Clinical and neurophysiological findings in oligoclonal band negative 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

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

Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients

Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.nul

Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients

Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.nul

Risk knowledge in relapsing multiple sclerosis (RIKNO 1.0) - Development of an outcome instrument for educational interventions

Background Adequate risk knowledge of patients is a prerequisite for shared decision making but few attempts have been made to develop assessment tools. Multiple Sclerosis (MS) is a chronic inflammatory disease of young adults with an increasing number of partially effective immunotherapies and therefore a paradigmatic disease to study patient involvement. Objective/methods Based on an item bank of MS risk knowledge items and patient feedback including perceived relevance we developed a risk knowledge questionnaire for relapsing remitting (RR) MS (RIKNO 1.0) which was a primary outcome measure in a patient education trial (192 early RRMS patients). Results Fourteen of the RIKNO 1.0 multiple-choice items were selected based on patient perceived relevance and item difficulty indices, and five on expert opinion. Mean item difficulty was 0.58, ranging from 0.14 to 0.79. Mean RIKNO 1.0 score increased after the educational intervention from 10.6 to 12.4 (p = 0.0003). Selected items were particularly difficult (e.g. those on absolute risk reductions of having a second relapse) and were answered correctly in only 30% of the patients, even after the intervention. Conclusion Despite its high difficulty, RIKNO 1.0 is a responsive instrument to assess risk knowledge in RRMS patients participating in educational interventions