Cerebral white matter Hyperintensities in HIV-positive patients.

White matter hyperintensities (WMHs) have been associated with neurological complications including cognitive impairment. WMHs have been often described in HIV positive subjects and they have been linked to neurocognitive impairment, cerebrospinal fluid (CSF) residual viral replication and biomarkers of monocyte activation. Aim of this study was to grade WMHs in HIV-positive individuals using a simple visual scale and to explore their severity with clinical, neurocognitive and biomarker characteristics. Brain MRIs were retrospectively evaluated by two reviewers who rated WMHs following the "age-related white matter changes (ARWMC)" scale. 107 adult HIV-positive patients receiving lumbar punctures for clinical reasons were included. 70 patients (66.6%) were diagnosed with WMHs. Average WMH scores were higher in treated [7 (1-11)] vs. naïve individuals [3 (0-6)] (p = 0.008). Higher WHMs scores were observed in patients with chronic renal impairment along with chronic hepatitis (naïve) and longer HIV duration (treated participants). No consistent associations between plasma, CSF biomarkers and WMHs scores were found. 45 patients underwent full neurocognitive tests and WMHs scores were non-significantly higher in patients diagnosed with HAND [6.5 (0.5-8.3) vs. 1.5 (0-7), p = 0.165]; screening (IHDS and FAB), visuo-spatial (Corsi's) and auditory-verbal memory (disillabic words repetition) tests scored worse in patients with higher WMHs. In our population of HIV-positive patients with low CD4 nadir and partial CD4 cell recovery the burden of WMHs was associated with the duration of HIV infection and with commonly observed comorbidities (such as renal and hepatic impairment). Given the association with worse neurocognition, further studies on tailored interventions are needed.

Classification and characterization of periventricular and deep white matter hyperintensities on MRI: A study in older adults.

White matter hyperintensities (WMH) are frequently divided into periventricular (PWMH) and deep (DWMH), and the two classes have been associated with different cognitive, microstructural, and clinical correlates. However, although this distinction is widely used in visual ratings scales, how to best anatomically define the two classes is still disputed. In fact, the methods used to define PWMH and DWMH vary significantly between studies, making results difficult to compare. The purpose of this study was twofold: first, to compare four current criteria used to define PWMH and DWMH in a cohort of healthy older adults (mean age: 69.58 ± 5.33 years) by quantifying possible differences in terms of estimated volumes; second, to explore associations between the two WMH sub-classes with cognition, tissue microstructure and cardiovascular risk factors, analysing the impact of different criteria on the specific associations. Our results suggest that the classification criterion used for the definition of PWMH and DWMH should not be considered a major obstacle for the comparison of different studies. We observed that higher PWMH load is associated with reduced cognitive function, higher mean arterial pressure and age. Higher DWMH load is associated with higher body mass index. PWMH have lower fractional anisotropy than DWMH, which also have more heterogeneous microstructure. These findings support the hypothesis that PWMH and DWMH are different entities and that their distinction can provide useful information about healthy and pathological aging processes.

Lesiones en la sustancia blanca en el paciente anciano: Utilización de la terminología adecuada / White matter lesions in an elderly patient: Using the proper terminology

En Neurorradiología los cambios de la sustancia blanca periventricular o subcortical en pacientes ancianos son descritos generalmente con leucoaraiosis, fenómenos hipóxico-isquémicos crónicos, leucoencefalopatía microangiopática o simplemente con alteraciones en la densidad o intensidad según el método elegido. Sin embargo, ¿es correcto el empleo de estas denominaciones?, ¿funcionan como sinónimos?, ¿tienen un mismo mecanismo de producción? Las lesiones que afectan a la sustancia blanca se aprecian hipodensas en tomografía computada, hiperintensas en las secuencias ponderadas en T2 o FLAIR e hipointensas en la resonancia magnética en ponderación T1. Describimos las distintas entidades que pueden afectar selectivamente la sustancia blanca en el paciente anciano y sus probables mecanismos de acción, para establecer una correcta denominación y realizar los diagnósticos diferenciales.

In Neuroradiology the changes in the deep or sub-cortical white matter in elderly people are generally described as leukoaraiosis, chronic hypoxic-ischaemic processes, microangiopathic leucoencephalopathy, or they are simply mentioned as density or intensity changes according to the selected imaging method. However, are these terms correct?, Are they synonyms?, Do they have the same aetiology? The lesions that affect white matter are hypodense in computed tomography, hyperintense in T2-weighted or FLAIR, or hypointense in T1 images in magnetic resonance. A description is presented on the different conditions that can selectively affect the white matter in the elderly patient and their probable mechanisms of action in order to establish a correct nomenclature, as well as make differential diagnoses.

Leukoaraiosis and NIHSS score help to differentiate subtypes of intracranial branch atheromatous disease in Southern Han Chinese patients with stroke.

Intracranial branch atheromatous disease (BAD) includes infarcts in the territories of the lenticulostriate arteries (LSA) and paramedian pontine arteries (PPA). The two subtypes of BAD are commonly underused in clinical practice and research. We assessed the clinicoradiologic characteristics of BAD-stroke patients in LSA territories and compared with those of BAD-stroke patients in PPA territories to investigate whether there is a close relationship between leukoaraiosis (LA) and BAD in Southern Han Chinese patients. According to the lesions present in different vascular distributions as shown by diffusion-weighted imaging (DWI), a total of 220 patients diagnosed with BAD, selected from a cohort of 1,458 consecutive patients with acute ischemic stroke, were classified into LSA and PPA groups, comprising 163 and 57 patients, respectively. The characteristics of the patients with BAD were analyzed and differences between the two groups were compared. A high prevalence of concomitant LA (n = 190, 86.36 % of patients with BAD) was observed in the cohort study. Patients in the PPA group had a significantly higher National Institutes of Health Stroke Scale (NIHSS) score on admission than those in the LSA group [6 (4-8) versus 5 (3-7); p = 0.031], and there was a higher prevalence of concomitant LA in the PPA group than the LSA group (96.4 versus 82.8 %; p = 0.010). Conversely, when the number of patients with LA grades ≥ 4 was evaluated, individuals in the LSA group were more frequently affected than those in the PPA group (47.9 versus 31.6 %; p = 0.033). LA showed a high prevalence in Southern Han Chinese patients with BAD. Patients in the LSA group were significantly different from those in the PPA group with respect to NIHSS score, LA and LA grade.

Silent brain infarcts, leukoaraiosis, and long-term prognosis in young ischemic stroke patients.

OBJECTIVE: To investigate prognostic relevance of silent brain infarcts (SBIs) and leukoaraiosis (LA) in young patients with ischemic stroke. METHODS: This observational cohort study included consecutive MRI-scanned patients aged 15 to 49 with first-ever ischemic stroke treated at Helsinki University Central Hospital (1994-2007) with long-term follow-up data available. Outcome measures were 1) nonfatal or fatal ischemic stroke, 2) composite vascular endpoint, and 3) death from any cause. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and Bamford criteria allowed for stroke subtyping. Number of SBIs was categorized into none, single, or multiple. LA fell into groups of none, mild, or moderate to severe (validated visual rating scale). RESULTS: The 655 patients (mean age 40.0 ± 8.0 years) included were followed for a mean 8.7 ± 3.8 years (survivors). Of the 86 (13.1%) patients with SBIs, 46 had single and 40 had multiple SBIs. In the 50 (7.6%) patients with LA, these changes were mild in 21 and moderate to severe in 29. In Cox regression analysis, multiple SBIs independently raised the risk for recurrent ischemic stroke (odds ratio 2.48; 95% confidence interval 1.24-4.94) adjusted for age, gender, risk factors, stroke etiology, and LA. After further adjustment for initial stroke severity, TOAST and Bamford subgroups, and presence of SBIs, moderate to severe LA increased the risk for death (3.43; 1.58-7.42). Neither SBIs nor LA associated with the composite vascular endpoint. CONCLUSIONS: MRI-defined SBIs and LA are prognostically valuable in young adults after their first-ever ischemic stroke.

Leukoaraiosis severity and list-learning in dementia.

In patients with dementia, leukoaraiosis (LA) was hypothesized to result in differential patterns of impairment on a verbal serial list-learning test. Using a visual rating scale, 144 dementia patients with ischemic scores <4 were re-categorized as having mild (n = 73), moderate (n = 44), or severe LA (n = 27). Mild LA was predicted to be associated with an amnestic list-learning profile, while severe LA was predicted to be associated with a dysexecutive profile. List-learning performances were standardized to a group of healthy older adults (n = 24). Analyses were conducted on a set of four factors derived from the list-learning paradigm, as well as error scores. Data indicate that LA severity is an important marker for understanding list learning in dementia.

Reduced perfusion reserve in Leukoaraiosis demonstrated using acetazolamide challenge 123I-IMP SPECT.

OBJECTIVE: We examined the relationship between the perfusion reserve as measured by acetazolamide (ACZ)-challenge N-isopropyl-I-123-p-iodoamphetamine (IMP)-single-photon emission computed tomography (SPECT) and the degree of leukoaraiosis (LA) as estimated using magnetic resonance imaging. METHODS: In 51 patients receiving IMP-SPECT with the resting state and ACZ challenge, the unaffected cerebral hemispheres were included in the present study. Mean cerebral blood flow (CBF) in the resting state and ACZ reactivity were acquired. Absolute CBF value and ACZ reactivity were compared among patients with LA grades 0, 1, and 2. The relationship between mean age and LA grade was also assessed. RESULTS: No significant difference in the absolute CBF value in the resting state was observed among the 3 LA groups. Although vasoreactivity in LA grade 0 did not differ from that in grade 1, vasoreactivity in LA grade 2 was significantly lower (P < 0.05) than that in grades 0 or 1. CONCLUSIONS: The perfusion reserve is impaired in advanced LA.

Cerebral white matter lesions and hypertension status in the elderly Korean: the Ansan Study.

There is evidence of an association of hypertension with white matter lesions (WMLs), leukoaraiosis, in the human brain in the United States, Europe and Japan. However, no study on this association has been reported in Korea. Community-dwelling elderly subjects aged over 61 years were randomly selected from samples of the Ansan Health Study, while their blood pressures (BPs) were measured using a highly standardized protocol. Hypertension was defined as a systolic BP> or =140 mmHg or a diastolic BP> or =90 mmHg or as reported treatment with hypertensive medication, and further subclassified with respect to its subtypes and control status. WMLs were determined by a 1.5-T MRI scan and further categorized into five subgroups with respect to its severity. Hypertension status, such as uncontrolled hypertension even after antihypertensive medication (adjusted odd ratio [OR]=6.07; 95% CI, 2.08-17.78), isolated systolic hypertension before medication (OR=2.66; 95% CI, 1.08-6.57), and hypertension before medication (OR=2.55; 95% CI, 1.19-5.46) were significantly and independently correlated with the presence and severity of WMLs. Advancing age (OR=1.76; 95% CI, 1.38-2.25), lacunar infarction (OR=3.19; 95% CI, 1.83-5.58), and cigarette smoking (OR=1.10; 95% CI, 1.03-1.18) were significantly related to the presence and severity of WMLs. Regular and tight control for hypertension should be exercised to prevent WMLs among the elderly with hypertension.

Pathological validation of a CT-based scale for subcortical vascular disease. The OPTIMA Study.

The validity of a computed tomography (CT)-based rating scale that separately rates leukoaraiosis, patchy lesions, and lacunes was tested using neuropathological findings collected on 87 subjects enrolled in the Oxford Project to Investigate Memory and Ageing. The CT-based score (range 0-64) was associated with both small vessel disease (p = 0.015) and microinfarcts (p = 0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on pathology was computed, 0 indicating absent/mild small vessel CVD and no microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher both conditions or severe small vessel CVD. Subjects with a sum score of 0 were decreasing with increasing severity of CT-based score (64, 46, and 25% in those with CT-based scores of 0, 1-38, and 39 and higher), while those with a sum score of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized assessment of subcortical CVD on CT films can be compounded into a unique score that is in good agreement with neuropathology. This supports the validity of the CT-based visual rating scale as a valid tool to detect subcortical vascular changes in elderly persons.