Longitudinal study on low-dose aspirin versus placebo administration in silent brain infarcts: the silence study

Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment. Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment. Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-A [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence. Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. EU Clinical trial is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease

Vertex-wise analysis of CTh in ALS patients related to HC.

<p>ALS patients revealed cortical thinning in bilateral precentral cortex, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. The colour bar scale represents t values.</p

Vertex-wise analysis of CTh in ALS patients with spinal onset related to HC.

<p>Spinal onset ALS patients showed a significant thinning in right precentral and paracentral gyri; no differences were revealed in the left hemisphere. The colour bar scale represents t values.</p

Scale for clinical evaluation of upper motor neuron burden.

<p>UL, Upper Limb; LL, lower limb.</p

Clinical findings according ALS clinical traits.

<p>ALS, amyotrophic lateral sclerosis; >UMN-ALS, higher upper motor neuron burden; </p

Example of the CTh boundaries of an ALS patients.

<p>Axial and coronal T1-weighted images of an ALS patient. White matter surface (yellow line) and pial surface (red line), which are the boundaries of cerebral cortex, have been automatically obtained by Freesurfer. The primary motor area (blu) has been automatically labeled according to the Desikan/Killiany Atlas.</p

Mean whole brain and primary motor areas cortical thickness in ALS subgroups.

*<p>p<0.05 vs HC, § p≤0.01 vs HC, Ω p<0.005 vs HC.</p><p>CTh, cortical thickness, expressed in millimeters (mean ± SD); ALS, amyotrophic lateral sclerosis; HC, Healthy Controls; >UMN-ALS, higher upper motor neuron burden; </p