CD8+ cell somatic mutations in multiple sclerosis patients and controls—Enrichment of mutations in STAT3 and other genes implicated in hematological malignancies

Somatic mutations have a central role in cancer but their role in other diseases such as common autoimmune disorders is not clear. Previously we and others have demonstrated that especially CD8+ T cells in blood can harbor persistent somatic mutations in some patients with multiple sclerosis (MS) and rheumatoid arthritis. Here we concentrated on CD8+ cells in more detail and tested (i) how commonly somatic mutations are detectable, (ii) does the overall mutation load differ between MS patients and controls, and (iii) do the somatic mutations accumulate non-randomly in certain genes? We separated peripheral blood CD8+ cells from newly diagnosed relapsing MS patients (n = 21) as well as matched controls (n = 21) and performed next-generation sequencing of the CD8+ cells’ DNA, limiting our search to a custom panel of 2524 immunity and cancer related genes, which enabled us to obtain a median sequencing depth of over 2000x. We discovered nonsynonymous somatic mutations in all MS patients’ and controls’ CD8+ cell DNA samples, with no significant difference in number between the groups (p = 0.60), at a median allelic fraction of 0.5% (range 0.2–8.6%). The mutations showed statistically significant clustering especially to the STAT3 gene, and also enrichment to the SMARCA2, DNMT3A, SOCS1 and PPP3CA genes. Known activating STAT3 mutations were found both in MS patients and controls and overall 1/5 of the mutations were previously described cancer mutations. The detected clustering suggests a selection advantage of the mutated CD8+ clones and calls for further research on possible phenotypic effects.

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Agreement analysis comparing iPad LCVA and Sloan testing in multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1177/1352458517713667 ◽

2017 ◽

Vol 24 (8) ◽

pp. 1126-1130 ◽

Cited By ~ 4

Author(s):

Neda Sattarnezhad ◽

Samantha Farrow ◽

Dorlan Kimbrough ◽

Bonnie Glanz ◽

Brian Healy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Visual Acuity ◽

T Test ◽

Computerized Testing ◽

Low Contrast ◽

Significant Difference ◽

Increased Sensitivity ◽

The Right ◽

Multiple Sclerosis Patients ◽

Paired T Test

Background: Visual symptoms are common in multiple sclerosis (MS). Low-contrast visual acuity (LCVA) testing using Sloan charts has demonstrated increased sensitivity for visual deficits compared to high-contrast acuity testing. Computerized testing of visual acuity may facilitate use in the clinic setting. Objectives: To evaluate the agreement between an iPad-based and Sloan testing of LCVA in a cohort of MS patients. Methods: A total of 38 patients with relapsing-remitting MS were enrolled after providing informed written consent at Partners MS Center, Brigham and Women’s hospital. Monocular LCVA was measured using retroilluminated Sloan chart and iPad-based LogMAR chart. Number of correct letters and agreement between two measurements were assessed for each eye using Bland–Altman analysis and paired t-test. Results: For both eyes, there was no significant difference in number correct between the two measurements using a paired t-test, and there was high correlation between two measurements (oculus dextrus (OD) r = 0.89, p < 0.001; oculus sinister (OS) r = 0.78, p < 0.001). The limits of agreement were −7.9 to +8.5 letters for the right eye and −10.9 to +11.2 letters for the left eye. Conclusion: An iPad-based LCVA test shows good agreement with Sloan testing in MS patients.

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Clinical and neurophysiological findings in oligoclonal band negative multiple sclerosis patients

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0304122m ◽

2003 ◽

Vol 131 (3-4) ◽

pp. 122-126 ◽

Cited By ~ 3

Author(s):

Sarlota Mesaros ◽

Jelena Drulovic ◽

Zvonimir Levic

Keyword(s):

Multiple Sclerosis ◽

Statistical Significance ◽

Progression Rate ◽

Positive Group ◽

Clinical Difference ◽

Initial Symptoms ◽

Significant Difference ◽

Intrathecal Igg Synthesis ◽

Edss Score ◽

Multiple Sclerosis Patients

Besides magnetic resonance imaging, the presence of locally produced oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) is the most consistent laboratory abnormality in patients with multiple sclerosis (MS). The most sensitive method for the detection of CSF OCB is isoelectric focusing (IEF) [6]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [7, 8]. This study was designed to compare clinical data and evoked potential (EP) findings between CSF OCB positive and OCB negative MS patients. The study comprised 22 OCB negative patients with clinically definite MS [11] and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score [12] and progression rate (PR). All patients underwent multimodal EP: visual (VEPs), brainstem auditory (BAEPs) and median somatosensory (mSEPs). The VEPa were considered abnormal if the P100 latency exceeded 117 ms or inter-ocular difference greater than 8 ms was detected. The BAEPs were considered abnormal if waves III or V were absent or the interpeak latencies I-III, III-V, or I-V were increased. The mSEPs were considerd abnormal when N9, N13 and N20 potentials were absent or when increased interpeak latencies were recorded. The severity of the neurophysiological abnormalities was scored for each modality as follows normal EP score 0; every other EP abnormality except the absence of one of the main waves, score 1; absence of one or more of the main waves, score 2 [13]. Both mean EDSS score (4.0 vs. 3.5) and PR (0.6 vs. 0.5) were similar in OCB positive and OCB negative group, (p>0.05). In the first group males were predominant, but without statistical significance (Table 1). Disease started more often with the brainstem symptoms in the OCB positive than in OCB negative MS group (p=0.028), while there was no differences in other initial symptoms between the groups (Graph 2). The frequency of (multimodal) EP abnormalities was higher in the OCB positive group but the differences were not statistically significant, except for bilateral SEP abnormalities (p=0.012). The severity of the AEPs abnormalities was similar in both groups while for the VEPs and SEPs abnormalities were more pronounced in the OCB positive group but not significantly (Table 2). The male preponderance of OCB negative MS patients in our study is in accordance with previous studies [14, 15]. This finding could be potentially ascribed to the well known gender-related differences in both humoral and cellular immune responses [17]. We found no statistically significant differences in either disability or PR between the two patient groups, although OCB negative MS patients had lower EDSS score and PR than OCB positive cases. In accordance with these findings, Fukazawa et al. also failed to show differences in disability between OCB negative and positive MS patients. On the other hand, few studies reported that OCB negative MS patients have a better prognosis [16 18]. The only clinical difference between two groups of patients that we found was that the disease more often started with brainstem symptoms in OCB positive MS patients (p=0.028). OCB positive MS patients had more often bilateral SEPs abnormalities (p=0.012). There was no statistically significant differences between two groups of patients in the severity of trimodal EPs abnormalities and the frequency of BAEPs and VEPs abnormalities although OCB negative patients had trend towards less pronounced EP disturbancies. In conclusion, our results did not reveal significant difference in clinical and neurophysiological(y) parameters between two groups of patients. However, they indicate a trend towards better prognosis of the disease in OCB negative MS patients.

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Early Cognitive Impairment in Multiple Sclerosis Patients In Relation To Brain Atrophy, Egyptian Sample

QJM ◽

10.1093/qjmed/hcaa054.008 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

M F Zakaria ◽

T A Abdo ◽

A A Abdelaziz ◽

D A Zamzam ◽

Y A Abdullah ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Brain Atrophy ◽

General Medicine ◽

Economic Consequences ◽

University Hospitals ◽

Cross Sectional ◽

Significant Difference ◽

Multiple Sclerosis Patients

Abstract Background Approximately half of all patients with multiple sclerosis (MS) experience cognitive impairment, most commonly with regard to new learning and memory. Cognitive dysfunction is a leading cause of disability in MS and it can have profound social and economic consequences for patients and their families. Objective This study was conducted to discover the early cognitive domains affected in multiple sclerosis patients concomitant with the postulated brain atrophy in an Egyptian sample of multiple sclerosis patients. Patients and Methods A cross-sectional observational case-control study conducted on seventy (60) patients who came for follow-up in Ain Shams University hospitals. 40 patients were taken as cases that followed up in MS unit in Ain-Shams university hospitals. 20 participants were taken as controls taken from the general medicine clinics age and sex matched to our patient group. An informed written consent was taken from parents of each person included in the study. Results There was a statistically significant difference between the two groups in brain volumetric changes and in the parameters of cognitive assessment Conclusion Early detection and examination of cognitive functions is important for patient evaluation, follow up and treatment regimen used.

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A pilot study of recombinant insulin-like growth factor-1 in seven multiple sclerosis patients

Multiple Sclerosis Journal ◽

10.1191/1352458502ms768oa ◽

2002 ◽

Vol 8 (1) ◽

pp. 24-29 ◽

Cited By ~ 17

Author(s):

J A Frank ◽

N Richert ◽

B Lewis ◽

C Bash ◽

T Howard ◽

...

Keyword(s):

Multiple Sclerosis ◽

Growth Factor ◽

Magnetic Resonance ◽

Disease Activity ◽

Secondary Outcome ◽

Insulin Like Growth Factor ◽

Recombinant Insulin ◽

Significant Difference ◽

Multiple Sclerosis Patients ◽

Clinical Measures

The purpose of this open-label, crossover study was to determine the safety and efficacy of recombinant insulin-like growth factor-1 (rhIGF-1) using magnetic resonance imaging (MRI) and clinical measures of disease activity in seven multiple sclerosis (MS) patients. Monthly clinical and MRI examinations were performed during a 24-week baseline and a 24-week treatment period with rhIGF-1. The primary outcome measure was contrast enhancing lesion (CEL) frequency on treatment compared to baseline. Secondary outcome measures included clinical and MRI measures of disease activity including: white matter lesion load (WMLL), magnetization transfer ratio (MTR), T1-Hypointensity volume, cervical spine cross-sectional area and proton magnetic resonance spectroscopic (MRS) imaging for determining regional metabolite ratios. rhIGF-1 (Cephalon) was administered at a dose of 50 mg subcutaneously twice a day for 6 months. rhIGF-1 was safe and well tolerated with no severe adverse reactions. There was no significant difference between baseline and treatment periods for any MRI or clinical measures of disease activity. Although rhIGF-1 did not alter the course of disease in this small cohort of MS patients, the drug was well tolerated. Further studies using rhIGF-1 alone or in combination with other therapies may be of value because of the proposed mechanism of action of this growth factor on the oligodendrocyte and remyelination.

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Correlation of optic neuritis and retinal nerve fibre thickness using optical coherence tomography in a cohort of multiple sclerosis patients

African Vision and Eye Health ◽

10.4102/aveh.v75i1.325 ◽

2016 ◽

Vol 75 (1) ◽

Author(s):

Izanne Roos ◽

Rajeshree Budhoo ◽

Linda Visser ◽

Ahmed I. Bhigjee

Keyword(s):

Multiple Sclerosis ◽

Optical Coherence Tomography ◽

Optic Neuritis ◽

Nerve Fibre ◽

Optical Coherence ◽

Macular Volume ◽

Rnfl Thickness ◽

Significant Difference ◽

History Of ◽

Multiple Sclerosis Patients

Background: Optical coherence tomography (OCT) is a fast, non-invasive imaging technology that produces 3D, high-resolution images of the retina. Direct visualisation of the retina allows a unique opportunity to study the effects of multiple sclerosis (MS)-associated neurodegeneration on retinal ganglion cells as well as effects of retrobulbar demyelination on axonal and retinal architecture through measurement of retinal nerve fibre layer (RNFL) thickness and total macular volume (TMV). These findings are clinically important as axonal loss is irreversible and correlates with disability.Aim: To determine the role and usefulness of OCT in a local cohort of MS patients.Setting: Neurology Clinic, Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, South Africa.Methods: Nineteen patients with MS currently being treated with interferon β-1b underwent OCT examination of both eyes. RNFL thickness and macular volume were measured and correlated with clinical disease characteristics, history of optic neuritis and level of disability.Results: Mean RNFL thickness was 77.3 μm with no significant difference in mean RNFL in eyes with a history of optic neuritis (ON) and those without (p = 0.4). Eyes with a history of ON did, however, have significantly thinner RNFL compared with the contralateral eye (p = 0.04). Despite a strong correlation between TMV and RNFL (p = 0.001), a subset of patients with normal RNFL had TMV that was less than 1% of what was expected. There was no correlation between RNFL and disability scores.Conclusion: OCT enables a direct axonal ‘optical biopsy’, for monitoring disease progression and treatment response in MS. RNFL thinning occurs independently of a history of optic neuritis and may represent a chronic optic neuropathy in patients with MS.Keywords: Multiple sclerosis; optical coherence tomography

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Multiple sclerosis patients and e-health system in Saudi Arabia

International Journal of Human Rights in Healthcare ◽

10.1108/ijhrh-01-2021-0007 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Foziah Alshamrani ◽

Hind Alnajashi

Keyword(s):

Multiple Sclerosis ◽

Treatment Adherence ◽

Statistical Significance ◽

Cross Sectional Study ◽

Adherence To Treatment ◽

Related Factors ◽

Cross Sectional ◽

Content Type ◽

Significant Difference ◽

Multiple Sclerosis Patients

Purpose Multiple sclerosis (MS) is a chronic autoimmune neurological disease. Disease-modifying therapies (DMTs) are mainstay lifelong treatment with no immediate benefits observed. Adherence to treatment is necessary, however, non-adherence is common problem in MS patients. This paper aims to evaluate patient-related factors and satisfactions affecting medication adherence in Saudi MS patients and their rights to discontinue them against medical advice. Design/methodology/approach In total, 409 patients diagnosed with MS, using self-administered DMT (oral and injectable), were randomly enrolled in a cross-sectional study. Electronic questionnaire was used in data collection. Findings Most participants (71.1%) did not know about their MS type. Average age of participants when diagnosed with MS was 27.9 ± 8 years (range 7–69), mean disease duration was 8.1 ± 6.6. Most patients received injectable therapy 363 (88%). Overall adherence in our sample was 67%. Age of participants and duration of disease had no impact on treatment adherence. No significant differences found between genders, educational level, marital status, and smoking in relation to treatment adherence. Route of administration did not reach statistical significance despite a higher percentage of adherence reported in patients on oral DMT [33% (n = 15)] versus injectable therapy [29% (n = 104)]. Conversely, there was significant difference between adherent and non-adherent patients according to anxiety (p = 0.002) and family history of MS (p = 0.011). Originality/value The results revealed that the age of the participants and the duration of the disease had no impact on adherence to treatment.

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Orem’s Self-Care Model with Multiple Sclerosis Patients’ Balance and Motor Function

Nursing Science Quarterly ◽

10.1177/0894318419881792 ◽

2019 ◽

Vol 33 (1) ◽

pp. 46-54

Author(s):

Ardashir Afrasiabifar ◽

Zahra Mehri ◽

Hamid Reza Ghaffarian Shirazi

Keyword(s):

Multiple Sclerosis ◽

Motor Function ◽

Intervention Group ◽

Self Care ◽

Nursing Intervention ◽

Control Group ◽

Care Model ◽

Significant Difference ◽

The Mean ◽

Multiple Sclerosis Patients

Orem’s self-care model has been introduced as a nursing model to empower participants with chronic diseases. This study aims to investigate the effectiveness of nursing interventions using Orem’s self-care model with multiple sclerosis participants’ balance and motor function. Sixty-three participants with multiple sclerosis were randomly assigned to intervention and control groups. The nursing intervention using Orem’s self-care model was performed for eight sessions of 45–60 minutes in the intervention group. In the intervention group, a significant increase (improvement) was observed in the mean scores of balance before (17.09 ± 1.97) and after the intervention (33.75 ± 6.01). A significant decrease (improvement) was observed in the mean of motor functions before (4.12 ± 0.34) and after the intervention (1.59 ± 0.71) ( p = 0.001). However, no significant difference existed in the mean scores of balance ( p = 0.10) and motor function in the control group ( p = 0.20). The nursing intervention using Orem’s self-care model improved balance and motor function of participants with multiple sclerosis.

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Quality of Life Among Multiple Sclerosis Patients in Terms of Mental Health

Asian Social Science ◽

10.5539/ass.v17n5p62 ◽

2021 ◽

Vol 17 (5) ◽

pp. 62

Author(s):

Dima Ibrahim Abu Maloh ◽

Hazem Nouri AlNahar ◽

Haya Ibrahim Abu Maloh

Keyword(s):

Quality Of Life ◽

Mental Health ◽

Multiple Sclerosis ◽

Outcome Measurement ◽

Demographic Data ◽

Physical Activities ◽

Data Form ◽

Significant Difference ◽

Multiple Sclerosis Patients

This study aimed to identify the mental health quality of life among patients with multiple sclerosis in Jordan. Thus, a descriptive quantitative design was used on a total of (N=100) Multiple Sclerosis patients that were randomly selected by using convenience sampling from the Health Insurance Center in the capital Amman, Jordan. Outcome measurement tools were the demographic data form and the Multiple Sclerosis Quality of Life-54 (MSQOL-54) Scale. The demographic data form consisted of questions about: age in years, gender, stage of multiple scleroses, and physical activities. The Multiple Sclerosis Quality of Life-54 (MSQOL-54) consisted of two domains the physical health composite and the mental health composite. In this study the mental health composite were used by the participants. The results revealed that the QOL- Mental Health Composite among patients with multiple sclerosis was 33.9 + 33.6. Moreover, there was no significant difference in score for male and females p=.874. In addition, there was no significant difference in QOL mental health scores for the age groups p=.165. Finally, there was a significant difference in scores for participants and non-participants in physical activity p=.000. Accordingly, this research concluded that Multiple sclerosis patients’ have a low quality of life in terms of mental health. In addition, practicing physical activities have a positive effect on the quality of mental health among multiple sclerosis patients.

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Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients

Cells ◽

10.3390/cells10123324 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3324

Author(s):

Diana Ferraro ◽

Sara De Biasi ◽

Anna Maria Simone ◽

Riccardo Orlandi ◽

Milena Nasi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Safety Data ◽

Absolute Number ◽

Clinical Relapse ◽

Inkt Cells ◽

Time Points ◽

Cell Counts ◽

Significant Difference ◽

One Year ◽

Multiple Sclerosis Patients

The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.

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Role of Mobile Technology in Multiple Sclerosis Patients' Health Education

QJM ◽

10.1093/qjmed/hcab102.021 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Muhammad Badr Ahmed ◽

Maged Zakaria ◽

Dina Zamzam ◽

Tamer H Emara

Keyword(s):

Multiple Sclerosis ◽

Health Education ◽

Medical Treatment ◽

Mobile Health ◽

Control Group ◽

Study Group ◽

Active Case ◽

Significant Difference ◽

Multiple Sclerosis Patients ◽

Arabic Speaking

ABSTRACT Background Many African and Asian randomized clinical trials stated that mobile health technology is helpful in health education and improvement of patients' compliance to medical treatment especially in chronic diseases like hypertension, diabetes mellitus and obesity. Objectives Mobile health applications can provide a health education method for MS patients and a tool for assessment of patients' compliance to medical treatment among MS patients of the Arabic speaking population. Patients and method Type of Study: Prospective comparative observational study, tool: android MS world App, study setting: arabic speaking communities, study duration: six months, study population: multiple sclerosis patients, sampling method: random, sample size 100 patients, 50 study group using the app, 50 control group non app users. Results In the present study, we revealed that total number of patients on the app of the studied group, 60(51.72%) were male and 56(46.28%) were female, and as regard number of active patients on the app of the studied groups, we found that 19(40.43%) were male and 28(59.57%) were female with 3cases dropped out. We analyzed patients in different Egyptian governments of the studied group, Most of our cases were from Cairo 66(69.47%), 9(9.47%) from Giza, 4(4.21%) from Damietta, 2(2.11%) from Alexandria, 2(2.11%) from Gharbia, 2(2.11%) from Qalyoubia, 2(2.11%) from Suez and 6(6.32%) from Upper Egypt. Regarding age characteristics of the studied group most of our cases in active case group and control group their age was ranged between 21—40 years 25(53.19%) and 27(54%) respectively there was statistically significant difference between study group where P < 0.001. Regarding duration since diagnosis of the studied groups, the present study demonstrated that most of cases in active case group and control group their duration since diagnosis was ranged between 1—5 years 30(63.83%) and 31(62%) respectively, and there was no statistically significant difference between study groups where P = 0.949. Regarding the MS world Application questions, we found that61.70%of studied cases find that the app easy and simple touse,87.23% that app present the information in easy and simple way, 89.36% find that app provide with satisfying answers about MS, 95.74% were confident about information presented in that app, 93.62% find that app increase the knowledge about the drugs are taking for MS and 74.47% reported that app made them not to miss taking their drugs doses regularly. On the other hand, we found that 63.83% of cases saw that app help them overcome the usual fatigue symptoms they used to have with MS, 89.36% of cases saw that doctors in the app are good, 93.62% will use that app again and 95.74% will suggest that app for friends and that app also a tool for storing information about the patient making the doctor able to take a decision and cope with the patient condition. We have found that patients are easy to get answer embarrassing questions like that asking about their sexual condition and satisfaction after being diagnosed with multiple sclerosis the results of the questionnaire revealed that about 19 (40.43%) patients aren’t satisfied while the rest of patients in the active case study group 28 (59.57%) patients reported they are satisfied meaning that all patients in the active group answered the question in contrast to the control group asked through paper questionnaire the results revealed that 23 patients reported they are not satisfied and about 15 patients reported they are satisfied about it meaning that not patients in the control group answered the question with 12 patients didn’t answer the question that could add the advantage of mobile health apps in recording easily embarrassing questions rather than conventional methods. Conclusion Mobile health applications can provide a health education method for MS patients and a tool for assessment of patients' compliance to medical treatment among MS patients of the Arabic speaking population.

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