Diffusion tensor imaging metrics associated with future disability in multiple sclerosis.

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients.

The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5-15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

The popularity of neurology in Spain: An analysis of specialty selection. / Popularidad de Neurología en España: análisis de la elección de la especialidad.

INTRODUCTION: Neurology is one of the medical specialties offered each year to residency training candidates. This project analyses the data associated with candidates choosing neurology residency programmes in recent years. METHODS: Data related to specialty selection were obtained from official reports by the Spanish Ministry of Health, Social Services, and Equality. Information was collected on several characteristics of teaching centres: availability of stroke units, endovascular intervention, national reference clinics for neurology, specific on-call shifts for neurology residents, and links with medical schools or national research networks. RESULTS: The median selection list position of candidates selecting neurology training has been higher year on year; neurology was among the 4 most popular residency programmes in 2016. Potential residents were mainly female, Spanish, and had good academic results. The median number of hospitals with higher numbers of beds, endovascular intervention, stroke units, and national reference clinics for neurology is significantly lower. This is also true when centers are analysed by presence of specific on-call shifts for neurology residents and association with medical schools or national research networks. The centres selected by candidates with the highest median selection list position in 2012-2016 were the Clínico San Carlos, 12 de Octubre, and Vall d'Hebron university hospitals. CONCLUSIONS: Neurology has gradually improved in residency selection choices and is now one of the 4 most popular options. Potential residents prefer larger centres which are more demanding in terms of patient care and which perform more research activity.

The visual pathway as a model to understand brain damage in multiple sclerosis.

Patients with multiple sclerosis (MS) almost always experience effects in the visual pathway; and thus, visual dysfunction is not only common but also highly relevant. The visual pathway represents a model of acute focal central nervous system (CNS) damage, through acute optic neuritis and retinal periphlebitis, as well as a model of chronic, diffuse CNS damage through chronic retinopathy and optic neuropathy. The optic pathway can be accurately evaluated in detail, due to the availability of highly sensitive imaging techniques (e.g. magnetic resonance imaging or optical coherent tomography) or electrophysiological tests (multifocal visual evoked potentials or electroretinography). These techniques allow the interactions between the different processes at play to be evaluated, such as inflammation, demyelination, axonal damage and neurodegeneration. Moreover, these features mean that the visual pathway can be used as a model to test new neuroprotective or regenerative therapies.

Is the incidence of optic neuritis rising? Evidence from an epidemiological study in Barcelona (Spain), 2008-2012.

It is currently believed that the incidence rate of optic neuritis (ON) ranges between 0.56 and 5.1 cases per 100,000 person-years. However, since these figures were generated, they have not been updated and there are suggestions that the incidence of ON is on the rise. When designing new therapies and clinical trials for ON, and to improve the management this disease, it is important to have accurate epidemiological data. Thus, we set out to obtain the prevalence and incidence rates of ON in Barcelona (Spain) from 2008 to 2012, by a retrospective evaluation of electronic hospital records at the Hospital Clinic of Barcelona (population of 300,000 in the catchment area) matching the following ICD-9-CM codes as search terms: 377.3-optic neuritis; 377.30-optic neuritis, unspecific; 377.31-optic papillitis; 377.32-retrobulbar neuritis, acute; 377.39-other optic neuritis and "optic neuropathy". Demographic and clinical data were collected from records with a confirmed diagnosis of ON, including cases of idiopathic ON, multiple sclerosis, neuromyelitis optica and CRION. The prevalence of acute ON on 31 December 2012 was 2.75 cases per 100,000 people. The mean annual prevalence of acute ON during the 2008-2012 period was 7.87 cases per 100,000 person-year and the mean annual incidence rate was 5.36 cases per 100,000 person-years. The incidence of ON in Barcelona during 2008-2012 was higher than previously reported. This increase may reflect the evolution of diagnostic criteria, the use of a referral-center approach instead of a population-based approach, increased awareness of demyelinating diseases, latitude-related factors and possibly a true increase in its incidence.

Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial.

OBJECTIVE: To assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet). DESIGN: Randomized trial after 6.5 years of nutritional intervention. SETTING: Eight primary care centers affiliated to the University of Navarra. PARTICIPANTS: A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1±5.7 years at cognitive evaluation). INTERVENTIONS: Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter. MEASUREMENTS: Cognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention. RESULTS: Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12-0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls. CONCLUSION: A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.

Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis.

OBJECTIVES: Previous studies have reported an increased risk for epileptic seizures in multiple sclerosis (MS) patients. However, data on the pathogenesis of seizures remain inconclusive. The aim of our study is to evaluate prevalence, clinical and paraclinical features of epileptic attacks in our MS cohort and to search MS-specific risk factors for epileptic seizures. MATERIALS AND METHODS: In this cohort of 428 MS patients, 13 patients were identified with epileptic seizures occurring at any point during the course of MS including at MS onset. As a control group, we selected 26 MS patients without seizures and matched for gender, age and date of MS onset. We compared demographic features and clinic-radiological findings between the both groups. RESULTS: Thirteen patients (3%) were identified as having epileptic attacks. Ten patients (77%) experienced focal seizures, half of whom had confirmed secondary generalization. We did not find an association between seizures and disease course. Most patients had a single or few (2-5) seizures. MS patients with seizures had a significantly higher number of cortical and juxtacortical lesions on T2-weighted/fluid attenuation inversion recovery magnetic resonance imaging than control group [OR = 2.6 CI95% (1.0-6.5); P = 0.047]. CONCLUSIONS: Our findings support a credible role of cortical and juxtacortical involvement in the development of epileptic seizures in MS.

Mediterranean diet and the incidence of cardiovascular disease: a Spanish cohort.

BACKGROUND AND AIM: The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area. METHODS AND RESULTS: We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score>6) exhibited a lower cardiovascular risk (hazard ratio=0.41, 95% confidence interval [CI]: 0.18-0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62-1.02) for total CVD and 0.74 (0.55-0.99) for coronary heart disease. CONCLUSIONS: There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.

Nut consumption and incidence of hypertension: the SUN prospective cohort.

BACKGROUND AND AIMS: The consumption of tree nuts could reduce the risk of hypertension, but scarce research has been done to evaluate this potential association. We assessed the association between nut consumption and the incidence of hypertension among 9919 Spanish university graduates followed-up biennially for a median of 4.3 years. METHODS AND RESULTS: Food habits were assessed with a validated 136-item food-frequency questionnaire. Nut consumption was classified into four categories: rarely/never, 1-3/month, 1/week, and 2+/week. A participant was classified as an incident case of hypertension when, being free of hypertension at baseline, he/she subsequently reported a physician-made diagnosis of hypertension in at least one of the follow-up questionnaires. The incidence of hypertension was 12.4 per 1000 person-years. We found no association between nut consumption and incidence of hypertension after adjusting for sex, age and other dietary and non-dietary potential confounders (hazard ratio [HR] for those in the highest vs. lowest nut consumption category=0.77 [IC 95%: 0.46-1.30] p=0.795). Results were not modified when we stratified them analyses according to sex or to body mass index. CONCLUSION: Our data do not provide evidence for an inverse association between nut consumption and incident hypertension in our cohort. Further results from cohorts and trials with a higher baseline risk of hypertension should be obtained to test this relationship.