Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis

OBJECTIVE: To examine the relation between the frequency of enhancing magnetic resonance imaging lesions and their characteristics of enhancement and atrophy in patients with early relapsing multiple sclerosis. DESIGN: Analysis of number of enhancing lesions, ventricular volumes and diameters, and lesion characteristics on monthly magnetic resonance imaging scans during natural history follow-up. SETTING: A clinical research institution. PATIENTS: Sixteen patients with confirmed early relapsing multiple sclerosis. MAIN OUTCOME MEASURE: Cerebral atrophy as measured by ventricular enlargement. RESULTS: Numbers of enhancing lesions correlated well with an increase of ventricular size. This correlation was strongest for patients with a high proportion of concentric ring-enhancing lesions with central contrast pallor. CONCLUSIONS: Inflammatory events, especially those within lesions with associated blood-brain barrier breakdown, affect the ensuing loss of brain parenchyma. Patients with a high proportion of lesions with central contrast pallor, which is likely associated with more extensive tissue damage, have a higher rate of atrophic changes.     

改进模糊C-均值分割算法在多发性硬化症MR脑部图像中的应用

背景：脑部MR图像是一种无纹理的图像,未被噪声污染的脑部MR图像的灰度值具有分片为常数的特点。因此,在聚类过程中灰度值有趋向于在同一个分割区域中相对接近的性质。 目的：寻找一个能够自动分割多发性硬化症病灶的模糊C-均值改进方法,为临床对于多发性硬化症的判断提供更方便的工具。 方法：考虑到脑部MR图像相邻象素属于同一分类的概率相近的特性,在迭代过程中对8邻域数据集进行滤波以降低噪声对聚类精度的影响,提出了一种改进的模糊C-均值聚类算法。就是将模糊C-均值聚类算法迭代过程中得到的灰度值看作一个数据集,用每个象素邻域象素的灰度值修正该象素的模糊隶属度取值,从而达到利用空间信息抑制噪声的目的。 结果与结论：选取了10个多发性硬化症患者的脑部MRI图像进行试验。通过对多发性硬化症患者MR T1脑部图像和T2液体衰减反转回复脑部图像的分割实验,结果显示该算法能够有效分割多发性硬化症病灶,与其他方法所做的多发性硬化症病灶分割相比,本算法更易于实现,运算时间短,同时结果与临床医生的勾画比较重叠率较高,对其临床辅助诊断具有重要作用。     

Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis

CONTEXT: Brain atrophy has emerged as a useful surrogate marker of disease involvement in multiple sclerosis (MS). The relationship between whole-brain or regional atrophy and cognitive dysfunction is poorly understood. OBJECTIVES: To determine whether the bicaudate ratio (BCR)-the minimum intercaudate distance divided by brain width along the same line-is increased in MS and to compare the ability of the BCR, whole-brain atrophy, and other magnetic resonance imaging markers to predict cognitive dysfunction. DESIGN: Case-control study. SETTING: University-affiliated clinic. PARTICIPANTS: Sixty patients with MS and 50 age- and sex-matched control subjects. MAIN OUTCOME MEASURES: Bicaudate ratio, whole-brain atrophy, T2 lesion load, T1 ("black hole") lesion load, and caudate volume were measured quantitatively using fluid-attenuated inversion recovery, T1-weighted, and gradient-echo magnetic resonance imaging scans. Symbol Digit Modalities Test was used to assess cognitive function. RESULTS: The BCR (mean [SD]) was higher in patients with MS (0.11 [0.03]) than in controls (0.09 [0.02]) (P<.001), suggesting subcortical atrophy in MS. The BCR was related to total T2 (r = 0.56, P<.001) and T1 (r = 0.40, P<.002) lesion volumes, but not caudate volume in patients with MS. Regression modeling selected BCR (P<.05), but not whole-brain atrophy, T1 or T2 lesion volume, or caudate volume as predictive of Symbol Digit Modalities Test score in patients with MS. CONCLUSIONS: The BCR is increased in MS and is more closely associated with cognitive dysfunction than are other magnetic resonance imaging surrogate markers including whole-brain atrophy. Increased BCR is best explained by frontal horn ventricular enlargement due to atrophy of deep frontal subcortical white matter. This highlights the close relationship between subcortical atrophy and cognitive impairment in patients with MS.     

Sequestrum-like appearance of a multiple sclerosis brain lesion on serial magnetic resonance images.

Using serial magnetic resonance imaging, we monitored an unique lesion of the brain in a 15-year-old girl with clinically definite and laboratory-supported remitting-relapsing multiple sclerosis. During initial phases of the disease course, cystic necrosis around the plaque was observed. Later, remyelination of the central core of the lesion was speculated, as similarities in signal intensity between the core and the normal appearing white matter were partially recovered both on the T1- and the T2-weighted images.     

Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging

BACKGROUND: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated. OBJECTIVE: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS. DESIGN: Open-label treatment vs baseline study. SETTING: Outpatient MS clinical center at a university hospital. PATIENTS: Fourteen patients with relapsing-remitting MS of short duration and at least 3 gadolinium-enhancing (Gd+) brain lesions observed within 6 months before treatment. INTERVENTION: Azathioprine, up to 3 mg/kg daily, individually adjusted according to blood lymphocyte number and the occurrence of adverse events. MAIN OUTCOME MEASURES: Brain Gd+ lesions evaluated by monthly magnetic resonance imaging for 6 months before and 6 months during treatment and new T2 lesions evaluated during the same periods and after an additional 6 months. RESULTS: The treatment reduced to 0 the median Gd+ lesion number and volume per magnetic resonance image (P<.001 for both), resulting in a Gd+ lesion number reduction of 50% or more in 12 of 14 patients (P<.01). An equivalent reduction in the new T2 lesion number was observed (P<.02); this activity also persisted during the additional treatment period evaluated using this outcome measure (P<.01). The median azathioprine dose administered (2.6-2.8 mg/kg daily) reduced the mean blood lymphocyte count to 57% of the baseline value. Adverse events were transient or reversible with dose adjustment. CONCLUSIONS: This study indicates for the first time that azathioprine, administered at lymphocyte-suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated.     

多发性硬化患者的脑部磁共振成像表现

目的　寻找多发性硬化(multiplesclerosis,MS)患者有诊断及鉴别诊断意义的脑部磁共振成像(MRI)征象。方法　分析41例临床确诊MS患者的常规脑部MRI表现,内容包括病灶数目、分布、大小、形态、信号特征及增强表现等。结果　脑部的MS灶可以单发和多发,单发者幕下多见,多发者以4~15个病灶者最多。少数病例的病灶弥漫分布,无法计数,呈现“白质变脏征”。斑块分布以两侧脑室旁最多见,其次为额顶叶皮层下、胼胝体、脑干,伴发小脑内病灶仅2例。斑块直径约几个毫米至2cm不等,约占75%; 2cm以上病灶者少见,最大病灶约6~7cm。根据形态和信号,病灶可以分为急性和慢性。急性病灶呈卵圆形或圆形,有明显膨胀感,T1WI呈低或略低信号,周围可见等或略高信号;T2WI呈高信号,但增高程度不同,表现为中央呈“核心”而周围呈“晕环”。此类病灶均表现强化,最典型为环形强化、强化环完整或呈不完整弓形,即使病灶较大仍具有上述特点。慢性病灶也可分为两种,一种为大体对称性的病灶,分布于两侧脑室旁,另一种病灶分布较分散,额、顶叶,侧脑室旁及脑干等处都有,病灶呈小条、片状,部分融合成较大片状。慢性病灶有收缩感,边缘较锐利,信号较均匀,周围无晕环征象,增强后无强化。结论　脑部MS有多种MRI表现,部分征象具有特征性。     

Quality of life of patients with multiple sclerosis

The main aim of the paper was to evaluate quality of life in SM patients and to establish its determinants. Participants in the study were 50 patients hospitalized at the Neurology Ward in Gostynin-Kruk and 100 patients undergoing 24-day rehabilitation in a sanatorium in Kowal. They were examined using the Functional Assessment of Multiple Sclerosis Quality of Life Questionnaire (FAMS) and a questionnaire concerning demographic data and the course of the disease, including the evaluation of motor disability level (EDSS, according to the Kurtzki scale). The group of patients at the Neurology Ward in Kruk consisted of 20 men and 30 women (mean age 35.8 years, mean duration of the disease 9.1 years). Their main source of income was paid employment (60%). In the Kowal sanatorium group there were 46 men and 54 women (mean age 44.6 years, mean duration of the disease 10.1 years). Their main source of income was disability pension (81%). In terms of the EDSS scale 56% of the Kruk patients represented the first level of motor disability (scores from 0.0 to 4.5), while 30% were classified as the second level (scores from 4.5 to 6.5). The proportions were reversed in the Kowal group: the second level (scores from 4.5 to 6.5) was represented by 57%, and the first level by 29% of the patients. Their quality of life (QoL) assessed by means of the FAMS scale was poor in 52% of cases and satisfactory in 48% of cases in the Kruk group, while in the Kowal group 35% of patients assessed their QoL as poor, and 59%--as satisfactory. The SM patients' quality of life was determined mainly by the degree of their motor self-dependence.     

Development of hypointense lesions on T1-weighted spin-echo magnetic resonance images in multiple sclerosis: relation to inflammatory activity

OBJECTIVE: To evaluate whether degree of inflammatory activity in multiple sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value for development of hypointense lesions on T1-weighted spin-echo magnetic resonance images, a putative marker of tissue destruction. DESIGN: Cohort design with long-term follow-up. Thirty-eight patients with multiple sclerosis who in the past had been monitored with monthly gadolinium-enhanced magnetic resonance imaging for a median period of 10 months (range, 6-12 months) were reexamined after a median period of 40.5 months (range, 33-80 months). SETTING: Magnetic Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands, referral center. MAIN OUTCOME MEASURES: The new enhancing lesion rate (median number of gadolinium-enhancing lesions per monthly scan) during initial monthly follow-up; hypointense T1 and hyperintense T2 lesion load at first and last visit. RESULTS: The number of enhancing lesions on entry scan correlated with the new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation coefficient). The new enhancing lesion rate correlated with yearly increase in T1 (r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01, Spearman rank correlation coefficient) lesion load. Initial T1 lesion load correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01, Spearman rank correlation coefficient). CONCLUSIONS: Degree of inflammatory activity only partially predicted increase in T1 (and T2) lesion load at long-term follow-up. Initial T1 lesion load strongly contributed to subsequent increase in hypointense T1 lesion load, suggesting that there is a subpopulation of patients with multiple sclerosis who are prone to develop destructive lesions.     

Memory performance in multiple sclerosis patients correlates with central brain atrophy

OBJECTIVE: To assess whole brain and central brain atrophy as well as their differential relation to memory, cognitive performance, fatigue, depression and quality of life in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A 3D flow compensated gradient recalled T1-weighted MRI was acquired in 45 RRMS patients. An automated analysis tool was used to calculate brain parenchymal fraction (BPF) and ventricular brain fraction (VF). All patients were assessed with neuropsychological tests focusing on memory and self-rating scales for depression, fatigue and quality of life. Age corrected partial correlations between brain atrophy, motor performance, psychological scales and test scores were calculated. RESULTS: BPF correlated moderately (0.3 < or = r < 0.5) with duration of symptoms and disease, the Expanded Disability Status Scale (EDSS), the upper extremity motor performance, and with mental aspects of quality of life. VF correlated moderately with EDSS, upper and lower extremity motor performance and memory functions. Neither BPF nor VF correlated with fatigue and depression. Results of several cognitive tests correlated moderately with depression and fatigue, the Paced Auditory Serial Addition Test (PASAT) showing the largest correlation. CONCLUSIONS: Memory performance shows a correlation with relative ventricular size in RRMS patients, indicating the strategic location of the ventricle system along the structures of the limbic system and its vulnerability in MS. The PASAT and several other cognitive tests show moderate correlations with depression and fatigue, arguing for an inter relation between the cognitive functioning and the emotional state of patients. However, this relation is independent of measurable brain atrophy.     

Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance

BACKGROUND: Various types of pathologic mechanisms in multiple sclerosis (MS) can alter magnetic resonance imaging (MRI) signals, and the appearance of remyelinated lesions on MRI is largely unknown. OBJECTIVE: To describe the MRI appearance of remyelinated lesions in MS. DESIGN: Comparison of postmortem MRI findings with histopathologic findings. SETTING: Brain donations from a general community.Patients Magnetic resonance images from 36 rapid autopsies yielded 161 areas that could be matched with histologic characteristics, including 149 focal T2-weighted abnormalities, with a range of signal intensities on T1-weighted images. In a subset of 49 lesions, magnetization transfer ratio could be determined. MAIN OUTCOME MEASURES: An observer blinded to the MRI findings assessed the presence of remyelination using light microscopic criteria; in 25 areas, in situ hybridization was used to assess the presence of oligodendrocytes expressing proteolipid protein messenger RNA. RESULTS: Remyelinated areas were found in 67 lesions (42%): partial remyelination was present in 30 lesions (19%), whereas 37 lesions (23%) were fully remyelinated. Remyelinated lesions contained enhanced numbers of oligodendrocytes containing proteolipid protein messenger RNA. All areas with remyelination shown histopathologically were hyperintense on T2-weighted images. Strong hypointensity on T1-weighted images was significantly associated (chi2 = 29.8, P<.001) with demyelinated and partially remyelinated lesions compared with fully remyelinated lesions. The magnetization transfer ratio of remyelinated lesions (mean [SD], 27.6% [41%]) differed (F = 46.3, P<.001) from both normal-appearing white matter (35.2% [32%]) and demyelinated lesions (22.3% [48%]). CONCLUSIONS: Remyelinated lesions return an abnormal signal on T2-weighted images. Both T1-weighted images and magnetization transfer ratio may have (limited) additional value in separating lesions with and without remyelination.     

Quality of life and impairment in patients with multiple sclerosis

OBJECTIVES: The aims of this study were to describe the quality of life in patients with multiple sclerosis (MS) given immunological treatment and in those not given immunological treatment and to investigate the relationship between impairment and quality of life. METHODS: Twenty nine patients given immunological treatment were matched with the same number of patients not given such treatment. Matching variables were sex, Kurtzke's Expanded Disability Status Scale (EDSS), years since diagnosis, and age (total n = 58). The patients were interviewed using the self-reported impairment checklist and they answered two questionnaires on quality of life, the 36-Item Short-Form Health Survey (SF-36) and the Subjective Estimation of Quality of Life (SQoL). RESULTS: The self-reported impairment checklist captured a more differentiated picture of the patients' symptoms of MS than the EDSS. Health related quality of life was markedly reduced, while the subjective quality of life was less affected. There was a stronger association between self-reported ratings of impairment and health related quality of life on the SF-36 than between impairment and global ratings of quality of life on the SQoL. Subjective quality of life on the SQoL was not directly dependent on impairment expressed in physical limitations. There were no statistically significant differences between the treated and untreated groups. A non-significant trend towards better health related quality of life was found in favour of the treated group with respect to emotional role, physical role, and social function on the SF-36. CONCLUSIONS: The self-reported impairment checklist and SF-36 proved to be valuable complements to the well established EDSS in describing the diverse symptoms of MS. Measuring both health related quality of life and subjective wellbeing provides valuable knowledge about the consequences of MS.     

Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity

BACKGROUND: Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment. OBJECTIVE: To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship. DESIGN: Post hoc analysis. SETTING: A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers.Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo. MAIN OUTCOME MEASURES: Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes. RESULTS: T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change. CONCLUSIONS: Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.     

Steroids and brain atrophy in multiple sclerosis

In this review, we focus on different pathogenetic mechanisms of corticosteroids that induce short- and long-term brain volume fluctuations in a variety of systemic conditions and disorders, as well as on corticosteroid-induced immunomodulatory, immunosuppressive and anti-inflammatory mechanisms that contribute to the slowdown of brain atrophy progression in patients with multiple sclerosis (MS). It appears that chronic low-dose treatment with corticosteroids may contribute to irreversible loss of brain tissue in a variety of autoimmune diseases. This side effect of steroid therapy is probably mediated by steroid-induced protein catabolism mechanism. Evidence is mounting that high-dose corticosteroids may induce reversible short-term brain volume changes due to loss of intracellular water and reduction of abnormal vascular permeability, without there having been axonal loss. Other apoptotic and selective inhibiting mechanisms have been proposed to explain the nature of corticosteroid-induced brain volume fluctuations. It has been shown that chronic use of high dose intravenous methylprednisolone (IVMP) in patients with MS may limit brain atrophy progression over the long-term via different immunological mechanisms, including downregulation of adhesion molecule expression on endothelial cells, decreased cytokine and matrix metalloproteinase secretion, decreased autoreactive T-cell-mediated inflammation and T-cell apoptosis induction, blood-brain barrier closure, demyelination inhibition and, possibly, remyelination promotion. Studies in nonhuman primates have confirmed that short-term brain volume fluctuations may be induced by corticosteroid treatment, but that they are inconsistent, potentially reversible and probably dependent upon individual susceptibility to the effects of corticosteroids. Further longitudinal studies are needed to elucidate pathogenetic mechanisms contributing to brain volume fluctuations in autoimmune diseases and multiple sclerosis.     

Quality of life in patients with multiple sclerosis in Serbia

OBJECTIVES: The aim of this investigation was to evaluate factors that might influence the health-related quality of life (HRQoL) in multiple sclerosis (MS) patients in Serbia. MATERIALS AND METHODS: This cross-sectional study was performed on a group of 156 patients with MS. HRQoL was assessed by using the SF-36 questionnaire. Expanded Disability Status Scale (EDSS) and Beck Depression Inventory (BDI) scale were assessed as variables affecting the HRQoL of MS patients. RESULTS: EDSS score correlated negatively with all SF-36 health dimensions, and the highest statistically significant coefficients were for physical functioning (r = -0.682), and social and role functioning (r = -0.407 and -0.405 respectively). BDI correlated statistically significantly negatively (P < 0.01) with all SF-36 health dimensions. CONCLUSIONS: Our findings suggest that both disability and depression significantly influence the HRQoL in Serbian MS patients, with depressive symptoms having the major influence.     

Health-related quality of life and its relationship to cognitive and emotional functioning in multiple sclerosis patients

The existing knowledge about the health-related quality of life (HRQoL) and its relationship to cognitive and/or emotional functioning in multiple sclerosis (MS) is scarce. We assessed differences between subgroups of MS outpatients (n = 209) on one HRQoL instrument: a version of the Functional Assessment of Multiple Sclerosis quality of life instrument; on two cognitive functioning tests: the Mini-Mental State Examination and the clock drawing test; and on two emotional functioning tests: the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Three disease-related characteristics were assessed: physical disability, duration of the illness, and clinical course. The results showed that each of these has an effect on at least one dimension of HRQoL and on one mental functioning test. Thus, the more severe, the more progressive, and the longer the illness duration, the lower the HRQoL. Likewise, cognitive mean scores decreased and emotional mean scores increased with greater illness severity and progressive the MS. Furthermore, we also found significant correlations between cognitive and emotional functioning tests and HRQoL dimensions. Thus, the worse cognitive functioning and the higher depressive and anxiety symptoms score the lower the HRQoL.     

Quality of life and social support in patients with multiple sclerosis

Background and purposeThe aim of the study was to evaluate quality of life (QoL) in multiple sclerosis (MS) patients and to assess the relationship between QoL and social support taking into account key clinical factors and other socio-demographic variables.Material and methodsTwo hundred and ten MS patients (150 women and 60 men) aged between 21 and 59 years were evaluated; the MS group was compared with 108 healthy controls. QoL (MSQOL-54), disease severity (Expanded Disability Status State, EDSS), social support (Social Provisions Scale, SPS), mood (Beck Depression Inventory, BDI) and basic clinical and demographic data were assessed.ResultsDisease severity was mild (EDSS < 4) in 85% of patients, and depressive symptoms (BDI > 13) were present in 41% of patients. Mean physical health composite of MSQOL-54 was 53.6 ± 20.7 and mean mental health composite was 60.0 ± 19.8. MS patients scored significantly lower than healthy subjects. Mean SPS was 78.2 ± 10.9 (range, 6–96) which indicated high social support. In bivariate analysis, social support correlated significantly with the majority of MSQOL domains; in multivariate analysis, however, this relationship was not significant. Emotional well-being was the main predictor of QoL, in both physical and mental domains.ConclusionsMS influences QoL but to a greater extent in the physical than the psychological domain. The role of social support in QoL is generally positive but its protective function may be weakened when interacting with other factors. Depression is the main predictor of QoL when adjusted for other factors. Thus, treatment of mood disturbances might significantly improve QoL in MS patients.     

多发性硬化患者智能改变与头颅磁共振成像测量及弥散张量成像研究

目的　研究多发性硬化 (MS)患者认知功能障碍的发生情况及认知改变的病理解剖基础。方法　对 70例MS患者进行韦氏智力量表测查及头颅MRI检查 ,对其中 5 0例患者的头颅MRI成像进行了定量测量 ;7例患者进行了弥散张量成像 (DTI)扫描。结果　智能测试发现MS组全量表智商低于正常 (<90分 )者为 4 0 % (2 8/ 70 ) ,与正常组比较差异有非常显著意义 (P <0 0 1)。智能测试与MRI测量中的两侧尾状核比率相关性最显著 ,其次为胼胝体指数。DTI显示病灶周围看似正常组织、看似正常白质及灰质较对照组相应部位脑组织的表观扩散系数增高 ,各向异性值减低。结论　MS患者中存在认知障碍。病灶的范围及其严重程度 ,包括看似正常白质中的微小病灶的数量和严重程度决定认知障碍的程度。灰质功能障碍也与认知改变有关。