Female Multiple Sclerosis Patients Research Articles

Epstein-Barr Virus (EBV) and Multiple Sclerosis Disease: A Biomedical Diagnosis.

Multiple sclerosis (MS) is a degenerative disease that affects 2.8 million people worldwide. It is a central nervous system disease (CNS), in which the myelin sheath covering the brain and spinal cord neurons is attacked. If the myelin sheath is damaged, a person can suffer permanent damage to the nerves. There are a number of factors that can increase a person's risk of developing MS, such as obesity, smoking, vitamin D deficiency, certain tissue types (HLADRB1∗15 : 01) and infection with the Epstein–Barr virus (EBV). The latter virus can cause infectious mononucleosis, which can, in turn, result in lifelong infection in the host. To establish the relationship between MS and EBV, the author conducted a study on 1176 MS patients admitted to Saudi Arabia King Abdulaziz City centers. The researcher determined that MS occurred twice as much in females as it did in males, and also that EBV was much more widespread in MS female patients than MS male patients (27 : 1). Age was not a factor in the occurrence of EBV. There were limitations on data completeness and availability. Other trials using larger cohorts of patients are needed.

Is There a Relationship Between Overactive Bladder and Sexual Dysfunction in Women With Multiple Sclerosis?

BackgroundLower urinary tract Symptoms (LUTS) and Sexual dysfunction (SD) are common in women with MS and affect quality of life. AimThe aim of this study was to determine the relationship between sexual dysfunction (SD) and overactive bladder in women with Multiple Sclerosis (MS). MethodsFrom January 2019 to January 2021, we evaluated 89 female MS patients admitted for LUTS in a Neuro-Urology Department. SD was investigated using the Female Sexual Function Index (FSFI). All subjects completed the Urinary Symptom Profile scale (USP) and Hospital Anxiety and Depression Scale (HAD A/HAD D). Neurological impairment was assessed using the Expanded Disability Status Scale (EDSS). All patients underwent neurological examination and urodynamic studies. Univariate analysis and Multivariate logistic regression analysis were performed to identify predictors of SD in women with MS (FSFI <26.55). OutcomesPrimary outcome was to determine the association between sexual dysfunction in women with MS and LUTS (overactive bladder, stress incontinence or voiding dysfunction). ResultsSexual dysfunction (FSFI<26,55) affected 74% of women with MS, even with low physical disabilities (EDSS<5). Univariate analysis showed that overactive bladder was more frequent in SD group, but no statistical difference was found (P < .12). No relationship was found between sexual dysfunction and stress incontinence (P = ,47), voiding dysfunction (P= 0.79) or urinary retention (P= .96). Multivariate logistic regression analysis identified overactive bladder to be an independent predictor of sexual dysfunction [aOR 0.03 (CI 0,0.98)]. Sexual dysfunction was not associated with detrusor overactivity on urodynamic studies or with impairment mobility but was strongly associated with the presence of depression (P < .01). Clinical implicationsSexual disorders in women with MS should be assessed as much as urinary disorder. Strengths and limitationsthis study included the largest cohort of women with MS. But the sample was obtained in an outpatient setting with low neurological impairment. ConclusionIn our study, SD was frequent affecting young women with no anticholinergic treatment and low physical impairment. Overactive bladder seemed to be independent predictor of sexual dysfunction. Conversely, SD was not associated with detrusor overactivity, neurological impairment, or duration of disease but was strongly associated with depression.Breton FL, Chesnel C, Lagnau P, et al. Is There a Relationship Between Overactive Bladder and Sexual Dysfunction in Women With Multiple Sclerosis?. J Sex Med 2022;19:729–737.

Lnc-HNF1A-AS1 and its target gene ATG5 is dysregulated in HLA-DRB1*15:01-negative female patients with multiple sclerosis

Human investigations and animal model studies have confirmed that autophagy process plays crucial roles in multiple sclerosis (MS) predisposition. In addition, the essential role of long noncoding RNAs (lncRNAs) in MS development has been recently reported. Current study aimed to investigate the expression level of lnc-HNF1A-AS1 as a new lncRNA and its target gene ATG5 in patients with MS. A total of 50 female patients with MS and 50 female healthy subjects were included in this observational case-control study. HLA-DRB1*15:01 allele, as a main risk factor for MS susceptibility, was ruled out in all included patients. The peripheral blood samples were obtained from all patients and total RNA was extracted and cDNA synthesis was performed. The gene expression level of lnc-HNF1A-AS1 and ATG5 was evaluated by Real-time quantitative PCR. Our results have shown that expression level of lnc-HNF1A-AS1 and ATG5 was significantly higher in total MS patients compared with controls (P-value = 0.0278 and P-value = 0.0064, respectively). In addition, there was statistically significant correlation between lnc-HNF1A-AS1 expression level with age of onset (r = 0.2937, P-value <0.05). Current study indicated abnormal up-regulation of two autophagy-related genes in the peripheral blood of HLA-DRB1*15:01-negative MS female patients compared with healthy controls. Therefore, autophagy-related mechanisms might be implicated in the pathobiology of MS in this subpopulation.

Home-based aerobic training and vitamin D improve neurotrophins and inflammatory biomarkers in MS patients

BackgroundLifestyle modifications (physical activity and diet) are among the most promising strategies in multiple sclerosis (MS) rehabilitation. This study aimed to investigate the effects of combined home-based AT and Vit D on the neurotrophins level and biomarker of inflammation in MS patients during COVID-19 outbreak. MethodsIn this randomized, single-blinded, placebo-controlled trial, 38 females with MS having EDSS: 3–5 (aged 20–40 years with body mass index [BMI] of 25–30 kg/m2) were randomly assigned into four groups: AT+Vit D (n = 10), AT (n = 9), Vit D (n = 9), and Control (C n = 10). The AT program consisted of 50–70% of HRMax, 25–40 min/day, three days/wk for eight weeks. Participants in the Vit D group consumed 50,000 IU of Vit D supplement capsules per week for eight weeks. The data were analyzed through paired t-test and one-way analysis of variance and Tukey's post hoc test at the signification level of P<0.05. ResultsAT+Vit D, AT, and Vit D compared to the control, increased BDNF and NGF, and downregulated CRP, TNF-a, IL-6, and IL-1β in MS patients. Additionally, the AT+Vit D group showed significantly lower CRP, TNF-a, IL-6, and IL-1β levels and significantly higher BDNF and NGF levels compared to the AT and Vit D groups. Also, the results of this study showed significant differences between AT and Vit D groups in the variable mentioned above. ConclusionsThese findings suggest that AT+Vit D improves neurotrophin and inflammatory biomarker levels in female MS patients more effectively than AT or Vit D alone.

Comparison of the Effects of the Choice Theory and Behavioral Activation Therapies with and Without Guided Imagery Rescripting on the Adversity Quotient and Cognitive Emotion Regulation of MS Patients in Ahvaz, Iran

Background: Complications of multiple sclerosis (MS) severely impact self-image and have debilitative effects on the adversity quotient. Objectives: The present study aimed to investigate the effects of the choice theory and behavioral activation therapies with and without guided imagery rescripting on the adversity quotient and cognitive emotion regulation of MS patients in Ahvaz, Iran. Methods: This quasi-experimental study was conducted with a pretest-posttest design and a control group. The sample population included the male and female MS patients visiting the Caspian Physiotherapy Center of Ahvaz, Iran in 2019. In total, 60 MS patients were selected via convenience sampling and randomly divided into three experimental groups and one control group (15 per each). Data were collected using the Adversity Response Profile Questionnaire (ARPQ) and the Cognitive Emotion Regulation Questionnaire (CERQ). Data analysis was performed using the multivariate analysis of covariance. Results: A significant difference was observed between the effects of the choice theory (CT) and behavioral activation (BA) therapies with and without guided imagery rescripting (ImRs) on the improvement of the adversity quotient (AQ) and positive cognitive emotion regulation (CER) of the MS patients, as well as the reduction of negative CER (P &lt; 0.001). Compared to the CT and BA therapies without guided ImRs, the BA therapy with guided ImRs more effectively enhanced the AQ and positive CER of the MS patients and decreased their negative CER (P &lt; 0.001). Conclusions: According to the results, BA with ImRs is a more effective method for enhancing the AQ and positive CER of MS patients and mitigating their negative CER compared to other approaches.

Significance of serum VIP and PACAP in multiple sclerosis: an exploratory case-control study.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. Vasoactive and intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are neuropeptides that play roles in anti-inflammation and neuroprotection in MS. In this study, we aimed to determine the serum levels of VIP and PACAP in MS patients versus healthy controls and to correlate them with demographics and clinical characteristics. Serum samples were collected from MS patients (n = 145) and healthy controls (n = 73) to measure serum levels VIP and PACAP. VIP serum levels were lower in MS patients than healthy controls (p < 0.001). Serum PACAP levels were the same among the two groups. Gender-based analysis showed that VIP levels were lower in healthy females (1238.840pg/ml) than healthy males (3300.105pg/ml; p < 0.001), and PACAP serum levels were significantly lower in male MS patients (48,516.214fg/ml) than female MS patients (62,466.400fg/ml; p = 0.029). ROC curve suggested that serum VIP level can discriminate patients with MS from healthy controls. Relapsing-remitting MS, progressive-MS, and clinically isolated syndrome groups were different in age, MS disease duration, EDSS score, and VIP levels (p < 0.05). MS disease type and history of previous relapses in the preceding 24months predicted serum VIP levels, while gender predicted PACAP levels. VIP serum levels are decreased in MS patients and can be used to differentiate between MS patients and healthy controls. Further studies with larger sample sizes are required to investigate VIP as a marker to reflect MS disease progression.

PD36-01 CORRELATION BETWEEN WHITE MATTER INTEGRITY AND LOWER URINARY TRACT SYMPTOMS (LUTS) IN FEMALE MULTIPLE SCLEROSIS PATIENTS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (PD36)1 Sep 2021PD36-01 CORRELATION BETWEEN WHITE MATTER INTEGRITY AND LOWER URINARY TRACT SYMPTOMS (LUTS) IN FEMALE MULTIPLE SCLEROSIS PATIENTS Darshil Choksi, Khue Tran, Bradley Schott, Christof Karmonik, Timonthy Boone, and Rose Khavari Darshil ChoksiDarshil Choksi More articles by this author , Khue TranKhue Tran More articles by this author , Bradley SchottBradley Schott More articles by this author , Christof KarmonikChristof Karmonik More articles by this author , Timonthy BooneTimonthy Boone More articles by this author , and Rose KhavariRose Khavari More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002040.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system and around 90% of MS patients experience LUTS. The degree of demyelination and signal disruption can be quantified by measuring the functional anisotropy (FA) and mean diffusivity (MD) of white matter tracts (WMTs) via diffusion tensor imaging (DTI). In this study, we analyzed the correlation between clinical variables evaluating LUTS (including urodynamics parameters and validated questionnaires) with both FA and MD values in a cohort of female MS patients. METHODS: Twenty-eight MS women with LUTS were enrolled in this prospective study. Urodynamics and validated questionnaires including the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were collected. DTI images were acquired (32 directions, one B0 image) for each subject using the standard MRI pulse sequence available on the Philips 3 Tesla Ingenia scanner. The AFNI software package was used to automatically align clinical DTI images onto the ICMB DTI81 atlas to extract the FA and MD values of 50 tracts for each subject. Pearson’s correlation was performed between FA and MD values versus each clinical variable for all 50 tracts. Any WMTs with a p-value less than 0.05 on the Pearson’s correlation with FA or MD in at least one of the clinical variables was considered a statistically significant correlation. A positive correlation coefficient (R) for MD and negative correlation for FA were noted as signs of WMT demyelination contributing directly to clinical symptoms whereas a negative correlation for MD and positive correlation for FA were noted to indicate compensatory strengthening of the WMT in an effort to maintain continence in the presence of MS. Only WMTs with |R| >0.3 were reported. RESULTS: Five WMTs (ML-L, CP-R, SS-R, UNC-L, and SFO-R) showed statistically significant demyelination in correlation to symptoms, whereas three WMTs (IFO-R, PCR-R, and CGH-L) displayed statistically significant compensatory strengthening (Table 1). CONCLUSIONS: The ability to correlate changes in WMT signaling to clinical symptoms strengthens our understanding of the demyelination that leads to LUTS in female MS patients and can enable the development of targeted therapies for patients early in the disease course. Source of Funding: Dr. Khavari reports that she is partially supported by K23DK118209, National Institute of Health, NIDDK (RK). Also supported by Houston Methodist Clinician Scientist Award (RK) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e595-e595 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Darshil Choksi More articles by this author Khue Tran More articles by this author Bradley Schott More articles by this author Christof Karmonik More articles by this author Timonthy Boone More articles by this author Rose Khavari More articles by this author Expand All Advertisement Loading ...

Evaluating the effects of transcutaneous tibial nerve stimulation or pelvic floor muscle training on sexual dysfunction in female multiple sclerosis patients reporting overactive bladder.

Sexual dysfunction (SD) is common in female patients with multiple sclerosis (MS) reporting overactive bladder (OAB) symptoms. The aim of the study was to evaluate the effects of transcutaneous tibial nerve stimulation (TTNS) and pelvic floor muscle training (PFMT) with biofeedback on SD in female patients with MS reporting OAB symptoms. Patients with overactive bladder and SD were allocated to receive TTNS or PFMT daily. Overactive bladder symptoms, sexual functions, and sexual quality of life were assessed at baseline and 6th weeks. Female Sexual Function Index (FSFI), Overactive Bladder Questionnaire (OABv-8), and Sexual Quality of Life-Female (SQoL-F) questionnaires were used. Thirty patients (TTNS = 10, PFMT = 20) were included in the study. Compared to baseline, total FSFIOABv-8, and SQoL-F scores improved in both TTNS (p = 0.005, p = 0.011, p = 0.444, respectively) and PFMT (p = 0.002, p = 0.001, p = 0.001, respectively) groups. Between-group comparisons did not show any significant differences. This study demonstrates the efficacy of both TTNS and PFMT for improving sexual function in female MS patients with OAB symptoms, but did not show superiority of any particular method. Further studies are required to investigate the differences between these two non-invasive methods.

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial

BackgroundVoiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals.MethodsTen adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement.DiscussionDespite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future.Trial registrationThis trial is registered at ClinicalTrials.Gov (NCT03574610, 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329)

The effects of Combine Training Program on Level Adipsin and Insulin Resistance in Female Multiple Sclerosis Patients (MS)

The effects of Combine Training Program on Level Adipsin and Insulin Resistance in Female Multiple Sclerosis Patients (MS)

Differences in physical, mental, and social functions between males and females in multiple sclerosis: A multicenter cross-sectional study in China

Background Sex-specific differences in multiple sclerosis (MS) have been recognized, but few were known about how sex influences the characteristics of MS in Asian and the social burden of MS. This study aimed to investigate the symptoms, mental health, and social functions of Chinese MS patients and find differences between sexes.Methods MS patients were enrolled from January 2004 to September 2018. A questionnaire was distributed by 47 medical centers. Patients’ physical symptoms, negative emotions, interpersonal communication, social intercourse, employment condition, and suicidal thoughts and behavior were collected. Patients were asked to fill in the questionnaire independently and undergo Expanded Disability Status Scale (EDSS) measurement. Unpaired t-tests between sexes were conducted for normally distributed continuous variables. Mann-Whitney u-tests were conducted for non-normally distributed data. Chi-square tests, Fisher exact tests and rank sum tests were performed for categorical variables.Results 931 patients were enrolled and 631 were female. Frequency of fatigue and pain were higher in female MS patients (P<0.05), while male patients complained more weakness, diplopia, sexual dysfunction, and micturition and defecation dysfunction (P<0.05). Females were more likely to experience sadness and helplessness than males (P<0.05) while males were more likely to experience nonacceptance than females (P<0.05). MS had a worse influence on male patients in relationships with family and friends (P<0.05). The employment rate of MS patients was 39.31%. The frequency of suicidal attempt was 2.36%, which was higher than general population.Conclusions The study provided evidence that characteristics of MS were different between males and females, and influence in mental and social function was a common problem among MS patients. More attention should be paid to the mental health and social function of MS patients.

Validation of the Italian version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19.

People with multiple sclerosis (MS) may experience sexual dysfunction throughout the disease course. Validated scales to assess sexual dysfunction in MS for Italian patients are lacking. Hence, we aimed at validating Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-19) for Italian MS patients. We included both male and female MS patients. Each patient completed the Italian translation of the MSISQ-19. Construct validity was explored by the exploratory factor analysis and the Cronbach's alpha coefficient. Test-retest stability and concurrent internal and external validity were examined by Pearson' correlation coefficients. We enrolled 369 MS patients (323 female and 46 male). Italian MSISQ-19 showed a Cronbach's alpha of 0.92. MSISQ-19 test and retest total scores correlated between each other (r = 0.48, p = 0.01). MSISQ-19 total score also correlated with primary, secondary and tertiary subscales (p < 0.001). The Italian Version of the MSISQ-19 showed satisfactory internal consistency and reliability with moderately adequate test-retest reproducibility, suggesting that it may be used as a valuable measure of sexual dysfunction in the Italian population.

The Effect of an Eight-week Pilates Training on Interleukine-18 Level, Fatigue, and Balance in Women With Multiple Sclerosis

Background: Proinflammatory cytokines increasingly cause inflammation in patients with Multiple Sclerosis (MS). In this regard, the current study aimed to shed light on the effectiveness of an eight-week Pilates training program in the level of interleukin-18, the severity of fatigue, balance, and physical disability, in females with MS. Methods: This study was a quasi-experimental research with a pre-test-post-test design and a control group and conducted in Sirjan City, Iran. A total of 30 female MS patients (Mean±SD age: 30.15±6.97 years; 2≤ expanded disability status scale≤5.5) were selected using a purposeful sampling method and divided into control and experimental groups. The experimental group conducted the Pilates exercises for eight weeks, three sessions per week (lasting 45-60 minutes), while the control group had no regular physical activity. Before and after the training program, we evaluated fatigue, physical disability, and balance using the fatigue severity scale, the expanded disability status scale, and the Berg balance scale, respectively. Also, 5 mL of blood was taken from each participant to evaluate the interleukin-18 level. Then, the independent t-test was used to compare the pretest-posttest scores. Results: The findings indicated that the Pilates training program significantly decreased the level of interleukin-18, the severity of fatigue, and the score of physical disability (P≤0.05), and increased the balance (P≤0.05), in females with MS. Conclusion: Therefore, patients with MS can make the best use of such exercises to strengthen their immune systems and performances.

Downregulation of Cancer-Associated lncRNAs in Peripheral Blood of Multiple Sclerosis Patients.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.

Effectiveness of the transcutaneous tibial nerve stimulation and pelvic floor muscle training with biofeedback in women with multiple sclerosis for the management of overactive bladder

Background: Overactive bladder (OAB) is common in patients with multiple sclerosis (MS) with a limited number of treatment options. Objective: To investigate the effect of transcutaneous tibial nerve stimulation (TTNS) and pelvic floor muscle training (PFMT) with biofeedback on OAB symptoms in female MS patients. Methods: This study was conducted at the outpatient MS clinic in Istanbul. At baseline bladder diary, post-voiding residue (PVR), OAB, and Qualiveen Scales (QoL: Quality of Life; Siup: Specific Impact of Urinary Problems on QoL) were assessed. Patients were allocated to receive TTNS or PFMT daily for 6 weeks and reevaluated using the same tests. Results: Fifty-five patients (TTNS = 28, PFMT = 27) were included. Compared with baseline, both TTNS and PFMT groups improved in terms of OAB (p = 0.0001, p = 0.0001), Qualiveen-siup (p = 0.0001, p = 0.0001), Qualiveen-QoL (p = 0.002, p = 0.006), PVR (p = 0.0001, p = 0.21), frequency (p = 0.0001, p = 0.69), nocturia (p = 0.0001, p = 0.19), urgency (p = 0.0001, p = 0.0001), and urge incontinence (p = 0.0001, p = 0.0001). Between-group comparisons showed significant differences in 24-hour frequency (p = 0.002) in favor of TTNS. Conclusion: Our study demonstrates the efficacy of both TTNS and PFMT for managing OAB symptoms in MS, associated with a significant impact on QoL, but did not show superiority of the methods. Further studies are needed to explore differences between these two non-invasive treatments.

A case of multiple sclerosis with negatively converted anti‐natalizumab antibodies

AbstractBackgroundThe therapeutic effect of natalizumab, a disease‐modifying drug for multiple sclerosis (MS), may be decreased in the presence of neutralizing antibodies. In particular, if the neutralizing antibody is persistently positive, the treatment must be stopped. We experienced a case in which anti‐natalizumab antibodies were persistently positive but then negatively reversed during the course of treatment.Case presentationThe case is a 38‐year‐old female MS patient. After three attacks of MS, she was treated with dimethyl fumarate, but the relapse continued. Anti‐JC virus titer of her serum was more than 2.5, but she selected to treatment with natalizumab. At her initial treatment, she had allergic symptoms and was found to be positive for anti‐natalizumab antibodies. In the second treatment, she received an infusion after taking antiallergic drugs, after which her allergic symptoms reduced. Thereafter, she received natalizumab treatment in the same manner. Two months later, reexamination of the anti‐natalizumab antibodies was persistently positive. However, she decided to continue natalizumab because there were no recurrences. Two years after the start of natalizumab treatment, the anti‐natalizumab antibodies were found to be negatively inversed. Because anti‐JC virus antibody remained elevated, she decided to continue the treatment with natalizumab by dosing intervals every 6 weeks. Thereafter, no recurrence was observed.ConclusionsEven if the neutralizing antibodies against natalizumab are positive, treatment continuation may be considered if the therapeutic effect is certain and the side effects are within the allowable range.

Impact of EBV on Multiple in a Sample of Iraqi Females: Immunological and Molecular Study

This study was designed to highlight the role of Epstein Barr viruses (EBV) as a possible causative effect in multiple sclerosis (MS) through testing the viral load along with both biochemical and immunological parameters in female MS patients. We also aimed at finding the effects of different types of treatment line on the various study aspects. The results of the enzyme-linked immunosorbent assay (ELISA) revealed first an increased level of EBV EBNA1IgG IL-17A (96.13±27.60 pg/ml) in sera of female MS patients (0.05±0.01 U/ml, n=50) compared with the control group (n=40). We confirmed this result using real-time polymerase chain reaction (RT-PCR) which also showed a significantly higher EBV load in MS patients (22.61±12.72 copies/ml) as compared to the control. This was associated with an increased level of IL-17A (96.13±27.60 pg/ml) in the patients, while levels of both melatonin hormone (0.63±0.19 pg/ml) and vitamin D3 (29.90±12.41 ng/ml) showed a significant decrease as compared to the normal values of the control group. Analysis of the relation between each of the studied parameters with the level of disability in the patients, as reflected by the expanded disability status score (EDSS), revealed no significant differences between the two categories of EDSS ˂3 and ≥3 patients in terms of EBV EBNA1IgG levels, whereas they were slightly different in terms of IL-17A and vitamin D3 (p &lt;0.001). With respect to differences between the treatment lines, the results from the showed analysis of variance (ANOVA) test showed no significant differences in all the tested parameters between patients treated with the first line (Rebif, Avonex, Betaferon) and second-line (Gilenya, Tysabri). However, the only significant difference in comparison to the control group was found in levels of IL-17.&#x0D; It could be concluded that EBV has a crucial role in the initiation and targeting MS disease, leading to increasing levels of IL-17A, and decrease serum levels of melatonin hormone for female patients.

PND91 MEASURING FATIGUE SEVERITY IN ADULT WOMEN WITH MULTIPLE SCLEROSIS IN THE UNITED STATES: BASELINE RESULTS OF THE FIRST MULTI-CENTER SYSTEMS-LEVEL QUALITY IMPROVEMENT RESEARCH COLLABORATIVE - THE MULTIPLE SCLEROSIS CONTINUOUS QUALITY IMPROVEMENT COLLABORATIVE (MS-CQI)

Fatigue is the most common and disabling symptom for people with multiple sclerosis (MS) and female gender is correlated with higher reported fatigue severity. This study analyzes fatigue severity in adult women with MS and identifies significant differences between centers on mean fatigue severity scores. We conducted a prospective 1-year baseline study across four MS-CQI centers (A,B,C,D). Participants were adult females (18+) with MS. Fatigue severity was measured using the Promis Fatigue MS Patient-Reported Outcome Measure (PROM). Descriptive statistics were evaluated for each center, as well as significance testing across and between centers. Continuous variables were analyzed using ANOVA, and categorical variables were analyzed using Chi-Square tests. 322 female MS patients were in the sample. 211 (65.5%) were white, 118 (36.6%) had full-time employment, 165 (51.2%) were married, 85 (26.4%) had an annual income of $50,000-$99,999, 222 (68.9%) were English-speaking, 27 (8.4%) lived alone, and 265 (82.3%) had employer health insurance. Socioeconomic variables demonstrating statistical significance (Chi-Square p<0.0001) included race, employment, marital status, language, housing, insurance and education. Significant center-level variation were also found compared to overall MS-CQI mean fatigue severity (ANOVA F=7.31, p<0.0001). Tukey’s Honest Significant Difference tests (HSD) revealed statistically significant differences (p<0.0001) between centers C-B, D-B, A-B, B-C, B-D, and B-A (Critical Value=3.65). Results suggest significant center-level differences in mean fatigue scores across and between centers. Future research is needed to investigate the factors influencing these differences and test the effects of targeted center-level improvement interventions on reducing population fatigue severity levels.

Decreased second to fourth digit ratios in female multiple sclerosis patients

BackgroundSex-related differences in multiple sclerosis (MS) suggest a possible role of prenatal sex hormones in the pathogenesis. The aim of this study was to investigate whether the 2D:4D ratio, considered a predictor of prenatal hormonal exposure, in MS patients differ from that in healthy controls. MethodsTwo hundred MS patients and one hundred seventy healthy control subjects with similar age and sex distribution enrolled. All participants were right-handed. The right hands of all participants were scanned using a digital scanner. Measurements of second and fourth digit lengths were made from digital scans. The 2D:4D ratio was calculated by dividing the length of the second digit by the length of the fourth digit. ResultsA total of 171 MS patients' and 159 healthy controls' digit scans included in the study. The MS group consisted of 94 females (mean age 38.32 ± 10.5) and 77 males (mean age 42.06 ± 11.8) and the control group of 86 females (mean age 40.24 ± 9.7) and 73 males (mean age 38.49 ± 11.6). 2D:4D ratios of female MS patients were significantly lower than those of healthy females (p=0.004). Although 2D:4D ratios of male patients with MS were lower than those of healthy males, this difference was not statistically significant (p=0.33). There was no significant correlation between the 2D:4D ratio, EDSS levels or duration of the disease in male or female MS patients (p<0.05). ConclusionAlthough our results suggest that a prenatal hormonal balance in favor of androgenic activity may be a risk factor for MS, complex factors mediating the actions of sex hormones on target cells should always be considered when evaluating the effects of sex hormones.

Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction?

Two white matter tracts (WMTs) are proposed to be involved in bladder function: anterior thalamic radiation and superior longitudinal fasciculus. Multiple sclerosis (MS) patients with voiding dysfunction (VD) may have distinct changes in these 2 WMTs. This study aims to compare the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging of MS females with and without VD versus healthy controls (HCs). Prospective observational cohorts of 28 female MS patients and 11 HCs were recruited. Multiple sclerosis patients were divided into 2 groups: voiders (patients without VD, n = 14) and VD (patients with VD, n = 14). Diffusion tensor imaging of each subject was obtained, from which FA and MD maps were generated. The mean FA and MD of each WMT on both sides were analyzed using one-way analysis of variance and pairwise comparison with adjusted P values. Overall MS patients had significantly lower mean FA (loss of coherence) and significantly higher mean MD (increased free diffusion) than HCs in both WMTs, indicating more damage. Furthermore, VD showed a trend of loss of integrity in both WMTs when compared with voiders with lower FA and higher MD. There is damage reflected by lower FA and higher MD values in the proposed WMTs involved in bladder function in MS women. Voiding dysfunction in this patient population can be attributed to these damages considering women with VD demonstrated a trend of deterioration in these WMTs compared with women without VD. Future studies with larger sample sizes should be done to further confirm this correlation.