多发性硬化与认知功能障碍

多发性硬化(multiple Sclerosis, MS)是中枢神经系统最常见的脱髓鞘疾病,常分为复发-缓解型(RRMS)、原发进展型(PPMS)及继发进展型(SPMS)三种类型.MS不仅可以导致患者躯体残疾,还常常造成不同程度认知功能损害.提高临床医师对MS认知障碍的认识,并及早采取有效的干预措施,可有效改善MS患者的预后.     

多发性硬化患者正电子发射体层成像显像与认知功能障碍的关系

目的 探讨正电子发射体层成像(PET)与多发性硬化(MS)患者认知功能障碍的关系.方法 对2例确诊的MS患者进行认知功能测定、头颅MRI及PET扫描,并对检查结果进行综合分析.结果 例1简易精神状态检查(MMSE)量表评分19分,低于正常;例2韦氏智商测试为正常水平.PET影像检查显示2例患者存在多处皮质、皮质下代谢减低区;MRI中未发现相应皮质或皮质下白质病灶.结论 MS患者存在皮质及皮质下代谢减低,可能与其认知功能障碍有关.     

多发性硬化的MRI特征

目的 探讨多发性硬化(MS)患者脑及脊髓的MRI特征.方法 回顾性分析110例临床确诊的MS患者的MRI检查资料.结果 MS患者脑部病灶以侧脑室旁白质多见(55.8%),其次是额叶深部白质(54.7%)、顶叶深部白质(44.2%)、脑干(25.6%)、基底节(23.3%)、丘脑(11.6%)等,灰质也可受累;病灶大小不一,形态可为斑片状、斑点状、圆形、类圆形.脊髓病灶以颈、胸髓多见,分别占75.0%和68.8%,形态可为斑片状、条片状、类圆形,脊髓灰白质可同时受累,10.0%的患者出现脊髓形态改变,如增粗、萎缩.MS患者脑及脊髓内病灶在影像学上因病程不同可表现为长T1、长T2或等T1、长T2信号.结论 MS的MRI特点主要是以脑和脊髓白质出现多个大小、形状不同的病灶.     

多发性硬化的认知功能障碍

多发性硬化是中枢神经系统脱髓鞘疾病,可以存在认知功能障碍。本文介绍了多发性硬化患者认知障碍 的临床表现、功能评价、病理基础及神经影像学检查等方面的研究进展。     

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。     

38例多发性硬化的MRI特异征象

目的:为提高多发性硬化(MS)的临床诊断水平。方法:本组38例MS均经临床、脑干诱发电位、脑脊液检查证实。在磁共振成像(MRl)中,24例使用GE0.5TMR仪成像,14例使用SIEMENS1.5TMR仪成像。结果:本组19例出现“帽徽征”(cap insignia sign),24例出现“串珠样”表现(bead manifestation),2例出现“假肿瘤征”(pseudomass sign)。静脉注射GD-DTPA(0.1mmol/kg体重)后大部分均出现不同形式强化。结论:在MRI中出现“帽徽征”、“串珠样”表现和“假肿瘤征”特异征象,对诊断MS有一定的特异性;并且“帽徽征”的出现提示MS病人处于急性期或活动期。     

多发性硬化的临床表现及MRI诊断

目的 提高对多发性硬化的临床MRI表现的认识.方法 回顾性分析58例多发硬化病例的临床及MRI表现.结果 临床上均具有反复发作病史.病灶分布于大脑半球皮质下白质区、半卵圆中心、侧脑室旁34例,其中垂直于侧脑室分布30例,脊髓颈段、中上胸段19例;其它部位单位发5例.病灶直径从3mm～5cm;病灶形态是团块样41例,条带状17例;病灶呈长T1长T2信号,新发病灶及活动期病灶增强后均见强化,呈斑片状、环状或线状强化,陈旧性病灶不强化.结论根据典型的临床表现和MRI特征,可对多发性硬化病例进行明显诊断及有效治疗.     

多发性硬化伴癫痫发作的临床与MRI

<正> 资料与方法:一、一般资料:24例患者来自我院住院病人。根据赵葆洵及Poser等制定的诊断标准,本组24例皆为临床确诊MS。男14例,女10例;年龄34～59岁,平均38.40岁。病程3～20年,平均9年,复发—缓解次数1～5次。 二、临床表现:头昏、头痛7例,眩晕6例,视力减退17例,肢体力弱23例,排尿障碍15例,感觉障碍10例,听力下降3例,视乳头苍白17例,眼球震颤5例,核间性眼肌麻痹2例,中枢性面瘫4例,偏瘫21例,双下肢瘫1例,共济运动障碍5例,病理征阳性5例。 三、癫痫发作:首发症状5例,复发期19例。全身性强直—阵挛发作19例,复杂部分性发作2例,单纯运动性发作2例,癫痫持续状态1例。     

认知康复治疗在多发性硬化认知功能损害中的积极作用

目的 探讨认知康复治疗在多发性硬化(MS)认知功能损害中的积极作用。 方法 对广州医学院第二附属医院神经内科自2008年9月至2010年10月收治的40例MS存在认知功能损害的患者采用神经心理学测验方法系统评价神经行为认知状况、执行功能及整体认知功能,针对其出现的不同类型认知功能损害早期实行认知康复治疗策略,比较治疗前后患者各神经认知功能评分的差异。 结果 与认知康复治疗前相比,治疗后MS患者智能损害明显改善,神经行为认知状况中定向能力、专注能力、理解、语言、空间结构、记忆、判断等项目评分明显增高,执行功能相关量表评分明显增高,差异均有统计学意义(P＜0.05)。 结论 认知康复治疗能明显改善MS患者认知损害中智商、神经行为认知状况、执行功能的损害,对MS患者的生活状况改善有积极的意义。     

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.     

APOE and risk of cognitive impairment in multiple sclerosis

OBJECTIVES: The APOE gene polymorphism and the -491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimer's disease. We examined these polymorphisms in multiple sclerosis (MS) patients, to determine if a genetic predisposition may explain the risk for developing cognitive decline in MS. MATERIAL AND METHODS: Eighty-nine relapsing-remitting and secondary progressive MS patients underwent to a full neuropsychological battery as well as to determination of APOE and -491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls. RESULTS: The APOE polymorphism was not associated with the risk of cognitive impairment in MS patients. The AA genotype of the -491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in cognitively preserved MS subjects. CONCLUSION: The AA homozygous state of the -491 A/T polymorphism of the APOE regulatory region is associated with cognitive impairment in patients with MS.     

Brain dysconnectivity relates to disability and cognitive impairment in multiple sclerosis

The pathophysiology of cognitive dysfunction in multiple sclerosis (MS) is still unclear. This magnetoencephalography (MEG) study investigates the impact of MS on brain resting‐state functional connectivity (rsFC) and its relationship to disability and cognitive impairment. We investigated rsFC based on power envelope correlation within and between different frequency bands, in a large cohort of participants consisting of 99 MS patients and 47 healthy subjects. Correlations were investigated between rsFC and outcomes on disability, disease duration and 7 neuropsychological scores within each group, while stringently correcting for multiple comparisons and possible confounding factors. Specific dysconnections correlating with MS‐induced physical disability and disease duration were found within the sensorimotor and language networks, respectively. Global network‐level reductions in within‐ and cross‐network rsFC were observed in the default‐mode network. Healthy subjects and patients significantly differed in their scores on cognitive fatigue and verbal fluency. Healthy subjects and patients showed different correlation patterns between rsFC and cognitive fatigue or verbal fluency, both of which involved a shift in patients from the posterior default‐mode network to the language network. Introducing electrophysiological rsFC in a regression model of verbal fluency and cognitive fatigue in MS patients significantly increased the explained variance compared to a regression limited to structural MRI markers (relative thalamic volume and lesion load). This MEG study demonstrates that MS induces distinct changes in the resting‐state functional brain architecture that relate to disability, disease duration and specific cognitive functioning alterations. It highlights the potential value of electrophysiological intrinsic rsFC for monitoring the cognitive impairment in patients with MS.     

Characterizing brain oxygen metabolism in patients with multiple sclerosis with T2-relaxation-under-spin-tagging MRI

In this study, venous oxygen saturation and oxygen metabolic changes in multiple sclerosis (MS) patients were assessed using a recently developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI), which measures the superior sagittal venous sinus blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO₂), an index of global oxygen consumption. Thirty patients with relapsing-remitting MS and 30 age-matched healthy controls were studied using TRUST at 3 T MR. The mean expanded disability status scale (EDSS) of the patients was 2.3 (range, 0 to 5.5). We found significantly increased Yv (P<0.0001) and decreased CMRO₂ (P=0.003) in MS patients (mean±s.d.: 65.9%±5.1% and 138.8±35.4 μmol per 100 g per minute) as compared with healthy control subjects (60.2%±4.0% and 180.2±24.8 μmol per 100 g per minute, respectively), implying decrease of oxygen consumption in MS. There was a significant positive correlation between Yv and EDSS and between Yv and lesion load in MS patients (n=30); on the contrary, there was a significant negative correlation between CMRO₂ and EDSS and between CMRO₂ and lesion load (n=12). There was no correlation between Yv and brain atrophy measures. This study showed preliminary evidence of the potential utility of TRUST in global oxygen metabolism. Our results of significant underutilization of oxygen in MS raise important questions regarding mitochondrial respiratory dysfunction and neurodegeneration of the disease.     

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Abstract. Background: Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimers Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons. Objective: To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS. Methods: Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms. Results: Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the 4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable. Conclusion: The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.This work was supported in part by a grant from FISM (Federazione Italiana Sclerosi Multipla).     

Correlations of brain MRI parameters to disability in multiple sclerosis

OBJECTIVES: The objective was to correlate magnetic resonance imaging (MRI) T2-weighted lesion load and measures of white matter atrophy in the brain to disability in a population-based sample of patients with multiple sclerosis (MS). MATERIAL AND METHODS: A well defined cohort of patients was drawn at random from the general MS population by using the Danish Multiple Sclerosis Registry. A semi-automated local thresholding technique was used to quantify T2-weighted lesions on MRI; whereas manual tracing was applied to measure the corpus callosum brain ratio (CCR) and the ventricle brain ratio (VBR). RESULTS: A sample of 86 patients with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD 4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified. The correlation between total lesion area of the brain (TLA) and disability (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient r=0.48, P<0.001). Also correlations of CCR and VBR to disability (r=0.32-0.46) were significant. CONCLUSIONS: Correlations of TLA and disability in this study were rather strong. Hence, T2-weighted MRI lesion load in the brain still plays an important role as a surrogate marker of disease and as a secondary outcome measure in phase III treatment trials.     

High numbers of perforin mRNA expressing CSF cells in multiple sclerosis patients with gadolinium-enhancing brain MRI lesions

Enhanced expression of pro- and anti-inflammatory cytokines is a common finding in MS, but attempts to correlate cytokine expression with disease activity have produced conflicting results. In this paper, gadolinium-(Gd-)enhancing lesions on brain MRI were used as markers for active inflammation in patients with MS not treated with any immunomodulatory drugs. In parallel, in situ hybridization was used to detect blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) expressing cytokine mRNA. An association was observed between numbers of perforin mRNA expressing CSF MNC and numbers of Gd-enhancing brain MRI lesions. Perforin mRNA expressing CSF MNC were not detected in any of the patients lacking active lesions on brain MRI. The expression of tumor necrosis factor-alpha, interleukin-10 (IL-10) and IL-12 mRNA in CSF MNC did not differ between MS patients with and without active MRI lesions. Based on the present finding, a role for perforin in the disruption of the blood-brain barrier in MS can be hypothesized.     

Cortical lesions at diagnosis predict long-term cognitive impairment in multiple sclerosis: A 20-year study

Background and purpose

Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, few studies (and with conflicting results) have evaluated early predictors of CI in the long term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.

Methods

We investigated in 170 MS patients the relationship between clinical/magnetic resonance imaging (MRI) data at diagnosis and cognitive status almost 20 years after MS onset. Among others, number and volume of both white matter lesions (WMLs) and cortical lesions (CLs) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted.

Results

CI patients showed higher focal cortical pathology at diagnosis compared to cognitively normal subjects (p < 0.001). Volumes of both WMLs and CLs emerged as the MRI metrics most associated with long-term CI. Moreover, number of CLs (especially ≥3) was also strongly associated with long-term CI (≥3 CLs: odds ratio [OR] = 3.7, 95% confidence interval = 1.8–7.5, p < 0.001), more than number of WMLs; the optimal cutoff of three CLs (area under the curve = 0.67, specificity = 75%, sensitivity = 55%) was estimated according to the risk of developing CI.

Conclusions

These results highlight the impact of considering both white and gray matter focal damage from early MS stages. Given the low predictive value of WML number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of number of CLs could represent a reliable prognostic marker of CI.     

Correlates of cognitive impairment and depressive mood disorder in multiple sclerosis

The psychopathological status of 25 inpatients suffering from clinically definite multiple sclerosis (MS) according to Poser criteria was assessed by using standardized methods (Structured Clinical Interview for DSM-III-R, Inpatient Multidimensional Psychiatric Scale, Hamilton and Montgomery-Asberg Depression Rating Scales and the Structured Interview for the Diagnosis of Alzheimer Dementia and Dementias of other Aetiology (SIDAM). Magnetic resonance (MRT) (0.5 T; T2-weighted sequence) of the brain was analysed by measuring the ventricular brain ratio (VBR), the area of the corpus callosum (CC) and the extension of hyperintense lesions of the brainstem, the temporal lobes and the brain at all. Six of 25 (24%) of these moderately disabled patients (mean Extended Disability Score (EDSS) 3.3) were diagnosed to suffer from depressive mood disorder (major depression or dysthymia); 2 were demented. In correlation analysis, depression was unrelated to age, gender, duration of illness, status of disability (EDSS) or the results of cognitive assessment. No relationship between the depression scores and the different MRT measures could be identified. The presence or absence of gadolinium enhancement was also uncorrelated to depressive symptoms. Fatigue as measured by the Fatigue Severity Scale was unrelated to depression or subcortical brain atrophy (increased VBR) but significantly correlated to the area of hyperintense MRT changes in brainstem and midbrain. Cognitive impairment (decreased SIDAM scores) was correlated to the total area of hyperintense MRT changes of the brain parenchyma. The type of clinical course (relapsing-remitting vs chronic progredient) was not found to influence the affective or cognitive state in our MS patient's sample.