Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.
To identify cognitive ...phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features.
This multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled.
Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype.
A total of 1212 patients with MS (mean SD age, 41.1 11.1 years; 784 women 64.7%) and 196 healthy control individuals (mean SD age, 40.4 8.6 years; 130 women 66.3%) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients 19.4%), mild-verbal memory/semantic fluency (n = 362 patients 29.9%), mild-multidomain (n = 236 patients 19.5%), severe-executive/attention (n = 167 patients 13.8%), and severe-multidomain (n = 212 patients 17.5%) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean SD age, 36.5 9.8 years and 38.2 11.1 years) and had shorter disease duration (mean SD 8.0 7.3 years and 8.3 7.6 years) compared with patients with mild-multidomain (mean SD age, 42.6 11.2 years; mean SD disease duration, 12.8 9.6 years; P < .001), severe-executive/attention (mean SD age, 42.9 11.7 years; mean SD disease duration, 12.2 9.5 years; P < .001), and severe-multidomain (mean SD age, 44.0 11.0 years; mean SD disease duration, 13.3 10.2 years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 0.68 mL vs 5.13 0.68 mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 35.40 mL vs 662.59 35.48 mL; P = .02), patients with severe-executive/attention had higher mean (SE) T2-hyperintense lesion volume (51.33 31.15 mL vs 99.69 34.07 mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala and caudate nucleus.
This study found that by defining homogeneous and clinically meaningful phenotypes, the limitations of the traditional dichotomous classification in MS can be overcome. These phenotypes can represent a more meaningful measure of the cognitive status of patients with MS and can help define clinical disability, support clinicians in treatment choices, and tailor cognitive rehabilitation strategies.
Treatment of pediatric-onset multiple sclerosis (POMS) has been tailored after observational studies and data obtained from clinical trials in adult-onset multiple sclerosis (AOMS) patients. There ...are an increasing number of new therapeutic agents for AOMS, and many will be formally studied for use also in POMS. However, there are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss the current state of the art of POMS therapy and will focus on the newer therapies (oral and infusion disease-modifying drugs) and on those still currently under investigation.
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma (HCC). ...Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism (SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis (NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
MicroRNAs play important roles in many cellular and biological functions via the regulation of mRNA target translation. In the cardiovascular field, microRNAs are now acknowledged as fundamental in ...regulating the expression of genes that governs physiological and pathological myocardial adaptation to stress. Here, we review recent progress in the understanding of microRNA functions and their involvement in heart disease.
Objective
We assessed the occurrence, extent, and frequency of formation of cortical lesions (CLs) in patients with relapsing‐remitting (RR) and secondary progressive (SP) multiple sclerosis (MS), ...and their relationship with cortical atrophy and disability progression.
Methods
One‐hundred seven MS patients (76 RRMS and 31 SPMS), enrolled in a prospective, longitudinal magnetic resonance imaging (MRI) study, were assessed clinically and by brain MRI (including a double inversion recovery sequence) 3 years after study initiation. CL number and volume, T2 white matter (WM) lesion volume, gray matter fraction, and expanded disability status scale (EDSS) were measured.
Results
At baseline, CLs were detected in 64.4% of RRMS and 74.2% of SPMS patients. During follow‐up, 132 new CLs were found in 44 RRMS patients (57.9%; 0.8 new CL/patient/yr) and 61 in 15 SPMS patients (48.4%; 1.0 new CL/patient/yr). Among these patients, only 31 also showed at least 1 new WM lesion. CL number and volume increases were higher in the 52 patients with a clinical worsening compared with those without (p < 0.001). Baseline CL volume correlated with baseline EDSS (r = 0.36, p < 0.001) and EDSS changes over time (r = 0.51, p < 0.001). Baseline CL volume was an independent predictor of EDSS accumulation and GM volume change at follow‐up in both patient groups. In SPMS patients, baseline T2 WM lesion volume was another independent predictor of EDSS worsening.
Interpretation
In relapse‐onset MS, CLs accumulate over time and are associated with disability progression. The quantification of CLs might represent an additional useful paraclinical tool to monitor MS evolution. ANN NEUROL 2010;67:376–383
Positioning via outdoor fingerprinting, which exploits the radio signals emitted by cellular towers, is fundamental in many applications. In most cases, the localization performance is affected by ...the availability of information about the emitters, such as their coverage. While several projects aim at collecting cellular network data via crowdsourcing observations, none focuses on information about the structure of the networks, which is paramount to correctly model their topology. The difficulty of such a modeling is exacerbated by the inherent differences among cellular technologies, the strong spatio-temporal nature of positioning, and the continuously evolving configuration of the networks. In this paper, we first show how to synthesize a detailed conceptual schema of cellular networks on the basis of the signal fingerprints collected by devices. We turned it into a logical one, and we exploited that to build a relational spatio-temporal database capable of supporting a crowdsourced collection of data. Next, we populated the database with heterogeneous cellular observations originating from multiple sources. In addition, we illustrate how the developed system allows us to properly deal with the evolution of the network configuration, e.g., by detecting cell renaming phenomena and by making it possible to correct inconsistent measurements coming from mobile devices, fostering positioning tasks. Finally, we provide a wide range of basic, spatial, and temporal analyses about the arrangement of the cellular network and its evolution over time, demonstrating how the developed system can be used to reconstruct and maintain a deep knowledge of the cellular network, possibly starting from crowdsourced information only.
Cerebrospinal fluid (CSF) albumincytologic dissociation represents a supportive diagnostic criterion of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Few studies have investigated ...possible systemic or intrathecal humoral immune response activation in CIDP.Aim of our study was to investigate whether the search of oligoclonal IgG bands (OCBs) might provide additional data helpful in CIDP diagnostic work-up.
Forty-eight consecutive patients with CIDP (34 men, mean age 59.4, range 16-83) were recruited. CSF analysis included nephelometric measurement of albumin and IgG concentrations, calculation of Q
, QAlb
and intrathecal IgG synthesis, and OCBs detection with isoelectric focusing. Data were compared with those from CSF and serum of 32 patients with Guillain-Barré syndrome (GBS), 18 patients with anti-myelin associated glycoprotein (MAG) antibody neuropathy, 4 patients with multifocal motor neuropathy and 32 patients with non-inflammatory neuropathies (NINPs).
Patients with CIDP and anti-MAG antibody neuropathy had significantly higher CSF albumin concentrations and Q
values than NINPs (p=0.0003 and p=0.0095, respectively). A total of 9 (19%) patients with CIDP presented identical serum and CSF OCBs ('mirror pattern') versus 3 patients (16.6%) with anti-MAG antibody neuropathy, 13 patients (40.6%) with GBS and 12.5% patients with NINPs. Only one patient with CIDP showed unique-to-CSF OCBs. First-line therapy was effective in 80.4% of patients with CIDP, irrespective of CSF findings.
Compared with NINP, CIDP, GBS and anti-MAG antibody neuropathies had a significantly increased CSF protein and blood-spinal nerve root barrier damage. Intrathecal humoral immune response is rare in our patients with CIDP. Systemic oligoclonal activation is more frequent, but not significantly different from what was detected in the control groups.
Double inversion recovery (DIR) detects only a minority (<20%) of cortical lesions (CL) in multiple sclerosis (MS). Phase-sensitive inversion recovery (PSIR) was suggested to be substantially ...superior to DIR in the detection of cortical lesions (CL). These two sequences might be complementary.
To analyze CL frequency and type in MS patients having different disease duration and disability, including patients at clinical onset, and to discern more correctly the artifacts, by combining DIR and PSIR images.
40 patients were enrolled in the study: 10 clinically isolated syndrome/early relapsing remitting MS (CIS/eRRMS), 24 relapsing remitting MS (RRMS), 6 secondary progressive MS (SPMS). DIR and PSIR images were jointly used to classify lesions as purely intracortical (IC), leukocortical (LC) and juxtacortical (JC).
PSIR disclosed CL in 100% of the patients and was capable of identifying more than four times lesions (455.5%, p<0.00001), especially IC (mean numbers: 36.5 in CIS/eRRMS, 45.0 in RRMS and 52.3 in SPMS) and LC (mean numbers: 10.9 in CIS/eRRMS, 20.1 in RRMS and 25.3 in SPMS), compared to DIR (p<0.00001). CL number was significantly higher in SPMS compared to RRMS (p<0.0001). Artifacts were more accurately identified by comparing the two sequences.
Our study confirms the higher ability of PSIR in disclosing and classifying CL. The presence of CL in all CIS patients further points out the relevance of cortical pathology in MS. Whether the parallel analysis of DIR and PSIR images may be useful for diagnostic purposes, especially when a diagnosis of MS is suspected but not confirmed by routine MRI, needs to be evaluated in larger patient series. The analysis of the cortex by DIR and PSIR may also allow a better stratification of the patients for prognostic and counseling purposes, as well as for their inclusion in clinical studies.
Objective
Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing–remitting to secondary progressive have not been clarified yet. We ...specifically designed a prospective 5‐year longitudinal study aimed at assessing demographic, clinical, and magnetic resonance imaging (MRI) parameters that could predict the changing clinical course of MS.
Methods
At study entry and after 5 years, clinical and MRI (ie, gray matter and white matter lesions, including spinal cord lesions, and global and regional cortical thinning) parameters were assessed in a training set of 334 consecutive relapsing–remitting MS patients and in an independent validation set of 84 relapsing–remitting MS patients.
Results
Sixty‐six (19.7%) relapsing–remitting MS patients changed their clinical course during the study and entered into the secondary progressive phase. Age (p = 0.001, odds ratio OR = 1.2), cortical lesion volume (p < 0.001,OR = 1.7), and cerebellar cortical volume (p < 0.001, OR = 0.2) at study entry were found to predict the changing clinical course. The model including only these 3 variables correctly identified 252 of 268 (94.0%) patients who maintained the relapsing–remitting course and 58 of 66 (87.8%) patients who became secondary progressive (cross‐validated error rate = 7.2%). When applied on the validation set, the model obtained a similar error rate (8.4%).
Interpretation
A prediction model based on age, cortical lesion load, and cerebellar cortical volume suitably explains the probability of relapsing–remitting MS patients evolving into the progressive phase. Gray matter damage appears to play a pivotal role in determining the changing clinical course of MS. Ann Neurol 2013;74:76–83
Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly ...improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.
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