Persistent brain damage in reversible cerebral vasoconstriction syndrome on 99mTc-ethyl cysteinate dimer single-photon emission computed tomography: A long-term observational study

Published:September 28, 2022DOI:


      • Irreversible or prolonged brain damage including BBB breakdown can persist in patients with RCVS.
      • 99mTc-ECD SPECT is useful to detect abnormalities over the entire course of RCVS.
      • Further research using radioactive substrates will help to elucidate the pathophysiological mechanisms of RCVS.



      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 99mTc-ethyl cysteinate dimer (99mTc-ECD) as a tracer, 99mTc-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 99mTc-ECD SPECT.


      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. 99mTc-ECD SPECT was performed repeatedly in each patient. SPECT data were statistically analyzed using an easy Z-score imaging system.


      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 99mTc-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.


      Reduced cerebral uptake of 99mTc-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. 99mTc-ECD SPECT is an effective neuroimaging method to detect brain functional abnormalities, reflecting BBB breakdown or tissue damages, throughout the treatment course of RCVS.



      RCVS (Reversible Cerebral Vasoconstriction Syndrome), MRA (Magnetic Resonance Angiography), PRES (Posterior Reversible Encephalopathy Syndrome), BBB (Blood-Brain Barrier), CE-FLAIR (Contrast-enhanced Fluid-attenuated Inversion-Recovery), MRI (Magnetic Resonance Imaging), 99mTc-ECD (99mTc-ethyl cysteinate dimer), SPECT (Single-Photon Emission Computed Tomography), eZIS (easy Z-score Imaging System), vbSEE (voxel-based stereotactic extraction estimation), ICHD-3 (The International Classification of Headache Disorders (2018), third edition), CT (Computed Tomography), CTA (CT angiography), CSF (Cerebrospinal Fluid), ASL (Arterial Spin Labeling), RCU (Reduced Cerebral Uptake)
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