Letter: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

Abstract

To the Editor: Recently, we read with great interest the article by Quon et al1 regarding the early diffusion magnetic resonance imaging (MRI) changes in normal-appearing brain in pediatric moyamoya disease (MMD). The authors found the significantly elevated apparent diffusion coefficient (ADC) values for MMD children in the representative brain regions could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve (CVR). We really appreciate the interesting observation for their conclusion. Meanwhile, we would like to highlight 3 important questions that it raises. First, in recent years, the researchers of MMD have gradually formed a consensus: prior to the obvious ischemic changes on MRI, the microstructural impairments caused by reduced blood supply had appeared in the brain of MMD patients.2,3 Hypoperfusion and cytotoxic edema have been considered as the major cause of microstructural impairments.4,5 There are 2 different types of cerebral ischemic edema: the early cytotoxic type and the later vasogenic type. When the stimulation of anaerobic metabolism leads to the increase of osmotic pressure of brain tissue, which leads to the swelling of permeable cells, cytotoxic edema occurrs.6 With the development of tissue necrosis and the degradation of basement membrane, the blood-brain barrier is destroyed, and serum protein begins to leak into the brain from the blood, thus further improving the water content of the tissue and a later vasogenic type occurrs.7 However, due to the insensitivity of conventional MRI to the cytotoxic edema, most MMD patients had already suffered serious brain parenchymal damage by the time they receive treatment. In the present study,1 via the high sensitivity of diffusion-weighted imaging in distinguishing cytotoxic and vasogenic edema,8 the authors found the ADC value could precisely differentiate pediatric MMD patients from normal controls in the absence of imaging evidence of ischemic stroke. This observation indicated that it is possible to detect the serious imbalance of energy supplies and demands via the ADC value before the occurrence of irreversible lesions in brain parenchyma in MMD patients, so as to timely implement the intervention measures to obtain the maximum clinical effect. Second, revascularization surgery is considered to be the most effective way to treat MMD. Previous studies have confirmed that the preoperative clinical and hemodynamic changes could indicate the outcomes and complications from revascularization surgery for MMD patients.9,10 However, which severity of the preoperative changes in MMD patients can maximize the benefits from bypass surgery has always puzzled neurosurgeons. Recently, many non-invasive examination methods and indicators, such as CVR,11 ivy sign,12 and cortical hyperintensity belt sign,13 were proposed to reflect the clinical severity of MMD before obvious (usually means serious) changes appear on conventional MRI. The same is true for the ADC value in present study. Third, the authors in present study1 tried to explain a possible relation between the elevated ADC value and the impaired CVR. Although previous studies have observed simultaneous appearance of reduced CVR and elevated ADC in MMD patients, the mechanism remains to be clarified.14 In our opinion, CVR reflects the compensatory ability of cerebral arteries to compensate for the hypoperfusion, and its mechanism may partially due to the vasodilatory stimulation of metabolites like lactate to arteries. Meanwhile, the early cytotoxic edema in MMD patients may also due to the change of metabolism in brain cells during hypoperfusion.6 Therefore, there may not be a direct causal relationship between impaired CVR and elevated ADC, they may be 2 simultaneous results of the same change (hypoperfusion). Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.