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Background: Blood-brain barrier (BBB) breakdown is considered a key step in the pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS); however, its temporal course remains unclear. Based on the characteristics and dynamics of 99m Tc-ethyl cysteinate dimer ( 99m Tc-ECD) as a tracer, 99m Tc-ECD single-photon emission computed tomography (SPECT) can detect not only hypoperfusion but also BBB breakdown and/or brain tissue damage. Therefore, this study aimed to investigate this course using 99m Tc-ECD SPECT., Methods: Between 2011 and 2019, we enrolled seven patients (one male and six female patients) with RCVS without ischemic or hemorrhagic stroke or posterior reversible encephalopathy syndrome. 99m Tc-ECD SPECT was performed repeatedly in each patient. SPECT data were statistically analyzed using an easy Z-score imaging system., Results: Thunderclap headache was the initial symptom in all the patients and was most commonly triggered by bathing (three patients). All the patients exhibited vasoconstriction and reduced cerebral uptake of 99m Tc-ECD during the acute stage. Follow-up assessment from 3 to 16 months showed that reduced cerebral uptake persisted in all the patients, even after the vasoconstriction had resolved., Conclusion: Reduced cerebral uptake of 99m Tc-ECD persisted in the late stage of RCVS, even after vasoconstriction and headache subsided. BBB breakdown and/or brain tissue damage may underlie this phenomenon. 99m Tc-ECD SPECT is an effective neuroimaging method to detect brain functional abnormalities, reflecting BBB breakdown or tissue damages, throughout the treatment course of RCVS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)