1873 Cerebral Hyperemia in MELAS T.I. Gropen, MD; I. Prohovnik, PhD; T.K. Tatemichi, MD; M. Hirano, MD Background The pathophysiology of strokelike episodes in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) is uncertain. Case Description We studied a 24-year-old man with MELAS who had fluent aphasia and right hemianopia. Magnetic resonance imaging and computed tomography showed a large infarction in the parietal, temporal, and occipital lobes. We performed serial planar 133Xe regional cerebral blood flow studies and single-photon emission computed tomography. Fifteen and 26 days after the strokelike episode, there was generalized hyperperfusion, highest in infarcted areas. Four and 8 months after the strokelike episode, the brain was still hyperemic, with highest flow in noninfarcted tissue. Reactivity to CO2 was less than normal within the infarct at 26 days but improved thereafter. In the noninfarcted region, vasomotor reactivity was impaired at 4 months, when resting flows were at their peak. Conclusions We observed generalized cerebral hyperemia and fluctuating CO2 reactivity in MELAS, possibly a consequence of local lactic acid production. In addition, this case suggests that nonquantitative functional imaging may be misleading in MELAS. (Stroke. 1994^5:1873-1876.) Key Words • cerebral blood flow • diagnostic imaging • MELAS syndrome • mitochondrial encephalomyopathy ince 1984, when Pavlakis et al1 introduced the acronym MELAS for mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, much progress has been made in understanding its underlying genetic and biochemical basis. In most reported cases, MELAS has been associated with a point mutation of mitochondrial DNA and complex I deficiency.2 However, the relation between laboratory abnormalities and clinical manifestations is not clear. Some characteristic symptoms such as nausea, vomiting, and exercise intolerance may be related directly to the lactic acidosis that results from impaired oxidative metabolism. The pathophysiology of strokelike episodes in MELAS is less certain. Some investigators have emphasized the importance of pathological changes in cerebral vessels,3-4 but abnormal brain metabolism has also been implicated.We carried out a serial quantitative study of cerebral perfusion and hypercapnic reactivity after a strokelike episode in MELAS. Our observations support the possibility that local production of lactic acid may be the basis for strokelike events and other cerebral manifestations of MELAS, and they underscore the limitations of nonquantitative functional imaging in investigation of diseases with diffuse alterations of cerebral blood flow. retardation in the brother of his maternal grandmother and short stature in his mother and one of his two brothers. He was well until age 24, when he was admitted to a local hospital after a generalized seizure at home. Cerebrospinal fluid protein was 56 mg/dL but was otherwise normal. Computed tomography (CT) demonstrated extensive calcification of the basal ganglia but was otherwise normal. The electroencephalogram (EEG) was normal. Five days after admission, another seizure occurred, and postictally the patient was found to have a right hemianopia and aphasia. CT and magnetic resonance imaging (MRI) performed after the event revealed infarction in the left parietal, temporal, and occipital lobes. Seven days after the strokelike episode, the EEG showed left-sided delta activity and sharp waves. Examination at Columbia-Presbyterian Medical Center 13 days after the strokelike episode revealed fluent aphasia with prosodic but empty speech; semantic paraphasic errors; severely impaired auditory comprehension, naming, reading, and writing; and less impaired repetition. In addition, we found poor memory, right hemianopia, pigmentary retinopathy, and right-sided hemisensory loss. Cerebral angiogram 14 days after the strokelike episode showed normal major vessels, including the carotid and vertebral arteries, but mild irregularity and slow filling of the calcarine branch of the left posterior cerebral artery. An EEG 26 days after the strokelike episode showed left-sided delta activity, left occipital sharp waves, and an isolated instance of a frontal maximal but diffusely reflecting spike and wave. No electrographic seizures were recorded. Other laboratory findings included a resting arterial lactate of 6.8 mmol/L (reference, 0.5 to 1.6 mmol/L), electromyographic evidence of myopathy, sensorineural hearing loss, and a point mutation in mitochondrial DNAencoded transfer RNA1^