Trajectory of fatigue severity in natalizumab treated multiple sclerosis patients

Fatigue is one of the most debilitating symptoms in multiple sclerosis (MS). The aim of this study was to observe the severity of MS associated fatigue in a community-based sample of natalizumab (ntz) treated patients over one year. In 48 relapsing remitting MS patients (mean age = 38.3 years) fatigue was longitudinally measured with the Modified Fatigue Impact Scale (MFIS) at two time points. The primary analysis of differences in MFIS was performed using non-parametric Wilcoxon test for dependent variables. Mean total MFIS Score increased significantly from 32.6 ± 20.9 to 49.1 ± 20.0 over the observation period of 12 months (p < 0.001). 83% of patients remained clinically disease activity free (no relapse, no progression in the Expanded Disability Status Scale, EDSS) over the observation period of one year. Age, gender, disease duration, spinal involvement, Gd-enhancement, depressive symptoms and EDSS had no influence on fatigue levels as measured with MFIS. Severity of fatigue symptoms during ntz treatment might increase despite very low disease activity.     

The prevalence of migraine in multiple sclerosis (MS): A systematic review and meta-analysis

ObjectivesWe designed this systematic review to estimate pooled prevalence of migraine in patients with multiple sclerosis (MS).MethodsWe searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, google scholar and gray literature including references from identified studies, conference abstracts which were published up to December 2019.The search strategy included the MeSH and text words as ((Disorder, Migraine OR Disorders, Migraine Disorder OR Migraine OR Migraines, OR Migraine Headache OR Migraine Headaches) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).ResultsThe literature search found 2100 articles. After eliminating duplicates, 1500 articles remained. Eleven articles and twelve abstract conference papers were included for final analysis.A total of 11,372 MS cases and 2627 MS patients with migraine included in the analysis. The prevalence of migraine ranged from 2% to 67%.The pooled prevalence of migraine in included studies was 31% (95%CI: 22%–40%) (I² = 99.3%, p < 0.001). The pooled prevalence of migraine in different continents were significantly different (p < 0.001).The pooled prevalence was 24% in Asian countries, 43% in American countries, 25% in European countries and 43% in African countries.ConclusionThe results of this systematic review shows that the prevalence of migraine in MS patients is 31% while the prevalence differs significantly among residents of different continents.     

Incidence and prevalence of multiple sclerosis in southeastern Iran

Background

Based on data available, Iran is located in a low risk area for multiple sclerosis (MS). The objective of the current study is to determine the age and sex adjusted prevalence and incidence of MS in southeastern Iran.

Methods

This cross-sectional case register study was conducted from January to August 2010. Considering that MS affects people aged between 16 and 50 years, we intended to find the incidence and prevalence of MS during this age range. Since all cases in this area are referred to our university hospital for confirmation of diagnosis, misdiagnosis is rare. Population data, based on the censuses carried out in 1996 and 2006, were obtained from the Iranian Bureau of Statistics to determine the number of people at risk.

Results

Totally 206 patients were identified according to the McDonald criteria. In 2009 the age-adjusted prevalence and incidence rates of MS for 16–50 year-old adults were 13.96 and 2.67 per 100,000 persons, respectively. Based on those values; the female to male ratio was 2.18. Between 2006 and 2009, the incidence rates increased 2.4 and 2.7 times in women and men, respectively. In 2009, the prevalence rates among the age ranges of <15, 16–35, 36–50 and ≥51 years were 1.44, 14.34, 12.24 and 1.45 per 100,000 persons, respectively, and the relapsing-remitting type of MS was the most prevalent form (65.8%).

Conclusion

According to the Kurtzke geographical distribution, the authors conclude that the prevalence of MS in southeastern Iran is in the intermediate range, and the incidence rate is showing a faster growth rate, compared to previous years.     

Low back pain in patients with multiple sclerosis: A systematic review and the prevalence in a French multiple sclerosis population

PurposeThe prevalence and management of back pain in MS patients was assessed by a systematic review, and the results of a survey on the characteristics of low back pain in a sample of French MS patients are reported.MethodsA systematic search was conducted according to the PRISMA guidelines. The outcomes of interest included the prevalence of back pain, severity of pain and impact on daily activities. Moreover, the prevalence of low back pain and its consequences on daily living in a large French MS population were assessed.ResultsFourteen studies were included in the systematic review. The prevalence of back pain in MS patients ranged from 8.6 to 50%, but that of low back pain in particular ranged from 41.6 to 52.4%. Concerning the survey, 237 patients participated in the online questionnaire. The prevalence of low back pain in the French MS patients was 76.4%. The patients with chronic low back pain had more limitations in their daily life activities than those without chronic low back pain.ConclusionPatients with MS commonly suffer from low back pain, but it is still an underdiagnosed cause of pain that reduces one's ability to perform activities in daily life.     

Incidence of multiple sclerosis in Bagheria City, Sicily, Italy

We investigated the incidence of multiple sclerosis (MS) in a Sicilian community located a sea level. The study was a retrospective search for MS patients. Incidence was studied in the period from 1 January 1985 to 31 December 1994. We searched for definite MS patients, according to Poser's criteria, among the population resident in Bagheria (Palermo province). There were 25 subjects affected by MS, of which 20 were incident MS patients. The average annual incidence was 4.4 per 100 000 persons (n = 453 385 person-years). The incidence increased over time (1985–1989 = 3.5, 1990–1994 = 5.3). A parallel decrease of the interval between onset and diagnosis of MS was observed (1985–1989, 3.7 years, 95% CI = 1.6–7.3; 1990–1994, 1.9 years, 95% CI = 1.0–3.3). These results confirm that MS is frequent in Sicily. Received: 19 October 2000 / Accepted in revised form: 18 December 2000     

Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis

Abstract.Background: Natalizumab, a humanized monoclonal anti-adhesion molecule antibody, reduces the frequency of new gadolinium (Gd) enhancing lesions and relapses in multiple sclerosis (MS). Its effect on evolution of new Gd enhancing lesions to T1 hypointense lesions is unknown.Methods: 213 patients were randomized to receive 3 mg/kg or 6 mg/kg natalizumab or placebo monthly for 6 months and then followed for a further 6 months. A subset of patients who had one or more new gadolinium enhancing lesions from Month 0 to Month 6 and available electronic data were analysed. Each new Gd enhancing lesion that developed during treatment (months 1–6) was investigated for conversion to a new T1 hypointense lesion at month 12. Lesions were classified as large or small if their cross-sectional area was greater or less than 20mm². Because of the similarity of both doses of natalizumab on the frequency of new Gd enhancing lesions, the two natalizumab arms were combined in all analyses.Results: Compared with the placebo group, the natalizumab group exhibited significant decreases in: (i) the proportion of patients with new Gd enhancing lesions that evolved to T1-hypointense lesions (10/38 [26 %] versus 27/40 [68 %]; p < 0.01); (ii) the proportion of patients who developed large T1 hypointense lesions (2/38 [5 %] versus 16/40 [40 %]; p < 0.01); (iii) the proportion of new Gd enhancing lesions that became T1 hypointense (11/75 [15 %] versus 118/466 [25 %]; p = 0.045); (iv) the mean proportion per patient of new Gd enhancing lesions that converted to T1-hypointense lesions (0.15 versus 0.28; p = 0.005), and (v) the odds ratio (OR) of converting from Gd enhancing to T1-hypointense lesions (OR = 0.48; 95% CI = 0.24, 0.94, p = 0.031)).Conclusion: Natalizumab significantly suppresses the evolution of new Gd enhancing to T1-hypointense lesions. This may reflect several mechanisms including reduced cell migration across the blood brain barrier, reduced T cell activation within lesions, an inhibitory effect on subsequent axonal damage within the new central nervous system lesion, and a reduced likelihood of recurrent lesion inflammation.     

干扰素-β治疗复发-缓解型多发性硬化系统评价

目的评价干扰素-β(IFN-β)治疗复发-缓解型多发性硬化的有效性和安全性。方法检索Cochrane临床对照试验中心注册库、美国国立医学图书馆、荷兰医学文摘、CINAHL、LILACS、PEDRO、中国生物医学文献数据库、临床试验注册中心和世界卫生组织国际临床试验注册平台(检索截止时间:2014年6月);并通过阅读相关论文参考文献,联系参与IFN-β治疗多发性硬化临床试验的研究者和企业,进一步获取研究信息或未发表的数据。由两名评价人员独立筛选研究、提取研究信息和数据、评价偏倚风险。应用Review Manager软件(Version 5.3.3)进行Meta分析,GRADEpro软件评价研究设计和实施过程中的局限性(偏倚风险)、结果的不一致性和不精确性、证据的间接性和发表偏倚对主体证据质量的影响。结果共检索相关文献576篇,阅读标题和摘要后初步筛选出26项研究;进一步阅读全文后纳入5项研究(共2129例复发-缓解型多发性硬化患者:高剂量IFN-β组1076例、安慰剂组1053例)。所有纳入的研究均为IFN-β单药治疗且随访时间≥1年的随机双盲安慰剂对照平行临床试验。大多数研究存在方法学局限性,主要缺陷为随访偏倚风险较高,且数据分析未使用意向治疗原则,仅919例受试者(43.17%)的数据可用于分析随访2年时的主要结局。Meta分析显示,IFN-β可轻微减少随访2年时复发病例数(RR=0.810,95%CI:0.740~0.890;P=0.000)和残疾进展病例数(RR=0.700,95%CI:0.550~0.880;P=0.002);敏感性分析(最差情况的演示分析)显示,IFN-β治疗无效(RR=1.110,95%CI:0.730~1.680,P=0.620;RR=1.310,95%CI:0.600~2.890,P=0.500)。共1581例患者(74.26%)的数据可用于分析随访1年时至少复发1次的病例数(RR=0.740,95%CI:0.590~0.930;P=0.010),绝对危险降低率为13.24%,需治疗的病例数为8例,表明需要治疗8例患者才可防止1例在第1年内复发。但在年复发率方面,IFN-β治疗无效。IFN-β常导致注射部位局部反应、寒颤、发热、肌肉疼痛、流感样症状、头痛、血清丙氨酸转氨酶和天冬氨酸转氨酶水平升高等不良事件,但并不增加外周血淋巴细胞和中性粒细胞减少、抑郁、自杀行为或自杀观念的发生。结论高质量证据显示,IFN-β治疗复发-缓解型多发性硬化可轻微降低第1年内的复发病例数,但超过1年的疗效尚不能确定。目前尚无足够证据证明IFN-β在减少残疾进展病例数方面的疗效,尚待高质量的随机对照临床试验评价其长期有效性。     

Incidence of multiple sclerosis: a periodic or stable phenomenon

Summary For diseases of unknown aetiology, the question as to whether the incidence is constant or variable is very important. A study on multiple sclerosis in a defined northern area of the German Democratic Republic showed a prevalence of 68.6 and an incidence rate of 3.0. Retrospective and prospective investigations concerning an observation period of 22 years revealed cyclic periods (6–7 years) of high incidence rates (up to 4.5) interrupted by shorter intervals (4–5 years) with low rates (about 1.8). The differences (1963–1968 vs. 1969–1973, 1974–1978 vs. 1979–1983) are significant. In accordance with the findings of Kurtzke et al. on a cyclic outbreak of multiple sclerosis in the Faroes and Iceland, our results are considered to be a consequence of environmental factors, such as epidemic viral infections.     

Prevalence of multiple sclerosis (MS) in Iran: a systematic review and meta-analysis

Neurological Sciences - Prevalence of multiple sclerosis (MS) is increasing world-wide. Iran is not exception. As the prevalence reported differently in various provinces, we designed this...     

External memory aids for memory problems in people with multiple sclerosis: A systematic review

Approximately 40–60% of people with multiple sclerosis (MS) have memory problems, which adversely impact on their everyday functioning. Evidence supports the use of external memory aids in people with stroke and brain injury, and suggests they may reduce everyday memory problems in people with MS. Previous reviews of people with MS have only evaluated randomised trials; therefore this review included other methodologies. The aim was to assess the efficacy of external memory aids for people with MS for improving memory functioning, mood, quality of life, and coping strategies. Seven databases were systematically searched. Intervention studies that involved training in the use of external memory aids, e.g., personal digital assistants, with at least 75% of people with MS, were included. Based on study design, quality was rated with the SCED or PEDro scale. Nine studies involving 540 participants were included. One single case experimental design (mean of 8 on SCED scale) and eight group studies (mean of 5 on PEDro scale) were included. One study reported a significant treatment effect on subjective memory functioning, two on mood, and two on coping strategies. There is insufficient evidence to support or refute the effectiveness of external memory aids for improving memory function in people with MS.     

The psychology of fatigue in patients with multiple sclerosis: A review

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS), but it is difficult to define and measure. Today, MS-related fatigue is not fully understood, and evidence related to explanatory pathophysiological factors are conflicting. Here, we evaluate the contribution of psychological factors to MS-related fatigue. Insight into the possible underlying psychological mechanisms might help us to develop adequate psychological interventions and to improve the overall management of fatigue. Conceptual issues and the relationships between MS-related fatigue and mood, anxiety, cognition, personality, and cognitive-behavioral factors are discussed, and the implications for clinical practice and research are presented.     

Everyday memory measures in multiple sclerosis: a systematic review

ABSTRACT

Everyday memory is one of the most affected cognitive functions in multiple sclerosis (MS). Assessing everyday memory problems is crucial for monitoring the impact of memory deficits on individuals’ day-to-day lives and evaluating the effectiveness of interventions that aim to improve cognitive functions. The aim of this systematic review was to identify the research literature on everyday memory measures used with people with MS, describe the types of measures used, and summarise their psychometric properties. Empirical studies of cognitive function in MS using standardised everyday memory measures were included. Online databases (MEDLINE, PsycINFO, PsycARTICLES, Embase) and Google Scholar were searched. Forty-four studies met the inclusion criteria. A total of 12 measures were identified, with varied uses and administration methods. The majority of papers did not report any psychometric properties for MS populations. The few papers that did, reported that the measures have good reliability and appear to have good face, concurrent, and ecological validity, but these need to be evaluated further. This review presents researchers and clinicians with an overview of the various everyday memory measures used in studies with people with MS, to help them choose the appropriate measure for their evaluations.     

The prevalence of COVID-19 infection in patients with multiple sclerosis (MS): a systematic review and meta-analysis

Neurological Sciences - The prevalence of COVID-19 is different in studies conducted in different countries. The aim of this systematic review and meta-analysis is to estimate the pooled prevalence...     

The prevalence of osteoporosis/osteopenia in patients with multiple sclerosis (MS): a systematic review and meta-analysis

Neurological Sciences - The prevalence of osteoporosis is reported differently. We designed this systematic review and meta-analysis to estimate pooled prevalence of osteoporosis and osteopenia in...     

A prospective study of the incidence, prevalence and mortality of multiple sclerosis in Leeds

Objective: To establish the prospective incidence of multiple sclerosis and mortality rates of people with multiple sclerosis in Leeds Health Authority and an updated prevalence of multiple sclerosis on 31 October 1999. Methods A population based prevalence register established on 30 April 1996 was maintained by prospectively registering all new cases of multiple sclerosis, flagging all cases with the National Health Service Central Register for notification of deaths and by registering all new clinical events. General practitioners notified patients with multiple sclerosis moving into or out of the area. Results 136 incident cases were prospectively registered from 30 April 1996 living in Leeds Health Authority (with an estimated resident population of 728 840). 57 deaths were notified. 792 people with multiple sclerosis were identified living in Leeds on 31 October 1999. The mean annual incidence rate for the three-year period 1996–1998 was 6.1/10⁵ (95 % CI: 5.1–7.2). The sex ratio of incident cases was 2.3 to 1 women to men. On 31 October 1999 the prevalence of multiple sclerosis in the Leeds Health Authority was 108.7/10⁵ (95 % CI: 101.2–116.5). This compares with a prevalence of 97.3/10⁵ (95 % CI: 90.3 –104.7) on 30 April 1996. The prevalence of definite and probable multiple sclerosis was 93.3/10⁵ (95 % CI: 86.4–100.6) and of suspected multiple sclerosis was 15.4/10⁵ (95 % CI 12.7 –18.5). Crude annual mortality rates of people with multiple sclerosis for 1997 and 1998 were 1.9/10⁵ (95 % CI: 1.1 to 3.2) and 3.2/10⁵ (95 % CI: 2.0 to 4.7). Multiple sclerosis was noted as the underlying cause of death in 8 (14 %) cases. Conclusion The incidence of multiple sclerosis in the Leeds Health Authority is similar to that in the south of the United Kingdom. The difference in successive prevalence figures is less than that published in other serial studies. Multiple sclerosis was notified as the underlying cause of death in a minority of deaths in people with multiple sclerosis. Received: 5 December 2000, Received in revised form: 23 March 2001, Accepted: 10 July 2001     

Epidemiology of multiple sclerosis in Sicily

From epidemiological data obtained over more than 20 years by surveys conducted in different parts of Sicily, it is evident that Sicily is a high-risk area for multiple sclerosis (MS). This is in sharp contrast with the gradient hypothesis. High frequencies have been found in different parts of the island having different geoclimatic features, but at least two cities (Monreale and Enna) had had a prolonged Norman domination. This is in agreement with the hypothesis that MS originated in Northern Europe and spread around the world throughout the raids of the northern peoples. The increase in frequency estimated by follow-up and incidence studies is well established and is only in part linked to the improvement in diagnostic techniques. Finally, it is noteworthy that in the islands of Malta, a few sea miles away from Sicily, the MS prevalence rates are in the range of 4–8 cases per 100 000 persons. This occurrence represents a natural model to investigate MS etiology through analytic studies and genetic analyses.     

The effect of tDCS on the fatigue in patients with multiple sclerosis: A systematic review of randomized controlled clinical trials

IntroductionFatigue is one of the most common disabling symptoms in patients with multiple sclerosis (MS) which is present in 75% of these patients and is usually associated with functional disabilities. According to the literature, there is no general agreement on the effectiveness of the existing treatments for fatigue in patients with MS. As transcranial direct current stimulation (tDCS) is a relatively new method in the treatment of fatigue symptoms in patients with MS, the purpose of this study was to systematically review published evidence conducted to assess the effects of tDCS on fatigue in patients with MS.Material & methodsA thorough literature search of published articles was conducted from 1996 to 2019 in different databases including PubMed, Science Direct, OVID, Google Scholar, Cochrane Library, Scopus, Embase, ProQuest and web of science with keywords of “tDCS”, “multiple Sclerosis” and “Fatigue”. Results yielded 1017 studies, which after excluding articles based on duplication and title and abstract, 8 of them were selected for review in this study.ResultsThe results from the literature revealed that six studies indicated positive effects of tDCS stimulation on fatigue reduction. In four studies stimulation was over the right dorsolateral prefrontal cortex (DLPFC); in three studies stimulation placed over the whole body’s primary somatosensory cortex (S1); and in one study stimulation applied over the posterior parietal cortex. In most studies, no serious side effects were reported.ConclusionMost studies revealed that tDCS can reduce the adverse effects of MS-related fatigue in particular cognitive type. As follow-ups were either absent or short period, as well as the application of treatment protocols and measurement instruments were different, it was very difficult to draw strong conclusion on the effects of tDCS in patients with MS. However, further large scale studies with long term follow-up are still recommended.     

环孢菌素治疗用激素类药无效的多发性硬化

目的探讨环孢菌素（ＣｓＡ）治疗用激素类无效的多发性硬化（ＭＳ）的效果。方法对激素等治疗５个月以上病情无明显好转或仍在加重的１０例ＭＳ，用ＣｓＡ５ｍｇ·ｋｇ－１·ｄ－１，疗程至少２个月，然后根据病情逐渐减量，最后小剂量维持用药。统计各个治疗期及最后随访（６～３２个月后）的扩充致残量表（ＥＤＳＳ）评分和脑ＭＲＩ病灶数。结果激素治疗前后ＥＤＳＳ差异无显著性意义（Ｐ＞０．２０）；ＣｓＡ足量治疗使ＥＤＳＳ评分下降及脑ＭＲＩ病灶数减少（Ｐ＜０．０５）；最后随访ＥＤＳＳ评分进一步下降（Ｐ＜０．０１），其中４例复查了ＭＲＩ，３例病灶数进一步减少。ＣｓＡ治疗未见严重毒副作用。结论ＣｓＡ可治疗用激素类无效的ＭＳ。     

The protein composition of myelin in multiple sclerosis (MS) and orthochromatic leukodystrophy (OLD)

Summary In 4 cases of MS, in which the progression of disease differed, and in one case of infantile OLD the proteins of a homogenate and a myelin fraction with and without plaques were separated electrophoretically with polyacrylamide gels in a buffer system of phenol/formic acid/water. The relation of proteolipid protein to basic protein was estimated planimetrically and compared with control cases.In myelin from plaque material of chronic running MS cases an average decrease of 41% in basic protein was observed, while in an acute progressing case no obvious alterations could be discerned. Myelin from apparently normal MS white matter showed an average decrease of 13% in basic protein. The results of the OLD case were similar to those obtained from the chronic MS cases. The decrease of basic protein (chronic MS, OLD) was markedly more in the homogenate fraction than in the purified myelin. In a control case with autolytic alterations (autopsy after 24 hours) the content of basic protein was also diminished.Our findings indicate that the reduction of basic protein in myelin is a non-specific effect in demyelinating diseases.Presented in part at the Third International Meeting of the International Society for Neurochemistry, July 5–9th, 1971, Budapest.Supported by Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 33), Stiftung Volkswagenwerk, and Forschungsmittel des Landes Niedersachsen.