Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and cognitive symptoms, thus leaving much of the variance in cognitive performance unexplained. The objective of the current study was to investigate the relationship between the location of subcortical ischaemic lesions and cognitive symptoms in small vessel disease. We applied a voxel-based lesion-symptom mapping approach to data from 215 patients with CADASIL, a genetically defined small vessel disease with mutations in the NOTCH3 gene. All patients were examined by magnetic resonance imaging and comprehensive neuropsychological testing. Lacunar lesions and white matter lesions were segmented on three-dimensional T(1) and fluid-attenuated inversion recovery sequences, respectively. One hundred and forty-five subjects had a total of 854 lacunar lesions (range 1-13 per individual). The normalized volume of white matter hyperintensities ranged from 0.0425% to 21.5% of the intracranial cavity. Significant clusters for cognitive performance were detected for both lacunar lesions and white matter hyperintensities. The most prominent results were obtained on a compound score for processing speed, the predominantly affected cognitive domain in this group of patients. Strategic locations included the anterior parts of the thalamus, the genu and anterior limb of the internal capsule, the anterior corona radiata and the genu of the corpus callosum. By combining the lesion-symptom mapping data with information from a probabilistic white matter atlas we found that the majority of the processing speed clusters projected on the anterior thalamic radiation and the forceps minor. In multivariate models that included demographic parameters, brain atrophy and the volume of ischaemic lesions, regional volumes of lacunar lesions and white matter hyperintensities in the anterior thalamic radiation predicted performance in processing speed tasks, whereas there was no independent contribution of the global volume of ischaemic lesions. These observations emphasize the importance of lesion location for both lacunar and ischaemic white matter lesions. Our findings further highlight the anterior thalamic radiation as a major anatomical structure impacting on processing speed. Together these findings provide strong support for a central role of frontal-subcortical circuits in cerebral small vessel disease and vascular cognitive impairment.

Background and Purpose-Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy remain unknown. This study aims to identify demographic, clinical, and magnetic resonance imaging predictors of incident strokes, incident dementia, clinical deterioration, and death in patients with this genetically proven disease. Methods-Two hundred ninety subjects (mean age, 50.6±11.4 years) were assessed at baseline and followed up for 36 months. Incident clinical events were recorded, and clinical scores included the Mini Mental State Examination, Mattis Dementia Rating Scale, modified Rankin Scale, and Barthel index. The number of lacunes and microbleeds, the volume of white-matter hyperintensities, and brain parenchymal fraction were assessed on baseline magnetic resonance imaging. Data were analyzed by ANCOVA, multivariable logistic regression, and Cox proportional hazard models. Results-Incident stroke occurred in 55 of 278 patients (19.8%). Moderate or severe disability developed in 19 of 210 (9%) nondisabled individuals, incident dementia in 49 of 231 (20%) nondemented subjects, and 4.8% of patients died. Active smoking, the number of lacunes, and brain parenchymal fraction independently predicted incident stroke during follow-up. Gait disturbance, dementia, and brain parenchymal fraction predicted progression toward moderate or severe disability. Active smoking, disability, and brain parenchymal fraction predicted incident dementia. Age was the only significant predictor of death. The clinical and imaging characteristics of CADASIL much resemble those of the most severe forms of sporadic SVD. We, thus, reasoned that information derived from a longitudinal study in CADASIL might offer insights relevant to SVD in general. Here, we report the final results of this study obtained in a large cohort of patients followed up for 3 years. Conclusions-Clinical Methods Study CohortSubjects were prospectively recruited between September 2003 and April 2011 through 2 major referral centers for CADASIL (University Hospital Lariboisière, Paris [n=178] and Ludwig Maximilians Universität, Munich [n=112]). They were included regardless of whether they had clinical manifestations of the disease if they were at least 18 years of age, had a documented mutation in the NOTCH3 gene, and were willing to be followed up. Details of the study protocol have been reported elsewhere.11 A follow-up interval of 3 years was chosen based on previous longitudinal data showing that significant changes in clinical scores can be detected within an interval of 2 years 8 when following up patients seen at major referral centers and to obtain a sufficient number of clinical events. In brief, clinical and demographic data were collected at study entry and included age, sex, years of education, and vascular risk factors (hypertension, diabetes mellitus, hypercholesteremia, smoking, and alcohol use). Blood pressure was measured at baseline and at follow-up.A history of transient ischemic attack...

Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. infections are major causes of morbidity and mortality, especially due to the emergence and spread of β-lactamases. Carbapenemases, which are β-lactamases with the capacity to hydrolyze or inactivate carbapenems, have become a serious concern as they have the largest hydrolytic spectrum and therefore limit the utility of most β-lactam antibiotics. Areas covered: Here, we present an update of the current status of carbapenemases in Latin America and the Caribbean. Expert commentary: The increased frequency of reports on carbapenemases in Latin America and the Caribbean shows that they have successfully spread and have even become endemic in some countries. Countries such as Brazil, Colombia, Argentina, and Mexico account for the majority of these reports. Early suspicion and detection along with implementation of antimicrobial stewardship programs in all healthcare settings are crucial for the control and prevention of carbapenemase-producing bacteria.

The results suggest that apathy is common in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), appears in association with cognitive impairment, global functional disability, and severe neuropsychiatric symptoms during the course of the disease, and can occur separately from depression. Apathy has an independent impact on the overall quality of life in CADASIL.

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Background and Aim: Dilated perivascular spaces (dPVS) have previously been associated with aging and hypertension-related cerebral microangiopathy. However, their risk factors, radiological features and clinical relevance have been poorly evaluated in CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a unique model to investigate the pathophysiology of ischemic small-vessel disease. The purpose of this study was to investigate these different aspects in a large cohort of patients with this disorder. Methods: Demographic and MRI data of 344 patients from a prospective cohort study were analyzed. The severity of dPVS was evaluated separately in the anterior temporal lobes, subinsular areas, basal ganglia and white matter, using validated semiquantitative scales. Logistic and multiple linear regression models were used to determine the risk factors associated with the severity of dPVS in these different regions and their relationships with cognition, disability and the MRI markers of the disease (white matter hyperintensities (WMH) lacunar infarcts, microbleeds and brain parenchymal fraction (BPF)). Results: The severity of dPVS was found to increase with age regardless of cerebral area (p < 0.001). In contrast with dPVS in other locations, the severity of dPVS in the temporal lobes or subinsular areas was also found strongly and specifically related to the extent of WMH (p < 0.001). Conversely, no significant association was detected with lacunar volume, number of microbleeds or BPF. A high degree of dPVS in the white matter was associated with lower cognitive performances independently of age and other MRI markers of the disease including BPF (p ≤ 0.04). Conclusions: In CADASIL, the progression of the hereditary microangiopathy with aging may promote the dilation of perivascular spaces throughout the whole brain but with variable extent according to cerebral location. In temporal lobes and subinsular areas, dPVS are common MRI features and may share a similar pathogenesis with the extension of WMH during the course of the disease. dPVS may also participate in the development of cognitive decline in this model of small-vessel disease, and their large number in white matter may alert clinicians to a higher risk of cognitive decline in CADASIL.

Background and Purpose-In the general population, migraine, cerebrovascular diseases, and vascular dementia differ in many aspects between men and women. CADASIL is considered a unique model to investigate migraine with aura, stroke, and dementia related to ischemic small vessel disease. This study aims to evaluate the effect of gender on the main clinical and neuroimaging characteristics of CADASIL. Methods-Cross-sectional data from 313 CADASIL patients including various clinical and cognitive scores and MRI parameters were compared between men and women, and between those younger and older than the median age of the population corresponding to the usual age of menopause (51 years). Results-At younger than 51 years, migraine with aura was 50% more prevalent in women and stroke was 75% more prevalent in men. After the fifth decade, men had higher National Institutes of Health Stroke Scale and Rankin scores than women and more severe executive dysfunction, although global cognitive scores were similar. Age at first stroke, the number of stroke events, and the prevalence of dementia and psychiatric symptoms did not differ between men and women. Brain volume was lower in men with a trend for a larger volume of lacunar infarcts. Conclusions-In CADASIL, migraine with aura is more frequent in women and stroke is more frequent in men before the age of menopause. This difference seems to vanish after this age limit but may result in a higher degree of cognitive impairment and cerebral atrophy in men at the late stage of the disease. The presumable role of ovarian hormones in these gender-related differences remains to be explored. (Stroke. 2012;43:137-141.)

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