Clinical Course Of Multiple Sclerosis Research Articles

Highly active multiple sclerosis: options for monoclonal antibody therapy

The clinical course of multiple sclerosis (MS) is characterized by great variability. 'Aggressive' MS, a concept used in the last 10 years, is associated with atypical course of the disease, which is manifested by more frequent exacerbations, the rapid increase in disability and pronounced signs of radiological activity according to MRI. The review presents data on the effectiveness of three monoclonal antibody drugs - natalizumab, alemtuzumab and ocrelizumab. In addition, updated data on the safety of monoclonal antibodies are presented to help the physician make a balanced choice of a drug and therapy strategy.

Highly active multiple sclerosis: options for monoclonal antibody therapy

The clinical course of multiple sclerosis (MS) is characterized by great variability. 'Aggressive' MS, a concept used in the last 10 years, is associated with atypical course of the disease, which is manifested by more frequent exacerbations, the rapid increase in disability and pronounced signs of radiological activity according to MRI. The review presents data on the effectiveness of three monoclonal antibody drugs - natalizumab, alemtuzumab and ocrelizumab. In addition, updated data on the safety of monoclonal antibodies are presented to help the physician make a balanced choice of a drug and therapy strategy.

A comprehensive review on the treatment approaches of multiple sclerosis: currently and in the future.

Multiple sclerosis (MS) is a chronic and autoimmune disease of the central nervous system (CNS), mainly characterized by inflammatory demyelination, which manifests as relapses and diffuse damage and brain volume loss, both accounting for neurodegeneration, and therefore, physical disability. MS typically affects young adults and is commonly diagnosed in the early years by acute relapses, which then followed through partial or complete remission period. The clinical course of MS is characterized as four major classifications, including relapsing-remitting (RRMS), primary progressive (PPMS), progressive relapsing (PRMS), and secondary progressive (SPMS). This review provides comprehensive overview of the current treatments and future innovative approaches in the treatment of MS. Currently, there is no definite cure for MS. The treatment of MS has mainly been based on the prescription of immunosuppressive and immune-modulating agents. However, a number of disease-modifying treatments (DMTs) have been designed that reduce the attack rate and delay progression and mainly target inflammation settings in these patients. Although remarkable advancements have occurred in the therapy of MS, the rate of progressive disability and early mortality is still worrisome. Recently, a monoclonal antibody (ocrelizumab) was demonstrated to be beneficial in a clinical trial of primary progressive MS. Furthermore, novel treatment strategies concentrating on the remyelination or neuroprotection are under evaluation. In spite of prosperous experiences in MS therapy, the future research, hopefully, will bring substantial improvements in the understanding and approaches of MS therapy.

Dietary Inflammatory Index and clinical course of multiple sclerosis.

This study aims at analyzing the association between the Dietary Inflammatory Index (DII) and the clinical condition of multiple sclerosis (MS) patients. It is a quantitative, cross-sectional analytical study that included 137 MS patients assisted at a reference center for MS treatment in the Brazilian northeast. Data was collated through a structured questionnaire and medical records consultation, also involving demographic, clinical, and nutritional variables. Clinical variables included the MS type, diagnosis and follow-up start dates, investigation of recent urinary tract symptoms, use of immunomodulatory, vitamin D supplementation, number of recent pulse therapies, relapse rate in the last 2 years, muscular strength assessment (MRC), disability degree (EDSS), and a gadolinium-enhanced magnetic resonance imaging (MRI) scan in the central white matter (CWM). The DII was calculated according to the Shivappa et al. methodology. There was no difference in any of the variables according to the DII (p > 0.05). The Dietary Inflammatory Index did not affect the clinical condition of individuals with multiple sclerosis.

The relationship between event-related potentials, stress perception and personality type in patients with multiple sclerosis without cognitive impairment: A pilot study.

The clinical course of multiple sclerosis (MS) can vary significantly among patients and is affected by exogenous and endogenous factors. Among these, stress and personality type have been gaining more attention. The aim of this study was to investigate the parameters of event-related potentials (ERPs) with regards to stress perception and personality type, as well as cognitive performance in MS patients. The study group consisted of 30 MS patients and 26 healthy controls. Auditory ERPs were performed in both groups, including an analysis of P300 and N200 response parameters. The Perceived Stress Scale (PSS) was used in the MS group to measure the perception of stress. The D-type Scale (DS14) scale was used to determine the features of Type D personality, characterized by social inhibition and negative affectivity. The score on the PSS corresponded with a moderate or high level of stress perception in 63% of MS patients, while 23% of patients presented with a Type D personality. P300 latencies were significantly longer (p = 0.001), N200 amplitudes were significantly higher (p = 0.004), and N200 latencies were longer in MS patients than in the controls. Strong positive correlations were found between N200 and P300 amplitudes, as well as between the DS14 and PSS results. Most MS patients experience moderate to severe stress. ERP abnormalities were found in MS patients who did not have overt cognitive impairment and showed correlations with stress levels and negative affectivity. Event-related potentials may be useful in assessing the influence of stress and emotions on the course of MS.

Recommendations and Extraction of Clinical Variables of Pediatric Multiple Sclerosis Using Common Data Elements.

The purpose of this article was to demonstrate the feasibility of using common data elements (CDEs) to search for information on the pediatric patient with multiple sclerosis (MS) and provide recommendations for future quality improvement and research in the use of CDEs for pediatric MS symptom management strategies Methods: The St. Louis Children's Hospital (SLCH), Washington University (WU) pediatrics data network was evaluated for use of CDEs identified from a database to identify variables in pediatric MS, including the key clinical features from the disease course of MS. The algorithms used were based on International Classification of Diseases, Ninth/Tenth Revision, codes and text keywords to identify pediatric patients with MS from a de-identified database. Data from a coordinating center of SLCH/WU pediatrics data network, which houses inpatient and outpatient records consisting of patients (N = 498 000), were identified, and detailed information regarding the clinical course of MS were located from the text of the medical records, including medications, presence of oligoclonal bands, year of diagnosis, and diagnosis code. There were 466 pediatric patients with MS, with a few also having the comorbid diagnosis of anxiety and depression. St. Louis Children's Hospital/WU pediatrics data network is one of the largest databases in the United States of detailed data, with the ability to query and validate clinical data for research on MS. Nurses and other healthcare professionals working with pediatric MS patients will benefit from having common disease identifiers for quality improvement, research, and practice. The increased knowledge of big data from SLCH/WU pediatrics data network has the potential to provide information for intervention and decision-making that can be personalized to the pediatric MS patient.

The Role of Vitamin D in Multiple Sclerosis: Biology and Biochemistry, Epidemiology and Potential Roles in Treatment.

Multiple sclerosis (MS) is a progressive, demyelinating condition of the central nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function. Of the various environmental and behavioural risk factors identified as playing a role in MS onset and progression, perhaps none has been as consistent as vitamin D. In this review, we will endeavour to present a general background on the role of vitamin D in human health and particularly in MS, as well as the substantial epidemiological evidence in support of vitamin D's role in MS. Initially identified via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin D has since been demonstrated to have a strong and consistent inverse association with MS risk and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25- hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have lower levels of 25(OH)D than other cases with less active disease. These case-control and crosssectional study results led the way to cohort studies which indicated significant inverse associations between serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational evidence have been the impetus for completed and ongoing randomised trials of vitamin D supplementation, alone or in addition to standard immunomodulatory medications, as an intervention in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin D has been demonstrated to interact with a variety of other risk factors, from genetic predictors like HLA-DR1 genotype to behavioural factors like smoking. There is an abundance of epidemiological evidence, both direct and indirect, as well as significant biological plausibility substantiating a role for vitamin D in the onset and progression of multiple sclerosis.

Sun Exposure across the Life Course Significantly Modulates Early Multiple Sclerosis Clinical Course.

Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

Clinical Course of Multiple Sclerosis.

The 1996 originally established multiple sclerosis (MS) subtypes, based solely on clinical impression and consensus, were revised in 2013 to review potential imaging and biological correlates and to reflect recently identified clinical aspects of MS. As a result, potential new disease phenotypes, radiologically isolated syndrome, and clinically isolated syndrome were considered along with the addition of two new descriptor subtypes: activity and progression applied to relapsing remitting and progressive MS phenotypes. In this way, the description of an individual patient's disease course is refined and provides temporal information about the ongoing disease process. There is still a lack of imaging and biological markers that would distinguish MS phenotypes and prognosticate the disease course on an individual patient's level, creating a pressing need for large collaborative research efforts in this field.

Americas Committee for Treatment and Research in Multiple Sclerosis Forum 2017: Environmental factors, genetics, and epigenetics in MS susceptibility and clinical course

The Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2017 brought together a multidisciplinary team of basic and clinical researchers to discuss the impact of environmental, genetic, and epigenetic factors on multiple sclerosis (MS) susceptibility and clinical course. The series of articles in this special edition reflect the breadth and depth of the topics that were discussed.

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis.

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.

Common genetic variation within miR-146a predicts disease onset and relapse in multiple sclerosis.

Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.

Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study.

To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort. We included newly diagnosed patients (2010-2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch. The study cohort included 2,076 patients. Data on comorbidities were available for 1,877/2,076 patients (90.4%). A total of 449/1,877 (23.9%) patients had at least 1 comorbidity at MS diagnosis. Age at diagnosis (odds ratio 1.05, 95% confidence interval [CI] 1.04-1.06; p < 0.001) was the only baseline factor independently related to the presence of comorbidities. Comorbidities were not significantly associated with the choice of the first disease-modifying treatment, but were significantly associated with higher risk to switch from the first treatment due to intolerance (hazard ratio 1.42, CI 1.07-1.87; p = 0.014). Association of comorbidities with risk of switching for intolerance was significantly heterogeneous among treatments (interferon β, glatiramer acetate, natalizumab, or fingolimod; interaction test, p = 0.04). Comorbidities at diagnosis should be taken into account at the first treatment choice because they are associated with lower persistence on treatment.

Clinical course of multiple sclerosis in Japanese patients treated with glatiramer acetate

Background: Although glatiramer acetate (GA) has been used in Western countries for treating patients with multiple sclerosis (MS) for more than 20 years, it was introduced in Japan only one year back.

Clinical course of multiple sclerosis after a therapy optimization to high-dose subcutaneous interferon β-1A: An observational study orca in the Czech Republic and Slovakia

Clinical course of multiple sclerosis after a therapy optimization to high-dose subcutaneous interferon β-1A: An observational study orca in the Czech Republic and Slovakia

CLINICAL CASE OF MENTAL DISORDERS IN THE DEBUTOF MULTIPLE SCLEROSIS

In a course of multiple sclerosis neurologic deficit could be overshadowed by psychotic signs such as catatonia, depression and dementia. Thus, ignoring these clinical manifestations can pre- vent early diagnosis of multiple sclerosis. Subsequently, an appropriate treatment will be delayed. In our article we report a case of multiple sclerisos in patient presented initially with catatonia, depression and dementia. Psychiatric, neurological, MRI picture and treatment impact thoroughly throughout the whole observation period are described. This case illustrates that catatonia can be dominating feature in the clinical course of multiple sclerosis and can overshadow other neurologic signs.

P381 Event-related potentials and personality type in patients with multiple sclerosis

Objectives The clinical course of multiple sclerosis (MS) can vary significantly among patients and is affected by many factors. Among these, psychoaffective aspects, including the type of personality, have been recently gaining attention. The aim of our study was to investigate the parameters of event-related potentials (ERP) with regards to personality type in MS patients. Methods 30 relapsing-remitting MS patients (26 women and 4 men, mean age 34.9 years) and 26 healthy, age- and gender-matched controls were included in the study. All the patients were being treated with disease-modifying agents (interferon beta or glatiramer acetate) and presented with mild degree of disability (up to 3.0 in Expanded Disability Status Scale) All MS patients and controls underwent auditory ERP with the assessment of N200 and P300 components. D-type Scale (DS 14) was performed in the patients to determine the features of type D personality, characterized by social inhibition and negative affectivity. Relationships were searched between ERP parameters and DS 14 results, using v.10 of STATISTICA statistical software. Results P300 and N200 latencies were significantly longer ( p p R = 0.53, p R = −0.28, p Conclusions MS patients presented with abnormalities of ERP in comparison with the controls. ERP parameters showed significant relationships with features of D-type personality, including negative affectivity.

Can pharmacological manipulation of LTP favor the effects of motor rehabilitation in multiple sclerosis?

Background: Synaptic plasticity, the basic mechanism of clinical recovery after brain lesion, can also remarkably influence the clinical course of multiple sclerosis (MS). Physical rehabilitation represents the main treatment option to promote synaptic long-term potentiation (LTP) and to enhance spontaneous recovery of neurological deficits. Objectives: To overview the role of pharmacological treatment and physical rehabilitation in modulating LTP and enhancing clinical recovery in MS. Results: Drug-induced LTP enhancement can be effectively used to promote functional recovery, alone or combined with rehabilitation. Also, as inflammatory cytokines alter synaptic transmission and plasticity in MS, pharmacological resolution of inflammation can positively influence clinical recovery. Finally, physical exercise could be an independent factor able to preserve or enhance LTP reserve both influencing signaling pathways involved in plasticity induction and maintenance, and decreasing inflammation. Future directions: Better knowledge of LTP determinants may be useful to design specific strategies to promote recovery after a relapse and to reduce the progressive neurological deterioration in MS patients.

Pregnancy in Multiple Sclerosis: A Portuguese cohort study

BackgroundPregnancy in Multiple Sclerosis (MS) has been a controversial issue, without international standardized treatment recommendations. The goal of our study was to evaluate the clinical course of MS during pregnancy and the respective therapeutic options, obstetrical outcomes and breastfeeding data. MethodsThis was a retrospective study including women with a diagnosis of relapsing-remitting MS at least one year before pregnancy. Three periods were evaluated: one year prior to pregnancy, pregnancy and one year postpartum. Information acquired included demographic and disease activity data, treatment options, and obstetrical and breastfeeding data. ResultsFrom a cohort of 1134 patients and 777 women, we included 127 pregnancies in 97 women (111 deliveries of a live infant, 11 spontaneous abortions, 3 fetal deaths and 2 voluntary abortions). The annualized relapse rate (ARR) decreased during pregnancy, mainly in the third trimester (prior to pregnancy 0.6 ± 0.8 vs. during pregnancy 0.3 ± 0.6, p = 0.006). There were no significant changes in the ARR in the year after delivery compared to baseline (0.6 ± 0.8 vs. 0.6 ± 0.8, p = 0.895). Patients with relapses in the postpartum period had a shorter disease duration at conception (5.4 ± 3.9 vs. 7.4 ± 4.7; p = 0.029) and breastfed less (53.5% vs. 72.1%, p = 0.046). In the multivariate analysis, relapses during pregnancy predicted postpartum relapses (OR = 4.9, p < 0.005). Neither the previous use of disease modifying therapy (DMT), given to 80.2% of women, nor breastfeeding, caesarean delivery (CD) or epidural analgesia (EA) had an impact on the presence of postpartum relapses. Compared to baseline, the Expanded Disability Status Scale (EDSS) increased in pregnancy and the postpartum period (1.6 ± 0.7 vs. 1.7 ± 0.9 vs. 2.1 ± 1.0, p < 0.001). CD was performed in 43.3% of patients, mainly because of fetal-pelvic incompatibility (35.7%) and EA was performed in 63.9%. The most frequent complications were restriction of fetal growth (4.5%) and gestational diabetes mellitus (3.6%). Concerning newborns, 6.4% had birth asphyxia and 6.1% low birth weight. No malformations were registered. ConclusionDespite a reduction in the relapse rate during pregnancy, the presence of relapses during pregnancy predicted postpartum relapses, with impact on disability. DMT appeared to have no influence on clinical or obstetrical outcome. MS did not have a deleterious effect on the pregnancy course. CD and EA were safe procedures, with a tendency towards CD in MS patients, compared to Portuguese women in general. Breastfeeding did not influence MS activity.

Multiple sclerosis - etiology and diagnostic potential.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.