Elevated cerebrospinal fluid IgG index in herpes simplex encephalitis post-HSV-1 clearance: A preliminary study.

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified seven patients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms.

Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis.

Background: Cerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate. Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods. Methods: Paired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). Conclusions: The κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease.

Objective: To analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). Methods: Patients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. Results: A total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5-82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF- group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. Conclusion: The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

The role of oligoclonal band count and IgG index in treatment response and disease activity in multiple sclerosis.

BACKGROUND/AIM: Multiple sclerosis (MS) is an inflammatory demyelinating central nervous system (CNS) disease. Among the paraclinical tests, brain and spinal Magnetic Resonance Imaging (MRI) is primarily involved in the diagnosis process, and cerebrospinal fluid (CSF) analysis is fundamental in diagnosing MS and the differential diagnosis. A positive relationship was demonstrated between oligoclonal band (OCB) positivity, CSF band number and immunoglobulin G(IgG) index. The study aimed to evaluate whether the number of OCB can predict disease activity and determine a correlation with the IgG index. METHODS: Our study included 401 MS patients who had relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), clinic isolated syndrome (CIS), radiologic isolated syndrome (RIS), Neuromyelitis optica spectrum disorder (NMOSD) and Acute disseminated encephalomyelitis (ADEM) with OCB number groups of 2-4, 4-8, 8-12, and 12 and above. RESULTS: No significant correlation was observed between IgG index, pre-and post-treatment EDSS (Expanded Disability Status Scale Scores) and disease-modifying therapies (DMT). Drug response was better in the patient group with band number between 2 and 8 and post-treatment EDSS scores were lower (1.62±0.44). CONCLUSION: The study results suggested that band number may be as valuable as the IgG index and a predictive biomarker for disease activity.

What an adult multiple sclerosis registry can tell us about pediatric onset multiple sclerosis?

BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated, chronic disease of the central nervous system that affects mainly adults. However, it is increasingly recognized that MS may start in childhood resulting in a relentlessly progressive disability and cognitive impairment. Registries across the globe are reporting inconstant data about their Pediatric-Onset Multiple Sclerosis (POMS) patients. Moreover, newer lines of treatments are emerging and showing efficacy in controlling the MS disease regardless of the onset. Therefore, there is a requirement for more research into the clinical profile of POMS in different populations and ethnicities. METHODS: This study was a cross-sectional study that included MS patients who visited the MS unit at Alexandria University from January 2019 to January 2021. We analyzed their epidemiological, clinical, radiological data, and cerebrospinal fluid (CSF) results from their updated records as well as follow-up interviews. RESULTS: Annual Relapse Rate (ARR) was marginally less in POMS than AOMS (0.72 ± 0.57 vs 1.04 ± 0.78 relapse/year, P =.008). POMS patients had a bigger gap to their first relapse (40.0 ± 47.35 vs 22.71 ± 34.33 months, p= .066). The difference in relapse rate between the two groups was abolished after the exclusion of patients who had a gap of more than 5 years to their first relapse. AOMS patients were significantly more likely to start with a second-line disease-modifying treatment (DMT) than POMS patients (11.5% vs 31%, p= .04), whereas POMS patients were more likely to be escalated to the second line (34.6% vs 19.3%, p= .07). ARR had a positive and significant correlation with expanded disability status scale (EDSS) progression per year (rs(24)= .57 p=.003). A Mann-Whitney test indicated that POMS patients who had infratentorial involvement in the initial MRI brain had higher EDSS (3.08 ± 1.99) than POMS who did not (1.07 ± 0.79) U=24 P =.013. IgG index had a significant and positive correlation with annual EDSS progression rate rs (8) = 0.8 p=.001. CONCLUSION: Early disease onset does not mean a higher relapse rate when including the full spectrum of POMS and longer follow-up duration. POMS patients relapsed more on the first-line DMT and escalation should be considered early. Infratentorial involvement in the initial magnetic resonance imaging (MRI) brain and high IgG index are potential predictors for aggressive disease course in POMS.

IgG index of cerebrospinal fluid can reflect pathophysiology associated with Lewy bodies in Parkinson's disease.

BACKGROUND: Neuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation. The IgG index of CSF is a marker of inflammation, and may also reflect the pathophysiology of PD. AIM: We examined if the IgG index reflects the pathophysiology of PD in drug-naïve PD patients. METHOD: The subjects were 20 consecutive PD patients who underwent 123I-MIBG scintigraphy for assessment of the heart to mediastinum (H/M) ratio and wash out rate, 123I-Ioflupane SPECT for examination of the specific binding ratio in the striatum, and lumbar puncture before treatment. The CSF IgG index and levels of pathogenic proteins (total α-synuclein, oligomeric α-synuclein, total tau, phosphorylated tau and amyloid Aß1-42) were determined. The IgG index was compared with the other parameters using Spearman correlation analysis. RESULTS: The IgG index showed a significant correlation with the H/M ratio in early (r = -0.563, p = 0.010) and delayed (r = -0.466, p = 0.038) images in 123I-MIBG scintigraphy and with the CSF total tau level (r = -0.513, p = 0.021). CONCLUSION: Neuroinflammation is involved in PD pathophysiology in some patients, and a higher IgG index indicates the presence of neuroinflammation accompanied by emergence of Lewy bodies.

Comparing clinical and imaging features of patients with MOG antibody-positivity and with and without oligoclonal bands.

Introduction: Myelin-oligodendrocyte glycoprotein antibody (MOG)-associated disorder (MOGAD) is a recently identified immune-mediated inflammatory disorder of the central nervous system (CNS). The significance of oligoclonal bands (OCBs) is not fully elucidated. This study investigated the clinical differences between patients with MOGAD who tested positive or negative for OCBs. Methods: The study was conducted on 23 patients with MOG-IgG-seropositivity who presented with central nervous system (CNS) symptoms. The patients were screened and divided into OCB-positive (n=10) and OCB-negative (n=13) groups, and their demographic, clinical, and magnetic resonance imaging (MRI) features were compared. Results: The results revealed that patients with OCB-positivity had a significantly higher frequency of relapse, and their IgG index was significantly higher. Discussion: OCBs were common in MOGAD met the consensus criteria. The study concluded that careful treatment decision-making is necessary in MOG antibody-positive cases with OCB-positivity.

Free light chains as a reliable biomarker of intrathecal synthesis in the diagnosis of CNS inflammatory diseases.

OBJECTIVE: To address the diagnostic performances of cerebrospinal fluid (CSF) free light chains (FLC) measurements compared to oligoclonal bands (OCB) to support multiple sclerosis (MS) diagnosis. RESULTS: kFLC index showed the highest diagnostic accuracy to detect MS patients with the highest AUC compared to OCB, IgG index, IF kFLC R, kFLC H, λFLC index and IF λFLC. CONCLUSIONS: FLC indices are biomarkers of intrathecal Immunoglobulin synthesis and central nervous system (CNS) inflammation. kFLC index can discriminate between MS and other CNS inflammatory disorders, while λFLC index is less informative for MS but can play a role to support the diagnosis of other inflammatory CNS disorders.

Variation in processes and reporting of cerebrospinal fluid oligoclonal banding and associated tests and calculated indices across Canadian clinical laboratories.

OBJECTIVES: Multiple sclerosis is diagnosed based on clinical and laboratory findings, including cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis. The lack of updated CSF OCB laboratory guidelines in Canada has likely led to variation in processes and reporting across clinical laboratories. As a first step to developing harmonized laboratory recommendations, we examined current CSF OCB processes, reporting, and interpretation across all Canadian clinical laboratories currently performing this test. DESIGN AND METHODS: A survey of 39 questions was sent to clinical chemists at all 13 Canadian clinical laboratories performing CSF OCB analysis. The survey included questions regarding quality control processes, reporting practices for CSF gel electrophoresis pattern interpretation, and associated tests and calculated indices. RESULTS: The survey response rate was 100%. Most (10/13) laboratories use ≥2 CSF-specific bands (2017 McDonald Criteria) as their CSF OCB positivity cut-off and only 2/13 report the number of bands with every report. Most (8/13 and 9/13) laboratories report an inflammatory response pattern and monoclonal gammopathy pattern, respectively. However, the process for reporting and/or confirming a monoclonal gammopathy varies widely. Variation was observed for reference intervals, units, and the panel of reported associated tests and calculated indices. The maximum acceptable time interval between paired CSF and serum collections varied from 24 h to no limit. CONCLUSIONS: Profound variation exists in processes, reporting, and interpretation of CSF OCB and associated tests and indices across Canadian clinical laboratories. Harmonization of CSF OCB analysis is required to ensure continuity and quality of patient care. Our detailed assessment of current practice variation highlights the need for clinical stakeholder engagement and further data analysis to support optimal interpretation and reporting practices, which will aid in developing harmonized laboratory recommendations.

Mollaret Meningitis Caused by Varicella-Zoster Virus: A Case Report.

Mollaret meningitis is a recurrent aseptic meningitis mostly caused by herpes simplex virus type 2. Other causes of the disease rarely exist, and its pathology is not well understood. Herein, we present a 57-year-old man who had been admitted to our hospital eight times with recurrent aseptic meningitis. Although the deoxyribonucleic acid (DNA) of varicella-zoster virus (VZV) was not detected in the cerebrospinal fluid (CSF), his genetic analysis, measurement of anti-VZV immunoglobulin-G (IgG) in the CSF, the VZV IgG index, IgG in the serum, and interleukin-1 beta in the CSF revealed that the Mollaret meningitis had been caused by the VZV. This case demonstrates that Mollaret meningitis can be caused by the VZV when specific factors are associated with decreased immune response. This case is valuable in elucidating the pathophysiology of Mollaret meningitis.

An Update on Laboratory-Based Diagnostic Biomarkers for Multiple Sclerosis and Beyond.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) inflammatory demyelinating disease in which analysis of clinical presentation, imaging studies, and laboratory tests aid in diagnosis. CONTENT: This review discusses laboratory tests ordered to rule out and rule in MS, such as the traditional measurement of cerebrospinal fluid (CSF) IgG index and oligoclonal bands. Biomarkers discovered in the past 2 decades, such as aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies, have been incorporated into clinical practice in the diagnosis of disorders referred to as MS mimics. The importance of test selection, assay methodology, optimal sample for testing, and diagnostic utility of these biomarkers is reviewed. Other laboratory testing that can aid in the differentiation between MS and these biomarker-defined CNS demyelinating diseases is described. There is a focus on emerging biomarkers such as the use of kappa immunoglobulin free light chain concentration in CSF and kappa CSF index measurement as an alternative to oligoclonal bands which has a potential for an improvement in laboratory workflows. Finally, the role of biomarkers of disease activity and prognosis are discussed, including neurofilament light chain, glial fibrillary acidic protein, and myelin basic protein. Future perspectives with improved laboratory testing tools and discovery of additional biomarkers are provided. SUMMARY: Laboratory testing for demyelinating disorders using CSF and serum are routine practices that can benefit from an update, as novel biomarker-defined entities have reduced the potential for MS misdiagnosis, and CSF/serum biomarkers reinstated in the diagnostic criteria of MS.

Relationship between hepatitis C virus (HCV) IgG index values and quantitative HCV RNA results in HCV IgG-reactive serum samples.

Centers for Disease Control guidelines recommend hepatitis C virus (HCV) RNA testing of all HCV IgG-reactive samples, although earlier studies found that IgG-reactive samples with low indices were negative in qualitative RNA assays. To determine if previous study results could be confirmed using current real-time RT-PCR technology, we investigated the relationship between HCV IgG index (Ortho VITROS) and quantitative HCV RNA results (cobas HCV) for 2368 consecutive IgG-reactive sera. Results were segregated into Low (1.00-16.0), Medium (16.1-30.0), and High (>30.0) IgG index groups. Although median viral load (VL) of RNA-positive samples was similar in all 3 groups, the percentage with low VL (1.18-4.16 log IU/mL) was increased for the Low group. Further analysis of the Low group revealed that 23 of 370 (6%) samples with IgG indices ≤8.00 were RNA-positive, and 13/23 (57%) had low VL. Our analysis supports the Centers for Disease Control recommendation to test all HCV IgG-reactive sera for HCV RNA.

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 (k = 0.4, p < 0.001) with the diagnosis while CSF-OCB failed to discriminate (k = 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 k > 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.

The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case-Control Study.

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort. Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis. Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P < 0.01). The QALB stratification analysis showed that the ranges of 10 < QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB > 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P < 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P < 0.01). Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.

Specificity and Diagnostic Utility of Cerebrospinal Fluid CXCL13 in Lyme Neuroborreliosis.

BACKGROUND: Demonstration of intrathecal production of Borrelia-specific antibodies (ITAb) is considered the most specific diagnostic marker of Lyme neuroborreliosis (LNB). Limitations include delayed detectability in early infection and continued presence long after successful treatment. Markers of active inflammation-increased cerebrospinal fluid (CSF) leukocytes, protein, and CXCL13-provide nonspecific markers of active infection. To assess the utility of CSF CXCL13, we measured its concentration in 132 patients with a broad spectrum of neuroinflammatory disorders, including LNB. METHODS: CSF CXCL13 was measured by immunoassay. Spearman rank correlation test was performed to explore its relationship to conventional markers of neuroinflammation and Borrelia-specific ITAb production. RESULTS: In non-LNB neuroinflammatory disorders, CSF CXCL13 elevation correlated with CSF immunoglobulin G (IgG) synthesis and leukocyte count. In LNB, CXCL13 concentration was far greater than expected from overall CSF IgG synthesis, and correlated with Borrelia-specific ITAb synthesis. Median CSF CXCL13 concentration in ITAb-positive LNB patients was > 500 times greater than in any other group. CONCLUSIONS: Intrathecal CXCL13 and IgG production are closely interrelated. CXCL13 is disproportionately increased in "definite LNB," defined as having demonstrable Borrelia-specific ITAb, but not "probable LNB," without ITAb. This disproportionate increase may help identify patients with very early infection or those with active vs treated LNB, or may help to differentiate ITAb-defined active LNB from other neuroinflammatory disorders. However, its reported specificity is closely related to the diagnostic requirement for ITAb. It may add little specificity to the demonstration of a pleocytosis or increased overall or specific IgG production in the CSF.

IgG Antibodies, SARS-CoV-2 Load, and Prognostic Indicators in Patients with Severe and Mild COVID-19 in Japan.

We assessed the association of severity of coronavirus disease 2019 (COVID-19) with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load, IgG antibody level, and prognostic indicators.Twenty-one patients hospitalized with COVID-19 were classified as having severe or mild disease on the basis of average respiratory rate during hospitalization (severe: ≥22 breaths/min; mild: <22 breaths/min). Viral load in nasopharyngeal samples, blood levels of C-reactive protein (CRP), lymphocytes, and D-dimer on admission and plasma immunoglobulin G (IgG) index on Day 7±2 after symptom onset were compared in relation to disease severity. Seven patients had severe disease and 14 had mild disease. Those with severe disease had a significantly higher IgG index (median: 3.75 vs 0.56, p=0.01) and CRP (median: 8.6 vs 1.0 mg/dL, p<0.001) and D-dimer levels (median: 1.65 vs 0.75 µg/mL; p=0.002) and a significantly lower lymphocyte count (median: 1,176 vs 666 cells/µL, p=0.005) and viral load (median: 8.7×106 vs 2.3×104 copies/mL, p=0.005). Furthermore, time from symptom onset to virus disappearance was significantly longer in severe patients (median: 24 vs 17 days, p=0.03). A high IgG index in the early phase of the disease was associated with severe disease and might serve as a prognostic indicator.

[Generalized spinal cord atrophy and oligoclonal IgG band in the cerebrospinal fluid due to chronic toluene intoxication: a case report].

We herein report the case of a 54-year-old man who abused toluene for 25 years and gradually developed gait disturbance. Neurological findings showed mild cognitive impairment, hearing impairment, dysarthria, marked hyperreflexia of the limbs, spastic paraplegia, slight impairment of deep sensation, and urinary disturbance; however, there was no muscular atrophy. Serum antibodies against human T-lymphocytic virus 1 and aquaporin 4 were negative. Biochemical analysis did not show an increase in very-long-chain fatty acids. The cerebrospinal fluid was normal for the cell number and protein level but positive for oligoclonal IgG band, with a mildly increased IgG index. Brain MRI showed marked high intensity in the bilateral periventricular, deep cerebral and subcortical white matter as well as atrophy of the cerebrum, cerebellum and brainstem, and thinning of the corpus callosum. Spinal MRI showed marked atrophy of the lower cervical spinal cord, thoracic spinal cord, and conus medullaris. Spinal cord lesions are extremely rare in chronic toluene intoxications, and there are no reports of spinal cord atrophy. Lateral and ventral columns of the spinal cord are responsible for pyramidal tract signs, and insidious ongoing inflammation related to chronic toluene intoxication in the central nervous system is predicted to underlie the pathogenesis.

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.

Immunoglobulin G index as a biomarker of relapse response to corticosteroids during early stages of multiple sclerosis.

BACKGROUND: Despite the considerable advances in disease modifying therapy in multiple sclerosis (MS), management of acute MS relapses remains understudied. The response to relapse therapy is heterogenous among patients, and the exact reason behind such response remains elusive. Identification of a reliable biomarker for relapse responsiveness would contribute considerably to optimizing the relapse outcome. OBJECTIVES: to explore whether the immunoglobulin G (IgG) index during acute relapse contributes to relapse response to corticosteroid therapy or not. METHODS: A prospective study was conducted on 46 MS patients attending MS clinic in relapse with a baseline EDSS≤3 before the relapse. IgG index was measured in all patients before corticosteroids therapy, and their EDSS was re-assessed after 3 months. RESULTS: The mean age of the recruited patients was 26.89±4.19 years, with females constituting 71.7% of the sample. IgG index was significantly higher in patients who recovered fully after relapse (1.44) than those who were partially recovered (0.95)(P<0.001), and it was inversely correlated with EDSS increase after the relapse (r=-0.390, P = 0.007). On regression analysis, the OR of IgG index to relapse response was 0.05 (CI: 0.07-0.31, 95%)(P = 0.003). CONCLUSIONS: IgG index can be a promising biomarker of relapse response to steroids in early stages of MS.

Relevance of cerebrospinal fluid findings in patients with multiple sclerosis and seizures.

Seizures occur 2-3 times more frequently in Multiple Sclerosis (MS) patients compared to the general population. The prevalence of seizures is reported to be 1.5-7.8% in MS population. However, it is unclear if seizure is an indirect symptom of neuroinflammation in MS. In our study, we explored the relevance of cerebrospinal fluid (CSF) findings in this unique patient cohort with MS and seizures. We retrospectively reviewed the charts of 32 MS patients with subsequent seizures (MSSS) and 12 patients with seizures followed by MS (SFMS). These two study groups were compared with two control groups - MS without seizures (MSNOS) and seizures without MS (SNOMS). Clinical characteristics and CSF findings between these groups were compared using boot strapped independent t-test. The CSF lymphocyte percentage of the SFMS group (95.6 ±â€¯3) was significantly higher compared to MSNOS (66.0 ±â€¯36.9, p = .04) and SNOMS (81.7 ±â€¯10.0, p = .03). The CSF IgG index was significantly higher in SFMS group (1.9 ±â€¯1.2, p = .02) as compared to MSSS group (0.99 ±â€¯0.4). Patients with seizures as initial symptom of MS may have higher degree of CNS inflammation. Nonspecific clinical symptoms and atypical imaging findings in patients presenting with seizures may warrant close monitoring for development of MS.