Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis.

Autor:	Ineichen BV; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden; Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Center for Reproducible Science, University of Zurich, Zurich, Switzerland; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health (NIH), Bethesda, MA, USA. Electronic address: Benjaminvictor.ineichen@uzh.ch., Cananau C; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden., Plattén M; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden., Ouellette R; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden., Moridi T; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center of Neurology, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden., Frauenknecht KBM; National Centre for Pathology (NCP), Laboratoire National de Santé, Dudelange, Luxembourg; Luxembourg Centre for Neuropathology (LCNP), Laboratoire National de Santé, Dudelange, Luxembourg., Okar SV; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health (NIH), Bethesda, MA, USA., Kulcsar Z; Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Kockum I; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Piehl F; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center of Neurology, Academic Specialist Center, Stockholm Health Services, Stockholm, Sweden., Reich DS; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health (NIH), Bethesda, MA, USA., Granberg T; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2023 Jun; Vol. 92, pp. 104631. Date of Electronic Publication: 2023 May 28.
DOI:	10.1016/j.ebiom.2023.104631
Abstrakt:	Background: Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate VRS to their histopathologic signature. Methods: In a cohort study comprising 142 MS patients and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) outcomes. Findings were corroborated in a validation cohort comprising 63 MS patients. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. Findings: In our actively treated clinical cohort, the count of dilated centrum semiovale VRS was associated with increased T1 and T2 lesion volumes. There was no systematic spatial colocalization of dilated VRS with MS lesions. At tissue level, VRS mostly corresponded to arteries and were not associated with MS pathological hallmarks. Interestingly, in our ex vivo cohort comprising mostly progressive MS patients, dilated VRS in MS were associated with signs of small vessel disease. Interpretation: Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with an accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature. Funding: NIH, Swedish Society for Medical Research, Swiss National Science Foundation and University of Zurich. Competing Interests: Declaration of interests F. Piehl reports having received grants from Merck KGaA, Janssen and UCB for different studies, payment from Novartis for expert testimony. He participated on Data safety monitoring board or advisory board for clinical trials with Chugai, Lundbeck and Roche. He is also chairman of the Neuro research committee (a Swedish patient organization), an unpaid role. The other authors report no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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