Long-term effectiveness of glatiramer acetate in clinical practice conditions

Glatiramer acetate currently represents one of the main treatments for relapsing-remitting multiple sclerosis (RRMS). However, the information available about its long-term effect in clinical practice is still limited. Thus, this multicenter retrospective cohort study aimed to assess the long-term effectiveness of glatiramer acetate in this setting. The study population included RRMS patients treated with glatiramer acetate for at least 5 years after its marketing authorization and the primary endpoint was long-term clinical effectiveness, defined as absence of disability progression for at least five consecutive years. A total of 149 patients were included into the study, who had received glatiramer acetate for a mean of 6.9 ± 1.4 years (5 years, n = 149; 6 years, n = 112; 7 years, n = 63; 8 years, n = 32; 9 years, n = 21). More than 85% of patients remained free from disability progression through years 1 to 9 of glatiramer acetate treatment, and 75.2% showed absence of disability progression for at least five consecutive years. Expanded Disability Status Scale (EDSS) scores were maintained, with most patients showing stable/improved EDSS and 92.6% sustaining EDSS <6. Decreased annual relapse rates and increased proportion of relapse-free patients were maintained during the whole glatiramer acetate treatment compared to the year prior to its authorization (p < 0.001). The number of gadolinium-enhanced T1-weighted lesions also decreased from pre-glatiramer-acetate assessment to last follow-up whilst on glatiramer acetate (p < 0.05). In conclusion, administration of glatiramer acetate shows long-term clinical effectiveness for RRMS treatment; its effect under clinical practice conditions slowed disability progression and reduced relapse occurrence for up to 9 years.     

Developing tools to evaluate quality of care management for patients living with multiple sclerosis: An original French initiative

IntroductionAssessing the quality of care management for patients with a chronic disease such as multiple sclerosis (MS) is a major challenge for healthcare systems around the world. It needs to be carried out using tools that are recognized by professionals and patients alike, and should concern practices, systems, and scientific data. No such tools are currently available in Europe. The purpose of the present study was to develop indicators to contribute to assess the quality of care management for patients with MS in France.MethodsAn expert panel comprising 25 professionals from well known teams across France selected the indicators on the basis of consensus. In accordance with the Rand/UCLA Appropriateness Method, each expert had to agree with the recommendations, and there had to be agreement among the experts.ResultsThe expert panel selected 48 indicators representing seven domains of care management for patients with MS: physical and rehabilitation medicine, disease progression, access to care, magnetic resonance imaging (MRI) management, relapse management, management of disease-modifying treatments, and management of the symptoms of disability progression. Some of these quality indicators (notably pertaining to MRI management) had not previously been identified in the literature.ConclusionThese indicators may allow professionals to comprehensively assess and compare their practices and cooperation, thereby contributing to improve the quality of care management for patients with MS in France.     

东北地区204例多发性硬化患者临床特征分析

目的 总结东北地区多发性硬化(MS)的临床特点.方法 对204例MS患者的临床表现、病变部位、影像学特点、实验室检查及激素治疗进行分析总结.结果 (1)性别:男69例(33.82％),女135例(66.18％);发病年龄:20 ～40岁95例(46.57％).(2)起病形式:急性或亚急性为主(65.69％),25例患者(12.25％)首次发病前存在明显诱因.(3)常见症状:肢体无力为主(70.59％),尿便障碍56例(27.45％);以复发-缓解型多见.(4)脑脊液IgG增高占60.19％;脑干视、听觉诱发电位阳性率为69.77％;体感诱发电位阳性率为2.94％.(5)病灶部位:脑部异常73例(35.78％),脊髓异常53例(25.98％),脑与脊髓均有病灶78例(38.24％).(6)均无MS家族史,自身免疫性疾病史者8例,3例为产后发病.(7)150例患者接受激素治疗,并采用扩展残疾状态量表(Expanded disability status scale,EDSS)评价其疗效,有效率为78.67％.结论 我国北方地区MS患者仍以女性为多;发病年龄以20～40岁为主;临床特点表现为发病较晚、起病急,以复发-缓解型为主;大多数患者发病前无明显诱因;神经系统症状以肢体运动及感觉障碍为主,尿便障碍较常见;本组患者颅内病灶主要见于皮质下白质、侧脑室旁及半卵圆中心,小脑受累较少;脊髓病灶主要以颈段受累为主;激素冲击治疗对本组患者有较好疗效.     

105例多发性硬化临床特点及治疗分析

目的 探讨多发性硬化的临床发病特点及临床治疗疗效.方法 从2005-01至2010-10月间收治的多发性硬化患者105例为研究对象.结果 105例患者中以20-40岁女性多见,以急性、亚急性起病,以肢体无力为首发症状最常见,病变部位多以脑和脊髓多见,脑脊液蛋白升高、IgG增高及寡克隆区带阳性常见,核磁共振较计算机断层扫...     

Reversible cerebral vasoconstriction syndrome in association with fingolimod use

Background: Reversible cerebral vasoconstriction syndrome (RCVS), also known as Call-Fleming syndrome, is characterized by thunderclap headaches, non-aneurysmal segmental cerebral vasoconstriction seen on arteriogram, and spontaneously resolves within 12 weeks. Fingolimod has been reported to cause posterior reversible encephalopathy syndrome (PRES) and one case of RCVS. Objective: We report a case of RCVS possibly related to fingolimod use, and compare to cases of adverse outcomes in fingolimod use. Methods: This is a single observational study without controls; therefore, level of evidence is IV. A literature review in pubmed with keywords, fingolimod, vasospasm, RCVS, Call-Fleming, stroke, PRES and hemorrhage. Results: One case of RCVS on fingolimod in the post-partum period. Two other cases in the literature were found one with hemorrhagic encephalitis and the other critical vasospasm in the upper extremity associated with fingolimod 1.25 mg daily in the FREEDOMS II trial and TRANSFORMS study, respectively. Additionally, Novartis reports nine cases of PRES related to fingolimod use. Conclusion: Fingolimod has the potential to cause vasoconstriction however appears to be rare and more likely on doses higher than 0.5 mg daily. Fingolimod may be associated in RCVS and should be considered in patients with severe headache on fingolimod.     

The practice of clinical neuropsychology in Australia

Objective: This paper describes the development and practice of clinical neuropsychology in Australia. Method: Clinical Neuropsychology has shown rapid growth in Australia over the past three decades. Comprehensive and specialized training programs are producing high quality graduates who are employed in a broad range of settings or private practice. Results: Australia now has a substantial number of clinical neuropsychologists with specialist training. Whilst the majority of Australian clinical neuropsychologists still undertake assessment predominantly, there are growing opportunities for clinical neuropsychologists in rehabilitation and in a broad range of research contexts. Cultural issues relating to the assessment of Indigenous Australians and immigrants from many countries present significant challenges. Some major contributions have been made in the realms of test development and validation across various age groups. Australian clinical neuropsychologists are also contributing significantly to research in the fields of traumatic brain injury, aging and dementias, epilepsy, memory assessment, rehabilitation, substance abuse, and other psychiatric disorders. Conclusion: Expansion of roles of clinical neuropsychologists, in domains such as rehabilitation and research is seen as essential to underpin continuing growth of employment opportunities for the profession.     

损害大脑灰质的多发性硬化的临床和影像学特征

目的分析损害大脑灰质的多发性硬化病例的临床和MRI特点。方法收集2004年1月～2006年6月期间住院并经多发性硬化专科门诊进行临床和MRI动态观察确诊[采用McDonald(2001)诊断标准]的多发性硬化患者共54例,将其中13例损害大脑灰质的多发性硬化患者的临床和MRI资料进行回顾性对比分析。结果损害大脑灰质的多发性硬化病例13例,占多发性硬化总病例数的24%(13/54),其中5例初诊时根据脑CT报告误诊为多发性脑梗死,3例初诊时误诊为病毒性脑炎和脑病,5例首诊为多发性硬化的患者得益于多系列的脑MR扫描、VEP和脑脊液IgG指数的帮助;损害大脑灰质的多发性硬化患者症状、体征较重,复发次数多,预后较差;大脑灰质的损害主要在大脑深部灰质(丘脑和基底节)。结论初次诊断多发性硬化相当困难,建议使用McDonald(2001)诊断标准,并参考脑/脊髓功能MRI,诱发电位及脑脊液IgG指数/OB;多发性硬化损害大脑灰质可能与神经元变性有关。     

多发性硬化20例临床分析

目的 :探讨多发性硬化的临床症状及MRI对其诊断的价值和意义。方法 :综合分析 2 0例多发性硬化患者一般资料、MRI、脑脊液检查及治疗转归。结果 :多发性硬化好发于 10～ 4 0岁 ,女性多见 ,起病形式及临床症状多样 ,病程呈复发与缓解 ,MRI对多发性硬化病灶的发现率可达 10 0 %。糖皮质激素治疗有效 ,但随着病程的延长 ,复发次数的增多 ,激素治疗欠佳。结论 :根据临床特点、影像学检查、脑脊液及神经电生理检查可提高多发性硬化的确诊率     

Experience with fampridine in clinical practice: analysis of a possible marker of clinical response

Purpose of the study: Approximately 85% of patients with multiple sclerosis experience reduced mobility, which negatively affects quality of life. Fampridine is the first symptomatic treatment aimed at improving gait. We analyzed effectiveness and tolerance in clinical practice. We also sought a prevalent gait pattern in responders as a potential clinical response marker. Material and methods: Six-month prospective study of fampridine in patients with multiple sclerosis. Response was evaluated using the Timed 25-Foot Walk Test (T25FW) and the 12-Item Multiple Sclerosis Walking Scale (MSWS-12). Response was defined as increased gait speed (≥20%) and decreased MSWS-12 score (≥4 points). Results: Fifty-five patients (67.3% women; mean age, 51.7 [11.1] years) with a baseline Expanded Disability Status Scale (EDSS) score of 5.8. Gait pattern was paraparetic (40%), hemiparetic (21.8%) and ataxic (38.2%). Of all patients, 70.9% demonstrated clinical benefit based on response criteria established, at the 14-d follow-up, 61.8% at 3 months and 45.5% at 6 months. A similar response pattern was observed in the MSWS-12. A significant decrease in the mean (SD) EDSS score was observed in responders at 6 months (6.1 [0.9] vs. 5.64 [0.1], p < 0.05). Adverse effects were recorded in 50.9%, although most were mild-moderate and resolved completely. We did not identify a prevalent gait pattern among responders. After a washout period, some patients received fampridine a second time obtaining response recovery. Conclusions: In our patients’ cohort, fampridine proved clinical benefit, being safe and well tolerated in most cases. We did not identify a gait pattern that was predictive of clinical response.     

中国同心圆硬化72例临床特点分析

目的了解我国同心圆硬化患者的临床特点。方法检索维普电子期刊全文数据库1989年-2015年间收录的同心圆硬化病例报告文献,并分析所报道病例的临床特点。结果共纳入46个相关研究,包括72例患者,其中男性35例,女性37例,发病年龄最小为17岁,最大63岁,平均发病年龄为(37.88±9.85)岁。2例发病前有疫苗接种史,另2例发病前有感冒前驱感染史。53例(73.61%)患者以运动障碍为首发症状,19例以头痛、头晕或言语不利等为首发症状。52例患者进行了脑脊液检查,其中30例正常、5例脑脊液压力增高、13例脑脊液蛋白增高、10例脑脊液寡克隆区带(OB)阳性。同心圆硬化病灶累及部位最多见于额叶,其余累及部位还包括顶叶及半卵圆中心等。大多数均为多发病灶,仅3例为单发病灶。个别同心圆硬化可伴随甲状腺功能减退(2例)与周围神经损害(1例)。结论中国同心圆硬化以中青年常见,男女发病无明显差异,大多数无诱发因素,常见首发症状包括肢体障碍、头晕、头痛,实验室检查常无明显异常,脑脊液寡克隆区带出现率较低,诊断依赖于头部MRI。     

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT 03375177).MethodsThe eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset.ResultsA total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7–4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively).Conclusion3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.     

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España

IntroductionAlemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.     

PBL教学法在神经病学临床实习中的应用

目的 探讨基于问题的学习(PBL)教学模式在神经病学临床实习教学中的应用效果.方法 根据PBL教学理论,选取首都医科大学2008级五年制学生共76人作为研究对象,按班级分为实验组(n=38)和对照组(n=38),实验组采用PBL教学法,对照组采用传统教学法,采用比较两组学生的出科考试成绩以及问卷调查评价教学效果.结果 实验组的出科考试成绩(87.58±4.77)分明显优于对照组(82.08±4.24)分,差异有统计学意义(P＜0.01);实验组肯定“有利于激发你的学习兴趣”“有助于只是的理解和记忆”“提高自学能力”和“有助于培养分析解决问题的能力”4个方面人数明显高于对照组,差异均有统计学意义(P＜0.05).结论 在神经病学临床实习教学中应用PBL教学模式,不影响学生对基础知识、知识要点难点的掌握,有助于提高学生学习的积极性和主动性,促进其对知识的理解与掌握,有利于培养其临床思维能力,促进学生自我认识和成长综合素质水平的提高.     

Mitoxantrone for worsening multiple sclerosis: Tolerability,toxicity, adherence and efficacy in the clinical setting

Background

The treatment of worsening Multiple Sclerosis (MS) remains challenging. Mitoxantrone, an anthracyclines, is approved as a treatment for worsening MS. However, systematic analyses of its tolerability and effectiveness outside of controlled trials are few. Certain advantages, including easy application and simple monitoring, need to be balanced against its toxicity.

Objective

To study efficacy, tolerability and feasibility of mitoxantrone treatment in a regular clinical setting.

Methods

Retrospective analysis of data from 96 MS patients with worsening MS before, during, and after mitoxantrone. Specifically, we addressed adherence and reasons for deviations from the intended treatment schedule regarding tolerability and safety, and consequences of deviations on clinical efficacy.

Results

Schedule deviations were frequent. Only a third of patients received the intended cumulative dose. Hematological toxicity was generally mild and transient. In 7 patients, treatment was withheld because of impact on ventricular ejection fraction, in the absence of clinical symptoms of cardiac failure. No malignancies were observed. With respect to clinical benefit, most patients remained stable and the relapse rate decreased with mitoxantrone initiation in both relapsing and secondary MS patients (p < 0.0001). A possible modest non-significant dose-effect on annualized relapse rates was observed.

Conclusion

Mitoxantrone may be considered for treatment of refractory MS. Poor tolerability impacted adherence but dose-limiting safety events were rare. Mitoxantrone needs to be carefully assessed in light of recent data on risk of cardiotoxicity and leukemia.     

多发性硬化的MRI与临床

报告４６例多发性硬化（ＭＳ）患者的ＭＲＩ与临床资料。其中临床确诊者３９例，实验室支持确诊者４例，临床近似确诊者３例。ＭＲＩ阳性２９例（６３．０４％）。病灶分布依序为脑室周围、大脑半球、脑干、基底节、小脑、胼胝体及视神经；本组临床定位病灶９３个，ＭＲＩ显示病灶４９个，其中３７个病灶与临床相符，１２个属亚临床病灶。结果提示ＭＲＩ对发现ＭＳ病灶虽有很高的敏感性，但ＭＳ的诊断仍需结合临床。     

视神经脊髓炎与多发性硬化的临床症状、脊髓MRI表现的对比分析

目的 结合视神经脊髓炎(NMO)与多发性硬化(MS)患者的临床症状和脊髓MRI特点探讨两者之间差异发生的机制.方法 回顾性分析中山大学附属第三医院自2004年1月至2007年1月收治的23例NMO患者及21例MS患者的临床资料,比较其临床症状及脊髓MRI上受损部位MRI上的差异.结果 NMO患者多为女性,且首次发病年龄、扩展病残状况评分(EDSS)评分均高于MS患者;双侧深感觉障碍、束带感、直肠或膀胱括约肌功能障碍3种临床症状在NMO、MS患者中的发生率不同,差异均有统计学意义(P<0.05);上述各临床症状基本能在脊髓MRI找到相应受损病灶.结论 NMO是不同于MS的脱髓鞘疾病,其特殊的发病机制导致其临床症状与脊髓MRI均有自己的特点.     

The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis

In 125 patients with multiple sclerosis, intrathecally synthesized antibodies against measles, rubella and zoster viruses were determined with an ELISA. 70% of patients with chronic progressive disease synthesized measles antibodies in comparison to 50% with a relapsing course. Women suffering from chronic progressive multiple sclerosis exhibited zoster antibodies 3 times as frequent as the other patients. These data indicate that relapsing and chronic progressive forms of multiple sclerosis exhibit different antiviral responses within the central nervous system which remain stable during the course of the disease.     

PBL在神经内科见习教学中的应用

以问题为基础的学习(PBL)是基于临床问题为基础、以学生为中心的教学方式.探讨PBL教学法在神经内科见习教学中的应用,分析了PBL教学在神经内科见习课中的优越性及存在问题.期望在神经内科见习教学中拓宽思路,寻找适合于医学生进入临床初期阶段培养的方法,以提高临床教学质量,达到培养高级医学人才的目的.     

Genetics for understanding and predicting clinical progression in multiple sclerosis

Introduction

Multiple sclerosis (MS) is a dys-immune disease of the central nervous system with highly variable and unpredictable long-term outcome.

State of the art

In the early 1970s association between HLA alleles and MS was established. Very recently, the power of Genome Wide Association Studies (GWAS) enabled the identification of several loci involved in immune functions as genetic risk factors in MS. Recent data suggest that common genetic variations might modulate the clinical phenotype of MS through a regulation of key pathophysiological pathways.

Perspectives

Identification of modifier genes might offer an opportunity to explore new relevant therapeutic targets and early prognostic markers. To date, studies of modifier genes in MS are numerous but results are still unclear. This research field may now benefit from large cohorts of patients available for association studies.

Conclusion

In this context, we propose a review of epidemiological and association studies of genetic modifying effect in MS.