Two clinically distinct lacunar infarct entities? A hypothesis.

Background and Purpose-Although cerebral small vessel disease, including white matter lesions (WML) and lacunar infarcts, is associated with gait disturbances, not all individuals with small vessel disease have these disturbances. Identical-appearing WML on MRI could reflect different degrees of microstructural integrity. Moreover, conventional MRI does not assess the integrity of normal-appearing white matter (NAWM). We therefore investigated the relation between white matter integrity assessed by diffusion tensor imaging in WML, NAWM, several regions of interest, and gait. Methods-A total of 484 nondemented elderly persons between 50 and 85 years old with cerebral small vessel disease were included in this analysis and underwent MRI and diffusion tensor imaging scanning. Mean diffusivity and fractional anisotropy within WML, NAWM, and regions of interest were related to quantitative and semiquantitative gait parameters. Results-Mean diffusivity in the WML was inversely related with gait (velocity ␤ϭϪ0.15; Pϭ0.002). For the fractional anisotropy, this relation was less evident. The same was found in the NAWM (velocity ␤ϭϪ0.21; PϽ0.001) and for some parameters also after additional adjustment for WML and lacunar infarcts. Conclusion-This study indicates that integrity of both WML and NAWM, beyond the detection limit of conventional MRI, is associated with gait disturbances. (Stroke. 2011;42:373-379.)

Section: Discussionmentioning

confidence: 71%

Diffusion Tensor Imaging and Gait in Elderly Persons With Cerebral Small Vessel Disease

Laat

Norden

Gons

et al. 2011

“…The hypothesis that distinct lacunar entities exist with differences in etiology and prognosis has also been proposed by clinical studies. 8,7 Alternatively, tissue characteristics may influence the survival as the neurons in the deep gray matter may react differently to ischemia than glial cells in the subcortical WM. The difference in risk factor profile support our MRI findings and suggest that incident lacunes in the subcortical WM may have a different pathogenesis than lacunes in the basal ganglia and infratentorial region.…”

Section: Methodsmentioning

confidence: 99%

“…4,5 The pathogenesis of lacunes has not been fully elucidated, and it has been proposed that distinct lacunar entities exist. 6,7,8 In this longitudinal study, we compared incident MRI-defined lacunes between brain regions, with respect to their relationship with WMH and risk factor profile. …”

mentioning

confidence: 99%

On the Etiology of Incident Brain Lacunes

Gouw

Flier

Pantoni

et al. 2008

on behalf of the LADIS Study GroupBackground and Purpose-We investigated regional differences in MRI characteristics and risk factor profiles of incident lacunes over a 3-year period. Methods-Baseline and 3-year follow-up MRI were collected within the LADIS study (nϭ358). Incident lacunes were characterized with respect to brain region, their appearance within pre-existent white matter hyperintensities (WMH), surrounding WMH size, and risk factors. Results-106 incident lacunes were observed in 62 patients (58 subcortical white matter [WM], 35 basal ganglia, and 13 infratentorial). Incident subcortical WM lacunes occurred more often within preexisting WMH (Pϭ0.01) and were mostly accompanied by new and expanded WMH (PϽ0.001), compared to incident basal ganglia and infratentorial lacunes. Risk factors for incident subcortical WM lacunes were history of hypertension and stroke, whereas atrial fibrillation predicted incident basal ganglia/infratentorial lacunes. Conclusion-Differences in relation to WMH and risk factor profiles may suggest that incident lacunes in the subcortical WM have a different pathogenesis than those in the basal ganglia and infratentorial region. Key Words: lacunes Ⅲ white matter hyperintensities Ⅲ MRI L acunes are often defined as subcortical ischemic infarcts, resulting from an occlusion of a small perforating artery and are regarded as an expression of cerebral small vessel disease on MRI. 1,2 They may cause typical lacunar syndromes but may also be clinically "silent". 2 Furthermore, they have been associated with subtle cognitive dysfunction and a higher risk of future stroke. 3 White matter hyperintensities (WMH) are another MRI expression of small vessel disease and develop because of several mechanisms including incomplete infarction as a consequence of diffuse hypoxia. 4,5 The pathogenesis of lacunes has not been fully elucidated, and it has been proposed that distinct lacunar entities exist. 6,7,8 In this longitudinal study, we compared incident MRI-defined lacunes between brain regions, with respect to their relationship with WMH and risk factor profile. MethodsData were collected within the multi-center Leukoaraiosis and Disability (LADIS) study in which 639 independently living elderly subjects, who were stratified for WMH severity, were followed for 3 years. 9 Vascular risk factors were assessed at baseline. 9 Baseline and 3-year follow-up MRI were available for 396 subjects. For this study concerning detailed characterization of incident lacunes, 358 subjects were available as subjects with 0.5Tesla MRI scans (nϭ37) and movement artifacts (nϭ1) were excluded.Incident lacunes were defined on MRI as newly emerged cavities with a diameter of 3 to 10 mm with signal intensities similar to cerebrospinal fluid in all performed scan sequences (1.5Tesla: T1-weighted 3D-magnetization prepared rapid-acquisition gradientecho, T2-weighted FSE, and fluid-attenuated inversion recovery images). 10 Incident lacunes were characterized with respect to brain region (subcortical white matter [WM], ...

“…Pathological studies have suggested that there may be 2 types of SVD that can be differentiated on brain imaging. 1 A diffuse arteriopathy of the perforating arteries with hyaline deposition: a pattern referred to as lipohyalinosis (diffuse-SVD) and localized small vessel microatheroma at the origin of the deep perforating arteries (focal-SVD). Diffuse-SVD is associated with multiple small lacunar infarcts with leukoaraiosis and focal-SVD with single large lacunar infarcts without leukoaraiosis.…”

mentioning

confidence: 99%

Plasma β-Amyloid 1-40 Is Associated With the Diffuse Small Vessel Disease Subtype

Gomis

Sobrino

Ois

et al. 2009

Background and Purpose-The underlying mechanisms of small vessel disease (SVD) subtypes are diffuse arteriopathy (diffuse-SVD) or microatheroma (focal-SVD). Endothelial dysfunction by ␤-amyloid peptide (A␤) deposition has been associated with lacunar infarcts and leukoaraiosis, but its specific relationship with SVD subtypes is unknown. We hypothesized that plasma A␤ levels can play a different role in SVD subtypes in patients with acute lacunar stroke. Methods-We studied 149 patients with acute ischemic stroke of SVD etiology according to Trial Of Org 10172 In Acute Stroke Treatment criteria and 25 age-matched control subjects. Patients were classified into focal-SVD: 39 patients with isolated lacunar infarct without leukoaraiosis and diffuse-SVD: 110 patients with an isolated lacunar infarct with leukoaraiosis or with multiple lacunar infarcts with or without leukoaraiosis. Baseline data included vascular risk factors and extensive laboratory tests, including plasma A␤ levels. Results-Median[quartiles] A␤ 1-40 levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not A␤ 1-42 levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (PϽ0.001) and control subjects (PϽ0.001). No differences in A␤ 1-40 levels were found between focal-SVD and control subjects. Logistic regression analysis showed that age (OR, 1.06; 95% CI, 1.01 to 1.12), history of hypertension (OR, 3.5; 95% CI, 1.3 to 9.2), and plasma ␤-amyloid 1-40 levels over the median value (OR, 17.3; 95% CI, 3.0 to 99 for the third quartile and OR, 6.0; 95% CI, 1.6 to 23 for the fourth quartile) were independently associated with the diffuse-SVD subtype. Key Words: acute stroke Ⅲ beta-amyloid protein Ⅲ leukoaraiosis Ⅲ small vessel disease T he pathogenesis of cerebral small vessel disease (SVD) is incompletely understood. Pathological studies have suggested that there may be 2 types of SVD that can be differentiated on brain imaging. 1 A diffuse arteriopathy of the perforating arteries with hyaline deposition: a pattern referred to as lipohyalinosis (diffuse-SVD) and localized small vessel microatheroma at the origin of the deep perforating arteries (focal-SVD). Diffuse-SVD is associated with multiple small lacunar infarcts with leukoaraiosis and focal-SVD with single large lacunar infarcts without leukoaraiosis. 2,3 Endothelial dysfunction may play an important role in the pathogenesis of the diffuse-SVD subtype. 4 -6 Plasma ␤-amyloid peptide (A␤) is a peptide consisting of either 42 (A␤ 1-42 ) or 40 (A␤ 1-40 ) amino acids derived from a proteolytic processing of the amyloid precursor protein. 7 Insoluble A␤ fibrils are the predominant constituents of senile plaques, one of the pathological hallmarks of Alzheimer disease, 8,9 and of cerebrovascular amyloid in the related condition of cerebral amyloid angiopathy. 10 Plaque amyloid is primarily comprised of A␤ 1-42 , whereas vascular amyloid is formed by the A␤ 1-40 species. Recent evidence suggests that amyloid precursor protein overexpression and A␤ accumulation impair cer...