A Comparison of IgG Index and Oligoclonal Band in the Cerebrospinal Fluid for Differentiating between RRMS and NMOSD

As the oligoclonal band in the cerebrospinal fluid (CSF-OCB) in predicting relapsing-remitting multiple sclerosis (RRMS) is less sensitive in Asian populations than that in westerners, it remains elusive whether the IgG index could serve as an alternative. The purpose of this study was to compare these two methods of differentiating between RRMS and neuromyelitis optica spectrum disorder (NMOSD) in Chinese patients. A total of 171 patients (81 RRMS and 90 NMOSD) were retrospectively recruited, of whom 82 (56 RRMS and 26 NMOSD) received the CSF-OCB testing additionally. When the onset age was ≤38.5 years, IgG index with the threshold of 0.67 had a significant agreement (к = 0.4, p < 0.001) with the diagnosis while CSF-OCB failed to discriminate (к = 0.1, p = 0.578). However, when the onset age was >38.5 years, both IgG index with the threshold of 0.8 and CSF-OCB were moderately consistent with the diagnosis (both к > 0.4, p < 0.05). In total, our optimized algorithm had the sensitivity, specificity, and predictive accuracy of 0.778, slightly outperforming the CSF-OCB model. Accordingly, a combination of the onset age and IgG index could serve as an alternative to CSF-OCB for differentiating between RRMS and NMOSD in Chinese patients.

Diagnostic significance of IgG and albumin indices versus oligoclonal band types in demyelinating disorders

AimsThe laboratory diagnosis of demyelinating inflammatory disorders (DIDs) relies on both intrathecal oligoclonal band (OCB) positivity and IgG index. Although OCB typing remains the gold-standard test for DIDs, it can be laborious and ambiguous, complicating diagnostics, and unduly increasing diagnostic time. We examined whether serum or cerebrospinal fluid (CSF) parameters can classify OCB types and, thus, be used as a replacement test to standard OCB typing.MethodsWe retrospectively analysed >1000 prospectively collected samples of patients with DIDs and quantified albumin and IgG levels in the CSF and serum. We determined OCB types by isoelectric focusing combined with immunofixation and evaluated the diagnostic accuracies of IgG and albumin indices in discriminating OCB types by receiver operating characteristic curves and multinomial regression.ResultsAn IgG index cut-off of 0.589 differentiated types 2/3 from types 1/4 (area under the curve 0.780, 95% CI 0.761 to 0.812, p<0.001; specificity: 71.10%, sensitivity: 73.45%). Albumin quotient cut-off values of 6.625 and of 6.707 discriminated type 1 from type 4 and type 2 from type 3, respectively (specificity: <55%, sensitivity: <75%). Female sex, age, IgG index, CSF IgG and serum albumin were associated with different OCB types.ConclusionsOur study reveals that IgG and albumin index can differentiate OCB types with adequate accuracy, especially if refined by age and gender.

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case.Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

Urinary retention with occult meningeal reaction: a ‘form fruste’ meningitis-retention syndrome

We report the case of a 70-year-old Japanese man who was referred from a local urologist because of acute urinary retention (detrusor underactivity revealed by a urodynamics examination). A neurogenic urinary retention workup failed to reveal the aetiology, but a spinal tap incidentally showed occult meningeal reaction with positive oligoclonal band. The patient had no headache, nausea/vomiting or fever. Considering his clinical laboratory findings, his neural lesions seemed to involve the meninges and spinal cord, suggestive of ‘form fruste’ meningitis-retention syndrome. When clinicians encounter patients with urinary retention of undetermined aetiology, a spinal tap should be considered.

The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis

Background Diagnostic criteria for multiple sclerosis have been developed to guide the diagnostic process. In the latest revision of the McDonald criteria, the presence of oligoclonal bands may replace the need for dissemination in time. The aim of this study is to investigate if the less time-consuming analysis of immunoglobulin G index in cerebrospinal fluid can safely predict the findings of oligoclonal bands. Methods This is a retrospective study of patients with multiple sclerosis at three hospitals in South-East Norway where lumbar puncture is performed routinely. We included patients diagnosed with multiple sclerosis after 2005 with known oligoclonal band status and an immunoglobulin G index score. Results Of 1295 patients diagnosed during or after 2005, 93.8% were oligoclonal band positive at diagnosis. Of 842 multiple sclerosis patients with known immunoglobulin G index and oligoclonal band status, 93.3% were oligoclonal band positive and 76.7% had an elevated immunoglobulin G index. The positive predictive value of a high immunoglobulin G index when oligoclonal bands are positive was 99.4% (95% confidence interval 98.4–99.8%). The negative predictive value of a normal immunoglobulin G index when oligoclonal bands are negative was 26.5% (95% confidence interval 23.5–29.9%). Conclusion An immunoglobulin G index >0.7 has a positive predictive value >99% for oligoclonal bands. An elevated immunoglobulin G index adds diagnostic value versus oligoclonal bands and saves time in the diagnostic process.

The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.