Attention Network Test reveals alerting network dysfunction in multiple sclerosis

Attention is one of the cognitive domains typically affected in multiple sclerosis. The Attention Network Test was developed to measure the function of the three distinct attentional networks, alerting, orienting, and executive control. The Attention Network Test has been performed in various neuropsychiatric conditions, but not in multiple sclerosis. Our objective was to investigate functions of attentional networks in multiple sclerosis by means of the Attention Network Test. Patients with relapsing—remitting multiple sclerosis (n = 57) and healthy controls (n = 57) matched for age, sex, and education performed the Attention Network Test. Significant differences between patients and controls were detected in the alerting network (p = 0.003), in contrast to the orienting (p = 0.696) and the conflict (p = 0.114) network of visual attention. Mean reaction time in the Attention Network Test was significantly longer in multiple sclerosis patients than in controls (p = 0.032), Multiple sclerosis patients benefited less from alerting cues for conflict resolution compared with healthy controls. The Attention Network Test revealed specific alterations of the attention network in multiple sclerosis patients which were not explained by an overall cognitive slowing.

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CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458513489853 ◽

2013 ◽

Vol 19 (14) ◽

pp. 1867-1877 ◽

Cited By ~ 10

Author(s):

Que Lan Quach ◽

Luanne M Metz ◽

Jenna C Thomas ◽

Jonathan B Rothbard ◽

Lawrence Steinman ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cytokine Production ◽

Clinical Signs ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

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Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318815513 ◽

2018 ◽

Vol 4 (4) ◽

pp. 205521731881551 ◽

Cited By ~ 3

Author(s):

L De Meijer ◽

D Merlo ◽

O Skibina ◽

EJ Grobbee ◽

J Gale ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Change ◽

Progressive Multiple Sclerosis ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Serial Addition ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

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Male fertility in relapsing-remitting multiple sclerosis patients treated with natalizumab and ocrelizumab: A prospective case-control study

Multiple Sclerosis Journal ◽

10.1177/13524585211009208 ◽

2021 ◽

pp. 135245852110092

Author(s):

Emanuele D’Amico ◽

Aurora Zanghì ◽

Aldo Eugenio Calogero ◽

Francesco Patti

Keyword(s):

Multiple Sclerosis ◽

Male Fertility ◽

Case Control ◽

Gonadal Steroids ◽

Sperm Parameters ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Scarce data are available about the impact of natalizumab (NTZ) and ocrelizumab (OCR) on male fertility in relapsing-remitting multiple sclerosis (RRMS). In this case–control prospective study, the gonadal steroids and the sperm parameters have been analysed at the time of the RRMS diagnosis and after 12 months from the beginning of the investigated therapies. Sixteen men with RRMS and sixteen matched healthy controls were included. At enrolment and after 12 months on therapy, the gonadal steroids and the sperm parameters of men with RRMS did not differ from the healthy controls. In conclusion, therapy with NTZ and OCR had no impact on fertility status in our cohort of men with RRMS. Further randomized and prospective studies are needed.

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The Effect of IFN-β Treatment on Plasma Levels of BDNF and IL-6 in Relapsing-Remitting Multiple Sclerosis Patients

NeuroImmunoModulation ◽

10.1159/000515595 ◽

2021 ◽

pp. 1-8

Author(s):

Mansour Shajarian ◽

Fereshteh Alsahebfosoul ◽

Masoud Etemadifar

Keyword(s):

Multiple Sclerosis ◽

Plasma Levels ◽

Case Group ◽

Healthy Controls ◽

Control Groups ◽

Relapsing Remitting ◽

Healthy Control ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Background: In recent investigations addressing neurodegenerative diseases, especially multiple sclerosis (MS), the roles of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) have been examined. Methods: Forty-five relapsing-remitting MS (RRMS) patients, including 32 IFN-β-treated and 13 newly identified untreated cases as well as 45 sex- and age-matched healthy controls, were recruited in the study. Plasma levels of BDNF and IL-6 were assessed using the ELISA method. Data were analyzed by SPSS (ver.21). Results: There were significant differences between the case and healthy control groups in terms of the plasma levels of BDNF (p value = 0.044) and IL-6 (p value <0.001). Besides, the treatment with IFN-β had no significant impact on the level of BDNF or IL-6 in RRMS patients as compared to healthy controls (p value = 0.716 and 0.623 for BDNF and IL-6, respectively). Furthermore, the increase in the plasma levels of BDNF and IL-6 indicated a direct correlation in the case group (r = 0.508, p value = 0.008). In detail, following the classification of the case group into 2 subgroups of IFN-β-treated and untreated patients, a direct positive correlation was observed between the plasma levels of BDNF and IL-6 in IFN-β-treated patients (r = 0.495, p value = 0.026). Conclusion: The IFN-β treatment seems not to be effective for upregulating BDNF and IL-6 in RRMS patients.

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Circadian Activity Rhythm in Early Relapsing–Remitting Multiple Sclerosis

Journal of Clinical Medicine ◽

10.3390/jcm8122216 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2216 ◽

Cited By ~ 1

Author(s):

Lorenzo Tonetti ◽

Federico Camilli ◽

Sara Giovagnoli ◽

Vincenzo Natale ◽

Alessandra Lugaresi

Keyword(s):

Multiple Sclerosis ◽

Activity Rhythm ◽

Healthy Controls ◽

Circadian Activity ◽

Linear Modeling ◽

Circadian Activity Rhythm ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

While relapsing–remitting is the most prevalent course of multiple sclerosis, the prognostic/predictive markers of the worsening of symptomatology are still debated. With reference to other diseases, the study of the circadian activity rhythm, according to the theoretical framework of the two-process model of sleep regulation and applying functional linear modeling, proved to be useful to identify a possible marker. The usefulness of the study of circadian activity rhythm in multiple sclerosis is strengthened by recent findings indicating a potential involvement of circadian factors in the multifactorial etiopathology of the disorder. The aim of the present study was to verify whether circadian activity rhythm of early relapsing–remitting multiple sclerosis patients presents specific alterations, through functional linear modeling. Thirty-five relapsing–remitting multiple sclerosis patients (24 females; mean age ± SD = 31.51 ± 7.74) and 35 healthy controls (24 females; mean age ± SD = 31.29 ± 8.02) were enrolled. They wore an actigraph around the non-dominant wrist for one week. Relapsing–remitting multiple sclerosis patients showed a peak in motor activity around 5:00 a.m., higher than that of healthy controls. The timing of the peak in motor activity in the patients could be explained according to the hyperactive hypothalamus-pituitary-adrenal axis and higher cortisol awakening response reported in these patients.

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Multiple Sclerosis Patients have an Altered Gut Mycobiome and Increased Fungal to Bacterial Richness

10.1101/2021.08.30.458212 ◽

2021 ◽

Author(s):

Meeta Yadav ◽

Soham Ali ◽

Rachel L. Shrode ◽

Shailesh K. Shahi ◽

Samantha N. Jensen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Intestinal Microbiome ◽

Healthy Controls ◽

Healthy Human ◽

Relapsing Remitting ◽

Bacterial Microbiome ◽

Fungal Microbiome ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis ◽

Functional Profiles

AbstractTrillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC.This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.

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Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458515622696 ◽

2016 ◽

Vol 22 (11) ◽

pp. 1421-1428 ◽

Cited By ~ 11

Author(s):

Seyed-Parsa Hojjat ◽

Charles Grady Cantrell ◽

Rita Vitorino ◽

Anthony Feinstein ◽

Zahra Shirzadi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Blood Flow ◽

Cognitive Impairment ◽

Temporal Cortex ◽

Surrogate Marker ◽

Healthy Controls ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

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Alerting Network Dysfunction in Early Multiple Sclerosis

Journal of the International Neuropsychological Society ◽

10.1017/s1355617712000410 ◽

2012 ◽

Vol 18 (4) ◽

pp. 757-763 ◽

Cited By ~ 14

Author(s):

Lucía Crivelli ◽

Mauricio F. Farez ◽

Claudio D. González ◽

Marcela Fiol ◽

Alejandra Amengual ◽

...

Keyword(s):

Multiple Sclerosis ◽

Executive Control ◽

Control Networks ◽

Attentional Networks ◽

Relapsing Remitting ◽

Attentional Network Test ◽

Computerized Task ◽

Remitting Multiple Sclerosis ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

AbstractThe objective of this study is to assess attention in recently diagnosed relapsing-remitting multiple sclerosis patients. Twenty-seven patients with early multiple sclerosis and low clinical disability scores (EDSS<2) and 27 sex-, age-, and education-matched healthy controls underwent attention assessment using the Attentional Network Test, a computerized task designed to measure efficiency independently in 3 attentional networks (Alerting, Orienting and Executive Control). MS patients had significantly less efficiency in the Alerting network (p = .006). In contrast, in the Orienting and Executive Control networks, they did not differ from controls. A significant interaction between Alerting and Executive Control was also found in the MS patients (p = .007). Early relapsing-remitting multiple sclerosis particularly affects the Alerting domain of attention, whereas the Orienting and Executive Control domains are not affected. (JINS, 2012, 18, 1–7)

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