The Clinical Characteristics of Patients with Pre-Existing Leukoaraiosis Compared to Those Without Leukoaraiosis in Acute Ischemic Stroke.

BACKGROUND: Leukoaraiosis (LA) is a finding in the elderly, that might be asymptomatic or can impact their motor and cognitive functions. We studied the presence of LA in the MRI of patients with AIS and its impact on functional outcome at 3 months. METHODS: 500 consecutive patients diagnosed as AIS were enrolled. Medical history included pre-medication by antiplatelets or statins, and vascular risk factors were reported by history and laboratory investigations. Severity of stroke was assessed by NIHSS and stroke outcome was evaluated on discharge and at 3 months by modified Rankin scale (mRS). LA was diagnosed by MRI-FLAIR sequence and delineated from acute infarction by diffusion-weighted image. And accordingly, patients were divided into group A (absent LA) and group B (present LA). RESULTS: 460 patients completed the study, with 53% of patients on antiplatelet therapy and 11.7% on statins prior to stroke. The percentage of patients with LA was significantly more than those without LA. Patients with LA showed a significantly higher age, more frequent and longer duration of diabetes and hypertension, ischemic heart disease, previous stroke/TIA and antiplatelet intake. Microbleeds were more and mRS was worse in LA group. CONCLUSION: The presence of LA in the background MRI of AIS patients is accompanied by the presence of more risk factors, and unfavorable outcome. Pre-medication with antiplatelets did not prevent the incidence of a new stroke especially in LA group. This might necessitate the identification of some medication for secondary prevention in patients with small vessel disease.

Leukoaraiosis severity and outcomes after mechanical thrombectomy with stent-retriever devices in acute ischemic stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis severity is associated with outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices. METHODS: In this retrospective multicenter study, we evaluated 251 acute stroke patients (pretreatment National Institutes of Health Stroke Scale score ≥8) treated with stent-retriever devices. Leukoaraiosis severity was graded as 0-2 (absent-to-moderate) versus 3-4 (severe) according to the van Swieten scale. The main clinical outcome was the proportion of good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. RESULTS: Significantly fewer patients in the severe LA group than in the absent-to-moderate LA group achieved a good functional outcome (18.4% vs 50.2%, P<0.001). In multivariable analysis, severe leukoaraiosis was a significant negative predictor of good functional outcome at 90 days (OR, 0.27; 95% CI 0.10-0.77; P=0.014). CONCLUSIONS: The severity of leukoaraiosis is independently associated with 90-day functional outcome in acute stroke patients undergoing mechanical thrombectomy with stent-retriever devices.

Ischemia in intracerebral hemorrhage is associated with leukoaraiosis and hematoma volume, not blood pressure reduction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesions have been identified both inside and outside the perihematoma region. We tested the hypotheses that larger hematoma volumes and blood pressure reduction are associated with DWI lesions. METHODS: Hematoma and perihematoma edema volumes were measured using planimetric techniques in 117 intracerebral hemorrhage (ICH) patients who underwent DWI. Perihematoma and remote DWI lesion volumes were measured using apparent diffusion coefficient thresholds for moderate (<730×10(-6) mm/s) and severe (<550×10(-6) mm/s) ischemia. Acute blood pressure change over the first 24 hours was calculated. RESULTS: The median (interquartile range) time to magnetic resonance imaging was 2 (1-5) days. Median hematoma volume was 9.8 (2.6-23.0) mL, and median perihematoma edema volume was 7.0 (2.9-18.6) mL. A small portion of the perihematoma region contained tissue below the thresholds for moderate (8.0 [2.9-14.5]%) and severe ischemia (1.1 [0.3-3.5]%). Ischemic perihematoma tissue volumes were correlated with hematoma volumes (R=0.52, P<0.001), but not maximal systolic blood pressure drop at 24 hours (R=-0.09, P=0.38). Remote DWI lesions were found in 17 (14.5%) patients (mean volume=0.44±0.3 mL). Patients with remote DWI lesions had higher rates of antiplatelet use (P=0.01), prior ICH (P=0.03), lobar ICH (0.04), and larger leukoaraiosis volumes (P=0.02). Maximal systolic blood pressure drop at 24 hours was similar in patients with (-20.5 [-55, -10] mm Hg) and without remote DWI lesions (-27 [-46, -13] mm Hg, P=0.96). CONCLUSIONS: Small DWI lesions within and outside the perihematoma region are common in primary ICH. Perihematoma DWI lesions were independently associated with larger hematoma volumes. Remote DWI lesions may be an epiphenomenon associated with the underlying microvascular pathogenesis. These data do not support a hemodynamic mechanism of ischemic injury after primary ICH.

White matter changes in dementia: role of impaired drainage of interstitial fluid.

White matter abnormalities on magnetic resonance imaging (MRI) are associated with dementia and include white matter hyperintensities (WMH; also termed leukoaraiosis) and visible perivascular spaces (PVS). We review the potential role of impaired drainage of interstitial fluid in the pathogenesis of WMH and PVS. Whereas the volume of extracellular space in the grey matter is tightly controlled, fluid accumulates and expands the extracellular spaces of the white matter in acute hydrocephalus, vasogenic edema and WMH. Although there are no conventional lymphatic vessels in the brain, there is very effective lymphatic drainage for fluid and solutes along restricted pathways in the basement membranes of cerebral capillaries and arteries in young individuals. Lymphatic drainage of the brain is impaired with age and in association with apolipoprotein E ε4, risk factors for Alzheimer's disease and cerebral amyloid angiopathy (CAA). Deposition of proteins in the lymphatic drainage pathways in the walls of cerebral arteries with age is recognized as protein elimination failure angiopathy (PEFA), as in CAA and cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL). Facilitating perivascular lymphatic drainage from the aging brain may play a significant role in the prevention of CAA, WMH and Alzheimer's disease and may enhance the efficacy of immunotherapy for Alzheimer's disease.

Leukoaraiosis predicts parenchymal hematoma after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy. METHODS: We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome. RESULTS: Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale≤2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001). CONCLUSIONS: Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.

Immediate regression of leukoaraiosis after carotid artery revascularization.

BACKGROUND: Leukoaraiosis (LA) affects cognition after stroke and reversal of LA may improve cognitive performance. We aimed to determine the impact of cerebral perfusion and circle of Willis (CoW) flow patterns on the extent of LA after carotid artery revascularization. METHODS: LA was scored on fluid-attenuated inversion recovery magnetic resonance (MR) images at the levels of the centrum semiovale and frontal horns in both cerebral hemispheres of 62 contiguous patients (men/women = 38/24, mean age = 63.2 ± 8.4 years, range 44-82) before and after unilateral carotid artery revascularization. The pre- and poststenting differences in LA scores, CoW flow pattern on MR angiography, and MR perfusion parameters were analyzed. RESULTS: The total LA score decreased from 9.87 ± 0.65 to 8.33 ± 0.72 after stenting (p = 0.03). The CoW was complete in 21 subjects and incomplete in 41 subjects. The incomplete CoW group had a higher preoperative LA load and higher cerebral interhemispheric asymmetry index, both of which decreased significantly postoperatively. CONCLUSIONS: CoW anomalies may contribute to LA in patients with carotid artery stenosis, and restoration of cerebral perfusion by carotid artery revascularization can reduce LA severity.

[Cognitive impairment associated to leukoaraiosis: its pathophysiology, clinical manifestations and treatment]. / Deterioro cognitivo asociado a la leucoaraiosis: fisiopatología, manifestaciones clínicas y tratamiento.

INTRODUCTION AND DEVELOPMENT: Leukoaraiosis is a radiological term which refers to white matter disturbances observed as a hypodensity in computed tomography and hyperintensity in T2-weighted magnetic resonance image. The most accepted theory to explain the mechanism of production of leukoaraiosis is chronic ischemia, due to a damage in penetrating arteries. It is an entity with increasing interest, since it is associated with the presence of cognitive impairment. Clinical manifestations in relation with cognitive functions range from mild affectation to dementia, affecting the processing speed and executive functions. CONCLUSIONS: It seems that the control of vascular risk factors slow the progression of leukoaraiosis and cognitive impairment, and although there are no really effective treatment, it seems that some drugs, such as acetylcholinesterase inhibitors or NMDA-receptor antagonists, exert a beneficial effect, although slight, in cognitive functions.

Treatment of leukoaraiosis: a futuristic view.

Leukoaraiosis (LA or white matter changes of the brain) is a common finding on brain imaging studies in the elderly people. LA predisposes to dementia, ischemic stroke, intracerebral hemorrhage, and cognitive decline as well as associates with a significant increase in falls and gait disorders. As population ages, the incidence of LA increases and is becoming a major global health problem. Therefore, strategies for its prevention and management are urgently needed. This review includes basic knowledge on the pathophysiology, patterns of clinical presentation, risk factors, and imaging findings of LA. The very last and the most comprehensive part of this review discusses potential therapeutic approaches of the future.