Perivascular spaces and their role in neuroinflammation

Ineichen, Benjamin Victor; Okar, Serhat V.; Proulx, Steven T.; Engelhardt, Britta; Lassmann, H.; Reich, Daniel S.

doi:10.1016/j.neuron.2022.10.024

Cited by 36 publications

(31 citation statements)

References 173 publications

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“…An increase of VRS has been consistently associated with ageing 8 , which is also confirmed by our data from MS patients, though naturally chronologically confounded by the disease duration. Based on this association with ageing, it has also been speculated that VRS represent a perivascular ex vacuo atrophy 3 . In MS, a study employing ultra-high-field MRI found that higher VRS counts were associated with lower brain parenchymal fraction 13 .…”

Section: Findings In the Context Of Existing Evidencementioning

confidence: 99%

“…Perivascular spaces surround blood vessels in the brain 1 . Macroscopically visible perivascular spaces, also referred to as Virchow-Robin spaces (VRS) or enlarged perivascular spaces, are readily detectable by magnetic resonance imaging (MRI) 2,3 . VRS appear as thin linear or small punctate structures with a signal similar to CSF on MRI 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence also suggests an association of VRS with neuroinflammatory disorders, including multiple sclerosis (MS) 3 . MRI studies have shown that MS patients harbor a higher VRS burden compared to control subjects 13,14 .…”

Section: Introductionmentioning

confidence: 99%

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Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis

Ineichen

Cananau

Plattén

et al. 2023

Preprint

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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. In a cohort study comprising 205 MS patients (including a validation cohort) and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) outcomes. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. 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, dilated VRS in MS were associated with signs of small vessel disease. Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature.

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Section: Findings In the Context Of Existing Evidencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis

Ineichen

Cananau

Plattén

et al. 2023

Preprint

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“…First described in detail by Virchow (1851) and confirmed as a feature of normal brain histology by Robin (1859), the perivascular space (PVS) is an anatomical compartment that follows the pial trajectories of brain vasculature, surrounding the arteries, veins, penetrating arterioles and venules (Troili et al, 2020;Wardlaw et al, 2020;Ineichen et al, 2022). Although PVS are a normal anatomic feature of brain vasculature that can be visualized using histology, they can also become visible on magnetic resonance imaging (MRI) if they exceed a certain diameter (depending on the resolution of the MRI).…”

Section: Introductionmentioning

confidence: 97%

“…Although PVS are a normal anatomic feature of brain vasculature that can be visualized using histology, they can also become visible on magnetic resonance imaging (MRI) if they exceed a certain diameter (depending on the resolution of the MRI). These macroscopically visible PVS have been referred to as enlarged PVS (EPVS), dilated PVS, or Virchow-Robin spaces ( Ineichen et al, 2022 ) ( Figure 1 ). In this review, we will use the term MRI-visible PVS (MVPVS) to acknowledge that temporal dynamics of PVS are insufficiently understood and thus to retain a more descriptive terminology.…”

Section: Introductionmentioning

confidence: 99%

The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

Okar

Shinohara

et al. 2023

Front. Neurosci.

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ObjectivesPerivascular spaces have been involved in neuroinflammatory and neurodegenerative diseases. Upon a certain size, these spaces can become visible on magnetic resonance imaging (MRI), referred to as enlarged perivascular spaces (EPVS) or MRI-visible perivascular spaces (MVPVS). However, the lack of systematic evidence on etiology and temporal dynamics of MVPVS hampers their diagnostic utility as MRI biomarker. Thus, the goal of this systematic review was to summarize potential etiologies and evolution of MVPVS.MethodsIn a comprehensive literature search, out of 1,488 unique publications, 140 records assessing etiopathogenesis and dynamics of MVPVS were eligible for a qualitative summary. 6 records were included in a meta-analysis to assess the association between MVPVS and brain atrophy.ResultsFour overarching and partly overlapping etiologies of MVPVS have been proposed: (1) Impairment of interstitial fluid circulation, (2) Spiral elongation of arteries, (3) Brain atrophy and/or perivascular myelin loss, and (4) Immune cell accumulation in the perivascular space. The meta-analysis in patients with neuroinflammatory diseases did not support an association between MVPVS and brain volume measures [R: −0.15 (95%-CI −0.40–0.11)]. Based on few and mostly small studies in tumefactive MVPVS and in vascular and neuroinflammatory diseases, temporal evolution of MVPVS is slow.ConclusionCollectively, this study provides high-grade evidence for MVPVS etiopathogenesis and temporal dynamics. Although several potential etiologies for MVPVS emergence have been proposed, they are only partially supported by data. Advanced MRI methods should be employed to further dissect etiopathogenesis and evolution of MVPVS. This can benefit their implementation as an imaging biomarker.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346564, identifier CRD42022346564.

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Quantifying dilated perivascular spaces in children with sickle cell disease

Karkoska,

Gollamudi,

Sawyer

et al. 2024

Pediatric Blood & Cancer

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Sickle cell disease (SCD)‐related neurological effects are particularly devastating. Dilated perivascular spaces (dPVS) are a well‐described component of cerebral small vessel disease in older adults without SCD. However, the burden and association of dPVS with neurological complications in children with SCD have not been described. In this study, we used the international consensus criteria to quantify dPVS in the centrum semiovale and basal ganglia in T2‐weighted magnetic resonance images (MRI) of children with SCD who were randomized as part of the Silent Cerebral Infarct Transfusion (SIT) trial. We examined the relationship between global and/or regional dPVS burden and presence or area of silent cerebral infarctions, hematological measures, demographic variables, and full‐scale intelligence quotient (FSIQ) scores. The study included 156 SIT trial participants who had pre‐randomization and study exit MRI. Their median age was 9.6 (5–15) years, 39% were female, and 94 (60%) participants had a high dPVS burden. Participants randomized to the blood transfusion arm and who had a high dPVS burden at baseline had a moderate decline in dPVS score over 36 months compared to no change in the observation group. On multivariable logistic regression, intelligence quotient was not associated with dPVS burden. Children with SCD included in the SIT trial have a high burden of dPVS compared to children without SCD. However, dPVS do not appear to have the same pathophysiology of silent cerebral infarcts. Further study is needed to determine both their etiology and clinical relevance.

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Perivascular spaces and their role in neuroinflammation

Cited by 36 publications

References 173 publications

Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis

Dilated Virchow-Robin Spaces are a Marker for Arterial Disease in Multiple Sclerosis

The etiology and evolution of magnetic resonance imaging-visible perivascular spaces: Systematic review and meta-analysis

Quantifying dilated perivascular spaces in children with sickle cell disease

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