Bands In Cerebrospinal Fluid Research Articles

Prediction of Conversion from Clinically Isolated Syndrome to Multiple Sclerosis According to Baseline Characteristics: A Prospective Study

Clinically isolated syndrome (CIS) is a clinical state that proceeds with inflammation and demyelination, suggestive of multiple sclerosis (MS) in the central nervous system in the absence of other alternative diagnoses. The purpose of this study was to determine in a prospective cohort, the predictor factors in conversion from CIS to MS on the basis of clinical, magnetic resonance (MR) imaging and cerebrospinal fluid (CSF) findings. Forty-one CIS patients were included in this study and followed up for at least two years. Clinically, polysymptomatic or sensorial involvement, good prognostic factors and complete response to pulse therapy were found to be of prognostic value in conversion to MS. A greater presence of oligoclonal bands in CSF was identified in the converted group (92.8%). In terms of localization, presence of callosal lesion (71.4%), periventricular lesion (97.1%), Gd-enhanced lesion (48.6%), black hole (54.2%) and brainstem lesion (57.1%) was statistically significant in terms of conversion to MS. A carefully performed neurological assessment of symptoms and signs, and evaluation of lesions on MR combined with CSF findings are important for identifying the risk of conversion to MS. This information may be useful when considering treatment in CIS patients instead of waiting for conversion to MS.

Agrupación de casos de síndrome de Guillain-Barré atípico: ¿es necesario redefinir los criterios diagnósticos y los protocolos microbiológicos?

Guillain-Barre syndrome is classically defined as a symmetrical ascending acute polyradiculoneuropathy, although there are atypical variants that make diagnosis difficult. The medical data of six patients in our hospital area are collected during the first quarter of 2013. Lumbar punctures, imaging, neurophysiological studies, ganglioside antibodies and serologies have been proposed in all cases. We focus on the atypical features as late hyporeflexia, increased frequency of asymmetry and distal paresis and initial fever. From a neurophysiological point of view, all patients presented sensorimotor axonal forms. The most consistent datas in early studies is the F wave's alteration. A Miller Fisher variant associated with faciocervicobraquial paresis and cerebral reversible vasoconstriction syndrome has been detected. A bilateral brachial paresis and lumbar polyradiculopathy in the context of influenza A infection is other interesting case. The saltatory variant with cranial nerve involvement and lower limbs paresis has been demonstrated in one patient. Bands in cerebrospinal fluid are positive in three cases and anti-ganglioside antibodies in one patient. The syndrome of inappropriate secretion of antidiuretic hormone may explain some of the hyponatremias registered. The first line of treatment are inmunoglobulins in all patients. Plasmapheresis exchanges has been used as an additional therapy in four cases. These clusters of six axonal cases with atypical clinical features justifies the need for knowledge of these variants in order to achieve an early treatment. Late hyporeflexia and brachialfaciocervico, saltatory and lumbar forms should be considered in the spectrum of Guillain-Barre syndrome. The etiological study should rule out a lots of pathogens as influenza A.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

Background:Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.Methods:Data including the patients’ serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables.Results:Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (χ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = −3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; χ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; χ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups.Conclusion:The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Semi-automated image analysis of gel electrophoresis of cerebrospinal fluid for oligoclonal band detection.

Detection of oligoclonal electrophoretic bands in cerebrospinal fluid (CSF) is an important diagnostic tool for Multiple Sclerosis (MS). Electrophoretic profiles are difficult to interpret due to low contrast and artefacts. A semi-automated method to ease analysis and to reduce subjectivity is presented. The method sequentially converts color images to grayscale, realigns bands, removes artifacts, then converts 2D images to a signal, before detecting, thresholding and editing peaks to optimize profiles. Such treated profiles (21 positive and 15 negative) are compared to ground truth analysis of an expert biologist. 16 profiles over 21 are well detected positive and 12 profiles over 15 are detected negative, results seem similar to inter-experts variability reported in literature.

High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients

Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS.

Nationwide Incidence of Acquired Central Nervous System Demyelination in Icelandic Children

IntroductionRecognizing acquired demyelinating syndromes and multiple sclerosis is important to commence early treatment. The objective of this study was to describe the incidence of acquired demyelinating syndromes and multiple sclerosis among the entire Icelandic pediatric population according to recently promoted criteria. Patients and MethodsThe study included all children in Iceland (<18 years) with acquired demyelinating syndromes and multiple sclerosis from 1990 to 2009 with a minimum of 5-year follow-up. Clinical data were gathered and radiological images reviewed. The cohort included all patients with acquired demyelinating syndromes and multiple sclerosis in the Icelandic pediatric population. ResultsEighteen patients with acquired demyelinating syndromes and multiple sclerosis were included, the total annual incidence being 1.15/100,000 (acquired demyelinating syndromes 1.02 and multiple sclerosis 0.45/100,000). The median age at diagnosis was 14.25 years (range 1.25-17.5 years). Thirteen patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the multiple sclerosis group. The gender ratio was equal. Of the nine girls, seven were diagnosed with clinically isolated syndrome. Most patients (11 of 18) were diagnosed during the period January through March. Oligoclonal bands in cerebrospinal fluid were exclusively found in patients with multiple sclerosis and clinically isolated syndrome and 13 of 14 available magnetic resonance images revealed clear abnormalities. ConclusionThe annual incidence of acquired demyelinating syndromes and multiple sclerosis in Iceland was 1.15/100,000 children. The risk of progression from clinically isolated syndrome to multiple sclerosis was high. There was no female preponderance.

What does an isolated cerebrospinal fluid band mean: a tertiary centre experience

What does an isolated cerebrospinal fluid band mean: a tertiary centre experience

Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis

ObjectivesTo investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies...

Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab.

Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti-John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid-specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9-339.3, p < 0.0001) in patients treated with natalizumab. They were also associated with significantly higher CSF CD4, CD8, and B-cell numbers. Patients positive for IgM bands and anti-JC antibodies had similar levels of reduced PML risk to those who were anti-JC negative (OR = 1.55, 95% CI = 0.09-25.2, p = 1.0). Higher risk was observed in patients positive for anti-JC antibodies and negative for IgM bands (19% of the total cohort, OR = 59.71, 95% CI = 13.6-262.2). The presence of IgM bands reflects a process that may diminish the risk of PML by counteracting the excess of immunosuppression that may occur during natalizumab therapy.

Oligoclonal Bands in Cerebrospinal Fluid of Black Patients with Multiple Sclerosis.

Genetic susceptibility is a well-recognized factor in the onset of multiple sclerosis (MS). The objective of this study was to determine the frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid, in an ethnically mixed group of MS patients in the city of São Paulo, Brazil. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. OCB were found in 49 (54.4%) out of 90 patients with clinically definite MS; out of the 23 brown/black patients, 17 (73.9%) were OCB+; out of the 66 white patients, 32 (48.5%) were OCB+; and the only patient yellow was OCB+ (p = 0.05). Analysis of the IgG index was also consistent with the findings, but with lower statistical significance. The data presented in our study show that the ethnic differences in MS extend to the immune response.

K Index in cerebrospinal fluid: a valid tool in multiple sclerosis diagnosis

Detection of oligoclonal IgG bands in cerebrospinal fluid by isoelectrocfocusing and immunodetection is the current gold standard to detect an inflammatory process in the central nervous system. It has been proposed that the presence of free light chains (FLCs) in CSF was associated with recent demyelination activity in MS and might be used as a prognosis marker. Our study’s objective is assessing the diagnostic accuracy of a new highly sensitive latex-enhanced nephelometric assay for k free light chain (kFLC) determination in CSF/serum as an alternative to traditional tests and its clinical application. kFLCs were measured in CSF/serum pairs from 80 patients by the use of a new highly sensitive latex-enhanced nephelometric automated immunoassay for detection of immunoglobulin FLC. The eighty patients were split into three groups according to the neurological diagnosis. In this study we confirm even more the use of the k Index as a diagnostic aid in multiple sclerosis. kFLC Index seems to be more accurate parameter respect the determination of oligoclonal immunoglobulin bands (OCBs). We recalculate the K Index sensitivity and specificity respect the precedent published result. Two patients previously diagnosed with leukoencephalopathy have gone to group 3 as confirmed the diagnosis of MS. These new data reinforce even more the use of the k Index to diagnose MS in comparison to classical methods and to the reference method, the OCBs.

Optimization of supervised self-organizing maps with genetic algorithms for classification electrophoretic profiles

&lt;p&gt;Standard electrophoresis methods were used in the classification of analyzed proteins in cerebrospinal fluid from patients with multiple sclerosis. Disc electrophoresis was carried out for detection of oligoclonal IgG bands in cerebrospinal fluid on polyacrylamide gel, mainly with multiple sclerosis and other central nervous system dysfunctions. ImageMaster 1D Elite and GelPro specialized software packages were used for fast accurate image and gel analysis. The classification model was based on supervised self-organizing maps. In order to perform the modeling in automated manner genetic algorithms were used. Using this approach and a data set composed of 69 samples we were able to develop models based on supervised self-organizing maps which were able to correctly classify 83 % of the samples in the data set used for external validation.&lt;/p&gt;

Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: Results from the Multi-Center SET study

ObjectivesTo investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. MethodsWe analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein–Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24months. ResultsAnti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. ConclusionsAntibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

The presence of oligoclonal IgG bands in human CSF during the course of neurological diseases

The analysis of cerebrospinal fluid (CSF) is an important tool for the diagnosis of neurological diseases. However, there is limited knowledge about the representativity of a single oligoclonal band (OCB) analysis for a neurological disease during its clinical course. In this study, we analyzed the presence of OCB in the CSF of patients who underwent lumbar puncture more than once. We retrospectively analyzed anonymized data from serial 17,002 CSF analyses done in the CSF laboratory of the Department of Neurology, University Hospital Zurich. We included cases with documented diagnosis in whom OCB were determined more than once. We included 144 patients. The median time span between the first and second OCB analysis was 274 days (range, 1-3,533 days). The result of the second OCB analysis was identical in 109 cases, and different in 35 (24 %). Twenty-five patients acquired and ten patients lost OCB over time. Three of 24 MS patients did not show OCB at the first CSF analysis, but in the second. In the entire group, newly occurring OCB were often associated with new symptoms or occurred after the acute phase of CNS infectious diseases, supposedly as a consequence of the immune reaction. A loss of OCB was often associated with remissions from diseases, e.g., during effective treatment. In patients with neurological diseases, both initially positive and negative OCB results may change over time, which often parallels the clinical condition. Such variability must be taken into account for the interpretation of OCB results.

Neuromyelitis Optica in Austria in 2011: To Bridge the Gap between Neuroepidemiological Research and Practice in a Study Population of 8.4 Million People

BackgroundIn 2008 the Austrian Task Force for Neuromyelitis Optica (NMO) started a nation-wide network for information exchange and multi-centre collaboration. Their aim was to detect all patients with NMO or NMO spectrum disorders (NMO-SD) in Austria and to analyse their disease courses and response to treatment.Methods(1) As of March 2008, 1957 serum samples (of 1557 patients) have been tested with an established cell based immunofluorescence aquaporin-4 antibody (AQP4-ab) assay with a high sensitivity and specificity (both >95%). All tests were performed in a single reference laboratory (Clinical Dept. of Neurology of the Innsbruck Medical University). (2) A nation-wide survey with several calls for participation (via email newsletters, articles in the official journal of the Austrian Society of Neurology, and workshops) was initiated in 2008. All collected data will be presented in a way that allows that every individual patient can be traced back in order to ensure transparency and to avoid any data distortion in future meta-analyses. The careful and detailed presentation allows the visualization and comparison of the different disease courses in real time span. Failure and response to treatment are made visible at one glance. Database closure was 31 December 2011. All co-operators were offered co-authorship.ResultsAll 71 NMO- or NMO-SD patients with AQP4-ab positivity (age range 12.3 to 79.6 years) were analysed in detail. Sex ratio (m:f = 1:7) and the proportion of patients without oligoclonal bands in cerebrospinal fluid (86.6%) were in line with previously published results. All identified patients were Caucasians.ConclusionsA nationwide collaboration amongst Austrian neurologists with good network communications made it possible to establish a database of 71 AQP4-ab positive patients with NMO/NMO-SD. This database is presented in detail and provides the basis for further studies and international cooperation in order to investigate this rare disease.

Aquaporin-4 antibody negative recurrent isolated optic neuritis: Clinical evidence for disease heterogeneity

Recurrent optic neuritis is frequently observed in multiple sclerosis (MS) and is a typical finding in neuromyelitis optica (NMO). Patients that lack further evidence of demyelinating disease are diagnosed with RION (recurrent isolated optic neuritis) or CRION (chronic relapsing inflammatory neuropathy) if they require immunosuppressive therapy to prevent further relapses. The etiology and disease course of this rare condition are not well defined.We studied a series of 10 patients who presented with recurrent episodes of isolated optic neuritis (ON, n=57) and were followed over a median of 3.5years. Visual acuity was severely reduced at the nadir of the disease (20/200 to 20/800). All patients had MRI non-diagnostic for MS/NMO and were aquaporin-4 antibody negative. Six patients fulfilled the CRION criteria. In two of these a single ON followed by a long disease-free interval preceded development of CRION for years, suggesting the conversion of an initially “benign” isolated ON into the chronic relapsing course. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis in 5 patients, identical oligoclonal bands in serum and CSF were observed in 2 patients, while the others remained negative. In conclusion, recurrent ON is a disease entity that requires aggressive glucocorticoid and eventually long-term immunosuppressive therapy to prevent substantial visual impairment.

Thalamic Atrophy Is Associated with Development of Clinically Definite Multiple Sclerosis

To investigate the association between the development of thalamic and cortical atrophy and the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). This prospective study was approved by the institutional review board. Informed consent was given by 216 CIS patients, and patients were treated with 30 µg of intramuscular interferon β1a once a week. They were assessed with a magnetic resonance (MR) imaging examination at baseline, 6 months, 1 year, and 2 years. Patients were evaluated within 4 months of an initial demyelinating event, had two or more brain lesions on MR images, and had two or more oligoclonal bands in cerebrospinal fluid. MR imaging measures of progression included cumulative number and volume of contrast agent-enhanced (CE) new and enlarged T2 lesions, and changes in whole-brain, tissue-specific global, and regional gray matter volumes. Regression and mixed-effect model analyses were used. Over 2 years, 92 of 216 patients (42.6%) converted to CDMS; 122 (56.5%) CIS patients fulfilled McDonald 2005 criteria and 153 (70.8%) fulfilled McDonald 2010 criteria for MR imaging dissemination in time and space. The mean time to first relapse was 3.1 months, and mean annual relapse rate was 0.46. In mixed-effect model analysis, the lateral ventricle volume (P = .005), accumulation of CE (P = .007), new total T2 (P = .009) and new enlarging T2 lesions (P = .01) increase, and thalamic (P = .009) and whole-brain (P = .019) volume decrease were associated with development of CDMS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes (P = .009) were MR imaging variables associated with the development of CDMS. Measurement of thalamic atrophy and increase in ventricular size in CIS is associated with CDMS development and should be used in addition to the assessment of new T2 and CE lesions.

The utility of cerebrospinal fluid analysis in patients with multiple sclerosis

Diagnosis of multiple sclerosis (MS) requires the exclusion of other possible diagnoses. For this reason, the cerebrospinal fluid (CSF) should be routinely analysed in patients with a first clinical event suggestive of MS. CSF analysis is no longer mandatory for diagnosis of relapsing-remitting MS, as long as MRI diagnostic criteria are fulfilled. However, caution is required in diagnosing MS in patients with negative MRI findings or in the absence of CSF analysis, as CSF investigation is useful to eliminate other causes of disease. The detection of oligoclonal IgG bands in CSF has potential prognostic value and is helpful for clinical decision-making. In addition, CSF analysis is important for research into the pathogenesis of MS. Pathophysiological and neurodegenerative findings of inflammation in MS have been derived from CSF investigations. Novel CSF biomarkers, though not yet validated, have been identified for diagnosis of MS and for ascertaining disease activity, prognosis and response to treatment, and are likely to increase in number with modern detection techniques. In this Review, we summarize CSF findings that shed light on the differential diagnosis of MS, and highlight the potential of novel biomarkers for this disease that could advance understanding of its pathophysiology.

Environmental Factors Associated with Disease Progression after the First Demyelinating Event: Results from the Multi-Center SET Study

ObjectivesTo investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.MethodsWe analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.ResultsThe time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.ConclusionsRelapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.

Differentiating patterns of oligoclonal banding in the cerebrospinal fluid improves diagnostic utility for multiple sclerosis

Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is an important adjunct to the diagnosis of multiple sclerosis (MS) and clinically isolated syndromes (CIS). OCBs are considered present if two or more extra IgG bands are present in CSF in comparison to a simultaneously collected serum sample. However, using isoelectric focusing and immunofixation with anti-IgG, we observed two distinct banding patterns, one in which the bands were numerous and prominent (which we termed 'delta') and a much more subtle pattern, with fewer, more indistinct bands ('theta'). To perform a prospective study to determine the diagnostic implications of the two OCB patterns for multiple sclerosis. Over a 2-year period, 56 consecutive CSF samples with OCBs were identified. Clinical information and radiological data were collected and correlated with the two banding patterns. : Of the 56 positive CSF samples, 46 (82%) demonstrated a delta pattern, and 10 (18%), a theta pattern. The delta pattern was associated with MS/CIS in 34 of 46 (74%) samples, compared with zero of the 10 theta samples (0%, p < 0.001). Exclusion of the theta pattern samples increased the positive predictive value of OCB testing from 61% to 74% for MS/CIS. The diagnostic significance of oligoclonal bands in CSF for MS/CIS can be improved by restricting interpretation to the delta banding pattern alone.