Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka
Multiple sclerosis (MS) is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response.
Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis.
Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP) results, oligoclonal bands (OCB), and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome.
The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient.
In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.
http://journals.plos.org/plosone/articl ... ne.0040431
Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients.
We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31%) patients with relapsing-remitting MS, 8 of 12 (67%) with secondary progressive MS and 5 of 8 (63%) with primary progressive MS, in 3 of 16 (19%) CNS autoimmune and 3 of 37 (8%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without.
Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.
Objective: Oligoclonal band (OCB) negative multiple sclerosis (MS) is well recognised but uncommon, studied in only a few usually small case series. These reached differing conclusions on whether its clinical features or course differ from OCB positive disease. The study hypothesis was that a definitive study would not only be of clinical and prognostic value but also potentially offer information about the possible role of CSF oligoclonal immunoglobulins in MS disease processes.
Methods: A collaborative cohort of well documented patients in southwest England and south Wales was used to identify and analyse a large group of patients with OCB negative MS and make comparisons with age and sex matched OCB positive controls.
Results: An approximate minimum 3% of patients with MS were OCB negative. They were significantly more likely to exhibit neurological or systemic clinical features atypical of MS (headaches, neuropsychiatric features and skin changes). Non-specific MRI, blood and (other) CSF abnormalities were also more common, emphasising the need for continued diagnostic vigilance, although the incautious application of McDonald diagnostic criteria in OCB negative cases renders categorisation as “definite” MS more likely. Studying the uniformly assessed Cardiff group (69 patients), we found the prognosis for neurological disability was significantly better for OCB negative cases. The age adjusted hazard ratio for OCB negative and OCB positive subjects to reach Disability Scale Status (DSS) 4 and DSS 6 was, respectively, 0.60 (95% CI 0.39 to 0.93; p = 0.02) and 0.51 (95% CI 0.27 to 0.94; p = 0.03).
Conclusion: There are clear clinical differences between OCB negative and OCB positive MS, in particular a better prognosis for disability. This is consistent with a secondary but nonetheless contributory role in disease process for intrathecally synthesised immunoglobulins.
Background Oligoclonal bands (OCBs) unique to the cerebrospinal fluid are used in the diagnosis of multiple sclerosis (MS). The precise prevalence of OCBs in MS and clinically isolated syndrome (CIS) is unknown. The influence of OCBs on clinical outcomes has not been quantified. OCB prevalence has been associated with latitude in a single study, if confirmed this would provide avenues for further study.
Methods Using a systematic review and meta-analysis approach, the proportion of OCB-positive MS and CIS and the influence of OCBs on clinical outcomes were calculated. The relationship between latitude and OCB prevalence was calculated using linear regression.
Results Seventy-one articles were included. Overall, 87.7% of 12 253 MS and 68.6% of 2685 CIS patients were OCB positive. OCB-positive MS patients had an OR of 1.96 of reaching disability outcomes, although a number of negative studies did not provide data. OCB-positive CIS patients had an OR of 9.88 of conversion to MS. Latitude predicted OCB status in MS patients (p=0.009) but not in CIS patients.
Conclusions This is the largest study of OCB prevalence in MS and CIS. OCB positivity strongly predicts conversion from CIS to MS. The relationship between latitude and OCBs is confirmed, and this finding warrants further investigation.
Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands
Oligoclonal IgG bands (OCB) in cerebrospinal fluid (CSF) are important in diagnosis of multiple sclerosis (MS).
We evaluated the MRI features of clinically definite MS subjects with and without CSF-OCB. Relapsing MS subjects were recruited from a prospective registry in a university center.
CSF-OCB were detected using isoelectric focusing and lgG-specific immunofixation. MRI metrics including brain volumes, lesion volumes and microstructural measures, were analyzed by FMRIB Software Library (FSL) and Statistical Parametric Mapping (SPM).
Seventy-five subjects with relapsing MS were analyzed. Forty-four (59%) subjects had an interval MRI at around 1 year. CSF-OCB were detected in 46 (61%) subjects.
The OCB-positive group had a higher proportion of cerebellar lesions than the OCB-negative group (23.9% vs. 3.4%, p = 0.057). Except for amygdala volumes which were lower in the OCB-positive group (p = 0.034), other regional brain volumes including the subcortical deep gray matter and corpus callosum were similar. The two groups also showed comparable brain atrophy rate.
For DTI, the OCB-positive group showed significantly higher mean diffusivity (MD) value in perilesional normal-appearing white matter (p = 0.043).
Relapsing MS patients with and without CSF-OCB shared similar MRI features regarding volumetric analyses and DTI microstructural integrity.
See also viewtopic.php?p=260123&hilit=OCB+negative#p260123
OBJECTIVES--To determine whether oligoclonal band (OCB) negative multiple sclerosis is a reliable diagnosis and, if so, whether it has a distinctive prognosis.
METHODS--Retrospective and matched prospective comparison of the clinical and laboratory features of patients with clinical definite multiple sclerosis with and without intrathecal synthesis of oligoclonal IgG.
RESULTS--Thirty four patients were identified with apparent OCB negative clinically definite multiple sclerosis. The results of oligoclonal banding proved to have been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was questionable in 8 of 34. The remaining 12 patients with "true" OCB negative multiple sclerosis were significantly less disabled than matched OCB positive controls. Re-examination of CSF-serum pairs from six OCB negative patients showed that three remained OCB negative while three showed evidence of intrathecal synthesis of OCBs.
CONCLUSIONS--OCB negative clinically definite multiple sclerosis is rare and should be diagnosed with caution; in unequivocal cases it seems to have a relatively benign prognosis.
Multiple sclerosis with and without CSF bands: Clinically indistinguishable but immunogenetically distinct
https://n.neurology.org/content/67/6/10 ... ticle-info
We sought to determine whether Swedish patients with multiple sclerosis (MS) with and without oligoclonal bands (OCBs) in the CSF constitute distinct subpopulations, clinically and immunogenetically. Our findings indicate that OCB-negative MS shares the same clinical features as OCB-positive MS regarding female predominance, age at onset, proportion of primary progressive cases, rate of MRI positivity, and disease severity. Our HLA-DRB1 genotyping results suggest, however, that OCB-positive and OCB-negative MS are immunogenetically distinct.
Immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are absent in a small group of multiple sclerosis (MS) patients. According to previous research, OCB-negative MS patients differ genetically but not clinically from OCB-positive MS patients. However, whether OCB-negative MS is a unique immunological and clinical entity remains unclear. The absence of OCB poses a significant challenge in diagnosing MS.
The objective of this study was twofold: (1) to determine the prevalence of OCB-negative MS patients in the Uppsala region, and (2) to assess the frequency of misdiagnosis in this patient group.
We conducted a retrospective study using data from the Swedish MS registry (SMSreg) covering 83% of prevalent MS cases up to 20 June 2020 to identify all MS patients in the Uppsala region. Subsequently, we collected relevant information from the medical records of all OCB-negative MS cases, including age of onset, gender, presenting symptoms, MRI features, phenotype, Expanded Disability Status Scale (EDSS) scores, and disease-modifying therapies (DMTs).
Out of 759 MS patients identified, 69 had an OCB-negative MS diagnosis. Upon re-evaluation, 46 patients had a typical history and MRI findings of MS, while 23 had unusual clinical and/or radiologic features. An alternative diagnosis was established for the latter group, confirming the incorrectness of the initial MS diagnosis. The average EDSS score was 2.0 points higher in the MS group than in the non-MS group (p = 0.001). The overall misdiagnosis rate in the cohort was 33%, with 22% of misdiagnosed patients having received DMTs.
Our results confirm that the absence of OCB in the CSF should raise suspicion of possible misdiagnosis in MS patients and prompt a diagnostic reassessment.
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