In the past decade, changes have occurred in the spectrum of multiple sclerosis courses. The natural history of multiple sclerosis appears milder from the first sign of demyelinating disease to the ...progressive course, probably as a result of an interplay between several factors including changes in the diagnostic criteria, changes in the epidemiology of multiple sclerosis, impact of early and appropriate disease-modifying treatment and improvement of the general state of health in the population. It has been suggested to regard incidental findings of demyelinating lesions in MRI in individuals without any history of clinical symptoms consistent with neurological dysfunction, so-called radiological isolated syndrome, as the initial course of multiple sclerosis. New diagnostic criteria have enabled the multiple sclerosis diagnosis in many patients at the first clinical demyelinating event, clinically isolated syndrome. The remaining patients with clinically isolated syndrome have a more benign prognosis, and for relapsing-remitting multiple sclerosis, the prognosis has become more favourable. Reduced disease activity in patients with relapsing-remitting multiple sclerosis can partly be ascribed to more efficacious new disease-modifying therapies but decrease in disease activity has also be seen in placebo-treated patients in clinical trials. This may be explained by several factors: change in the diagnostic criteria, more explicit inclusion criteria, exclusion of high-risk patients e.g. patients with co-morbidities, and more rigorous definitions of relapses and disease worsening. However, these factors also make the disease course in patients treated with disease-modifying therapies seem more favourable. In addition, change in the therapeutic target to stable disease (no evidence of disease activity = no relapses, no disease worsening and no MRI activity) could by itself change the course in relapsing-remitting multiple sclerosis. The effectiveness of disease-modifying drugs has reduced the transition from relapsing-remitting to secondary progressive multiple sclerosis. The concept of progressive multiple sclerosis has also evolved from two very distinct categories (primary progressive and secondary progressive multiple sclerosis) to a unified category of progressive multiple sclerosis, which can then be split into the categories of active or inactive. Also, an increasing tendency to treat progressive multiple sclerosis with disease-modifying therapies may have contributed to change the course in progressive multiple sclerosis. In conclusion, during the past decade the entire course of multiple sclerosis from the first sign of a demyelinating disorder through the progressive course appears to be milder due to a complex interplay of several factors.
To investigate demographic and clinical factors associated with employment in MS.
The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31st 2010. ...The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment.
After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing -remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed.
Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual 's needs in order to improve working ability among MS patients.
Identifying effective treatment combinations for MS patients failing standard therapy is an important goal. We report the results of a phase II open label baseline-to-treatment trial of a humanized ...monoclonal antibody against CD25 (daclizumab) in 10 multiple sclerosis patients with incomplete response to IFN-β therapy and high brain inflammatory and clinical disease activity. Daclizumab was very well tolerated and led to a 78% reduction in new contrast-enhancing lesions and to a significant improvement in several clinical outcome measures.
Objective:
To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients.
Methods:
Whole and sub-regional cerebellar volumes, brain volumes, ...T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores.
Results:
Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models.
Conclusion:
Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior–inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.
Background:
Epstein–Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS).
Objective:
To evaluate associations between EBV-specific humoral ...response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs).
Methods:
The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini–Hochberg–adjusted p-values < 0.05 were considered significant.
Results:
MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR (r = –0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR (r = –0.524, p = 0.001) and NAGM MTR (r = –0.308, p = 0.043). These associations were not present in HCs or SPMS patients.
Conclusion:
Greater EBV humoral response is associated with lower GM MTR changes and focal destructive lesion pathology in RRMS patients.
Predictive and prognostic biomarkers for multiple sclerosis (MS) remain a significant gap in MS diagnosis and treatment monitoring. Currently, there are no timely markers to diagnose the transition ...to secondary progressive MS (SPMS).
This study aims to evaluate the discriminatory potential of the High temperature requirement serine protease (HTRA1)/Macrophage migration inhibitory factor (MIF) cerebrospinal fluid (CSF) ratio in distinguishing relapsing-remitting (RRMS) patients from SPMS patients.
The MIF and HTRA1 CSF levels were determined using ELISA in healthy controls (n = 23), RRMS patients before (n = 22) and after 1 year of dimethyl fumarate treatment (n = 11), as well as in SPMS patients before (n = 11) and after 2 years of mitoxantrone treatment (n = 7). The ability of the HTRA1/MIF ratio to discriminate the different groups was determined using receiver operating curve (ROC) analyses.
The ratio was significantly increased in treatment naïve RRMS patients while decreased again in SPMS patients at baseline. Systemic administrated disease modifying treatment (DMT) only significantly affected the ratio in RRMS patients. ROC analysis demonstrated that the ratio could discriminate treatment naïve RRMS patients from SPMS patients with 91% sensitivity and 100% specificity.
The HTRA1/MIF ratio is a strong candidate as a MS biomarker for SPMS conversion.
•HTRA1/MIF ratio is a strong candidate as a biomarker for RRMS to SPMS conversion.•The HTRA1/MIF ratio, initially high in RRNMS, decreases with 1-year DMF treatment.•The HTRA1/MIF ratio decreases with disease progression to SPMS, indicating a shift from RRMS inflammation.•MTX treatment has limited impact on HTRA1/MIF CSF ratio in SPMS patients.•Combining HTRA1 and MIF improves prognostic accuracy over individual markers.
ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of ...case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.
This review provides a brief update of new research findings on the changing epidemiology, disease course, and prognosis of multiple sclerosis (MS).
Evidence not only continues to support the female ...predominance in incidence and prevalence of the disease but also supports an increase in incidence of MS in geographic areas that were previously considered to be low incidence for the disease.
An increased interest in population-based registries and databases will provide more valid epidemiological measures and observational studies conducted in well-defined study populations. Such studies are crucial for an accurate description of both changing prognosis of MS and differential characteristics of the various MS phenotypes.
The time to diagnosis of multiple sclerosis (MS) is of great importance for early treatment, thereby reducing the disability and burden of the disease. The purpose of this study was to determine the ...time from the onset of clinical symptoms to the diagnosis of MS and to evaluate the factors associated with a late diagnosis in Iranian MS patients.
The present cross-sectional study was conducted on patients with MS who were registered in the National MS Registry System of Iran (NMSRI).
Overall, 23291 MS patients registered in 18 provinces of Iran were included in this study. The mean (standard deviation) interval between the onset of the disease and diagnosis of MS was 13.42 (32.40) months, and the median was one month. The diagnostic interval of 41.6% of patients was less than one month, and 14.8% of them had a one-month time to diagnosis. Patients with an age of onset below 18 years and those diagnosed after the age of 50 years had a longer time to diagnosis (P<0.001). Patients with primary progressive MS (PPMS) had the longest time to diagnose and those with relapsing-remitting MS (RRMS) had the shortest time (P<0.001). The results of negative binominal regression showed that the average rate of delay in diagnosis in women was 12% less than that in men. The average delay in diagnosis in patients with a positive family history of MS was 23% more than that in others. The rate of delay in the diagnosis of patients with PPMS and secondary progressive MS was 2.22 and 1.66 times higher, respectively, compared with RRMS.
The findings of the present study revealed that more than half of the MS patients were diagnosed within a one-month interval from the symptom onset, which is an acceptable period. More attention should be paid to patients’ access to medical facilities and MS specialists.
•The mean time from clinical symptoms onset to diagnosis of MS was 13.42 months.•in cases registered in the National MS Registry of Iran.•More than half of the MS cases were diagnosed within one-month interval.•Age at symptoms onset, age at the time of diagnosis, male sex and type of MS.•were associated factors to a late diagnosis in Iranian MS subjects.
Diagnosis and Treatment of Multiple Sclerosis: A Review McGinley, Marisa P; Goldschmidt, Carolyn H; Rae-Grant, Alexander D
JAMA : the journal of the American Medical Association,
02/2021, Letnik:
325, Številka:
8
Journal Article
Recenzirano
IMPORTANCE: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects ...an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. OBSERVATIONS: MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging MRI T2 lesions), and laboratory findings (eg, cerebrospinal fluid–specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. CONCLUSIONS AND RELEVANCE: MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.
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