OBJECTIVETo assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis.
...METHODSUsing peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed.
RESULTSIn DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses.
CONCLUSIONSDMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4 and CD8 T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients.
TRIAL REGISTRATION NUMBERSEUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770.
Unlike cigarette smoking, environmental tobacco smoke (ETS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression.
We ...systematically reviewed the association between ETS and the risk of onset and/or progression of MS.
We systematically screened MedLine/PubMed, Science Direct, LILACs, and SciELO searching for publications between January 1st, 2010, and July 5, 2021, with the following keywords: "multiple sclerosis and smoking"; "multiple sclerosis and passive smoking"; "multiple sclerosis and secondhand smoking".
Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of ETS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between ETS and MS development, and one study that did not find a significant association between ETS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between ETS and MS. Seven observational studies reported higher odds of MS onset when associated with ETS. Four observational studies did not show a relationship between ETS and MS onset or progression.
Most articles showed a positive association between ETS exposure and the risk of developing MS. On the other hand, an association between ETS and a higher risk for MS progression could not be established.
Introduction
The long-term safety of dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly Caucasian patients. The present interim analysis ...aimed to evaluate the 72-week safety of DMF in Japanese patients with RRMS.
Methods
Safety data of Japanese subjects enrolled in the 24-week randomised, double-blind, placebo-controlled APEX study (Part I) and its following open-label extension (Part II) were analysed at 72 weeks from the beginning of Part I. In Part I, subjects were randomised to DMF treatment or matching placebo while all subjects received DMF treatment during Part II. Adverse events (AEs) reported throughout the study period were recorded.
Results
Overall, 109 Japanese subjects completed 72 weeks of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively, in the DMF group compared with 84% and 18%, respectively, in the placebo group at 24 weeks. Common AEs (at least 5%) reported with treatment included nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash, headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). AEs led to discontinuation of DMF in 5% of patients and included MS relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an initial decrease from baseline of 17% in the DMF group at week 24, the mean lymphocyte counts stabilised and were maintained until week 72. No opportunistic/serious infections nor malignancies were reported with DMF treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs were similar between the DMF and the placebo groups.
Conclusion
The 72-week safety profile of DMF in Japanese patients with RRMS was consistent with previous studies that enrolled mostly Caucasian patients, with a lower incidence of flushing and related symptoms and a lower reduction in the lymphocyte count compared with previous reports.
Trial Registration
ClinicalTrials.gov identifier NCT01838668.
Funding
Biogen Japan Ltd.
The aim of the present study was to assess the prevalence of symptoms of temporomandibular disorders (TMD) in patients with the relapsing-remitting form of multiple sclerosis (MS), the relationship ...between TMD and the severity of MS, and the presence of TMD symptoms in the evaluated groups. Sixty individuals were evaluated: 30 patients diagnosed with relapsing-remitting MS and 30 control individuals matched for gender and age range with no neurologic pathology. In order to investigate the TMD symptoms, the questionnaires of the EACD (European Academy of Craniomandibular Disorders) and the RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders), both validated for TMD research, were administered. To assess the extent of disability produced by MS, the Expanded Disability Status Scale (EDSS) was used. The prevalence of TMD symptoms in patients with MS was 56.7% versus 16.7% for the control group, with a statistically significant difference between the groups (p=0.0016). No correlation was found between the severity of MS and the prevalence of TMD symptoms (Fisher's test, p=1.0).
Background
The use of dimethyl fumarate has not been reported in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis.
Objectives
The purpose of this study was to evaluate ...the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis.
Methods
APEX was a phase 3, multinational trial, which consisted of a 24-week, randomized (1:1), double-blind study where patients received dimethyl fumarate 240 mg or placebo twice daily, followed by an open-label extension where all patients received dimethyl fumarate 240 mg. The primary endpoints were the total number of new gadolinium-enhancing (Gd+) lesions in Weeks 12–24 (Part I) and long-term safety (Part II). This post-hoc subgroup analysis evaluated the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis (n=52) up to Week 72 (24 weeks Part I and 48 weeks Part II).
Results
Dimethyl fumarate reduced the mean total number of new gadolinium-enhancing lesions at Weeks 12–24 by 94% versus placebo; the number of patients who had a relapse over 24 weeks was reduced by 72%. Adverse events leading to discontinuation of the study drug were reported in 9% of patients receiving placebo/dimethyl fumarate and 4% of patients in dimethyl fumarate/dimethyl fumarate.
Conclusions
Dimethyl fumarate demonstrated sustained efficacy and acceptable tolerability in treatment-naïve Japanese patients with relapsing–remitting multiple sclerosis for 72 weeks.
Botulinum Neurotoxin Type A in Neurology: Update Orsini, Marco; Leite, Marco Antonio Araujo; Chung, Tae Mo ...
Neurology International,
09/2015, Letnik:
7, Številka:
2
Journal Article, Book Review
Recenzirano
Odprti dostop
This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to ...neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.
Abstract Risk factors for development of multiple sclerosis (MS) are still a matter of debate. Latitude gradient, vitamin D deficiency and season of birth are among the most investigated ...environmental factors associated with the disease. Several international studies suggest that birth in spring is a substantial risk factor for MS. We investigated the season of birth as a potential risk for MS in different geographical regions of Brazil. We conducted a cross-sectional retrospective study with 2257 clinically definite MS patients enrolled in 13 Brazilian MS clinics in the south, southeast, and northeast regions of Brazil. Demographic and clinical data relating to date of birth and clinical features of the disease were collected and analysed, and subsequently compared with birth date among the general Brazilian population. The distribution of date of birth of MS patients showed an increase in spring and a decrease in autumn, with no difference being observed in the other seasons. In conclusion, season of birth is a probable risk factor for MS in most parts of Brazil. These findings may be related to the role that vitamin D plays in MS pathogenesis.
Highlights • An integrative look at our systems of care during the Zika virus epidemics is timely pointed out. • The ICF as a framework to support families and organize research on Zika virus-related ...disabilities. • A discussion on potential developmental outcomes in children born with microcephaly due to Zika virus is presented.
Purpose: Children with cerebral palsy (CP) may present varied ophthalmological problems. Paradoxically, however, investigation of visual function and possible related disorders is not routinely ...conducted in this population during medical consultations.
Method: This paper proposes a simple, practical guide for assessing vision and ocular motricity in children with CP. One-hundred and twenty-three patients (mean age: 8.4 years ± 2.3) from the Sarah Network of Rehabilitation Hospitals (Brasilia, Rio de Janeiro and São Luis units) were studied. Various parameters were investigated (smooth pursuit movements, strabismus, visual acuity, visual field, visuospatial neglect and nystagmus) using the following assessment tools: adapted smooth pursuit test for ocular motricity; Snellen test for visual acuity; confrontation method for visual field; cancellation test (star test) for visual neglect; and cover test for strabismus. Nystagmus was assessed based on patient observation.
Results: Eighty-one children completed all the evaluations. Among these, 38 (47%) had no visual problems (hemiplegia 60.5%; diplegia 41.4%; triplegia 12.5%; mixed tetraplegic 33.3%); 23 had difficulties in one of the tested items; and 20 had problems in two or more areas of vision.
Conclusions: Visual and oculomotor tests are of significant importance in children with CP and provide relevant information for creating a rehabilitation programme aimed at the individual as a whole.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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