Background
The coronavirus disease 2019 (COVID-19) pandemic has dramatically stressed the health care system and has provoked changes in population use of digital technologies. Digital divide is any ...uneven distribution in Information and Communications Technologies between people.
Aims
The purpose of this work was to describe the digital divide of a population of patients with dementia contacted by telemedicine during Italian lockdown for COVID-19 pandemic.
Method
One hundred eight patients with cognitive impairment were contacted by video call to perform a telemedicine neurological evaluation. Information on patients and caregivers attending the televisit were recorded.
Results
Seventy-four patients connected with neurologist (successful televisit, 68.5%) and 34 patients were not able to perform televisit and were contacted by phone (failed televisit, 31.5%). No significant differences were observed among the two groups concerning age, gender, and education, but the prevalence of successful televisit was higher in the presence of younger caregivers: televisits performed in the presence of subjects of younger generation (sons and grandsons) had a successful rate higher (86% successful, 14% failed) than the group without younger generation caregiver (49% successful, 51% failed). This difference is mainly due to the ability of technological use among younger people.
Discussion
The most impacting factors on digital divide in our population are the social support networks and the experience with the technology: the presence of a digital native caregiver. The COVID-19 pandemic is unmasking an emerging form of technology-related social inequalities: political and community interventions are needed to support the most socially vulnerable population and prevent social health inequalities.
Background:
The importance of neurodegeneration in multiple sclerosis (MS) is increasingly well recognized.
Objectives:
To evaluate retinal pathology using optical coherence tomography (OCT) and to ...investigate possible associations between retinal layers’ thickness and specific patterns of gray matter volume in patients with a new diagnosis of MS.
Methods:
A total of 31 patients underwent OCT scans and brain magnetic resonance imaging. In total, 30 controls underwent the same OCT procedure. The association between focal cortical volume and OCT measurements was investigated with voxel-based morphometry (VBM).
Results:
Compared to controls, patients’ macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness were significantly reduced (p = 0.0009, p = 0.0003, p = 0.0049, and p = 0.0007, respectively). Peripapillary RNFL (pRNFL) and temporal sector pRNFL (T-pRNFL) did not show any significant changes, although there was a trend toward T-pRNFL thinning (p = 0.0254). VBM analysis showed that mGCIPL and pRNFL were significantly correlated with the volume reduction of occipital-parietal cortex (p < 0.005).
Conclusion:
mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.
Background:
The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed.
Objectives:
To investigate the ...prognostic role of cerebrospinal fluid (CSF) amyloid beta1–42 (Aβ) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages.
Methods:
Sixty patients were recruited and followed up for 3–5 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine Aβ levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads.
Results:
Lower CSF Aβ levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS; r = −0.65, p < 0.001). The multiple regression analysis confirmed CSF Aβ concentration as a predictor of patients’ EDSS increase (r = −0.59, p < 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690–0.933, p = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed (p > 0.05).
Conclusion:
Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS.
► Increased expression of miR-21, miR-146a and-b was observed in (RR)MS patients. ► SP- and PPMS patients have a miRNA profile similar to controls. ► No differences in the frequencies of rs2910164 ...was found between patients and controls. ► miRNA dysregulation may contribute to the pathogenesis of MS.
MicroRNA (miRNA)-mediate RNA interference has been identified as a novel mechanism that regulates protein expression. It is recognised that miRNAs play essential roles in the immune system and for correct function in the brain. Moreover, it is now clear that abnormal miRNA expression is a common feature of several diseases involving the immune system including multiple sclerosis (MS). Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19 controls. Subsequently, a case control study for
miR-146 rs2910164 variant was performed in an overall population of 346 MS cases and 339 controls. A statistically significant increased expression of miR-21, miR-146a and -b was observed in relapsing remitting (RR)MS patients as compared with controls (1.44
±
0.13 vs 0.79
±
0.06,
P
=
0.036; 1.50
±
0.12 vs 0.84
±
0.08,
P
=
0.039; 1.54
±
0.15 vs 0.72
±
0.08,
P
=
0.001 respectively). On the contrary, no differences were found in the expression levels of both miR-150 and miR-155 in patients as compared with controls (
P
>
0.05). The genetic association study failed to find any differences in the frequencies of rs2910164 between patients and controls. miRNA dysregulation may contribute to the pathogenesis of MS and highlights the possibility to define different disease entities with specific miRNAs profile.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that is caused by autoreactive T cells and associated with viral infections. However, the ...phenotype of pathogenic T cells in peripheral blood remains to be defined, and how viruses promote MS is debated.
We aimed to identify and characterize potentially pathogenic autoreactive T cells, as well as protective antiviral T cells, in patients with MS.
We analyzed CD4+ helper T-cell subsets from peripheral blood or cerebrospinal fluid for cytokine production, gene expression, plasticity, homing potentials, and their reactivity to self-antigens and viral antigens in healthy subjects and patients with MS. Moreover, we monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS.
TH1/TH17 central memory (TH1/TH17CM) cells were selectively increased in peripheral blood of patients with relapsing-remitting MS with a high disease score. TH1/TH17CM cells were closely related to conventional TH17 cells but had more pathogenic features. In particular, they could shuttle between lymph nodes and the CNS and produced encephalitogenic cytokines. The cerebrospinal fluid of patients with active MS was enriched for CXCL10 and contained mainly CXCR3-expressing TH1 and TH1/TH17 subsets. However, while TH1 cells responded consistently to viruses, TH1/TH17CM cells reacted strongly with John Cunningham virus in healthy subjects but responded instead to myelin-derived self-antigens in patients with MS. Fingolimod and natalizumab therapies efficiently targeted autoreactive TH1/TH17CM cells but also blocked virus-specific TH1 cells.
We propose that autoreactive TH1/TH17CM cells expand in patients with MS and promote relapses after bystander recruitment to the CNS, whereas TH1 cells perform immune surveillance. Thus the selective targeting of TH1/TH17 cells could inhibit relapses without causing John Cunningham virus–dependent progressive multifocal encephalomyelitis.
To assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls.
Eighty-five participants were ...recruited: 65 with newly diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. β-amyloid
(Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Aβ levels (Aβ(+)), while 23 had normal CSF Aβ levels (Aβ(-)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses.
We found an increased WM-LL in Aβ(+) compared with both, healthy controls (p=0.003) and Aβ(-) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Aβ(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001).
WM damage is crucial in AD pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.
LncRNA PCR arrays containing 90 common LncRNAs were used to screen lncRNA expression levels in PBMC from a discovery population of patients with MS. Data from discovery and replications cohorts ...showed a generalized dysregulation of lncRNA levels in MS patients compared with controls. MALAT1, MEG9, NRON, ANRIL, TUG1, XIST, SOX2OT, GOMAFU, HULC, BACE-1AS were significantly downregulated in MS patients in comparison with controls. Therefore, we performed a validation analysis in an independent cohort of Belgian origin. In this study, NRON and TUG1 downregulations in MS patients compared with controls were confirmed (p ≤ .05 and p ≤ .0001 respectively), whereas considering the other lncRNAs, the statistical threshold was not reached. LncRNAs profiling could thus represent a new challenge in the research of easy detectable biomarkers of disease susceptibility and progression.
Display omitted
•Long non coding RNAs (lncRNAs) have recently found to be dysregulated in MS patients.•LncRNA PCR arrays were used to screen lncRNA expression levels in PBMC from MS patients.•Several lncRNAs were significantly downregulated in MS patients.•NRON and TUG1 downregulations were then confirmed in the Belgian population.•LncRNAs profiling could represent a new challenge in the research of easy detectable biomarkers of disease.
Objectives
To investigate the normal-appearing white matter (NAWM) susceptibility in a cohort of newly diagnosed multiple sclerosis (MS) patients and to evaluate possible correlations between NAWM ...susceptibility and disability progression.
Methods
Fifty-nine patients with a diagnosis of MS (
n
= 53) or clinically isolated syndrome (CIS) (
n
= 6) were recruited and followed up. All participants underwent neurological examination, blood sampling for serum neurofilament light chain (sNfL) level assessment, lumbar puncture for the quantification of cerebrospinal fluid (CSF) β-amyloid
1-42
(Aβ) levels, and brain MRI. T2-weighted scans were used to quantify white matter (WM) lesion loads. For each scan, we derived the NAWM volume fraction and the WM lesion volume fraction. Quantitative susceptibility mapping (QSM) of the NAWM was calculated using the susceptibility tensor imaging (STI) suite. Susceptibility maps were computed with the STAR algorithm.
Results
Primary progressive patients (
n
= 9) showed a higher mean susceptibility value in the NAWM than relapsing-remitting (
n
= 44) and CIS (
n
= 6) (
p
= 0.01 and
p =
0.02). Patients with a higher susceptibility in the NAWM showed increased sNfL concentration (
ρ
= 0.38,
p
= 0.004) and lower CSF Aβ levels (
ρ
= −0.34,
p
= 0.009). Mean NAWM susceptibility turned out to be a predictor of the expanded disability status scale (EDSS) worsening at follow-up (
β
= 0.41,
t
= 2.66,
p
= 0.01) and of the MS severity scale (MSSS) (
β
= 0.38,
t
= 2.43,
p
= 0.019).
Conclusions
QSM in the NAWM seems to predict the EDSS increment over time. This finding might provide evidence on the role of QSM in identifying patients with an increased
risk
of early disability
progression
.
Key Points
•
NAWM-QSM is higher in PPMS patients than in RRMS.
•
NAWM-QSM seems to be a predictor of EDSS worsening over time.
•
Patients with higher NAWM-QSM show increased sNfL concentration and lower CSF Aβ levels.
Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed ...that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients versus controls. Here, the expression levels of these candidate miRNAs were determined in peripheral blood mononuclear cells (PBMCs) and the serum of MS patients, in addition to three genotyped single nucleotide polymorphisms (SNPs). Mapping in the genomic regions of miR-223, miR-23a and miR-15b genes, 399 cases and 420 controls were tested. Expression levels of miR-223 and miR-23a were altered in PBMCs from MS patients versus controls. Conversely, there were no differences in the expression levels of miR-15b. A significantly decreased genotypic frequency of miR-223 rs1044165 T/T genotype was observed in MS patients. Moreover, the allelic frequency of miR-23a rs3745453 C allele was significantly increased in patients versus controls. In contrast, there were no differences in the distribution of miR-15b SNP. In conclusion, our results suggest that miR-223 and miR-23a could play a role in the pathogenesis of MS. Moreover, miR-223 rs1044165 polymorphism likely acts as a protective factor, while miR-23a rs3745453 variant seems to act as a risk factor for MS.
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