of revascularization treatment on cognitive functioning.

No abstract

Moyamoya vasculopathy (MMV) leads to chronic hypoperfusion predominantly in the middle cerebral artery (MCA) and anterior cerebral artery (ACA) territories. Most revascularization techniques focus on revascularization of the MCA territory. Augmentation of blood flow in the frontal area is important for neurocognition and lower extremity function. In this article we describe a new combined (direct and indirect) one-stage bypass technique consisting of a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with encephalo-duro-synangiosis (EDS) for unilateral MCA revascularization, along with an encephalo-duro-periosteal-synangiosis (EDPS) for bifrontal blood flow augmentation. The strength of this technique is the revascularization of three vascular territories during a single surgical intervention: the MCA unilaterally; and the frontal territories bilaterally. Bifrontal EDPS may also be considered as a supplementary independent procedure for patients who previously underwent revascularization treatment in the MCA territory, but develop symptoms due to frontal hypoperfusion. bypass with an encephalo-duro-myo-synangiosis (EDMS) for unilateral MCA revascularization, along with a encephalo-duro-periosteal-synangiosis (EDPS) for bifrontal blood flow augmentation. The strength of this technique is the revascularization of 3 vascular territories during a single surgical intervention: the MCA unilaterally and the frontal territories bilaterally. Bifrontal EDPS can also be considered as a supplementary independent procedure for patients who previously underwent revascularization treatment in the MCA territory, but develop symptoms due to frontal hypoperfusion.