Giovanna Carlucci

Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes. Design Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints. Setting 11 European centres. Participants 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy. Main outcome measure Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke. Results Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect. Conclusion The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Corpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis

Cognitive impairment and gait disturbances are the most frequent clinical findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has been associated with dementia in patients with LA, as well as with gait disturbances in patients with normal pressure hydrocephalus. We investigated, in patients with LA, the possible association between gait impairment and CC atrophy, taking into account cognitive deficits and the other brain lesions commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5±6.3 years) with gait disturbances and brain CT images consistent with LA underwent an assessment of gait and a cognitive assessment of global and selective functions. Magnetic resonance imaging (MRI) was used to measure thickness and area of the CC, total LA volume, lacunar infarcts and size of lateral ventricles. We examined the effect of every MRI change on each performance measure. Reduction of CC thickness, particularly that of the anterior segment, had a significant effect on severity of gait impairment, as measured using the gait scale’s score. It was independent of any other brain changes revealed by MRI, including LA. An independent, significant association was also found between CC area and the Left Hand Praxis test results. In patients with LA, CC atrophy is associated with gait impairment independently of LA and other brain abnormalities usually present in these patients.

White matter changes: the clinical consequences in the aging population.

Neuroimaging changes in the cerebral subcortical white matter (WMC) are recognized with the highest frequency in elderly subjects, particularly in those with vascular risk factors. WMC have been consistently reported to be associated with global or selective cognitive deficits, depression, motor and gait impairment. All these deficits are main contributors to disability in the elderly. Moreover, subjects with WMC have an increased risk of cardiovascular events and death from vascular causes. Functional status in subjects with WMC is variable, from normal to severely (physically or cognitively) disable. The association of WMC with age and with some of the clinical manifestations of aging suggests that WMC could be one of the age-related processes involved in the transition to disability in the elderly. Large cohorts of patients with WMC of different severity and detailed follow-up observation may help elucidating this issue. If WMC are shown to have an impact on disability in the aged population, efforts could be made to prevent WMC and WMC-related motor and cognitive deficits, and to identify measures aimed to halt or slow their progression.

Longitudinal evaluation of leukoaraiosis with whole brain ADC histograms.

FLAIR and diffusion-weighted MRI were obtained twice (mean interval 20 ± 4 months) in 10 patients with leukoaraiosis. At follow-up, visual extension of leukoaraiosis was unchanged, whereas the median of whole brain apparent diffusion coefficient (WB-ADC) histogram was increased (p = 0.008) and brain volume index (BVI) was decreased (p = 0.006). WB-ADC histogram and BVI are sensitive to leukoaraiosis and might be considered for monitoring progression of the disease.

Italian Stroke Guidelines (SPREAD): evidence and clinical practice

Evidence-based medicine’s aims are to retrieve, screen and compound the best external evidence with the experience of the physician, and to best respond to the specific medical need of each individual patient. Clinical questions are better answered when good systematic reviews of randomised trials or good randomised clinical trials are available. On the other hand, in a clinical scenario, difficulties in applying the evidence may be amplified due to variability of disease conditions, feasibility of intervention and patient’s preferences. Guidelines are recommendations, based as much as possible on evidence, aimed at supporting clinical judgement/diagnostic skills/treatment decisions in everyday practice. Guidelines may improve the quality of care received by the patient and may contribute towards better consistency of care in a definite geographical area. However, guidelines risk reducing physician skills to critically appraising the evidence. In a clinical scenario, guidelines do not always provide substantial help, especially when no conclusive evidence supports them. The Italian Stroke Guidelines (SPREAD) have contributed towards more evidence-based and better harmonised stroke care in Italy. However, the number of high grade recommendations in SPREAD is still limited. Professionals should not forget that clinical decisions often reflect several issues, not only scientific ones, including personal experience, applicability of intervention and patient’s preferences.

Validity of Different Linguistic Versions of the Alzheimer’s Disease Assessment Scale in an International Multicentre Alzheimer’s Disease Trial

Owing to the involvement of Italian Centres in a multicentre, German-Italian therapeutical trial with Alzheimer’s dementia patients, to be assessed with the Alzheimer’s Disease Assessment Scale (ADAS), it was decided that the Italian centres would use an Italian version of the scale, derived from that used by the German centres. However, the lists of words for exploring verbal memory are not merely translated from the German version, but are composed of selective Italian words chosen according to linguistic criteria. This Italian version was validated following the same procedure adopted for validating the German version. We submitted this Italian version to an interrater reliability, test-retest reliability, concurrent validity, internal consistency and sensitivity evaluation, using demented patients. Based on the results of these tests this Italian version of the ADAS proved valid and reliable. Moreover, the results were strikingly comparable to those from the validation of the German version. Our work supports the validity, reliability and transnational comparability of national versions of the ADAS constructed following definite linguistic criteria.

Selective risk factors profiles and outcomes among patients with stroke and history of prior myocardial infarction. The European Community Stroke Project

BACKGROUND AND OBJECTIVE Previous myocardial infarction (MI) has been linked with poorer stroke outcome. Whether this depends on a greater stroke severity is still uncertain. The aim of the study was to assess the effect of previous MI on characteristics and outcome of stroke in a large hospital cohort of patients. METHODS In a European Union Concerted Action, patients hospitalized for first-in-a-lifetime stroke were assessed for demographics, risk factors, clinical presentation, and 3-month survival and handicap. RESULTS Out of 4190 study patients, 460 (11%) reported a history of MI. Compared with patients without previous MI, those with MI were significantly older, more often males, smokers, alcohol consumers, and with a more severe pre-stroke level of handicap. They had more frequently atrial fibrillation and a history of transient ischemic attack. The acute neurological state and the 28-day mortality did not differ between the two groups. At 3 months, death or severe handicap were more frequent in the MI group (28.3% vs. 21.7%, P=0.001; 74.8% vs. 65.8%, P=0.008). Controlling by logistic regression analysis for age, sex, vascular risk factors, comorbidities, prior to stroke therapy, pre-stroke level of handicap, and clinical acute phase variables, prior MI remained an independent predictor of 3-month death (OR 1.30; 95% CI, 1.02-1.66) and 3-month handicap (OR 1.46; 95% CI, 1.01-2.11). CONCLUSIONS Previous MI has no impact on clinical severity of acute stroke, but significantly affects 3-month outcome in terms of handicap and mortality.

Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the “central vein sign”) improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS‐mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS).

Moyamoya in a patient with Sneddon's syndrome.

NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy SOD Neurologia 2, Neuroscience Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy SOD Oculistica, Department of Translational Surgery and Medicine, Florence, Italy Department of Surgery and Translational Medicine, Division of Dermatology, University of Florence, Florence, Italy Department of Surgery and Translational Medicine, Division of Pathological Anatomy, University of Florence, Florence, Italy Stroke Unit and Neurology, Cardiovascular Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy