Methylene blue "avatar" brain.

Methylene blue is a safe and effective therapeutic agent used in a variety of different clinical settings, including as treatment for methemoglobinemia, reversing ifosfamide-induced encephalopa-thy, severe hepatopulmonary syndrome, and as a pressor during catecholamine-refractory septic shock (1). Of more relevance to neuropathologists, it has recently been experimentally tested as a dye in multimodal confocal imaging of brain tumors for intraoperative detection of brain tumors (2), for ischemic/reperfusion injury (3), and, because it seems to prevent aggregation of tau and A-amyloid, as a potential therapeutic agent for neurode-generative disorders such as Alzheimer disease (4) and Huntington disease (5, 6). As such, neuropathologists may encounter patients at autopsy treated with methylene blue. Methylene blue generates a clinically innocuous, self-limiting, but striking blue-green discoloration to the urine, skin, and mucosa of treated individuals as a by-product of its use (1, 7, 8). This systemic tissue discoloration is more well known than is discoloration of brain tissues , which, to our knowledge, has only been reported once previously (9). The tissues were reported to transform into a bright blue-green color when the color-less leukomethylene blue molecule undergoes oxidation to methylene blue on exposure to air (9). We share our recent experience with brain tissue discolor-ation and methylene blue use, capturing the transition from colorless to colorful during a very short time interval at the time of autopsy. A 20-year-old woman with asthma and surgically repaired coarctation of aorta was transferred to our hospital for refrac-tory respiratory failure, hepatopulmonary syndrome, and possible cirrhosis. Her hospital course was complicated by persistent altered mental status, respiratory failure, acute kidney injury, and hypotension. Hypotension became refractory to cate-cholamines, necessitating the use of methylene blue to maintain stable pressures and to reduce possible shunting. She succumbed soon after transfer; autopsy demonstrated that her demise was caused by acutely decompensated high-output heart failure with left-to-right shunting from a clinically suspected and autopsy-demonstrated subdiaphragmatic vascular malformation. On opening the cranial vault, the brain surface quickly transformed on exposure to air to a pale blue-green color (Fig. A) that intensified and darkened even during a short time interval after removal of the brain (Fig. B). The color became particularly striking after forma-lin tissue fixation (Fig. C). The blue color relatively spared the dura (Fig. C), optic and cranial nerves (Fig. B), and deep white matter on coronal section (Fig. D), contrasting with the intense discoloration in cortical and subcortical gray matter (Fig. …