Multiple sclerosis with and without CSF bands: Clinically indistinguishable but immunogenetically distinct

Imrell, Kerstin; Landtblom, Anne‐Marie; Hillert, Jan; Masterman, Thomas

doi:10.1212/01.wnl.0000237343.93389.35

Cited by 95 publications

(111 citation statements)

References 8 publications

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“…Such MS patients with the DRB1*0405 allele are characterized by an earlier age of onset, lower EDSS scores, lower progression indexes, lower frequencies of brain lesions fulfilling Barkhof criteria, and lower frequencies of CSF oligoclonal IgG bands (OBs) and/or increased IgG indexes, as compared with patients without this allele (Table 5.1) [51]. This is in accord with previous reports showing that DRB1*04 is associated with OB-negative MS in Swedish [52] and Japanese populations [53]. The existence of MS patients with DRB1*0405 may partly explain the low prevalence of OB (54 %) in Japanese MS patients, a unique feature compared with MS in Westerners [3,54].…”

Section: Human Leukocyte Antigen (Hla) Genessupporting

confidence: 88%

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

Kira

2016

Neuroimmunological Diseases

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Multiple sclerosis (MS) is a disease that targets myelin in the central nervous system (CNS). It is thought to be an autoimmune disease but this is not yet proven. Genome-wide association studies have revealed many susceptibility genes for MS, and the functions of these genes are mostly immune-related, supporting the autoimmune hypothesis. Increased numbers of T cells showing inter-and intramolecular epitope spreading against myelin proteins; increased cerebrospinal fluid (CSF) levels of interferon (IFN)-γ, interleukin (IL)-17, and downstream pro-inflammatory cytokines; exacerbation of disease following IFN-γ administration; and increased percentages of T helper (Th)1 cells secreting IFN-γ and of Th17 cells secreting IL-17 at relapse all support T-cell involvement in MS lesion formation. B-cell infiltration in the CNS parenchyma is not prominent, while B-cell follicles in the meninges appear to have a close correlation with subpial demyelination, suggesting an involvement of autoantibodies. However, no specific autoantibodies for MS have been detected, although anti-aquaporin-4 antibodies are a specific biomarker for neuromyelitis optica (NMO). We reported the extensive loss of connexins (Cxs) 43, 32, and 47 in acute lesions in patients with Baló's concentric sclerosis, MS, and NMO. Such loss of astroglial and oligodendroglial Cxs could induce widespread disruption of the glial syncytium, leading to failure of energy source transfer. Thus, loss of Cxs in acute MS lesions may contribute to extensive lesion formation. In the Japanese population, HLA-DRB1*0405 is the most common susceptibility allele for non-NMO MS. DRB1*0405 carriers comprise >40 % of all Japanese MS patients, and this proportion is higher in younger generations. HLA-DRB1*0405-positive MS patients show characteristic features, such as younger age at onset, fewer brain lesions, fewer CSF IgG abnormalities, and a slower progression. The recent increase in the number of MS patients in this subgroup may explain the overall decrease in onset age, as shown by the fourth nationwide survey of Japanese MS patients. Therefore, changes in environmental factors may have increased susceptibility to MS in Japanese populations with certain genetic backgrounds.

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Section: Human Leukocyte Antigen (Hla) Genessupporting

confidence: 88%

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

Kira

2016

Neuroimmunological Diseases

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“…Considering the OCB rates in geographically different Caucasian populations so far [3,5,6,9,10,32,33], it seems that Northern Caucasian populations present higher percentages of OCB. In the very recent meta-analysis of Dobson and colleagues [34], latitude predicts OCB status in MS patients but not in CIS patients, and the presence of OCB strongly predicts conversion from CIS to MS.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of OCB is thought to provide supportive evidence of the immune and inflammatory nature of demyelinating lesions, specifically when imaging criteria fall short or lack specificity or when the clinical presentation is atypical. The significance of OCB is constantly increasing, with studies clearly claiming that OCB can inform prognosis in MS [2][3][4] and be related to different lesion patterns in magnetic resonance imaging (MRI) [5], though controversies are reported worldwide [6,7]. More than 90 % of MS patients in Western countries present OCB [8], whereas decreasing rates are recorded in Caucasian population from Northern [3,6] to Southern countries [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…The significance of OCB is constantly increasing, with studies clearly claiming that OCB can inform prognosis in MS [2][3][4] and be related to different lesion patterns in magnetic resonance imaging (MRI) [5], though controversies are reported worldwide [6,7]. More than 90 % of MS patients in Western countries present OCB [8], whereas decreasing rates are recorded in Caucasian population from Northern [3,6] to Southern countries [9,10]. In other racial groups, such as Japanese MS patients, this OCB rate is 56.1 % [11] and shows a direct correlation to different human leukocyte antigens (HLA) and disease subtypes, emphasizing the significance of different immunogenetic background, immune response and disease profile.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients

et al. 2015

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The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring.

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“…The latter occur in 95-98% of Caucasian MS patients [30,37,38]. The remaining 2-5% OCB-negative patients appear clinically indistinguishably with regard to age, gender, disease duration, and severity [8,17,20], however, are immunogenetically distinct from OCB-positive subjects [10].…”

Section: Introductionmentioning

confidence: 98%

MRI criteria in MS patients with negative and positive oligoclonal bands: equal fulfillment of Barkhof’s criteria but different lesion patterns

et al. 2009

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In multiple sclerosis (MS) more than 95% of the patients have positive oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Previous studies have reported differences between patients with and without OCB mainly with regard to clinical parameters such as age, gender, disease duration, and clinical severity. However, several MRI characteristics have also been hypothesized to be distinct, and a varying lesion load in OCB-negative and -positive patients is proposed. In this study, we aimed to evaluate whether Barkhof's diagnostic MRI criteria are unequally frequently fulfilled in OCB-negative and -positive MS patients. We screened our database for all OCB-negative MS patients who had (1) been treated with the diagnosis of a clinical definite relapsing-remitting MS in our institution as well as (2) undergone CSF analysis and MR brain imaging during hospital stay between January 2004 and December 2007. Eleven OCB-negative patients were identified who fulfilled these criteria. In a second step, we carefully matched each of them to two OCB-positive controls according to age, gender, EDSS, and disease duration. The separate analysis of the several parameters of Barkhof's criteria revealed a less frequent prevalence of infratentorial (3/11 vs. 18/22; P = 0.005) and a more frequent occurrence of juxtacortical lesions (10/11 vs. 10/22; P = 0.022) in OCB-negative as compared to OCB-positive patients. The overall fulfillment of the Barkhof criteria did not differ in OCB-negative and -positive patients (7/11 vs. 16/22; P = 0.696). Further analyses of MRI findings between OCB-negative and -positive MS patients might contribute to a better pathophysiological understanding of the genesis and evidence of OCB in the CSF of MS patients.

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Multiple sclerosis with and without CSF bands: Clinically indistinguishable but immunogenetically distinct

Cited by 95 publications

References 8 publications

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

Multiple Sclerosis: Etiology and Mechanism, with Special Reference to Asians

Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients

MRI criteria in MS patients with negative and positive oligoclonal bands: equal fulfillment of Barkhof’s criteria but different lesion patterns

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