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1.
Kamm CP, Heldner MR, Vanbellingen T, Mattle HP, Müri R, Bohlhalter S. Limb apraxia in multiple sclerosis: prevalence and impact on manual dexterity and activities of daily living.ObjectiveTo evaluate the prevalence and impact of limb apraxia on manual dexterity and activities of daily living (ADLs) in patients with multiple sclerosis (MS).DesignSurvey.SettingUniversity hospital.ParticipantsConsecutive patients (N=76) with clinically isolated syndrome, relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS), Expanded Disability Status Scale (EDSS) score from 0 to 6.5, and aged from 18 to 70 years were included.InterventionsNot applicable.Main Outcome MeasuresApraxia was assessed by the apraxia screen of TULIA (AST). The relationship of apraxia with ADLs and manual dexterity was evaluated using a dexterity questionnaire and the coin rotation task, respectively.ResultsOverall, limb apraxia was found in 26.3% of patients (mean AST score ± SD, 7.3±1.3; cutoff <9). Apraxia was significantly correlated with higher EDSS scores, longer disease duration, and higher age with the EDSS being predictive. Furthermore, patients with SPMS and PPMS were more apraxic than patients with RRMS. Finally, limb apraxia was significantly associated with impaired ADLs and manual dexterity.ConclusionsLimb apraxia is a frequent and clinically significant symptom contributing to disability in MS. It should therefore be evaluated and possibly treated, particularly in patients with MS reporting manual difficulties in everyday life.  相似文献   

2.
ABSTRACT

Introduction: Natalizumab is an efficacious monoclonal antibody approved for use in relapsing-remitting multiple sclerosis (RRMS). Multiple studies have demonstrated reduced relapse rate, decreased disability progression and prolonged disease-free intervals with natalizumab use. However, natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), thus restricting its widespread use with populations at high risk for developing PML. Recently, the effect of natalizumab in secondary-progressive (SPMS) population has been explored.

Areas covered: This review highlights the pathophysiology behind disease progression in MS and summarizes various attributes of natalizumab including: its pharmacological properties and global economic impact, results of clinical efficacy studies, its role in SPMS, pregnancy and its adverse events profile including PML and discontinuation protocols.

Expert opinion: Despite an established role in reducing RRMS disease activity, natalizumab has found limited use in SPMS due to insufficient evidence of efficacy. Current disease-modifying therapies exert modest overall benefit in SPMS owing to its complex pathophysiology, higher prevalence of comorbidities and increased PML risk with age and lack of reliable outcome measures. Finding more appropriate MRI and clinical outcome measures is quintessential for designing future randomized trials and possibly exploring primary neuroprotective agents for treating SPMS.  相似文献   

3.
BackgroundOxidative stress plays an important role in multiple sclerosis (MS).Objective and methodsThe present study was designed to evaluate the modifications of plasma proteins by estimation markers of oxidative/nitrosative stress: carbonyl groups and 3-nitrotyrosines (3-NT) levels in relapsing-remitting (RR) (n = 10) and secondary progressive (SP) (n = 10) clinical course of multiple sclerosis. Moreover, we estimated the level of uric acid (UA) in plasma of MS patients.ResultsCompared to controls (n = 10), the levels of carbonyl groups in plasma proteins were elevated (P < 0.0001) as well in RRMS as in SPMS. The highest concentration of 3-NT was observed in plasma proteins obtained from SPMS patients (P < 0.0005). The level of uric acid in plasma was significantly lower in RRMS (P < 0.0001) than SPMS.ConclusionThis is the first report which presented differences between SPMS and RRMS patients in 3-NT and protein carbonyl groups in plasma proteins.  相似文献   

4.
BACKGROUND: Mitoxantrone, an intravenously administered immunosuppressant that inhibits T-cell, B-cell, and macrophage proliferation, is indicated for reducing neurologic disability and relapse frequency in patients with secondary progressive multiple sclerosis (SPMS), progressive relapsing MS, or worsening relapsing-remitting MS (RRMS). OBJECTIVE: This article reviews the pathogenesis and natural history of MS and examines the available treatment options for patients with RRMS, worsening RRMS, or SPMS, with a focus on mitoxantrone. METHODS: MEDLINE (1966-present) and the Cochrane Central Register of Controlled Trials (1994-present) were searched for relevant randomized, blinded, controlled clinical trials using the terms mitoxantrone, Novantrone, and multiple sclerosis. RESULTS: Five randomized, blinded, controlled trials and an ongoing open-label Phase IV safety study were identified and included in this review. In one randomized, double-blind trial (N=25), patients with RRMS who received mitoxantrone 8 mg/m2 monthly had significantly reduced relapse rates at 1 year compared with those who received placebo (P=0.014). In a 2-year, randomized, partially blinded trial (N=51), patients with active RRMS who received mitoxantrone 8 mg/m2 monthly had significantly fewer relapses compared with those who received placebo (P<0.001), and significantly fewer patients had confirmed progression of disability (1-point increase in Expanded Disability Status Scale [EDSS] score) (P=0.02). In a randomized, double-blind trial (N=49), patients with relapsing SPMS who received mitoxantrone 12 mg/m2 monthly for 3 months followed by 12 mg/m2 g3mo for up to 32 months had significant improvements in EDSS scores compared with those who received methylprednisolone 1 g IV monthly for 3 months followed by 1 g IV g3mo (P=0.002 at 1 year, P=0.045 at 2 years) and significant reductions in the number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) (P=0.002 at 1 and 2 years, P=0.03 at 3 years). In a randomized, partially blinded Phase II trial in 42 patients with active RRMS or SPMS, patients who received mitoxantrone 20 mg IV monthly and methylprednisolone 1 g IV monthly had significantly fewer new gadolinium-enhancing lesions on MRI (P<0.001) and significantly fewer relapses (P<0.01) at 6 months compared with those who received methylprednisolone alone. In a pivotal Phase III trial (N=194), patients with worsening RRMS or SPMS who received mitoxantrone 12 mg/m2 g3mo for 2 years had significantly fewer relapses (P<0.001) and significantly less deterioration in disability, as measured by change in EDSS score (P=0.019), compared with those who received placebo. In a nonrandomized subgroup of patients from this study (n=110), those who received mitoxantrone 12 mg/m2 g3mo had a significant reduction in the number of T2-weighted MRI lesions at 24 months (P=0.027). The most common adverse events in these studies included nausea and/or vomiting (18%-85%), alopecia (33%-61%), amenorrhea (8%-53%), urinary tract infections (6%-32%), and upper respiratory tract infections (4%-53%). Leukopenia was reported in 10% to 19% of patients. Use of mitoxantrone can lead to serious adverse effects, particularly cardiotoxicity, myelosuppression, and, rarely, leukemia. Long-term use of mitoxantrone may compromise left ventricular function. Limited cardiotoxicity was reported in the clinical studies; in the pivotal clinical trial, 2 patients who received mitoxantrone 12 mg/m2 had decreases in left ventricular ejection fraction to <50% of baseline. CONCLUSIONS: In the available clinical trials, mitoxantrone provided effective treatment for worsening RRMS or SPMS. When mitoxantrone is used as recommended, the risks of substantial myelosuppressive and cardiotoxic effects can be reduced by careful patient selection, drug administration, and monitoring. The lifetime cumulative dose should be strictly limited to 140 mg/m2, or 2 to 3 years of therapy.  相似文献   

5.
目的 利用扩散张量纤维束示踪成像评估多发性硬化(MS)边缘系统纤维通路损害。方法 对20例复发缓解型MS患者(MS组)和20名健康志愿者(对照组)进行纤维束示踪成像。追踪扣带束、穹窿、钩束,获得相应纤维条数、FA值、MD值。并进行统计学分析。结果 与对照组比较,MS组扣带束、穹窿、钩束FA值均减低(P均<0.01),MD值均升高(P均<0.05)。MS组穹窿纤维条数较对照组减少(P<0.001)。MS组中左侧与右侧钩束纤维条数、对照组中左侧与右侧钩束FA值、纤维条数差异均有统计学意义(P均<0.05)。MS组扣带束、钩束FA值与EDSS评分呈负相关(r=-0.572、-0.665,P均<0.05),MD值与EDSS评分呈正相关(r=0.627、0.603,P均<0.05)。结论 纤维束示踪成像对评估MS边缘系统纤维通路损害及监测临床进程有重要应用价值。  相似文献   

6.
Purpose:The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS.

Method: Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data.

Results:Four major themes were identified: “Is this really happening?”; “Becoming a reality”; “A life of struggle”; and “Brushing oneself off and moving on.” Findings suggested a process of moving from uncertainty towards confirmation of one’s diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated.

Conclusions: Understanding pwMS’ experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition.
  • Implications for Rehabilitation
  • The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered.

  • Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking.

  • The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS.

  • Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately.

  相似文献   

7.
8.
Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes.

Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor.

Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network.

Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.  相似文献   

9.
Glatiramer acetate(GA) is a synthetic molecule composed of four amino acids: glutamine, lysine, alanine, and tyrosine. These four amino acids are represented in myelin basic protein, which is a suspect antigen involved in the induction of autoimmunity in multiple sclerosis (MS). Subcutaneous GA 20 mg/day showed a reduction of the mean relapse rate and a slower decline of Expanded Disability Status Scale(EDSS) in patients with relapsing-remitting MS(RRMS). In addition, GA is effective in reducing magnetic resonance imaging(MRI) measured activity in patients with RRMS. The drug is generally well tolerated and is not associated with the influenza-like symptoms. Mitoxantrone(MX), a cytotoxic drug exhibiting very potent immunosuppressive properties, has been found effective on relapse rate and progression of disability in patients with worsening RRMS or secondary progressive MS. An induction phase with the monthly intravenous administration of 12 mg/m2 followed by a maintenance phase with 12 mg/m2 every 3 months for 2 years seems the most effective and safe treatment regimen, not exceeding the maximum cumulative dose of 140 mg/m2. Cardiotoxicity, the major long-term toxicity, is clearly dose-dependent and is a strict treatment duration limiting factor.  相似文献   

10.
To assess regional grey matter (GM) changes in a large cohort of multiple sclerosis (MS) patients with different clinical phenotypes, using voxel-based morphometry (VBM) and their correlation with the extent of global and regional T2 lesion volumes (LV), we acquired conventional MRI scans from 71 MS patients with different clinical phenotypes (26 with relapsing-remitting [RR] MS, 27 with secondary progressive [SP] MS and 18 with primary progressive [PP] MS), 28 patients with a clinically isolated syndrome (CIS) suggestive of MS, and 21 controls. No GM loss was found in CIS patients. Compared to CIS patients, those with RRMS had a significant GM loss in the right pre and postcentral gyri. Compared to RRMS, SPMS patients had a significant GM loss in several regions of the fronto-parieto-temporo-occipital lobes, the cerebellum and superior and inferior colliculus, bilaterally, and deep GM structures. Compared to PPMS, SPMS patients had a significant GM loss in the postcentral gyrus, the cuneus, the middle occipital gyrus, the thalamus, the cerebellum, and the superior and inferior colliculus. In all MS groups, regional GM loss was strongly/moderately correlated with brain T2 LV. In SPMS and PPMS patients, a correlation was found between cortical regional GM loss and T2 LV of the corresponding or adjacent lobes. In MS patients, GM volume loss follows different patterns of regional distribution according to the clinical phenotype of the disease, is likely secondary to the presence and topography of focal WM inflammatory-demyelinating lesions, and is more evident in the progressive forms of the disease.  相似文献   

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