Onset Of Multiple Sclerosis Research Articles

Vitamin D status in patients with multiple sclerosis: an association with insolation, disease course, and HLA-DRB1 gene polymorphism

Recent systematic reviews and a meta-analysis have shown that there is insufficient evidence on the relationship of multiple sclerosis (MS) to vitamin D supplementation Objective : to assess the relationship of vitamin D status in MS patients to insolation, disease course, and HLA-DRB1 gene polymorphism. Patients and methods. The one-stage study enrolled 90 patients with relapsing-remitting MS (a study group) and 87 volunteers without this disease (a control group). The enrolled were born and live in the Altai Territory of the Russian Federation. The serum level of 25(OH)D was measured by enzyme immunoassay. Results and discussion . 25(OH)D <30 ng/ml was more common in patients with MS than that in the controls. There were no intergroup differences in the time spent in the sun for 6 months before inclusion in the study (p=0.020). The level of 25(OH)D was higher in the high insolation period from April to September than that in the low insolation period from October to March in both patients with MS (p<0.005) and controls (p<0.001). There was no association of 25(OH)D levels with urban and rural residence, gender, age at MS onset, severity of neurological disorders, their progression rate, and MS risk alleles within the HLA-DRB1 gene (03, 13, 15). Conclusion . Vitamin D deficiency is more common in patients with MS than in those without this disease. This is unlikely to be due to the differences in the radiation received from the sun. The final conclusion on the relationship of vitamin D to MS can be made after obtaining the results of a prospective follow-up.

Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis

Serum neurofilament light chain (NfL) is emerging as an important biomarker in multiple sclerosis (MS). Our objective was to evaluate the prognostic value of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes. In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of routine clinical follow-up. Levels of serum NfL were quantified in patients and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix). Sixty-seven patients had a median follow-up of 18.9 years (range 15.0–27.0). The median serum NfL level in patient baseline samples was 10.1 pg/mL, 38.5% higher than median levels in 37 controls (7.26 pg/mL, p = 0.004). Baseline NfL level was most helpful as a sensitive predictive marker to rule out progression; patients with levels less 7.62 pg/mL were 4.3 times less likely to develop an EDSS score of ≥ 4 (p = 0.001) and 7.1 times less likely to develop progressive MS (p = 0.054). Patients with the highest NfL levels (3rd-tertile, > 13.2 pg/mL) progressed most rapidly with an EDSS annual rate of 0.16 (p = 0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p = 0.022). This study demonstrates that baseline sNfL is associated with long term clinical disease progression. sNfL may be a sensitive marker of subsequent poor clinical outcomes.

Peripapillary Vessel Density as Early Biomarker in Multiple Sclerosis.

Background: To evaluate retinal vessel density (VD) in macular and in peripapillary regions in patients with recent onset of multiple sclerosis, at initial demyelinating event (IDE) and in matched relapsing-remitting multiple sclerosis (RRMS) patients.Methods: We evaluated VD in superficial capillary plexus, deep capillary plexus, choriocapillaris and radial peripapillary capillary plexus in IDE, RRMS patients and in matched healthy controls (HCs) through Optical Coherence Tomography Angiography (OCT-A). Clinical history, including history of optic neuritis, Expanded Disability Status scale and disease duration of patients were collected.Results: Thirty patients (20 with IDE and 10 with RRMS) and 15 HCs were enrolled. IDE patients showed a lower VD in radial peripapillary capillary plexus compared with controls (coeff. β = −3.578; p = 0.002). RRMS patients displayed a lower VD in both superficial capillary plexus and radial peripapillary capillary plexus compared with HCs (coeff. β = −4.955; p = 0.002, and coeff. β = −7.446; p < 0.001, respectively). Furthermore, RRMS patients showed a decreased VD in radial peripapillary capillary plexus compared with IDE patients (coeff. β = −3.868; p = 0.003).Conclusions: Peripapillary region vessel density reduction, revealed through OCT-A, might be considered as an early event in MS, and might be relevant as a biomarker of disease pathology.

The Use of Motor-Evoked Potentials in Clinical Trials in Multiple Sclerosis.

Motor-evoked potentials (MEPs) can be used to assess the integrity of the descending corticospinal tract in the laboratory. Evoked potentials (EPs) have been widely used in the past for the diagnosis of multiple sclerosis (MS), but they are now becoming more useful in assessing the prognosis of the disease. Motor-evoked potentials have been included in EP scales that have demonstrated good correlations with clinical disability. Soon after the onset of MS, it is possible to detect an ongoing process of neurodegeneration and axonal loss. Axonal loss is probably responsible for the disability and disease progression that occurs in MS. Given the good correlations of EPs in detecting disease progression in MS, they have been used to monitor the effects of drugs used to treat the disease. Several clinical trials used MEPs as part of their EP evaluation, but MEPs have never been used as a measure of efficacy in clinical trials testing neuroprotective agents, although MEPs could be a very promising tool to measure neuroprotection and remyelination resulting from these drugs. To be used in multicenter clinical trials, MEP readings should be comparable between centers. Standardized multicenter EP assessment with central reading has been demonstrated to be feasible and reliable. Although MEP measurements have been correlated with clinical scores and other measures of neurodegeneration, further validation of MEP amplitude measurements is needed regarding their validity, reliability, and sensitivity before they can be routinely used in clinical drug trials in MS.

Real-world effectiveness of cladribine for Australian patients with multiple sclerosis: An MSBase registry substudy

Background/objective: Observational clinical data from cladribine-treated patients with relapsing forms of multiple sclerosis (MS) were recorded in the Australian MS registry powered by the MSBase registry platform (5-year follow-up) and analysed to complement information from the pivotal cladribine clinical trials in MS. Methods: A cohort of 90 cladribine-treated patients with follow-up data reported by treating physicians and recorded in the Australian MSBase registry (database lock February 2016) were examined. Clinical data included Expanded Disability Status Scale (EDSS) scores, relapses and other disease-modifying drugs (DMDs) administered before and after cladribine treatment. Results: Mean age on starting cladribine was 47 years; mean age at MS onset was 34 years, and median baseline EDSS score was 5.25. Disability trajectories in patients with sufficient follow-up suggested an overall increasing trend prior to cladribine treatment which was reduced during the 2-year post-treatment. Approximately 80% of patients were EDSS progression-free, 65% remained relapse-free after 2 years and median time to next DMD was 1.7 years. Conclusion: These observational data suggest a disease-modifying effect in this cohort of relapsing MS patients characterised by older and more disabled patients. Since these data represent a single-arm cohort, clinical trials and larger comparative post-marketing studies are needed to validate and extend these findings.

Genetic analysis of nucleotide-binding leucine-rich repeat (NLR) receptors in multiple sclerosis.

Genetic and functional analyses of the inflammasome suggest a role for this multiprotein complex in the biological mechanisms leading to the onset and progression of multiple sclerosis (MS). Nucleotide-binding, leucine-rich repeat (NLR) receptors trigger the activation and assembly of specific inflammasomes in response to danger signals. Mining exome sequencing data from 326 MS patients identified 17 rare missense or nonsense variants in NLR family pyrin domain containing 1 (NLRP1), NLRP3, NLRP6, NLRP7 and NLR family CARD domain containing 4 (NLRC4). Genotyping these variants in 2503 MS cases and 1076 healthy controls did not result in statistically significant differences between groups, and segregation analysis within MS families was largely unsupportive of co-segregation of these variants with disease. However, the identification of MS patients harboring rare homozygote variants in NLRP1 (p.Ile601Phe and p.Ser1387Ile), a variant in NLRP3 (p.Leu832Ile) resulting in the substitution of a critical amino acid for the formation of its leucine-rich repeat domain, and several MS patients with NLRC4 variants (p.Arg310Ter and p.Glu600Ter) causing protein truncations suggest that rare protein-altering variants in inflammasome-activating NLR receptors may contribute to MS risk.

Hospital diagnosed pneumonia before age 20 years and multiple sclerosis risk

IntroductionRespiratory inflammation has been proposed as a risk factor for MS. This study aims to determine if hospital-diagnosed pneumonia in adolescence (before age 20 years) is associated with subsequent multiple...

Endothelial nitric oxide synthase (NOS3) rs2070744 polymorphism and risk for multiple sclerosis.

The possible role of oxidative stress and nitric oxide (NO) in the pathogenesis of multiple sclerosis (MS) has been suggested by several neuropathological, biochemical, and experimental data. Because the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) showed association with the risk for MS in Iranians, we attempted to replicate the possible association between this SNP and the risk for MS in the Caucasian Spanish population. The frequencies of NOS3rs2070744 genotypes and allelic variants in 300 patients diagnosed with MS and 380 healthy controls were assessed with a TaqMan-based qPCR assay. The possible influence of the genotype frequency on age at onset of MS, the severity of MS, clinical evolutive subtypes of MS, and HLA-DRB1*1501 genotype were also analyzed. The frequencies of rs2070744 genotypes and allelic variants were not associated with the risk of developing MS and were not influenced by gender, age at onset and severity of MS, the clinical subtype of MS or the HLA-DRB1*1501 genotype. This study found a lack of association between NOS3 rs2070744 SNP and the risk for MS in Caucasian Spanish people.

Predicting self-reported depression after the onset of multiple sclerosis using genetic and non-genetic factors

Background: Persons with multiple sclerosis (PwMS) are disproportionately burdened by depression compared to the general population. While several factors associated with depression and depression severity in PwMS have been identified, a prediction model for depression risk has not been developed. In addition, it is unknown if depression-related genetic variants, including Apolipoprotein E (APOE), would be informative for predicting depression in PwMS. Objective: To develop a depression prediction model for PwMS who did not have a history of depression prior MS onset. Methods: The study population included 917 non-Hispanic white PwMS. An optimized multivariable Cox proportional hazards model for time to depression was generated using non-genetic variables, to which APOE and a depression-related genetic risk score were included. Results: Having a mother who had a history of depression, having obstructive pulmonary disease, obesity and other physical disorders at MS onset, and affect-related symptoms at MS onset predicted depression risk (hazards ratios (HRs): 1.6–2.3). Genetic variables improved the prediction model’s performance. APOE ε4/ε4 and ε2/x conferred increased (HR = 2.5, p = 0.026) and decreased (HR = 0.65, p = 0.046) depression risk, respectively. Conclusion: We present a prediction model aligned with The Precision Medicine Initiative, which integrates genetic and non-genetic predictors to inform depression risk stratification after MS onset.

Neuroprotective effects of exercise in people with progressive multiple sclerosis (Exercise PRO-MS): study protocol of a phase II trial

BackgroundNeurodegeneration, rather than inflammation, plays a key role in the progressive phase of multiple sclerosis (MS). Current disease modifying treatment options for people with progressive MS (PMS) do not specifically target neurodegeneration. Preliminary evidence suggests that exercise therapy might have neuroprotective effects. However, neuroprotective effect studies of exercise interventions in PMS are scarce and the possible mode of action underlying neuroprotective effects of exercise are unknown and need to be elucidated. The main aim of this phase II trial is to assess whether progressive resistance training (PRT) and high intensity interval training (HIIT), can slow down neurodegeneration in people with PMS.MethodsIn a single-blinded phase II clinical trial with an extended baseline period, 60 people with PMS will be randomly assigned to PRT or HIIT. The participants should have had a relapse onset of MS with confirmed disease progression, however still ambulatory. The duration of the study is 48 weeks, consisting of 16 weeks baseline period (no intervention), 16 weeks intervention and 16 weeks follow-up. Patient-tailored training will be performed 3 times per week for one hour in groups, led by an experienced physiotherapist. The primary outcome measure is neurodegeneration, measured as whole brain atrophy on magnetic resonance imaging (MRI). Secondary outcome parameters will include other biomarkers associated with neurodegeneration (i.e. regional brain atrophy, lesion load, white matter integrity, resting state functional connectivity, blood biomarkers (brain derived neurotrophic factor (BDNF) and serum neurofilament light (sNFL)), patient functioning (physical and cognitive) and cardiovascular risk factors.DiscussionBesides the primary outcome measures, this study will examine a large variety of biomarkers associated with neurodegeneration after an exercise intervention. Combining outcome parameters may help to elucidate the mode of action underlying neuroprotective effects of exercise.Trial registrationThis trial is prospectively registered at the Dutch Trial Registry (number NL8265, date 06-01-2020).

Cognitive reserve is a determinant of social and occupational attainment in patients with pediatric and adult onset multiple sclerosis

There is limited information on socio-professional attainment in pediatric-onset multiple sclerosis (POMS) compared with adult-onset MS (AOMS). To assess socio-professional outcomes in POMS and AOMS and variables influencing these outcomes. One-hundred-fifteen AOMS and 111 POMS patients underwent neuropsychological testing (Brief Repeatable Battery, Stroop test), assessment of cognitive reserve (CR) (education, National Adult reading Test -NART, Barratt Simplified Measure of Social Status), fatigue (Fatigue Severity Scale), depression (Montgomery-Åsberg Depression Rating Scale), socio-professional performance (Work and Social Adjustment Scale -WSAS). Prognostic factors were assessed using logistic and linear multivariable regression analyses. 34.5% of patients showed CI without significant differences between AOMS and POMS. Cognitively impaired patients were older (p=0.024), had higher EDSS scores (p=0.041) and lower IQ (p<0.001) compared with cognitively preserved patients. Better WSAS scores were associated with younger age (p=0.007), lower EDSS (p<0.001) and higher educational levels (p=0.001). Fourteen POMS (13%) and six AOMS (5%) achieved a lower educational level compared with their parents (p=0.06). POMS exhibiting a lower than expected educational level, had a lower median IQ compared with the remaining subjects (101 vs 106.5; p=0.03). Unemployment rate was predicted by higher disability (p=0.044) and lower educational levels (p<0.001). Occupational complexity was positively correlated to educational level (<0.001) and NART scores (<0.040). This study underscores the complex relationships between cognition and educational, socioeconomic and professional attainment in MS and supports a protective role of CR in both POMS and AOMS.

Clinical Characteristics and Disability Progression of Early- and Late-Onset Multiple Sclerosis Compared to Adult-Onset Multiple Sclerosis.

Background: Compared to the adult onset of multiple sclerosis (AOMS), both early-onset (EOMS) and late-onset (LOMS) are much less frequent, but are often under- or misdiagnosed. The aims of the present study were: 1. To compare demographic and clinical features of individuals with EOMS, AOMS and LOMS, and 2. To identify predictors for disability progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS). Method: Data were taken from the Isfahan Hakim MS database. Cases were classified as EOMS (MS onset 18 years), LOMS (MS onset >50 years) and AOMS (MS >18 and 50 years). Patients’ demographic and clinical (initial symptoms; course of disease; disease patterns from MRI; disease progress) information were gathered and assessed. Kaplan–Meier and Cox proportional hazard regressions were conducted to determine differences between the three groups in the time lapse in conversion from relapsing remitting MS to secondary progressive MS. Results: A total of 2627 MS cases were assessed; of these 127 were EOMS, 84 LOMS and 2416 AOMS. The mean age of those with EOMS was 14.5 years; key symptoms were visual impairments, brain stem dysfunction, sensory disturbances and motor dysfunctions. On average, 24.6 years after disease onset, 14.2% with relapsing remitting MS (RRMS) were diagnosed with secondary progressive MS (SPMS). The key predictor variable was a higher Expanded Disability Status Scale (EDSS) score at disease onset. Compared to individuals with AOMS and LOMS, those with EOMS more often had one or two relapses in the first two years, and more often gadolinium-enhancing brain lesions. For individuals with AOMS, mean age was 29.4 years; key symptoms were sensory disturbances, motor dysfunctions and visual impairments. On average, 20.5 years after disease onset, 15.6% with RRMS progressed to SPMS. The key predictors at disease onset were: a higher EDSS score, younger age, a shorter inter-attack interval and spinal lesions. Compared to individuals with EOMS and LOMS, individuals with AOMS more often had either no or three and more relapses in the first two years. For individuals with LOMS, mean age was 53.8 years; key symptoms were motor dysfunctions, sensory disturbances and visual impairments. On average, 14 years after disease onset, 25.3% with RRMS switched to an SPMS. The key predictors at disease onset were: occurrence of spinal lesions and spinal gadolinium-enhancement. Compared to individuals with EOMS and AOMS, individuals with LOMS more often had no relapses in the first two years, and higher EDSS scores at disease onset and at follow-up. Conclusion: Among a large sample of MS sufferers, cases with early onset and late onset are observable. Individuals with early, adult and late onset MS each display distinct features which should be taken in consideration in their treatment.

Evidence of an increased prevalence of multiple sclerosis: a population-based study of Tehran registry during 1999\u20132018

BackgroundThe epidemiological characteristics of multiple sclerosis (MS) have been investigated in various studies, which have revealed that the prevalence of MS varies across countries. The present study was conducted to investigate the longitudinal prevalence of MS in Tehran, Iran.MethodsThe present population-based study was conducted in Tehran, the capital of Iran from 1999 to 2018 based on the annual report data provided by the Iranian MS Society (IMSS) registry system. The age-standardized and crude prevalence were estimated using population data presented by the Statistical Centre of Iran.ResultsA total of 21,580 MS cases were registered and included in the analysis. Among the participant patients, 24.99% (5393) and 75.01% (16,187) of cases were male and female, respectively. The mean age of MS onset was 28.8 years (S.D: 8.7). The age-standardized prevalence (ASP) of MS increased from 73.7 (95%CI: 72.1–75.2) per 100,000 people in 2006 to 137.6 (95% CI: 135.7–139.5) per 100,000 people in 2018. The ASP of MS in 2018 was estimated to be 67.9 (95%CI: 66.0–69.8) and 207.3 (95%CI: 204.0–210.7) per 100,000 people among males and females, respectively. The age-standardized female-to-male ratio of MS ranged from 3.7 (in 2010) to 2.06 (in 2017).ConclusionThe findings of this study suggested that the prevalence of MS in Tehran province is relatively high, and the occurrence of the disease is more common in the age groups under 40 years as compared with older-aged groups. In line with reports provided for various regions of the world, the prevalence of MS was higher among women. Similarly, the findings of this study revealed that the female-to-male ratio was 2.14 in 2018.

Predicting onset of secondary-progressive multiple sclerosis using genetic and non-genetic factors.

Predicting the transition from relapsing-remitting (RR) to secondary-progressive (SP) multiple sclerosis (MS) from early in the disease course is challenging. To construct prediction models for SPMS using sociodemographic and self-reported clinical measures that would be available at/near MS onset, with specific considerations for MS genetic risk factors. We conducted a retrospective cross-sectional study based on 1295 white, non-Hispanic individuals. Cox proportional hazard prediction models were generated for three censored SPMS outcomes (ever transitioning, transitioning within 10years, and transitioning within 20years) using sociodemographic, comorbid health information, symptomatology, and other measures of early disease activity. HLADRB1*15:01 and HLA-A*02:01, as well as a genetic risk score, were iteratively considered in each model. We also explored the relationships for all 200MS risk variants located outside the major histocompatibility complex. Nomograms were generated for the final prediction models. An older age of MS onset and being male predicted a short latency to SPMS, while a longer interval between the first two relapses predicted a much longer latency. Comorbid conditions and onset symptomatology variably predicted the risk for transitioning to SPMS for each censored outcome. The most notable observation was that HLA-A*02:01, which confers decreased risk for MS, also contributed to decreased hazards for SPMS. These results have the potential to advance prognostication for a person with MS using information available at or near onset, potentially improving care and quality of life for those who live with MS.

Efficacy and Tolerability of Disease Modifying Therapies in Late Onset Multiple Sclerosis (2176)

Efficacy and Tolerability of Disease Modifying Therapies in Late Onset Multiple Sclerosis (2176)

Late Onset Multiple Sclerosis: an Epidemiologic Study from the First Brazilian MS Center (4625)

Late Onset Multiple Sclerosis: an Epidemiologic Study from the First Brazilian MS Center (4625)

A Retrospective Chart Review of the Safety and Tolerability in Ocrelizumab in Pediatric and Young-Adult Onset Multiple Sclerosis (4568)

A Retrospective Chart Review of the Safety and Tolerability in Ocrelizumab in Pediatric and Young-Adult Onset Multiple Sclerosis (4568)

PREDICTION OF MULTIPLE SCLEROSIS COURSE: RESULTS OF PROSPECTIVE STUDY

Background: The course of multiple sclerosis is variable and unpredictable. Despite considerable efforts and research over the decades, one of the major challenges for both neurologists and patients is still to determine the prognosis of multiple sclerosis as well as the factors and markers affecting its progression. Prospective studies can partially contribute to assessment of the factors predetermining the prognosis of the course of multiple sclerosis.&#x0D; Objective: To evaluate the factors affecting the course of multiple sclerosis according to a 5-year prospective dynamic observation.&#x0D; Materials and methods: 175 patients with multiple sclerosis were examined over a 5-year follow-up period. The methodology employed was as follows: statistical analysis by using Microsoft Excel for Windows and SPSS; standard descriptive statistics; calculation of Pearson's chi-square for categorical analysis; single-factor analysis of variance. The magnitude and directivity of the correlation dependence were estimated using the Spearman non-parametric correlation coefficient.&#x0D; Results: 175 patients with multiple sclerosis (123 women and 52 men) were examined over a 5-year follow-up period. Mean age of patients at the onset of multiple sclerosis was 28.46 ± 9.13 years; mean age at the time of diagnosis of the disease was 31.77 ± 9.28 years; the mean length of the disease was 15.48 ± 7.69 years prior the start of the observation. At the time of the patients’ status assessment in 2013, the Expanded Disability Status Scale value was 3.83 ± 1.68 scores and 4.21 ± 1.83 scores in 5 years. The degree of functional disability according to the Expanded Disability Status Scale baseline was statistically significant (p = 0.02). A single-factor analysis of variance showed that sex (p &lt;0.007) was of the highest significance for the degree of difference by the Expanded Disability Status Scale.&#x0D; Conclusions: According to results obtained, we can suggest the most influential factor for a patient's disability due to multiple sclerosis is sex. Men may develop multiple sclerosis at younger age, the disease in men progresses faster, thus, the degree of functional disability is higher compared with women.

MP48-16 COMPARATIVE EVALUATION OF WHITE MATTER DEMYELINATION BY MAGNETIC RESONANCE IMAGING AND NEUROGENIC VOIDING DYSFUNCTION IN A VIRAL MURINE MODEL OF MULTIPLE SCLEROSIS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (MP48)1 Apr 2020MP48-16 COMPARATIVE EVALUATION OF WHITE MATTER DEMYELINATION BY MAGNETIC RESONANCE IMAGING AND NEUROGENIC VOIDING DYSFUNCTION IN A VIRAL MURINE MODEL OF MULTIPLE SCLEROSIS Li Lu, Alison Xie, Natalie Serkova, and Anna Malykhina* Li LuLi Lu More articles by this author , Alison XieAlison Xie More articles by this author , Natalie SerkovaNatalie Serkova More articles by this author , and Anna Malykhina*Anna Malykhina* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000903.016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lower urinary tract symptoms (LUTS) are present in 70–80% of patients with multiple sclerosis (MS), having a negative effect on the quality of the individual’s life. In 10–15% of patients, neurogenic LUTS are present at the onset of MS when there may be only few lesions identified in the CNS. In this study, we aimed to establish if early white matter demyelination could be detected by MRI, and whether it could be associated with the first signs of neurogenic LUTS. METHODS: Adult mice were inoculated with A59 strain of mouse hepatitis virus (coronavirus-induced encephalomyelitis model, CIE). The level of neurodegeneration was assessed by the Clinical Symptom Score (CSS). MRI experiments were performed on a 9.4 Tesla/ 20-cm BioSpec MRI scanner. Bladder function was evaluated in vivo by a filter paper assay, and in vitro by detrusor contractility studies. RESULTS: The spines from control and CIE mice (CSS≤1-2, 10 wks) were subjected to a FLASH MRI ultra-high resolution sequence, and DTI-EPI protocols. The mean diffusivity (D) and fractional anisotropy (FA) parameters were used to assess the integrity and organization of the white matter. The representative T2 MRI and DTI images, and FA maps are included in Fig. 1. The D values were significantly reduced in CIE mice (5.36±0.21x10-4 mm2/s) in comparison to control (6.98±0.37x10-4 mm2/s, p≤0.01). The FA parameters were also significantly lower in CIE mice (0.39±0.02 vs 0.56±0.02 in control, p≤0.002). Micturition patterns in CIE mice were not significantly changed, but the differences were detected in the contractile responses of the detrusor to various stimuli. CONCLUSIONS: The early changes in D and FA parameters reflect the ongoing changes in white matter structural integrity of the spinal cord. These early signs of demyelination are associated with modified detrusor contractile responses, which likely reflect the early stage of neurogenic LUTS development. Source of Funding: The study was supported by the NIH/NIDDK grant DK121506 and Department of Surgery AEF grant. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e700-e701 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Li Lu More articles by this author Alison Xie More articles by this author Natalie Serkova More articles by this author Anna Malykhina* More articles by this author Expand All Advertisement PDF downloadLoading ...

Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset.

BackgroundAutoimmune thyroid disease (AITD) occurs in 40%–50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves’ Disease (GD).ObjectiveTo explore contributory factors for alemtuzumab-related AITD in pwMS.MethodsA retrospective patient chart review was performed.ResultsSixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% (n = 9), the majority (n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier (r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes (p < 0.01).ConclusionAlemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.