No correlation between number of MRI-evident lesions in cerebrum and the soleus stretch reflex in multiple sclerosis patients

The aim of the study was to investigate if the stretch reflex of the soleus muscle was useful in quantifying upper motor neuron lesions. The soleus stretch reflex was recorded in 10 healthy subjects and 20 patients with active relapsing-remitting multiple sclerosis and correlated to the number of MRI lesions in cerebrum and clinical scores (expanded disability status scale and regional functional scoring system). The short latency stretch reflex was elicited by rotating the left ankle joint 4 degrees with a rise time in the interval of 40-640 ms. The amplitude of the stretch was larger in multiple sclerosis patients being 88.5 microV in patients and 12.8 microV in controls, P = 0.007. The sensitivity of the stretch reflex expressed as the slope of the best linear fit was increased in MS patients to 2.6 microVs/degree compared with 0.6 microVs/degree (0.1-2.2) in controls, P = 0.009. There was no correlation between amplitude of the stretch reflex and number of MRI lesions (r = -0.03). In conclusion, the soleus stretch reflex might be useful to quantify spasticity but is not useful in detecting dysfunction of upper motor neurons in MS.     

Brain MRI in late-onset multiple sclerosis

Multiple sclerosis (MS) with clinical onset after 50 years of age is unusual (between 1 and 6%) and is frequently misdiagnosed. Furthermore, brain magnetic resonance imaging (MRI) abnormalities are frequently observed in subjects over 50 years of age. The aim of this study was to describe brain MRI in late-onset MS to evaluate the sensitivity and specificity of radiological MS criteria in patients aged over 50 years. We evaluated the brain MRI of 20 patients with onset of MS after 50 years of age. We compared these MRI with 26 controls matched for age, sex and vascular risk factors. MRI were blindly analysed by two neuroradiologists according to Paty et al.'s [Neurology38 (1988) 180] criteria, Fazekas et al.'s [Neurology38 (1988) 1822] criteria and Barkhof et al.'s [Brain120 (1997) 2059] criteria. The mean age at MRI scanning was 58 years. Sensitivity was 90% for Paty et al.'s criteria, 80% for Fazekas et al.'s criteria and 85% for Barkhof et al.'s criteria. Specificity was 54% for Paty et al.'s criteria, 69% for Fazekas et al.'s criteria and 65% for Barkhof et al.'s criteria. Barkhof et al.'s criteria are less specific in older patients than in young patients. We suggest that spinal cord MRI and cerebrospinal fluid analysis should be systematically performed in suspected late-onset MS in order to increase the specificity of the diagnosis.     

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.     

Cross-cultural adaptation and validation of multiple sclerosis quality of life questionnaire (MSQOL-54) in a Turkish multiple sclerosis sample

OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive disease with multiple neurological impairments. The disease can also dramatically affect the health-related quality of life of patients. The objective of this study was to investigate the validation of the translated and cross-culturally adapted MSQOL-54 in 183 Turkish MS patients. METHODS: 183 adults classified as having definite MS patients were enrolled into the study. Patients were classified into four severity groups according to the expanded disability status scale (EDSS); group I (EDSS 0-4), group II (EDSS 4.5-5.5), group III (EDSS 6-6.5) and group IV (EDSS 7-8). MSQOL-54 questionnaire were translated and culturally adapted into Turkish. Associations between age, gender, disease duration, EDSS score, marital status, education and health insurance and the MSQOL-54 physical and mental health composite scores were determined. RESULTS: The mean age of the 183 patients (138 female and 45 male) was 39+/-10 years. The questionnaire was well accepted but small cultural adaptations were required. EDSS scores showed significant associations with the MSQOL-54 physical and mental health composite scores. From the different EDSS groups only, the group I (EDSS 0-4) score was significantly associated with the physical health composite as well as the disease duration showed significant correlation with the physical and mental composite scores. None of the other EDSS groups and the other parameters showed correlation with physical health composite or mental health composite. CONCLUSION: Assessment of quality of life of MS patients in addition to disease severity and disability level is important, because it provides unique information that is important to patients and to clinicians. A translation of an existing MS-targeted HRQOL measure from US English into Turkish was easily administered and well accepted in a Turkish MS sample.     

Transitional progressive multiple sclerosis: MRI and MTI findings

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.     

Clinical outcome of relapsing remitting multiple sclerosis among Hong Kong Chinese

Background

Clinical outcome of Chinese relapsing remitting multiple sclerosis (RRMS) patients is uncertain.

Aim

To study the long-term clinical outcome of Chinese RRMS patients.

Method

RRMS patients with duration of 10 years or longer followed up in our hospital is retrospectively studied.

Results

61 RRMS patients (75% female) were studied. Their mean symptom onset age was 25.9 years and mean duration was 20.6 years (range 10-33); 36% patients had received β-interferon and 30% azathioprine. Their mean EDSS scores were 3.3 (range 1-7) and 4.7 (range 1-8) at 10 years and latest follow-up (mean duration 20.6 years) respectively. At 10 years, 30% patients had EDSS score ≤2, 34% EDSS 2.5-3.5, 20% EDSS 4.0-5.5 and 16% ≥6; 18% developed SPMS. At latest follow-up, 15% patients had EDSS ≤2, 20% EDSS 2.5-3.5, 19% EDSS 4.0-5.5 and 46% ≥6.0; 53% developed SPMS. The median time from symptom onset to EDSS 6 was 22 years. No differences were detected in demographic characteristics, presenting neurological features, number of attacks in first 2 years, neuroradiological findings and disease modifying therapies between patients with EDSS <6 and ≥6 at ten years. EDSS scores at 10 years and latest follow-up were similar for patients who had received β-interferon and those who had not.

Conclusion

Hong Kong Chinese RRMS patients may have worse long-term clinical outcome than Caucasian patients.     

Quality of life in patients with multiple sclerosis: the impact of fatigue and depression

Quality of Life (QOL) is impaired in multiple sclerosis (MS) in part due to physical disability. MS-associated fatigue (MSF) and depression (MSD) are common and treatable features of MS, which could also impact on QOL, independent of physical disability. We prospectively studied 60 consecutive patients with MS. QOL was assessed using Multiple Sclerosis Quality of Life (MSQOL)-54. Group differences in QOL scores were assessed after adjusting for Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS) and Hamilton Depression Inventory scores. MS patients were grouped into relapsing-remitting (RR) or secondary-progressive (SP), MSF (FSS> or =5) or MS-nonfatigue (MSNF) (FSS< or =4), and MSD or MS-nondepression (MSND). After accounting for disability and depression, fatigue was associated with impaired QOL with respect to health perception (p=0.03) and limitations due to physical dysfunction (p=0.008). After accounting for disability and fatigue, depression was associated with lower QOL with respect to health perception (p=0.02), sexual dysfunction (p=0.03), health distress (p=0.03), mental health (p=0.006), overall QOL (p=0.006), emotional dysfunction (p=0.04), and limitations due to emotional dysfunction (p=0.03). This study demonstrates that fatigue and depression are independently associated with impaired QOL in MS, after accounting for physical disability, suggesting that their recognition and treatment can potentially improve QOL.     

Prognostic value of spinal cord MRI in multiple sclerosis patients

Multiple sclerosis [MS] is a common inflammatory, demyelinating and neurodegenerative disease of the central nervous system that affects both the brain and the spinal cord. In clinical practice, spinal cord MRI is performed far less frequently than brain MRI, mainly owing to technical limitations and time constraints. However, improvements of acquisition techniques, combined with a strong diagnosis and prognostic value, suggest an increasing use of spinal cord MRI in the near future. This review summarizes the current data from the literature on the prognostic value of spinal cord MRI in MS patients in the early and later stages of their disease. Both conventional and quantitative MRI techniques are discussed. The prognostic value of spinal cord lesions is clearly established at the onset of disease, underlining the interest of spinal cord conventional MRI at this stage. However, studies are currently lacking to affirm the prognostic role of spinal cord lesions later in the disease, and therefore the added value of regular follow-up with spinal cord MRI in addition to brain MRI. Besides, spinal cord atrophy, as measured by the loss of cervical spinal cord area, is also associated with disability progression, independently of other clinical and MRI factors including spinal cord lesions. Although potentially interesting, this measurement is not currently performed as a routine clinical procedure. Finally, other measures extracted from quantitative MRI have been established as valuable for a better understanding of the physiopathology of MS, but still remain a field of research.     

MRI and visual-evoked potentials in partners of multiple sclerosis patients

Hawkes CH, Chawda S, Derakshani S, Muhammed N, Visentin E, Boniface D. MRI and visual‐evoked potentials in partners of multiple sclerosis patients.
Acta Neurol Scand: 2012: 125: 424–430.
© 2011 John Wiley & Sons A/S. Objective – Some epidemiological evidence, particularly concerning the role of Epstein Barr Virus implies that multiple sclerosis (MS) may be transmissible and if correct, this might be revealed by increased prevalence of MS in cohabiting partners. Methods – We addressed this problem by neurological assessment, visual‐evoked potentials (VEP) and magnetic resonance imaging (MRI) in 112 partners of patients with MS in comparison to a control group of 93 individuals with clinically non‐significant head or neck pain and in comparison to UK prevalence. Results – We found one instance of conjugal definite MS. Including this case, VEP were abnormal in five instances with either significant delay (n = 3) or increased interocular latency difference (IOLD) (n = 2) in partners of MS patients thus raising the possibility of subclinical optic nerve demyelination. The mean absolute value of IOLD in partners was greater than the value in controls (P = 0.033). There were no significant differences in MRI findings between the two groups. Conclusion – The finding of one conjugal pair and abnormal VEP in a further four MS partners could have several explanations. It is compatible with the concept of a transmissible agent, although our observations could be due to several biases as well as the play of chance alone.     

Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis

Active motor functional magnetic resonance imaging (fMRI) studies have shown that pediatric multiple sclerosis (MS) patients have a strictly lateralized pattern of activations and a preserved functional connectivity (FC) within the motor system when compared to age‐matched healthy controls. However, it is still not clear whether a preserved FC in pediatric MS is present only in the motor system, or involves other relevant functional system. Resting‐state (RS) fMRI is a valuable tool for an unbiased investigation of FC abnormalities of multiple networks. This study explored abnormalities of RS FC within and between large‐scale neuronal networks from 44 pediatric MS patients and 27 controls and their correlation with clinical, neuropsychological, and conventional MRI measures. Compared to controls, pediatric MS patients had a decreased FC of several regions of the sensorimotor, secondary visual, default‐mode (DMN), executive control, and bilateral working memory (WMN) networks. They also experienced an increased FC in the right medial frontal gyrus of the attention network, which was correlated with T2 lesion volume. Cognitively impaired patients had decreased RS FC of the right precuneus of the left WMN. An increased FC between the sensorimotor network and the DMN, and between the L WMN and the attention network as well as a decreased FC between L WMN and the DMN were also found. A distributed pattern of FC abnormalities within large‐scale neuronal networks occurs in pediatric MS patients, contributes to their cognitive status, and is partially driven by focal white matter lesions. Internetwork connectivity is relatively preserved in these patients. Hum Brain Mapp 35:4180–4192, 2014. © 2014 Wiley Periodicals, Inc .     

多发性硬化患者的认知功能障碍及其与头颅MRI病灶的相关性

目的　研究多发性硬化 (MS)患者认知功能障碍的特点及其与头颅MRI病灶的相关性。方法　对 70例MS患者进行韦氏智力量表 (WAIS)测试及头颅MRI检查 ,并用多元回归分析方法对各相关因素进行分析。结果　MS组全量表智商 (FIQ)异常 (<90分 )率为 4 0 %(2 8/70 ) ,与对照组比较差异有显著性 (P <0 0 1)。对智商成绩影响最显著的因素为病变部位 (脑部病变 )。MRI显示病灶的等级与病程呈显著正相关(r=0 348,P <0 0 5 ) ,胼胝体病灶数与FIQ呈负相关 (r=- 0 2 8,P <0 0 5 ) ,其他均无显著相关性 (均P >0 0 5 )。结论　MS患者存在认知障碍 ,MS的病变部位 (脑部病变 )对智能影响最显著 ,头颅MRI所示病灶与MS患者的认知障碍的相关性大多不显著。     

HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR 19.9, 95% C. I. 16.2–24.3, uncorrected (uncorr)- p<0.00001, corr-p<0.0006), -DQB1*03 (OR 16.8, 95% C. I. 13.6–20.5, uncorr-p<0.00001, corrp< 0.0006), -DRB1*15 (OR 4.6, 95% C. I. 3.7–5.6, uncorrp= 0.0001, corr-p=0.006), and -DRB1*03 (OR 3.9, 95% C. I. 3.2–4.8, uncorr-p=0.0001, corrp= 0.006) alleles were associated with MS. T2-, T1-LL, BPF and EDSS were not significantly different according to the carrier status of these HLA alleles. No differences were found in the ratios of disease severity/disease duration according to the HLA car rier status. Multiple regression analysis showed that a higher T2-LL was associated with the presence of DRB1*04 (uncorr- R2=0.15, p=0.006 and corr- R2=0.11, p=0.025) and B7 alleles (uncorr-R2=0.08, p=0.02 and corr-R2=0.07, p=0.018), T1-LL was associated with B7 (uncorr- R2=0.30, p<0.0001 and corr- R2=0.27, p=0.0001) and DRB1*12 (uncorr-R2=0.25, p<0.0001 and corr-R2=0.21, p=0.0002) alleles, whereas the BPF was predicted only by the presence of DRB1*12 allele (uncorr-R2=0.24, p=0.002 and corr-R2=0.20, p=0.004). The study findings suggest that some HLA alleles may predict the destructive pathological processes visible on MRI. Since the size of the sample studied is relatively small, further studies are needed to draw any firm conclusion about genotype/phenotype correlation in patients with MS.     

多发性硬化认知障碍评估及其影响因素分析

目的了解多发性硬化(MS)患者认知功能障碍的特点及其相关因素分析。方法对41例MS患者及41例健康对照组进行蒙特利尔认知评估量表(MoCA)智能测试和常规头颅磁共振(MRI)检查,对41例MS患者进行扩展功能障碍状态量表(EDSS)检查。结果 MS组MoCA得分较对照组明显降低,差异具有统计学意义(P0.01);MoCA评分降低的项目主要以视空间与执行功能、延迟记忆、命名、语言为著,而注意力、抽象能力、计算力及定向力未见明显受损;MoCA评分除与受教育程度、MS分型具有相关性(Pearson相关系数分别为0.576、0.366,P值分别为0.000、0.019)外,与性别、年龄、病程、EDSS评分及常规头颅MRI病灶等级等临床资料均无相关性(P0.05)。结论 MS患者存在认知功能障碍,以视空间与执行功能、命名、延迟记忆、语言为著,注意、计算、抽象、定向能力未见明显受损;MS患者认知功能障碍与患者性别、年龄、病程、神经功能缺损程度、常规头颅MRI所示病灶等级无相关;躯体功能障碍越严重,视空间与执行功能得分越低,即操作智商得分越低。     

Correlation between brain MRI lesion volume and disability in patients with multiple sclerosis

In this study we evaluated the relationships between clinical variables and lesion volumes measured from magnetic resonance imaging (MRI) scans in a large cohort of multiple sclerosis (MS) patients. One hundred and thirty patients with MS entered the study: 36 patients had relapsing-remitting (RR), 39 benign (B), 42 secondary progressive (SP) and 13 primary progressive (PP) courses. There was a significant correlation (r=0.3; p=0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered. This correlation increased (r=0.5) when only patients with RRMS and SPMS were considered. Our data indicate that a correlation between disability and MRI lesion volume in MS exists, but its strength is moderate.     

脊髓多发性硬化的MRI表现与临床对照分析

目的 探讨脊髓多发性硬化(multiple sclerosis,MS)的MRI表现及其与临床的相关性。方法 分析13例脊髓MS患者,对病变的部位、范围及病变处脊髓的形态、MR信号及病变的强化程度进行分析评价并与临床症状进行对照。结果 13例脊髓MS主要发生在颈髓,急性期局部脊髓肿胀,T1加权像病变呈等信号或边缘模糊的稍低信号。T2加权像呈高信号。活动期病灶呈斑片状、环状或弓形强化。反复发作病例、多发病灶其强化多样性,临床症状多变性。结论 脊髓MS有其特征性MRI表现,其与临床有较强的相关性,能为临床诊断和治疗提供可靠的依据。     

Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes of plaques and atrophy correlated with neurological disability

In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.     

Comparing MRI metrics to quantify white matter microstructural damage in multiple sclerosis

Quantifying white matter damage in vivo is becoming increasingly important for investigating the effects of neuroprotective and repair strategies in multiple sclerosis (MS). While various approaches are available, the relationship between MRI‐based metrics of white matter microstructure in the disease, that is, to what extent the metrics provide complementary versus redundant information, remains largely unexplored. We obtained four microstructural metrics from 123 MS patients: fractional anisotropy (FA), radial diffusivity (RD), myelin water fraction (MWF), and magnetisation transfer ratio (MTR). Coregistration of maps of these four indices allowed quantification of microstructural damage through voxel‐wise damage scores relative to healthy tissue, as assessed in a group of 27 controls. We considered three white matter tissue‐states, which were expected to vary in microstructural damage: normal appearing white matter (NAWM), T2‐weighted hyperintense lesional tissue without T1‐weighted hypointensity (T2L), and T1‐weighted hypointense lesional tissue with corresponding T2‐weighted hyperintensity (T1L). All MRI indices suggested significant damage in all three tissue‐states, the greatest damage being in T1L. The correlations between indices ranged from r = 0.18 to r = 0.87. MWF was most sensitive when differentiating T2L from NAWM, while MTR was most sensitive when differentiating T1L from NAWM and from T2L. Combining the four metrics into one, through a principal component analysis, did not yield a measure more sensitive to damage than any single measure. Our findings suggest that the metrics are (at least partially) correlated with each other, but sensitive to the different aspects of pathology. Leveraging these differences could be beneficial in clinical trials testing the effects of therapeutic interventions.