The DOI matches its Crossref record; 163 of the 168 references it cites were found in a registry or an index; 2 of the 208 sources its claims cite were checked for support.
Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging
Open accessAbstract
The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study.
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118 Not checked yet · 19 Own interpretation · 16 No basis given · 3 Own result · 1 Own method · accuracy not yet measured
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“although basal ganglia lesions more often had any proximal embolic source (e.g. carotid stenosis, atrial fibrillation; 13 vs 4%) than centrum semiovale lesions (although note that the absolute proportion, 13%, is still very low).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
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“Some years ago we observed that in the centre of an acute symptomatic lacunar infarct it was sometimes possible to see an abnormal perforating arteriole.14”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > If not ‘traditional’ ischaemic mechanisms, then what?
What the sources say
- Not checked yetcites [14] Wardlaw, 2001, Imaging appearance of the symptomatic perforating artery in patients with lacunar infarction: occlusion or other vascular pathology?, Ann Neurol source
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“We found that lacunar infarct size (</>15mm), shape (ovoid/tubular) or location (basal ganglia/centrum semiovale)65 did not vary with a range of vascular risk factors (e.g. hypertension, hypercholesterolaemia, diabetes),”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [65] Macdonald, 1995, Emboli enter penetrating arteries of monkey brain in relation to their size, Stroke source
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“Death resulting directly from lacunar stroke is rare, so most pathology reflects late stage disease,19”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [19] Bailey, 2012, Pathology of lacunar ischaemic stroke in humans—a systematic review, Brain Pathol source
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In the paper
“Death resulting directly from lacunar stroke is rare, so most pathology reflects late stage disease,19”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [19] Bailey, 2012, Pathology of lacunar ischaemic stroke in humans—a systematic review, Brain Pathol source
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In the paper
“endothelial damage leads to increased permeability with leakage of material into the vessel wall and perivascular tissue”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
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In the paper
“These perforating vessels are essential for maintaining optimal functioning of the brain’s most metabolically active nuclei and complex white matter networks.2”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [2] Bullmore, 2012, The economy of brain network organization, Nat Rev Neurosci source
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In the paper
“Modern concepts concerning aetiology and pathogenesis derive from the seminal post-mortem work of C. Miller Fisher undertaken between 1955 and 1973.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Recent history of concepts about SVD pathophysiology
What the sources say
- Not checked yetcites [27] Fisher, 1965, Lacunes: small, deep cerebral infarcts, Neurology source
- Not checked yetcites [28] Fisher, 1969, The arterial lesions underlying lacunes, Acta Neuropathol source
- Not checked yetcites [29] Fisher, 1979, Capsular infarcts: the underlying vascular lesions, Arch Neurol source
- Not checked yetcites [30] Fisher, 1982, Lacunar strokes and infarcts: a review, Neurology source
- Not checked yetcites [31] Fisher, 1991, Lacunar infarcts: a review, Cerebrovasc Dis source
plaindirectn = 20- Asserted: passes — The authors put it forward as true.
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In the paper
“The lesion underlying most lacunar strokes42 is an infarct, rounded, ovoid or tubular in shape, less than 20 mm in axial diameter.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [42] Donnan, 1993, Subcortical infarction: classification and terminology, Cerebrovasc Dis source
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In the paper
“Terminology for clinical, imaging23 and pathology24 of SVD is highly varied.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [23] Potter, 2010, Wide variation in definition, detection, and description of lacunar lesions on imaging, Stroke source
- Not checked yetcites [24] Alafuzoff, 2012, The need to unify neuropathological assessments of vascular alterations in the ageing brain: multicentre survey by the BrainNet Europe consortium, Exp Gerontol source
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 92
- Probably not a substantial claim. 15
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In the paper
“inflammatory cell infiltrates were noted pathologically over 110 years ago in the penetrating arterioles and perivascular tissue in SVD,60 and consistently ever since (Figure 5, Supplementary Figure 3);19 plasma inflammatory markers are elevated in lacunar stroke56,127 and also associated genetically with WMH progression and lacunar infarcts.128”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Could not verifycites [60] Greenberg, 2009, Cerebral microbleeds: a guide to detection and interpretation, Lancet Neurol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [19] Bailey, 2012, Pathology of lacunar ischaemic stroke in humans—a systematic review, Brain Pathol source
- Not checked yetcites [56] Wuerfel, 2008, Perivascular spaces—MRI marker of inflammatory activity in the brain?, Brain source
- Could not verifycites [127] Bell, 2012, Apolipoprotein E controls cerebrovascular integrity via cyclophilin A, Nature sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The arteriolar wall appeared thickened as it passed through the ‘infarct’ not proximal to it (as one might expect with a typical cortical atherothromboembolic infarct), with signal indicating thrombus in the lumen and blood products in and around the arteriole wall.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > If not ‘traditional’ ischaemic mechanisms, then what?
hedgedSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“In earlier work, where the subject was lying supine in the MR scanner for more than half an hour, we identified an increasing gradient of gadolinium from the frontal to the occipital white matter suggesting some gravity-dependence of BBB permeability143”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [143] Topakian, 2010, Blood-brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis, J Neurol Neurosurg Psychiatry source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Increasing age and WMH scores were independently associated with lower MCA flow velocities (on average, a 0·2 cms−1 fall in velocity per year increase in age, p=0·045; a 3·75 cms−1 fall in flow velocity per point increase in WMH score, p=0·004).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
What the sources say
- Not checked yetcites [70] Wong, 2002, Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study, Ann Neurol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Reliance on clinical features and CT scanning to differentiate lacunar from non-lacunar stroke is imprecise and has probably confounded epidemiological and observational studies of risk factor associations.17”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [17] Potter, 2010, Associations of clinical stroke misclassification (‘clinical-imaging dissociation’) in acute ischemic stroke, Cerebrovasc Dis source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Imaging shows that acute lesions are usually larger than old lesions, has questioned the maximum permissible sizes of acute lacunar infarcts45 and emphasised the importance of noting the age of the lesion (Figure 3).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [45] Doubal, 2011, Characteristics of patients with minor ischaemic strokes and negative MRI: a cross sectional study, J Neurol Neurosurg Psychiatry source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“However, arteriolar occlusion may be a late stage phenomenon and does not explain the early pathology.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Only about 50% of recent infarcts are visible on CT,43 whereas at least 70% are visible on MR DWI.44”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [43] Franke, 1991, Residual lesions on computed tomography after intracerebral hemorrhage, Stroke source
- Not checked yetcites [44] Wardlaw, 2003, Visible infarction on computed tomography is an independent predictor of poor functional outcome after stroke, and not of haemorrhagic transformation, J Neurol Neurosurg Psychiatry source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Stroke subtyping on clinical features alone is imperfect, misdiagnosing about 20% of acute lacunar clinical syndromes as cortical stroke and vice versa,17 and will lead to ‘noise’ in studies that do not include DWI.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [17] Potter, 2010, Associations of clinical stroke misclassification (‘clinical-imaging dissociation’) in acute ischemic stroke, Cerebrovasc Dis source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Fisher’s pathological studies, mostly conducted long after the original stroke, focused on the lacune (fluid filled cavity) that was thought to represent the originally symptomatic lacunar infarct.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Recent history of concepts about SVD pathophysiology
What the sources say
- Not checked yetcites [31] Fisher, 1991, Lacunar infarcts: a review, Cerebrovasc Dis source
plainn = 20- Asserted: passes — The authors put it forward as true.
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In the paper
“there are few studies of human lacunar stroke pathology,19 and few pathology-imaging correlations.20”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [19] Bailey, 2012, Pathology of lacunar ischaemic stroke in humans—a systematic review, Brain Pathol source
- Not checked yetcites [20] Gouw, 2011, Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations, J Neurol Neurosurg Psychiatry source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Many trials have not differentiated ischaemic stroke subtypes explicitly, potentially overlooking any differences in treatment response between subtypes.18”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
What the sources say
- Not checked yetcites [18] Palacio, 2012, Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials, Stroke source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“vessel wall thickening and stiffness, impaired autoregulation”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additional “sub-visible” damage detectable on advanced MRI (e.g. diffusion tensor imaging, DTI, magnetization transfer ratio, MTR) includes altered white matter integrity and disrupted axonal connections,38,39 increased brain water content,40 altered myelination,39 and secondary focal thinning of the cortical grey matter.41”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging
What the sources say
- Not checked yetcites [38] O'Sullivan, 2010, Imaging small vessel disease: lesion topography, networks, and cognitive deficits investigated with MRI, Stroke source
- Not checked yetcites [39] Bastin, 2009, Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age, Neurobiol Aging source
- Not checked yetcites [40] MacLullich, 2009, Higher systolic blood pressure is associated with increased water diffusivity in normal-appearing white matter, Stroke source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“damage to the vessel wall, inflammation, demyelination, glial scarring”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The lacune still dominates the field,9 being much more likely to be recognised as responsible for a clinical lacunar stroke than are non cavitated lesions.23”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Recent history of concepts about SVD pathophysiology
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Whatever the true proportion, not all lesions cavitate: some quite large acute DWI-confirmed lacunar infarcts disappear completely (Figure 3) while others appear long term like a non-cavitated WMH.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“On MR imaging, PVS appear round where perpendicular to and linear where parallel to the imaging plane, so typically on axial imaging are round in the basal ganglia and linear in the subcortical white matter of the lateral parts of the temporal, parietal and frontal lobes (Figures 1 and 4).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Visible PVS around perforating arterioles, although observed for many years histologically in older people often in association with other SVD features, were often dismissed as an artefact of tissue processing (Figure 4).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Other features of SVD include microbleeds, which are small punctuate areas of hypointensity on T2* or susceptibility-weighted imaging measuring up to 10mm in diameter corresponding to small collections of haemosiderin-laden macrophages around small perforating vessels.20,57”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“They are distributed in the periventricular and deep white matter of the cerebral hemispheres, in the basal ganglia (i.e. deep grey matter), in the pons and occasionally in other parts of the brainstem and cerebellar white matter. They are almost always symmetrically distributed and are usually numerous in the cerebral hemispheres before appearing in the brainstem. Eventually, when very numerous,”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Probability mapping shows that the main location of acute DWI-proven symptomatic lacunar infarcts is in the primary motor and sensory pathways (note distribution in all images shown),47 explaining why such small lesions present as stroke whereas other SVD lesions accumulate ‘silently’ but otherwise have very similar long term appearances.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [47] Donnan, 1991, The stroke syndrome of striatocapsular infarction, Brain
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial to reduce recurrent stroke in patients with intracranial artery stenosis, only 38/347 (11%) were randomised in the trial following a lacunar stroke the rest being cortical territorial; all recurrent strokes in the 11 patients entering WASID with a lacunar index stroke were non-lacunar.67”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [67] Bang, 2007, Clinical MRI cutoff points for predicting lacunar stroke may not exist: need for a grading rather than a dichotomizing system, Cerebrovasc Dis source
plainn = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“Infarct patterns associated with atheromatous MCA stenosis vary between studies, perhaps related to patient selection; many appearing large enough to be striatocapsular rather than true lacunar.66”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [66] Del Bene, 2012, Do risk factors for lacunar ischaemic stroke vary with the location or appearance of the lacunar infarct?, Cerebrovasc Dis
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Many lacunes were never symptomatic but appear silently in the brain (Supplementary Figure 3 for pathology examples).9”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [9] Vermeer, 2007, Silent brain infarcts: a systematic review, Lancet Neurol source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“An acute lacunar infarct can be caused by embolism, but no more than 10-15% of lacunar infarcts and few WMH can be traced to emboli across a range of individual cohort studies and meta-analyses.61-63”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Emboli
What the sources say
- Not checked yetcites [61] Ferrand, 1902
- Not checked yetcites [62] Jackson, 2010, Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy?, Stroke source
- Not checked yetcites [63] Mead, 2002, Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders?, J Neurol source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lesions larger than 15mm in some literature are considered as lacunes, but in general the larger the lesion the more likely that the lesion was caused by mechanisms other than SCD (Supplementary Figure 2).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“WMH are more common and more extensive in patients with acute lacunar stroke (vs. other stroke subtypes),32 associated with lacunes,50 perivascular spaces,33 microbleeds34 and brain atrophy.35”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [32] Rost, 2010, White matter hyperintensity volume is increased in small vessel stroke subtypes, Neurology source
- Not checked yetcites [50] Moreau, 2012, Cavitation after acute symptomatic lacunar stroke depends on time, location, and MRI sequence, Stroke source
- Not checked yetcites [33] Doubal, 2010, Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Microbleeds are associated with lacunar stroke and WMH,34,58 and are clearly part of the spectrum of SVD.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [34] Cordonnier, 2007, Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting, Brain source
- Not checked yetcites [58] Shoamanesh, 2011, Cerebral microbleeds: histopathological correlation of neuroimaging, Cerebrovasc Dis source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Virchow-Robin, or visible perivascular spaces (PVS) surround the small deep perforating arterioles as they pass through the deep grey and white matter, made visible on T2- or T1-weighted MR by containing increased fluid of similar signal to CSF.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“White matter hyperintensities (WMH) are rounded areas of decreased attenuation on CT, increased signal on T2-weighted and FLAIR, often decreased on T1-weighted MR imaging with respect to normal brain, but not as attenuated or intense as CSF (Figure 1 and 3).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While a few visible PVS may be normal at any age,51 many are not normal.33,52,53”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [51] Vermeer, 2003, Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study, Stroke source
- Not checked yetcites [33] Doubal, 2010, Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease, Stroke source
- Not checked yetcites [52] Groeschel, 2006, Virchow-Robin spaces on magnetic resonance images: normative data, their dilatation, and a review of the literature, Neuroradiology source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Lacunes are small cerebrospinal fluid-containing cavities located in the deep grey or white matter, typically larger than 3mm and (most consider) smaller than 15mm in diameter (Figure 1 and 3).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Fisher suggested that atherosclerosis and embolism affected the largest perforating arterioles (200-850μm diameter).31”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH
What the sources say
- Not checked yetcites [31] Fisher, 1991, Lacunar infarcts: a review, Cerebrovasc Dis source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The relevance of PVS to SVD is illustrated by their presence in larger numbers in association with WMH33,53 and with symptomatic lacunar ischaemic stroke.33,54”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [33] Doubal, 2010, Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease, Stroke source
- Not checked yetcites [53] MacLullich, 2004, Enlarged perivascular spaces are associated with cognitive function in healthy elderly men, J Neurol Neurosurg Psychiatry source
- Not checked yetcites [54] Zhu, 2010, Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The commonest abnormality described pathologically19,27,30,31 is a diffuse, intrinsic disease of the smaller (40-200μm diameter) arterioles, referred to by Fisher as arteriolosclerosis, lipohyalinosis or fibrinoid necrosis depending on its severity, which he thought largely to result from hypertension.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH
What the sources say
- Not checked yetcites [19] Bailey, 2012, Pathology of lacunar ischaemic stroke in humans—a systematic review, Brain Pathol source
- Not checked yetcites [27] Fisher, 1965, Lacunes: small, deep cerebral infarcts, Neurology source
- Not checked yetcites [30] Fisher, 1982, Lacunar strokes and infarcts: a review, Neurology source
plainconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The few acute lacunar infarcts that are due to emboli are more likely to be in the basal ganglia, but in all other respects appear similar to acute lacunar infarcts due to intrinsic arteriolar disease.65”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Emboli
What the sources say
- Not checked yetcites [65] Macdonald, 1995, Emboli enter penetrating arteries of monkey brain in relation to their size, Stroke source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“They are not simply a consequence of global brain atrophy53 as they are frequently seen in patients who have little atrophy, although they might be an alternative manifestation of atrophy.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [53] MacLullich, 2004, Enlarged perivascular spaces are associated with cognitive function in healthy elderly men, J Neurol Neurosurg Psychiatry source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Tight internal carotid and intracranial artery stenosis is equally frequent on the contralateral as on the ipsilateral side to an acute lacunar stroke suggesting that the stenosis is unlikely to have caused the infarct.62”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Emboli
What the sources say
- Not checked yetcites [62] Jackson, 2010, Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy?, Stroke source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
In the paper
“Acute lesions larger than 20mm axial diameter are likely to be striatocapsular, i.e. due to middle cerebral artery (MCA) embolism/occlusion or atheroma occluding multiple perforating arterioles.46”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Features of SVD on MR imaging > Lacunar infarction
What the sources say
- Not checked yetcites [46] Bang, 2004, The course of patients with lacunar infarcts and a parent arterial lesion: similarities to large artery vs small artery disease, Arch Neurol source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, hypertension is likely to add harm and is at least modifiable.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Intracranial stenosis, although apparently common in some ethnic groups, is very uncommon (<1-2%) in Caucasians70 and yet 25% of ischaemic strokes are lacunar in type in Caucasians.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [70] Wong, 2002, Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study, Ann Neurol source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“High field MR (7T) may identify microatheromatous perforating arteriolar plaques45 but the reliability and relevance is yet to be determined.77”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [45] Doubal, 2011, Characteristics of patients with minor ischaemic strokes and negative MRI: a cross sectional study, J Neurol Neurosurg Psychiatry source
- Not checked yetcites [77] Benavente, 2012, The Secondary Prevention of Small Subcortical Strokes (SPS3) study: results of the antiplatelet trial, Cerebrovasc Dis
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Clopidogrel plus aspirin versus aspirin alone caused an excess of haemorrhage (mostly systemic) and death in patients with lacunar stroke,13,76 possibly because patients with lacunar as opposed to other ischaemic stroke subtypes lacked any large artery atheromatous disease to prevent (eg myocardial infarction, large artery stroke, etc),18 further evidence of the largely non-atheromatous nature of”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [13] 2012, Effects of clopidogrel added to aspirin in patients with recent lacunar stroke, N Engl J Med source
- Not checked yetcites [76] Bezerra, 2012, Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study, Neurology source
- Not checked yetcites [18] Palacio, 2012, Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials, Stroke source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The perforating arteriolar lumen and atheroma in the perforating arteriole wall are difficult to identify on conventional imaging.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus while MCA stenosis may occasionally lead to lacunar stroke,68,69 most strokes (>90%) in patients with intracranial stenosis are non-lacunar.67”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
What the sources say
- Not checked yetcites [67] Bang, 2007, Clinical MRI cutoff points for predicting lacunar stroke may not exist: need for a grading rather than a dichotomizing system, Cerebrovasc Dis source
- Not checked yetcites [68] Khan, 2012, Risk factors and outcome of patients with symptomatic intracranial stenosis presenting with lacunar stroke, Stroke source
- Not checked yetcites [69] Adachi, 2002, MRI findings of small subcortical “lacunar-like” infarction resulting from large vessel disease, J Neurol source
plainconditionaln = 11- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hypertension is a key risk factor for WMH79-83 but the relationship with blood pressure (BP) is complex.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [79] Lammie, 1997, Nonhypertensive cerebral small-vessel disease. An autopsy study, Stroke source
- Not checked yetcites [80] Dufouil, 2001, Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort, Neurology source
- Not checked yetcites [81] de Leeuw, 2002, Hypertension and cerebral white matter lesions in a prospective cohort study, Brain source
- Not checked yetcites [82] van Dijk, 2004, The association between blood pressure, hypertension, and cerebral white matter lesions: Cardiovascular Determinants of Dementia Study, Hypertension source
- Not checked yetcites [83] Gottesman, 2010, Blood pressure and white-matter disease progression in a biethnic cohort. Atherosclerosis Risk in Communities (ARIC) Study, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If the apparent WMH-hypertension relationship is partly explained by genetic co-association, then antihypertensive treatment may not be as effective in preventing SVD as is hoped, even if it is very effective in preventing large artery atheromatous disease.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In terms of other common vascular risk factors, concurrent smoking also appears to be a key risk factor for WMH and their progression,97 whereas statins did not prevent WMH progression.12”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [97] Schmidt, 2011, Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease, Brain source
- Not checked yetcites [12] ten Dam, 2005, Effect of pravastatin on cerebral infarcts and white matter lesions, Neurology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may be related to the short intervention period or youngish age range of the included patients.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Many patients with SVD are not hypertensive, e.g. amongst 70 consecutive autopsies in patients with pathologically-verified SVD, vascular risk factors were mostly absent.78”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [78] Kang, 2010, Lenticulostriate arteries in chronic stroke patients visualised by 7 T magnetic resonance angiography, Int J Stroke source
plainn = 70- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Elevated BP some years previously appears to be more strongly associated with WMH in some studies than concurrent BP, although it is unclear whether diastolic84,85 or systolic82 BP are more important.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [84] Godin, 2011, Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)-Dijon Magnetic Resonance Imaging Study, Circulation source
- Not checked yetcites [85] Marcus, 2011, Baseline and longitudinal increases in diastolic blood pressure are associated with greater white matter hyperintensity volume: the northern Manhattan study, Stroke source
- Not checked yetcites [82] van Dijk, 2004, The association between blood pressure, hypertension, and cerebral white matter lesions: Cardiovascular Determinants of Dementia Study, Hypertension source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While homocysteine appears not to be related to large artery atherothrombotic disease (eg myocardial infarction), there may be an association with SVD.98”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [98] van Dijk, 2008, Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study, Stroke source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both white matter tract integrity88,89 and WMH burden90-93 are highly heritable.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [88] Dufouil, 2005, Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy, Circulation source
- Not checked yetcites [89] Chiang, 2009, Genetics of brain fiber architecture and intellectual performance, J Neurosci source
- Not checked yetcites [90] Kohannim, 2012, Predicting white matter integrity from multiple common genetic variants, Neuropsychopharmacology source
- Not checked yetcites [91] Carmelli, 1998, Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins, Stroke source
- Not checked yetcites [92] Turner, 2004, Heritability of leukoaraiosis in hypertensive sibships, Hypertension source
- Not checked yetcites [93] Atwood, 2004, Genetic variation in white matter hyperintensity volume in the Framingham Study, Stroke source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many sporadic cases and the monogenetic variants of SVD occur in normotensive patients.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is possible that the association between SVD and BP is at the genetic locus level rather than being directly causal.94,95”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > ‘Traditional’ vascular risk factors
What the sources say
- Not checked yetcites [94] Kochunov, 2009, Analysis of genetic variability and whole genome linkage of whole-brain, subcortical, and ependymal hyperintense white matter volume, Stroke source
- Not checked yetcites [95] Kochunov, 2010, Whole brain and regional hyperintense white matter volume and blood pressure: overlap of genetic loci produced by bivariate, whole-genome linkage analyses, Stroke source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Up to age 60, the increase in BBB permeability per decade is probably less marked, suggesting that, as with many ageing-related features, loss of endothelial integrity may start in different people at different ages and progress at different rates, with some evidence of an exponential rather than linear decline in function with advancing age.121”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [121] Pollock, 1997, Perivascular spaces in the basal gangli of the human brain: their relationship to lacunes, J Anat source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Autoregulation largely occurs at arteriolar level, but local rapid blood flow responses to neuronal activity also involve capillary responses mediated through pericytes.114,116”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The arteriolar wall changes would be patchy and diffuse and result both in vessel lumen dilation and narrowing, as described by Fisher, and stiffened vessels with loss of normal autoregulation, as long suspected in SVD.102,103”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > If not ‘traditional’ ischaemic mechanisms, then what?
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“there are more glia, endothelial cells and pericytes in the brain than there are neurons”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [114] Abbott, 2004, Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology, Neurochem Int source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The hypothetical consequence is that the effects of endothelial failure would be seen earlier in the larger proximal perforating arterioles than in capillaries, leading for example as seen in some patients, to differential development of proximal arteriolar disease and lacunar infarcts in the basal ganglia in advance of more diffuse WMH in the centrum semiovale where tissue is served by smaller ar”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The regional differences in PVS anatomy could explain this complex association, with SVD pathology leading to visible PVS as well as perforating arteriolar damage and lacunar infarcts mainly in the basal ganglia, whereas multiple WMH tend to form mainly in the centrum semiovale.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“the surface area of the cerebrovascular endothelium approximates that of a tennis court”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [114] Abbott, 2004, Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology, Neurochem Int source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“around 20% of the cardiac output at rest is required to service the metabolic demands of the brain.114”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [114] Abbott, 2004, Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology, Neurochem Int source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“At the capillary level, the endothelium forms a key part of the blood-brain barrier (BBB),109”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [109] Simpson, 2010, Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain, Neurosci Lett source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“The concept emerging from these new observations was that the loss of normal endothelial function would result in leakage of plasma fluid components and migration of cells into the vessel wall with disruption of the normal architecture including damaged arteriolar smooth muscle and fibrin deposition (recognised as lipohyalinosis and fibrinoid necrosis, Figure 5).101”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > If not ‘traditional’ ischaemic mechanisms, then what?
What the sources say
- Not checked yetcites [101] Wardlaw, 2003, Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?, Stroke source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“High dietary salt intake raises blood pressure and increases stroke risk,130 although the salt-stroke association is non-linear and not wholly accounted for by hypertension.131”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [130] Fornage, 2008, Biomarkers of inflammation and MRI-defined small vessel disease of the brain: the Cardiovascular Health Study, Stroke source
- Not checked yetcites [131] Huber, 2001, Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression, Am J Physiol Heart Circ Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“the basal ganglia perforating arterioles having two leptomeningeal layers whereas arterioles entering the deep white matter from the superficial cortex having one leptomeningeal layer.118,119”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“the cerebrovascular endothelium becomes increasingly permeable with normal ageing:121 normal subjects aged 70-80 have a near two-fold more permeable BBB compared with younger subjects.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [121] Pollock, 1997, Perivascular spaces in the basal gangli of the human brain: their relationship to lacunes, J Anat source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“basal ganglia PVS are associated with lacunar stroke, while total brain PVS (ie basal ganglia and centrum semiovale combined) are associated with WMH.33,54”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [33] Doubal, 2010, Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease, Stroke source
- Not checked yetcites [54] Zhu, 2010, Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“First, the endothelial tight junctions are tightest in capillaries where the barrier function is most important, and relatively looser in arteriolar and venular endothelium.109”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Proposed role for early endothelial failure
What the sources say
- Not checked yetcites [109] Simpson, 2010, Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brain, Neurosci Lett source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Loss of the normal autoregulatory ability in the thickened, stiffened vessels would contribute further to tissue damage through reduced ability to vasodilate when required, leading to “ischaemic” changes107 superimposed on the endothelial failure.108”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > If not ‘traditional’ ischaemic mechanisms, then what?
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly,WMH appear around PVS on imaging (Figure 4), suggesting focal failure of interstitial fluid drainage136 with increased focal brain water,39 or some effect of focal inflammatory cell activity as in multiple sclerosis.55”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [136] Bailey, 2011, Cerebral small vessel endothelial structural changes predate hypertension in stroke prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5-to 21-week old rats, Neuropathol Appl Neurobiol source
- Not checked yetcites [39] Bastin, 2009, Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age, Neurobiol Aging source
- Not checked yetcites [55] Potter G, Doubal F, Jackson CA, et al. Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke (in press).
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Increased endothelial expression of endothelial thrombomodulin is seen in arterioles in SVD, possibly indicating a protective mechanism against local thrombosis due to changes in blood flow secondary to altered arteriolar structure.157”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
What the sources say
- Not checked yetcites [157] Young, 2008, Neuropathologic correlates of white matter hyperintensities, Neurology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The presence of hypoxia-inducible factors in WMH at autopsy in elderly patients may be secondary to impaired autoregulation due to SVD, as vessel walls were thickened without luminal reduction; but capillary endothelial and microglial activation were also observed.107”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
What the sources say
- Not checked yetcites [107] Fazekas, 2005, MTI of white matter hyperintensities, Brain source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Salt affects human vascular function by reducing nitric oxide and impairing vasodilatation.133”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [133] Strazzullo, 2009, Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies, BMJ source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Perivascular spaces drain interstitial fluid from the brain parenchyma120 and dilate visibly on MR in overt inflammatory neurological disorders like MS,55,136 in SVD (Figure 1),56 and associate with increased endothelial permeability in SVD.122”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [120] Zhang, 1990, Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum, J Anat
- Not checked yetcites [55] Potter G, Doubal F, Jackson CA, et al. Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke (in press).
- Not checked yetcites [136] Bailey, 2011, Cerebral small vessel endothelial structural changes predate hypertension in stroke prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5-to 21-week old rats, Neuropathol Appl Neurobiol source
- Not checked yetcites [56] Wuerfel, 2008, Perivascular spaces—MRI marker of inflammatory activity in the brain?, Brain source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Ischaemia, which might occur secondary to endothelial dysfunction and impaired autoregulation,102 e.g. in stiffened vessels unable to respond to vasodilatory stimuli during exertion, induces matrix metalloproteinase activity which damages the endothelial tight junction proteins claudins and occludins, and could accelerate endothelial damage.137,138”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [137] Bailey, 2011, Is the spontaneously hypertensive stroke prone rat a pertinent model of subcortical ischaemic stroke? A systematic review, Int J Stroke source
- Not checked yetcites [138] Weller, 2009, Lymphatic drainage of the brain and the pathophysiology of neurological disease, Acta Neuropathol source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Studies in CADASIL transgenic mice found no evidence for BBB dysfunction,149 but these mice also develop very little brain parenchymal pathology.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [149] Yao, 2012, Extensive white matter hyperintensities may increase brain volume in CADASIL, Stroke source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“SVD is the commonest cause of vascular dementia140 and SVD commonly occurs with Alzheimer’s disease.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [140] Zlokovic, 2008, The blood-brain barrier in health and chronic neurodegenerative disorders, Neuron source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“While some, particularly larger lacunar lesions with cystic degeneration may be a consequence of end-stage occlusive SVD, as suggested by Fisher, the pathophysiology of PVS and localised white matter changes is less well understood.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
What the sources say
- Not checked yetcites Fisher
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In general, while tissue pathology changes seen at post mortem are frequently interpreted as “ischaemic”, there are changes that also support the endothelial dysfunction concept.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“although the gadolinium signal detected in the brain with these MR techniques is very low, nonetheless it was still possible to demonstrate increasing BBB permeability with increasing age and with increasing numbers of PVS122”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [122] Carare, 2008, Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology, Neuropathol Appl Neurobiol source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Damaged endothelium, passage of plasma proteins into the vessel wall and vessel wall damage,154 leakage of fluid,78,101 albumin,108 other plasma proteins, inflammatory cells120,155,156 into the perivascular tissue have long been observed (Figure 5).”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
What the sources say
- Not checked yetcites [154] Smallwood, 2012, Cerebral subcortical small vessel disease and its relation to cognition in elderly subjects: a pathological study in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort, Neuropathol Appl Neurobiol source
- Not checked yetcites [78] Kang, 2010, Lenticulostriate arteries in chronic stroke patients visualised by 7 T magnetic resonance angiography, Int J Stroke source
- Not checked yetcites [101] Wardlaw, 2003, Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?, Stroke source
- Not checked yetcites [108] Fernando, 2006, White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury, Stroke source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“High dietary salt exacerbates oxidative stress in salt-sensitive people;132 reduced salt intake not only reduced BP but also reduced oxidative stress and vascular stiffness.132”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [132] Gardener, 2012, Dietary sodium and risk of stroke in the Northern Manhattan Study, Stroke source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interstitial fluid drainage along the perivascular spaces may be dependent on ’milking‘ of fluid by pulsation of the adjacent arterioles.139 The ‘milking’ could become less effective as arterioles stiffen e.g. with SVD.139”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [139] Rosenberg, 2009, Inflammation and white matter damage in vascular cognitive impairment, Stroke source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence for endothelial dysfunction in SVD also comes from CADASIL, a hereditary SVD caused by Notch3 mutations,146 where extensive WMH were associated with increased brain volume on MRI suggesting an increase of brain water content147 and CSF/plasma albumin ratios were increased,148 in keeping with BBB failure.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [146] Johnson, 2007, Imaging of amyloid burden and distribution in cerebral amyloid angiopathy, Ann Neurol source
- Not checked yetcites [147] Wardlaw, 2013, Blood-brain barrier permeability and long term clinical and imaging outcomes in cerebral small vessel disease, Stroke source
- Not checked yetcites [148] Chabriat, 2009, Cadasil, Lancet Neurol source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“using gadolinium contrast-enhanced MR imaging, that the background BBB in white matter remote from any acute infarct is more permeable in patients with lacunar than with large artery cortical stroke (Figure 7),122 in WMH than in normal appearing white matter,141 and in WMH in patients with vascular dementia.142”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [122] Carare, 2008, Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology, Neuropathol Appl Neurobiol source
- Not checked yetcites [141] Schley, 2006, Mechanisms to explain the reverse perivascular transport of solutes out of the brain, J Theor Biol source
- Not checked yetcites [142] Dichgans, 2012, Prevention of Vascular Cognitive Impairment, Stroke source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In an animal model of spontaneous SVD, even modest short term salt exposure exacerbated inflammation, oxidative stress and small vessel pathology and to a lesser but nonetheless measureable extent in control rats without raising BP.134,135”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Other models of human SVD using quite different mechanisms such as induction of mild carotid stenosis with external carotid coils151 also show evidence of BBB failure early after induction predating brain damage and consistent with the notion that various stimuli might induce SVD through effects on the cerebrovascular endothelium.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [151] Joutel, 2010, Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease, J Clin Invest source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations support the concept that, while pathological changes seen at post mortem are frequently interpreted as “ischaemic”, based on their histological similarities to thromboembolic infarcts, there are changes that also support the altered BBB permeability concept.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Additionally BBB was impaired in WMH, and there was increased astrocyte staining with IgG, suggesting BBB failure in deep white matter.155”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Insights from pathology of SVD
What the sources say
- Not checked yetcites [155] Hughes, 1965, Origin of lacunes, Lancet source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
In the paper
“In a small longitudinal study, greater BBB permeability soon after non-disabling stroke was associated with dependency at three year follow-up, older age, and having more WMH at initial stroke presentation, suggesting that BBB may predate progression of SVD, but larger studies are required.145”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [145] Starr, 2003, Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging, J Neurol Neurosurg Psychiatry source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The SHRSP shows inflammation (again non-specific) and increased BBB permeability early in life,21 predating any rise in BP or development of overt vessel wall or tissue damage.150”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the most relevant experimental model of sporadic SVD, the spontaneously-hypertensive stroke prone rat (SHRSP),21,22,135 has multiple modest endothelial and perivascular tissue defects in early life,21 including impaired endothelial tight junctions, poor myelination, overactive microglia, and tendency to glial scarring detectable in protein expression.134”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Why should the endothelium fail?
What the sources say
- Not checked yetcites [21] Bailey, 2009, Potential animal models of lacunar stroke: a systematic review, Stroke source
- Not checked yetcites [22] Hainsworth, 2008, Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review, J Cereb Blood Flow Metab source
- Not checked yetcites [135] Bragulat, 2001, Endothelial dysfunction in salt-sensitive essential hypertension, Hypertension source
- Not checked yetcites [134] Al-Solaiman, 2009, Low-sodium DASH reduces oxidative stress and improves vascular function in salt-sensitive humans, J Hum Hypertens source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However other factors that might be associated both with jugular venous reflux and WMH, such as lung disease, were not evaluated.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“CBF and blood flow velocities fall with normal ageing.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Jugular venous reflux increases with advancing age as do WMH. Elderly subjects with more WMH had more jugular venous reflux detected on Doppler ultrasound not accounted for by hypertension, diabetes, hyperlipidaemia or smoking.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
What the sources say
- Not checked yetcites [161] ten Dam, 2007, Decline in total cerebral blood flow is linked with increase in periventricular but not deep white matter hyperintensities, Radiology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A reduction in CBF was observed using MR imaging methods in patients with more WMH in some,158 but not other159 studies; both found associations between CBF and atrophy suggesting that declining CBF might occur secondary to tissue loss, rather than that tissue loss and WMH occur secondary to falling CBF.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Earlier, we described the general lack of association between acute lacunar infarcts or WMH and carotid stenosis, suggesting that carotid stenosis is not a common mechanical cause in humans.”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Other mechanisms suspected from imaging
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The authors state this as an assumption.
The core mechanism underlying SVD-related brain injury is ischaemia acting through arteriolar narrowing or occlusion, whether structural or functional.
“The core mechanism underlying SVD-related brain injury is usually assumed to be ischaemia, acting through arteriolar narrowing or occlusion either structural or functional (e.g. vasospasm, impaired autoregulation, or hypotension).”
The paper relies on this without support.
Features of SVD develop over many years before they become clinically evident.
“Features of SVD probably develop over many years before becoming clinically evident.”
The paper relies on this without support.
Perivascular oedema is toxic to neurons, glia and astrocytes.
“In earlier stages, the perivascular oedema, which is toxic to neurons, glia, astrocytes, in fact all”
The authors state this as an assumption.
Subacute lesions observed at post mortem, on the basis of size and absence of significant relevant clinical dysfunction in life, are asymptomatic lacunes.
“Rarely, subacute lesions are observed (Supplemental Figure 3) which, on the basis of size and in the absence of any significant relevant clinical dysfunction in life, are assumed to be asymptomatic lacunes (Supplemental Figure 3a).”
The paper relies on this without support.
Having a few lacunes may have similar impact in terms of cognition or stroke or dementia risk as having some WMH.
“having a few lacunes may have similar impact in terms of cognition or stroke or dementia risk as do having some WMH.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Also, MRI captures aspects that are usually not in the focus of pathological assessment, such as edema. 82”
From Vascular Cognitive Impairment (2017) · cites this paper as [82]
In the citing paper
“SVD is common in hypertensive patients, many of whom are concurrently diabetic or smokers, and it progresses silently for years before dementia is clinically evident (99).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [99]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
“only 38/347 (11%) were randomised in the trial following a lacunar stroke”
§ Mechanisms underlying sporadic cerebral small vessel disease: insights from neuroimaging > Mechanisms underlying most acute lacunar infarcts, lacunes and WMH > Atheroma of the parent artery or perforating arteriole
“all recurrent strokes in the 11 patients entering WASID with a lacunar index stroke were non-lacunar.”
Citations
Cites
Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Gorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811
Pantoni, L. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70104-6 · Cited by 3,405
The economy of brain network organization
Bullmore, E., & Sporns, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3214 · Cited by 3,284
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
The blood-brain barrier/neurovascular unit in health and disease
Hawkins, B. T., & Davis, T. P. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.2.4 · Cited by 2,661
Debette, S., & Markus, H. S. (2010) · BMJ · doi:10.1136/bmj.c3666 · Cited by 2,328
Cerebral microbleeds: a guide to detection and interpretation
Greenberg, S. M., Vernooij, M. W., Cordonnier, C., Viswanathan, A., Al-Shahi Salman, R., Warach, S., Launer, L. J., Van Buchem, M. A., & Breteler, M. M. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70013-4 · Cited by 1,798
Pathologic correlates of incidental MRI white matter signal hyperintensities
Fazekas, F., Kleinert, R., Offenbacher, H., Schmidt, R., Kleinert, G., Payer, F., Radner, H., & Lechner, H. (1993) · Neurology · doi:10.1212/wnl.43.9.1683 · Cited by 1,619
Research works printed but not linked: 3
- Valdes-Hernandez, 2012, Does the differential distribution of acute lacunar infarcts and white matter lesions in the brain explain why lacunar infarcts but not white matter lesions present with acute symptoms?, Cerebrovasc Dis, 33, 69
- Del Bene, 2012, Do risk factors for lacunar ischaemic stroke vary with the location or appearance of the lacunar infarct?, Cerebrovasc Dis, 33, 21
- Benavente, 2012, The Secondary Prevention of Small Subcortical Strokes (SPS3) study: results of the antiplatelet trial, Cerebrovasc Dis, 33, 79
Cited by
Sorted by citations
Items 101–108 of 108
Genetic factors in cerebral small vessel disease and their impact on stroke and dementia
Haffner, C., Malik, R., & Dichgans, M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.71 · Cited by 109
Self-citationPeres, R., De Guio, F., Chabriat, H., & Jouvent, E. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15625352 · Cited by 36
Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease
van der Land, V., Mutsaerts, H. J. M. M., Engelen, M., Heijboer, H., Roest, M., Hollestelle, M. J., Kuijpers, T. W., Nederkoorn, P. J., Cnossen, M. H., Majoie, C. B. L. M., et al. (2016) · British Journal of Haematology · doi:10.1111/bjh.13819 · Cited by 30
In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL
De Guio, F., Reyes, S., Vignaud, A., Duering, M., Ropele, S., Duchesnay, E., Chabriat, H., & Jouvent, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106311 · Cited by 28
Wang, Z., Williams, V. J., Stephens, K. A., Kim, C., Bai, L., Zhang, M., & Salat, D. H. (2020) · Human Brain Mapping · doi:10.1002/hbm.24871 · Cited by 28
Shaaban, C. E., Rosano, C., Cohen, A. D., Huppert, T., Butters, M. A., Hengenius, J., Parks, W. T., & Catov, J. M. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.637574 · Cited by 27
Riba‐Llena, I., Nafría, C., Mundet, X., López‐Rueda, A., Fernández‐Cortiñas, I., Jarca, C. I., Jiménez‐Balado, J., Domingo, M., Tovar, J. L., Orfila, F., et al. (2016) · European Journal of Neurology · doi:10.1111/ene.12979 · Cited by 25
Dichgans, M., & Leys, D. (2017) · Circulation Research · doi:10.1161/circresaha.116.308426 · Cited by 581
Self-citation
Metadata
- Authors
- Wardlaw, J. M., Smith, C., & Dichgans, M.
- Affiliations
- Western General Hospital (GB)
- University of Edinburgh (GB)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Wardlaw, Joanna M
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 12
- Issue
- 5
- Pages
- 483-497
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC3836247
- OpenAlex
- W2140621953
- Cited by
- 1,657
- References
- 168
- Citations by year
- 2026: 120 · 2025: 116 · 2024: 124 · 2023: 128 · 2022: 171 · 2021: 166 · 2020: 162 · 2019: 165 · 2018: 144 · 2017: 121 · 2016: 88 · 2015: 72 · 2014: 63 · 2013: 13
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DZNE Pub (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (088134)
- Medical Research Council (MR/K026992/1, MR/J006971/1)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- cerebral small vessel disease, pathogenesis, vascular risk factors, neuroimaging biomarkers, dementia, stroke, cognitive impairment
- MeSH terms
- Brain, Humans, Dementia, Vascular, Cerebral Small Vessel Diseases, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-04, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-04 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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