Post-Stroke Detection of Subclinical Paroxysmal Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source in the Real World Practice: The Empoli ESUS Atrial Fibrillation (E 2 AF) Study.

BACKGROUND: Subclinical paroxysmal atrial fibrillation (AF) is one of the main occult causative mechanisms of embolic stroke of undetermined source (ESUS). Aim of this study was to identify AF predictors, and to develop a score to predict the probability of AF detection in ESUS. METHODS: We retrospectively analyzed ESUS patients undergoing 2-week external electrocardiographic monitoring. Patients with and without AF detection were compared. On the basis of multivariate analysis, predictors of AF were identified and used to develop a predictive score, which was then compared with other existing literature scores. RESULTS: Eighty-two patients, 48 females, mean age±SD 72±10 years, were included. In 36 patients (43.9%) AF was detected. The frequency of age 75 years or above and arterial hypertension, and the median CHA 2 DS 2 -VASc score were significantly higher in patients with AF compared with those without. National Institutes of Health Stroke Scale (NIHSS) score ≥8 was the only independent variable associated with AF detection. We derived the Empoli ESUS-AF (E 2 AF) score (NIHSS ≥8 5 points, arterial hypertension 3 points, age 75 years or above 2 points, age 65 to 74 years 1 point, history of coronary/peripheral artery disease 1 point, left atrial enlargement 1 point, posterior lesion 1 point, cortical or cortical-subcortical lesion 1 point), whose predictive power in detecting AF was good (area under the curve: 0.746, 95% confidence interval: 0.638-0.836) and higher than that of CHA 2 DS 2 -VASc and other scores. CONCLUSIONS: In our study NIHSS score ≥8 was the only independent predictor of post-ESUS-AF detection. The E 2 AF score appears to have a good predictive power for detecting AF. External validations are required.

Voxel-wise assessment of progression of regional brain atrophy in relapsing-remitting multiple sclerosis.

OBJECTIVE: To perform voxel-wise assessments of regional brain atrophy state and rate in subjects with relapsing-remitting (RR) multiple sclerosis (MS). BACKGROUND: Recently, attention has focused on defining the tissue compartments and regions within which brain atrophy occurs. These regional measures of brain volume changes may help to better define the nature of the pathology underlying MS. In this context, specific regional measures of grey matter (GM) volume changes can be obtained by using the voxel-based morphometry (VBM) approach. METHODS: Fifty-nine subjects with RR MS underwent conventional MRI at baseline and after a mean follow-up period of 3 years. Cross-sectionally, two VBM analyses (SPM-VBM, based on the Statistical Parametric Mapping software package, and FSL-VBM, based on the FMRIB Software Library tools) were performed to assess cortical GM volumes in RR MS patients compared to 25 age- and sex-matched normal controls (NC). Longitudinally, FSL-VBM and the regional extension of the SIENA method (SIENAr) were both used to assess regional brain atrophy rate in the RR MS patients and its relationship with increases in T(2)-weighted white matter (WM) lesion volume over the follow-up period. RESULTS: Widespread decrease in cortical GM volume was found in the RR MS patients compared to NC. Both SPM-VBM and FSL-VBM showed similar involvement of cortical regions (frontal, temporal, parietal, occipital lobes and insula), with a close correlation between the numbers of significant voxels obtained with the two different procedures (r=0.73, p<0.001). After 3-year follow-up, both FSL-VBM and SIENAr showed a further significant reduction in GM volume in the lateral frontal and parietal cortices, bilaterally. Regional volume changes also appeared significantly pronounced in correspondence to the increase in T(2)-weighted WM lesion volume over the follow-up period. CONCLUSIONS: By using different methodologies, we showed similar widespread tissue loss in the cerebral cortex of patients with RR MS. This brain tissue loss further progresses over time, particularly in the fronto-parietal cortex and seems to be partially dependent upon the increase of lesion load.

Voxel-based assessment of differences in damage and distribution of white matter lesions between patients with primary progressive and relapsing-remitting multiple sclerosis.

BACKGROUND: Several studies have reported lower focal demyelination and inflammatory activity in primary progressive multiple sclerosis (PPMS) than in relapsing-remitting MS (RRMS). However, very little is known about possible differences in damage and distribution that may occur within lesions visible on magnetic resonance imaging in the 2 forms of the disease. OBJECTIVE: To evaluate differences in spatial distribution and structural damage of focal demyelinating lesions in patients with PPMS and RRMS. DESIGN: We acquired conventional magnetic resonance and magnetization transfer images in 24 PPMS and 36 RRMS patients (matched for sex, age, and disease duration) and 23 healthy sex- and age-matched controls. In each participant, we measured T2- and T1-weighted lesion volumes and magnetization transfer ratios in lesional and nonlesional brain tissues. The spatial distribution of focal demyelination was assessed using T2- and T1-weighted lesion probability maps in each patient group. Voxel-based procedures were performed. SETTING: University hospital. RESULTS: Patients with PPMS had greater disability than those with RRMS, with 70% of PPMS patients and 11% of RRMS patients having relevant motor symptoms. The T1- and T2-weighted lesion volumes were higher in PPMS than in RRMS patients (P < .001). T1- and T2-weighted lesion probability maps showed that the maximum probability for lesions was higher in PPMS (peak probability, 45% and 29%, respectively) than in RRMS (peak probability, 33% and 19%, respectively) patients and was localized in the corona radiata. Voxelwise analysis of lesional magnetization transfer ratios gave overlapping results. CONCLUSIONS: Differences in cerebral pathologic involvement exist between RRMS and PPMS and contribute to variations in clinical disability.

Magnetic resonance spectroscopy as a measure of brain damage in multiple sclerosis.

Recent MR studies have emphasised the importance of neuronal and axonal damage in multiple sclerosis. In this respect, proton MR spectroscopy (by monitoring levels of N-acetylaspartate, a putative marker of axonal integrity) has been particularly illuminating by showing indirect evidence of neurodegeneration in both lesional and non-lesional brain tissues from the earliest stages of the disease. The importance of these changes to patients' clinical disability argues for the primary role of neuronal pathology in the pathogenesis of the disease.

Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability.

BACKGROUND: Although in situ pathological studies and in vivo magnetic resonance (MR) investigations have shown that axonal injury can be significant in the early stages of multiple sclerosis (MS), diffuse axonal injury is generally considered a secondary event. Cerebral axonal damage can be specifically assessed in vivo by measuring levels of brain N-acetylaspartate (NAA, a specific index of axonal integrity detected by MR spectroscopy). Other new MR measurements such as magnetization transfer ratio (MTr) or computed estimation of brain volume can provide less specific indexes of tissue damage. OBJECTIVE: To determine whether diffuse axonal and tissue injury is present in patients with definite MS who do not show clinically significant disability. METHODS: We measured brain NAA levels (normalized to creatine [Cr]), MTr values, and cerebral volumes in patients with definite MS who had low T2-weighted MR imaging lesion volumes and no clinical disability, and also in age-matched healthy control subjects. RESULTS: Values of central brain NAA/Cr and MTr in normal-appearing white matter were significantly lower in the MS patients than in controls (P<.001). In contrast, total brain volumes were not significantly different between these groups. Similar results were found for MS patients with early disease (duration, <3 years) and with a particularly low cerebral T2-weighted MR imaging lesion load (< or = 2 cm(3)). CONCLUSIONS: Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability. This suggests that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral demyelination.

MR correlates of cerebral atrophy in patients with multiple sclerosis.

OBJECTIVE: To investigate the in-vivo correlates of brain atrophy in patients with multiple sclerosis (MS) by assessing the relationship between normalized measures of brain volume (NBV) and other magnetic resonance (MR) measures of tissue damage. BACKGROUND: Brain atrophy diffusely occurs and progressively increases in patients with MS. Nevertheless, the mechanisms leading to brain atrophy in this disease are not fully understood. METHODS: MR examinations were performed in 20 patients with relapsing-remitting MS. Conventional MRI was used to assess NBV and total brain T2-hyperintense and T1-hypointense lesion volumes. Proton MR spectroscopic imaging and diffusion tensor MR imaging were also performed for large portions of brain containing mainly normal-appearing tissue to provide indices of tissue damage, including N-acetylaspartate to creatine ratio (NAA/Cr) and mean diffusivity (D). RESULTS: Values of NBV correlated significantly with those of average brain (r = -0.58, p = 0.007) and NAA/Cr (r = 0.67, p < 0.001). The relationship of these markers of tissue damage to NBV was also found when NAA/Cr and were computed together in a composite MR score (r = 0.70, p < 0.001). In contrast, NBV values did not correlate with measurements of average lesion, T(2) and T(1) weighted total brain MRI lesion volumes. CONCLUSIONS: This study suggests that brain atrophy in MS is not simply due to axonal loss, but rather reflects a more generalized process that involves various brain tissue components. Damage to the normal-appearing tissue rather than the extent and intrinsic pathology of macroscopic lesions seems to be important in the destructive process leading to MS-related irreversible cerebral atrophy.