Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The ...association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.
To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.
Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.
The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).
Conversion to objectively defined secondary progressive MS.
Of the 1555 patients, 1123 were female (mean baseline age, 35 years SD, 10). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% 49 of 407 vs 27% 58 of 213; median follow-up, 7.6 years IQR, 5.8-9.6), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% 6 of 85 vs 32% 56 of 174; median follow-up, 4.5 years IQR, 4.3-5.1); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% 16 of 82 vs 38% 62 of 164; median follow-up, 4.9 years IQR, 4.4-5.8); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% 4 of 44 vs 25% 23 of 92; median follow-up, 7.4 years IQR, 6.0-8.6). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% 16 of 235 vs 12% 46 of 380; median follow-up, 5.8 years IQR, 4.7-8.0). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% 4 of 120 vs 6% 2 of 38; median follow-up, 13.4 years IQR, 11-18.1). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% 25 of 307 vs 14% 46 of 331, median follow-up, 5.3 years IQR, 4.6-6.1).
Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.
•Description of electromagnetic fields and evaluation of its possible effects on biological systems.•The association between the electromagnetic field and neurodegenerative diseases.•Experimental and ...clinical studies on the electromagnetic field.
In the modern world, people are exposed to electromagnetic fields (EMFs) as part of their daily lives; the important question is “What is the effect of EMFs on human health?” Most previous studies are epidemiological, and we still do not have concrete evidence of EMF pathophysiology. Several factors may lead to chemical, morphological, and electrical alterations in the nervous system in a direct or indirect way. It is reported that non-ionizing EMFs have effects on animals and cells. The changes they bring about in organic systems may cause oxidative stress, which is essential for the neurophysiological process; it is associated with increased oxidization in species, or a reduction in antioxidant defense systems. Severe oxidative stress can cause imbalances in reactive oxygen species, which may trigger neurodegeneration. This review aims to detail these changes. Special attention is paid to the current data regarding EMFs’ effects on neurological disease and associated symptoms, such as headache, sleep disturbances, and fatigue.
•People with MS have higher voice handicap.•Voice-related quality of life is worse in people with MS.•EDSS score, attack number age and gender have no significant effect on dysphonia severity index ...in MS.
Impairments in voice quality in Multiple Sclerosis (MS) have recently been investigated and different results were found. A voice-centered multidimensional assessment protocol with patient-reported outcome measures was conducted to evaluate all the aspects of the voice changes.
The study aimed to compare the objective, subjective, and perceptual measures of voice between the people with MS and the healthy control group.
A total of 128 participants, including 64 people with MS age, and gender-matched healthy controls were enrolled in the study. Subjective, objective, and auditory-perceptual voice assessments of the participants were performed. The auditory-perceptual evaluation was performed with GRBAS. The Dysphonia Severity index was computed for both groups. All the participants completed the Turkish version of The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (VRQoL).
Acoustic and aerodynamic parameters of voice were found significantly different for both males and females between the MS and control group. DSI was found significantly different for both males and females in the MS group compared to the control group (p<0.05). All components of the GRBAS scale were significantly higher in the MS group (p<0.001). Using a multivariate regression model, it was determined that age, gender, EDSS score, number of MS attacks, and disease duration did not affect the DSI. The overall VHI-10 score was higher in the MS group (median=1.0 range= 0–28) and lower in the control group (median=0 range= 0–4). The mean VRQoL was lower in the MS group (median=95 range= 62.5–100) than in controls (median=100 range= 85–100) (p<0.001).
Our results indicated that people with MS have significant differences in acoustic and aerodynamic parameters of voice compared to healthy individuals. A significant number of persons with MS are aware that their voice problem affects their quality of life. People with MS must be monitored for voice changes and a multidimensional voice assessment protocol should be implemented.
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Nutrition modulation can reduce multiple sclerosis (MS) related symptoms and fatigue severity. Mediterranean diet may be beneficial regarding anti-inflammatory components. However, previous studies ...are limited. This study aims to investigate the relationship between Mediterranean diet adherence and MS-related symptoms and fatigue severity.
One hundred and two adult MS patients were enrolled in this cross-sectional study. Dietary adherence was assessed using the Mediterranean diet assessment tool (MEDAS). MS-related symptoms were determined using the MS-related symptom checklist (MS-RS), and the fatigue severity scale (FSS) was applied. Linear regression models were established to assess predicted factors of MS-RS and FSS.
The mean age of the participants was 33.1 ± 9.81 years. Being female and having higher education degree was 71.6% and 60.8%, respectively. In the linear regression model, MEDAS were not associated with MS-RS but negatively associated with FSS scores. MS-RS scores were significantly higher among participants who consumed more than one serving of red meat or products per day. Those who consumed less than one serving of butter, margarine, or cream per day reported lower FSS scores. Some trend significances were shown to consume limited sweet and lower FSS scores. Likewise, MS-RS scores were lower in those ≥three serving/week intake of fish.
Following a Mediterranean-style diet should be encouraged to improve fatigue severity. Components, such as reduced consumption of red meat, saturated fatty acids, sweets and increased fish consumption, could be promising to reduce MS symptoms or fatigue severity. These findings should be proven with further intervention studies.
Behcet's disease, a multisystemic vascular inflammatory disorder of unknown origin, is relatively rare and central nervous system involvement is seen in 5% of affected individuals. This form of the ...disease, called as neurobehcet's disease (NB), can be misdiagnosed as multiple sclerosis (MS), a demyelinating disorder of central nervous system, so their differential diagnosis is important. In this study, to identify the parameters of electrophysiological testing that might be useful in their differential diagnosis, we performed evoked potentials (EPs) and electroneuromyography (ENMG) on patients with MS and NB, and on normal volunteers. A total of 95 persons, 55 MS patients, 20 NB patients and 20 normal volunteers between ages 31 and 55, were studied electrophysiologically. Visual evoked potential (VEP), brainstem auditory evoked potential (BAEP), posterior tibial somatosensory evoked potential (SEP) and nerve conduction and needle electromyography studies were performed on all patients and volunteers. All parameters of EPs were compared among the groups. The results of the BAEP and SEP studies did not show statistically significant difference between NB and MS. However, the VEP study indicated that the amplitude values of cortical VEP potentials (P100) in the NB and MS groups were lower than those of the normal group (p < 0.01), and that the amplitudes in the NB group were lower than for the MS group (p < 0.05). Therefore, P100 amplitude measured from peak to peak seems to be more reliable and thus should be used in the differential diagnosis of MS and NB.
The aim of this study is to validate the speech pathology-specific questionnaire for persons with Multiple Sclerosis (SMS) in Turkish.
A total of 218 participants were included in the study. The ...study group was composed of 104 persons diagnosed with MS, and the control group was 114 healthy participants without any neurological deficits. The translated version of the SMS was administered to all participants. Test-retest reliability, internal consistency, construct validity, floor and ceiling effects were investigated. Dysphagia in multiple sclerosis questionnaire (DYMUS) was used for criterion validity. Finally, sensitivity and specificity of the SMS-TR was calculated using a ROC curve analysis.
SMS-TR has an excellent internal consistency (Cronbach's alpha = 0.92). Item-total correlations range between 0.45 and 0.78. The intraclass correlation coefficient (ICC) obtained for the test-retest indicates a good level of reproducibility (ICC = 0.86). According to confirmatory factor analysis, the fit measures of the scale were found to be acceptable. A significant difference was found between the total SMS scores of the study group and the control group (20.6 ± 10.4 and 1.9 ± 2.8, P < 0.001, respectively). A statistically significant correlation was observed between SMS and DYMUS (r = 0.833, P < 0.001). There were no floor and ceiling effects found in the study group. According to the ROC curve analysis, the area under the curve of SMS-TR was 0.98. The optimal cut-off value was 8, with a sensitivity of 91.3% and a specificity of 95.6%.
SMS-TR is a valid and reliable patient-reported outcome measure suitable for the assessment of language, speech, and swallowing disorders in persons with MS. A score >8 is an indicator of language, speech, and swallowing pathology for persons.
Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on ...progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common in younger patients, relapsing-remitting disease course, and after a smaller change in disability, and was inflated by higher visit frequency. These results suggest that the disability outcomes based on 3-6-month confirmed disability progression overestimate the accumulation of permanent disability by up to 30%. This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapsing-remitting disease. Extension of the required confirmation period increases the persistence of progression events.
•During and after pulse therapy, the concentration of methylprednisolone in breast milk is quite low.•Absolute infant dose is below levels likely to cause harm.•Transfer of methylprednisolone from ...maternal serum to breast milk is low.•Intravenous methylprednisolone treatment has no adverse effects on infants in short term.
It is commonly known that women with multiple sclerosis (MS) have an increased risk for relapses during the post-partum period. High-dose IV methylprednisolone is the first-line treatment for acute relapses. Methylprednisolone is administered to lactating women although there is insufficient data as to the levels of concentration in breast milk and serum, and the calculated steroid exposure to infants.
The study aimed to measure the transfer of methylprednisolone into breast milk and the correlation of milk and serum methylprednisolone concentrations in breastfeeding MS patients during and after infusion therapy.
IV methylprednisolone pulse therapy was given to 12 lactating MS patients. Breast milk and maternal serum samples were obtained; before infusion, 30 minutes into the infusion, at the end of infusion and at the 1st, 2nd, 4th, 8th, 12th and 24th hours subsequently.
The highest level of methylprednisolone concentration in breast milk (2.09 μg/ml) and serum (6.09 μg/ml) was detected at the end of the infusion. According to the measurements recorded at the 1st, 2nd, 4th, 8th, 12th, and 24th hours after infusion, the concentrations showed a gradual decrease both breast milk and serum. The milk and serum methylprednisolone concentrations were below detection limits just before infusion and at the 24th hour after infusion. A highly significant correlation was found between breast milk and maternal serum levels. The absolute infant dose was calculated to be 69.50 μg/kg/day and the relative infant dose (RID) was 0.50%.
Results have shown that the transfer of methylprednisolone into breast milk seems to be low. Although, concentration levels may not seem to pose a threat to the infant, mothers can choose to wait 2 to 4 hours to further limit the level of exposure.
Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.
We identified all patients with ...relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).
The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).
The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.
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