Brain MRI in patients with multiple sclerosis with oligoclonal cerebrospinal fluid bands

Locally produced oligoclonal IgG bands (OCB) are present in the cerebrospinal fluid (CSF) of 95% patients with multiple sclerosis (MS)[2,3]. The most sensitive method for the detection of OCB is isoelectric focusing (IEF) [1]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [2,9]. This study was designed to compare brain magnetic resonance imagining (MRI) findings between CSF OCB positive and negative MS patients. The study comprised 22 OB negative patients with clinically definite MS and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In the both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score. T2 weighted MRI of the brain was performed on a Siemens Magnetom (1.0 T). Lesions were countred and sized for 15 anatomically defined locations:7 periventricular (PV) and 8 non-periventricular (NPV) regions. An arbitrary scoring system weighted for lesions size was used to estimate total and regional lesions loads: a)1 point was given for each lesion with a diameter 1-5 mm, b) 2 points for one lesion with a diameter 6-10 mm, c) 3 points for one over 10 mm, and confluent lesions scored one extra point [16]. Atrophy were scored as follows: 0-normal size, 1-mild atrophy, 2-moderate atrophy and 3-severe atrophy. Mean score of total brain MRI loads was lower in OCB negative than in OCB positive MS patients (44 vs. 50) but the difference was not statistically significant. Mean periventricular (32 vs. 23) non-periventricular (26 vs. 19) and infratentorial (11 vs. 9) scores were higher in OCB positive MS group in comparison with OCB negative patients but non-significant (figure 1). There was no correlation between EDSS score and total MRI lesions load in OCB negative MS patients, while in OCB positive group we detected significant correlation between EDSS score and total MRI lesions load (p=0.026) (figure 2). The results of this study demonstrate that by using conventional brain MRI the extent end severity of the pathological process seems to be similar in OCB negative and OCB postive MS patients. On the other hand, we found statistically significant correlation between brain MRI total lesion load and EDSS in the OCB positive MS patients, while this correlation was not detected in OCB negative MS patients. Differences in brain MRI findings between OCB positive nad OCB negative MS patients have been already analyzed [9,12]. In the first, Zeman et al. reported that OCB negative MS patients have lower total MRI brain lesion loads in comparison to OCB positive group, but the differences was not statistically significant [9]. In accordance with these findings Fukazawa et al. also failed to show differences in the distribution, extent shape and number of brain MRI lesions between OCB positive and negative MS patients. [12]. On the other hand, it has been demonstrated that the rate of intrathecal IgG synthesis apparently correlates with plaque volume in the brain, as demonstrated on MRI, in MS patients [17]. However, our results along with those from two above-mentioned previous studies do not support this notion. In conclusion, trend towards lesser MRI lesion load and lack of its correlation with EDSS in OCB negative MS patients, warrants further investigations with new MRI techniques (magnetic resonance spectroscopy and magnetisation transfer), including the thorough exploration of normal-appearing white matter, in OCB negative MS patients.

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Clinical and neurophysiological findings in oligoclonal band negative multiple sclerosis patients

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0304122m ◽

2003 ◽

Vol 131 (3-4) ◽

pp. 122-126 ◽

Cited By ~ 3

Author(s):

Sarlota Mesaros ◽

Jelena Drulovic ◽

Zvonimir Levic

Keyword(s):

Multiple Sclerosis ◽

Statistical Significance ◽

Progression Rate ◽

Positive Group ◽

Clinical Difference ◽

Initial Symptoms ◽

Significant Difference ◽

Intrathecal Igg Synthesis ◽

Edss Score ◽

Multiple Sclerosis Patients

Besides magnetic resonance imaging, the presence of locally produced oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) is the most consistent laboratory abnormality in patients with multiple sclerosis (MS). The most sensitive method for the detection of CSF OCB is isoelectric focusing (IEF) [6]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [7, 8]. This study was designed to compare clinical data and evoked potential (EP) findings between CSF OCB positive and OCB negative MS patients. The study comprised 22 OCB negative patients with clinically definite MS [11] and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score [12] and progression rate (PR). All patients underwent multimodal EP: visual (VEPs), brainstem auditory (BAEPs) and median somatosensory (mSEPs). The VEPa were considered abnormal if the P100 latency exceeded 117 ms or inter-ocular difference greater than 8 ms was detected. The BAEPs were considered abnormal if waves III or V were absent or the interpeak latencies I-III, III-V, or I-V were increased. The mSEPs were considerd abnormal when N9, N13 and N20 potentials were absent or when increased interpeak latencies were recorded. The severity of the neurophysiological abnormalities was scored for each modality as follows normal EP score 0; every other EP abnormality except the absence of one of the main waves, score 1; absence of one or more of the main waves, score 2 [13]. Both mean EDSS score (4.0 vs. 3.5) and PR (0.6 vs. 0.5) were similar in OCB positive and OCB negative group, (p>0.05). In the first group males were predominant, but without statistical significance (Table 1). Disease started more often with the brainstem symptoms in the OCB positive than in OCB negative MS group (p=0.028), while there was no differences in other initial symptoms between the groups (Graph 2). The frequency of (multimodal) EP abnormalities was higher in the OCB positive group but the differences were not statistically significant, except for bilateral SEP abnormalities (p=0.012). The severity of the AEPs abnormalities was similar in both groups while for the VEPs and SEPs abnormalities were more pronounced in the OCB positive group but not significantly (Table 2). The male preponderance of OCB negative MS patients in our study is in accordance with previous studies [14, 15]. This finding could be potentially ascribed to the well known gender-related differences in both humoral and cellular immune responses [17]. We found no statistically significant differences in either disability or PR between the two patient groups, although OCB negative MS patients had lower EDSS score and PR than OCB positive cases. In accordance with these findings, Fukazawa et al. also failed to show differences in disability between OCB negative and positive MS patients. On the other hand, few studies reported that OCB negative MS patients have a better prognosis [16 18]. The only clinical difference between two groups of patients that we found was that the disease more often started with brainstem symptoms in OCB positive MS patients (p=0.028). OCB positive MS patients had more often bilateral SEPs abnormalities (p=0.012). There was no statistically significant differences between two groups of patients in the severity of trimodal EPs abnormalities and the frequency of BAEPs and VEPs abnormalities although OCB negative patients had trend towards less pronounced EP disturbancies. In conclusion, our results did not reveal significant difference in clinical and neurophysiological(y) parameters between two groups of patients. However, they indicate a trend towards better prognosis of the disease in OCB negative MS patients.

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Oligoclonal Immunoglobulin Gamma Bands and Long-Term Disability Progression in Multiple Sclerosis: A Retrospective Cohort Study

10.21203/rs.3.rs-207684/v1 ◽

2021 ◽

Author(s):

Virginija Danylaité Karrenbauer ◽

Sahl Bedri ◽

Jan Hillert ◽

Ali Manochehrinia

Keyword(s):

Multiple Sclerosis ◽

Cox Regression ◽

Brain Mri ◽

Oligoclonal Bands ◽

Clinical Aspects ◽

Positive Group ◽

Mri Features ◽

Edss Score ◽

Immunoglobulin Gamma

Abstract Background Multiple sclerosis (MS) patients without the typical oligoclonal bands (OCB) distribution of immunoglobulin gamma (IgG) in the cerebrospinal fluid (CSF) has a different genetic background and brain MRI features than OCB-positive MS patients. It is less clear if OCB presence indicates differences in clinical aspects of MS. Objective To determine whether CSF OCB status is associated with long-term disability outcomes. Methods We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, MS onset and date at sustained Expanded Disability Status Scale (EDSS) score milestones 3, 4, 6, date at conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. Results The OCB-positive group reached disability milestones at an earlier time and at younger age. OCB positivity significantly increased the risk of reaching EDSS score 3.0 (HR = 1.29, 95%CI: 1.12 to 1.48, P < 0.001) and 4.0 (HR = 1.38, 95%CI: 1.17 to 1.63, P < 0.001) but non-significantly for EDSS 6. The OCB-positive group had a 20 % higher risk to convert to SPMS. Conclusion Patients with or without CSF OCBs share a risk of long term progression and for conversion to SPMS. Presence of OCBs in the CSF is associated with higher risk to reach EDSS milestones and a higher risk to convert to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

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Cerebrospinal Fluid Oligoclonal Immunoglobulin Gamma Bands and Long-term Disability Progression in Multiple Sclerosis: a Retrospective Cohort Study

10.21203/rs.3.rs-307710/v1 ◽

2021 ◽

Author(s):

Virginija Karrenbauer ◽

Sahl Bedri ◽

Jan Hillert ◽

Ali Manouchehrinia

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Cox Regression ◽

Brain Mri ◽

Positive Group ◽

Mri Features ◽

Edss Score ◽

Different Genetic Background ◽

Immunoglobulin Gamma

Abstract Multiple sclerosis (MS) patients with and without the oligoclonal band (OCB) distribution of immunoglobulin gamma (IgG) in the cerebrospinal fluid (CSF) has a different genetic background and brain MRI features. In this study we have aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, MS onset and date at sustained Expanded Disability Status Scale (EDSS) score milestones 3, 4, 6, date at conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. The OCB-positive group reached disability milestones at earlier time and at younger age. OCB-positivity significantly increased the risk of reaching EDSS score 3.0 (HR=1.29, 95%CI: 1.12 to 1.48, P<0.001) and 4.0 (HR= 1.38, 95%CI: 1.17 to 1.63, P<0.001). The OCB-positive group had a 20 % higher risk to convert to SPMS. CSF-OCBs presence is associated with higher risk to reach EDSS milestones and to convert to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

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T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation

Multiple Sclerosis Journal ◽

10.1177/135245859800400502 ◽

1998 ◽

Vol 4 (5) ◽

pp. 408-412 ◽

Cited By ~ 18

Author(s):

J I O'Riordan ◽

M Gawne Cain ◽

A Coles ◽

L Wang ◽

D AS Compston ◽

...

Keyword(s):

Multiple Sclerosis ◽

Strong Correlation ◽

Measurement Techniques ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Lesion Volume ◽

Mri Findings ◽

Lesion Load ◽

Post Contrast ◽

Secondary Progressive

Magnetic resonance imaging (MRI) is increasingly being used as a monitoring tool for disease activity in therapeutic trials in multiple sclerosis. There is, however, only a limited relationship between MRI findings and clinical outcome measurements. It has been suggested that hypointense lesion load on T1 weighted imaging has a better correlation with disability than the more conventional T2 hyper intense lesion load. This study was undertaken to (i) evaluate different measurement techniques used to quantify T1 hypointense lesion load, and (ii) to compare lesion load as measured using different parameters and disability. Twenty-five patients with secondary progressive multiple sclerosis, mean age of 40 years (23-57), mean EDSS 5.7 (4-7) were analysed. T2 lesion load on FSE correlated well with both the hypointense lesion load on T1 pre-gadolinium (r=0.8, P50.0001) and T1 post-gadolinium (r=0.8, P50.0001) but less so with the enhancing lesion load (r=0.4, P50.05). There was a very strong correlation with T1 hypo-intense lesion volume pre and post gadolinium (r=0.96, P50.001). However, the EDSS was not correlated with the T2 lesion load (r=70.27, P=0.2), T1 pre-gadolinium load (r=70.3, P=0.1), T1 post gadolinium load (r=70.4, P=0.7) and enhancing lesion load (r=70.28, P=0.2), or with the degree of hypointensity of T1 weighted images determined using the threshold technique. There is a strong correlation between T1 hypointense lesion volume both pre and post gadolinium and also between T1 and T2 lesion volumes.

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Brain Function Assessment of Patients with Multiple Sclerosis in the Expanded Disability Status Scale

International Journal of MS Care ◽

10.7224/1537-2073.2018-084 ◽

2020 ◽

Vol 22 (1) ◽

pp. 31-35

Author(s):

Ricardo N. Alonso ◽

Maria B. Eizaguirre ◽

Berenice Silva ◽

Maria C. Pita ◽

Cecilia Yastremiz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Function ◽

Cognitive Assessment ◽

Functional System ◽

Expanded Disability Status Scale ◽

Disability Status ◽

Before And After ◽

Survey Results ◽

Edss Score ◽

The Brain

Abstract Background: There is no consensus regarding assessment of the brain function functional system (FS) of the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS). We sought to describe brain function FS assessment criteria used by Argentinian neurologists and, based on the results, propose redefined brain function FS criteria. Methods: A structured survey was conducted of 113 Argentinian neurologists. Considering the survey results, we decided to redefine the brain function FS scoring using the Brief International Cognitive Assessment for MS (BICAMS) battery. For 120 adult patients with MS we calculated the EDSS score without brain function FS (basal EDSS) and compared it with the EDSS score after adding the modified brain function FS (modified EDSS). Results: Of the 93 neurologists analyzed, 14% reported that they did not assess brain function FS, 35% reported that they assessed it through a nonstructured interview, and the remainder used other tools. Significant differences were found in EDSS scores before and after the inclusion of BICAMS (P < .001). Redefining the brain function FS, 15% of patients modified their basal EDSS score, as did 20% of those with a score of 4.0 or less. Conclusions: The survey results show the importance of unifying the brain function FS scoring criteria in calculating the EDSS score. While allowing more consistent brain function FS scoring, including the modified brain function FS led to a change in EDSS score in many patients, particularly in the lower range of EDSS scores. Considering the relevance of the EDSS for monitoring patients with MS and for decision making, it is imperative to further validate the modified brain function FS scoring.

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Cyclophosphamide Versus Rituximab in Progressive Forms of Multiple Sclerosis

ACTA MEDICA IRANICA ◽

10.18502/acta.v57i8.2413 ◽

2020 ◽

Author(s):

Masoud Etemadifar ◽

Shadi Ghourchian ◽

Nazanin Mahinparvar ◽

Mehri Salari ◽

Fatemeh Etemadifar ◽

...

Keyword(s):

Multiple Sclerosis ◽

Progressive Multiple Sclerosis ◽

The Other ◽

Medical Sciences ◽

Mri Findings ◽

Disability Score ◽

Radiologic Findings ◽

Spss Software ◽

And Gender

This study aimed to compare the efficacy of rituximab versus Cyclophosphamide on active secondary progressive multiple sclerosis (SPMS). The randomized clinical trial was performed from 2015 to 2017 in multiple sclerosis (MS) clinics affiliated to Isfahan MS society (IMSS). Patients were randomized to two groups, and one of them received Rituximab that was repeated every six months in case of medical indication. The other one received a monthly pulse of methylprednisolone plus cyclophosphamide (Endoxan, Baxter, UK) until two years. Expanded disabilities status scale (EDSS), clinical, and MRI findings were assessed every six months. Statistical analysis was performed using SPSS software. 39 patients in the Rituximab group and 30 in the Cyclophosphamide group with similar age and gender distribution were entered for analysis. At baseline, the mean number of attacks in the Rituximab group was significantly more than the Cyclophosphamide group (P=0.0001). After 6, 12, and 18 months of treatment, the rate of attacks was similar between groups although it increased significantly in the Rituximab group (P=0.030) after 24 months of treatment. EDSS was increased in the Rituximab group more than the other group at the end of the study. Both drugs were well-tolerated by patients. The EDSS was increased in the Rituximab group but the disability score did not worsen in the Cyclophosphamide group. Both therapies were associated with a reduction in disease attacks and improvement in radiologic findings in a two-year period of follow-up. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(8):484-491.

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Cerebrospinal fluid transferrin levels are reduced in patients with early multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514530020 ◽

2014 ◽

Vol 20 (12) ◽

pp. 1569-1577 ◽

Cited By ~ 8

Author(s):

M Khalil ◽

B Riedlbauer ◽

C Langkammer ◽

C Enzinger ◽

S Ropele ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Iron Metabolism ◽

Iron Homeostasis ◽

Biochemical Study ◽

Iron Deposition ◽

Lesion Load ◽

Transporter Protein ◽

In Cis ◽

The Brain

Background: Previous magnetic resonance imaging (MRI) studies have demonstrated increased iron deposition in the basal ganglia of multiple sclerosis (MS) patients. However, it is not clear whether these alterations are associated with changes of iron metabolism in body fluids. Objectives: The purpose of this study was to investigate if iron metabolism markers in cerebrospinal fluid (CSF) and serum of clinically isolated syndrome (CIS) and MS patients differ from controls and how they relate to clinical and imaging parameters. Methods: We analysed serum ferritin, transferrin and soluble transferrin-receptor and CSF ferritin and transferrin by nephelometry in non-anaemic CIS ( n=60) or early MS ( n=14) patients and 68 controls. In CIS/MS we additionally assessed the T2 lesion load. Results: CSF transferrin was significantly decreased in CIS/MS compared to controls ( p<0.001), while no significant differences were seen in serum. Higher CSF transferrin levels correlated with lower physical disability scores ( r= −0.3, p<0.05). CSF transferrin levels did not correlate with other clinical data and the T2 lesion load. Conclusion: Our biochemical study provides evidence that altered iron homeostasis within the brain occurs in the very early phases of the disease, and suggests that the transporter protein transferrin may play a role in the increased iron deposition known to occur in the brain of MS patients.

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