Highlights
- •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.
Abstract
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 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.
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. 99mTc-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 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.
Conclusion
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.
Keywords
Abbreviations:
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)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Narrative review: reversible cerebral vasoconstriction syndromes.Ann. Intern. Med. 2007; 146: 34-44
- Hyperintense vessels: an early MRI marker of reversible cerebral vasoconstriction syndrome?.Cephalalgia. 2014; 34: 1038-1039
- The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients.Brain. 2007; 130: 3091-3101
- Long-term outcomes after reversible cerebral vasoconstriction syndrome.in: Cephalalgia. 36. 2015: 387-394
- The international classification of headache disorders, 3rd edition.in: Cephalalgia. 38. 2018: 1-211
- Reversible cerebral vasoconstriction syndrome: current and future perspectives.Expert. Rev. Neurother. 2011; 11: 1265-1276
- Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: implications for pathophysiology and diagnosis.Ann. Neurol. 2017; 81: 454-466
- Temporal profile of blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome.Stroke. 2020; 51: 1451-1457
- Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases.J. Neurol. Sci. 2007; 260: 57-64
- A multicenter validation of regional cerebral blood flow quantitation of using [123I] iodoamphetamine and single-photon emission computed tomography.J. Cereb. Blood Flow Metab. 1996; 16: 781-793
- A new method for evaluation of mild traumatic brain injury with neuropsychological impairment using statistical imaging analysis for Tc-ECD SPECT.Ann. Nucl. Med. 2013; 27: 187-202
- Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation.Ann. Nucl. Med. 2003; 17: 289-295
- Differential vascular pathophysiologic types of intracranial atherosclerotic stroke: a high-resolution wall magnetic resonance imaging study.Stroke. 2015; 46: 2815-2821
- A method for attenuation correction in radionuclide computed tomography.IEEE Trans. Nucl. Sci. 1978; 25: 638-643
- Stereotactic statistical imaging analysis of the brain using the easy Z-score imaging system for sharing a normal database.Radiat. Med. 2006; 24: 545-552
- Reversible cerebral vasoconstriction syndrome: treatment with combined intra-arterial verapamil infusion and intracranial angioplasty.Am. J. Neuroradiol. 2011; 32: E184-E187
- Reversible cerebral vasoconstriction syndrome and headache.Clin. Neurol. (Japanese). 2016; 84: 387-398
- Centripetal propagation of vasoconstriction at the time of headache resolution in patients with reversible cerebral vasoconstriction syndrome.Am. J. Neuroradiol. 2016; 37: 1594-1598
- Early and delayed Tc-99m ECD brain SPECT in SLE patients with CNS involvement.Ann. Nucl. Med. 2000; 14: 25-32
- Quantifying local cerebral blood flow by N-isopropyl-ρ-[123I] iodoamphetamine (IMP) tomography.J. Nucl. Med. 1982; 23: 196-203
- Hyperfixation of HMPAO in subacute ischemic stroke leading to spuriously high estimates of cerebral blood flow by SPECT.Stroke. 1993; 24: 193-194
- Metabolism of 99mTc-l, l-ethyl cisteinate dimer in healthy volunteers.Neuropharmacology. 1991; 30: 283-292
- Assessment of postischemic reperfusion and diamox activation test in stroke using Tc-99m ECD SPECT.J. Cereb. Blood Flow Metab. 1994; 14: S49-S57
- A case of reversible cerebral vasoconstriction syndrome presenting with recurrent neurological deficits: evaluation using noninvasive arterial spin labeling MRI.Clin. Neurol. Neurosurg. 2014; 126: 96-98
- Quantitative arterial spin labeling magnetic resonance imaging analysis of reversible cerebral vasoconstriction syndrome: a case series.Headache. 2021; 61: 687-693
- Functional and structural alterations in the migraine cerebellum.J. Cereb. Blood Flow Metab. 2017; 39: 730-739
- Altered experimental pain perception after cerebellar infarction.Pain. 2014; 155: 1303-1312
- Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing.Cortex. 2010; 46: 831-844
- Fear of pain as a prognostic factor in chronic pain: conceptual models, assessment, and treatment implications.Curr. Pain Headache Rep. 2010; 14: 88-95
Article info
Publication history
Published online: September 28, 2022
Accepted:
September 25,
2022
Received in revised form:
August 24,
2022
Received:
February 27,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.