Cerebrospinal Fluid Oligoclonal Bands Research Articles

Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors

To chart remaining complaints 1 year after treatment for neuroborreliosis, and to identify risk factors for a non-favorable outcome. We followed patients treated for neuroborreliosis prospectively, and assessed outcome by a composite clinical score. The impact on outcome of clinical, demographic and laboratory factors were analyzed by univariate analyses and logistic regression. Out of 85 patients 41 (48%) had remaining complaints; 14 had objective findings and 27 subjective symptoms. Remaining complaints were associated with pre-treatment symptom duration >or=6 weeks (OR = 4.062, P = 0.044), high pre-treatment cerebrospinal fluid (CSF) cell count (OR = 1.005, P = 0.001), and female gender (OR = 3.218, P = 0.025). Presence of CSF oligoclonal bands (OCBs) was not analyzed in the logistic regression model due to many missing observations, but was found to be more frequent both pre-treatment (P = 0.004) and after 12 months (P = 0.015) among patients with remaining complaints as compared to patients with complete recovery. Further evaluation showed that objective remaining findings, and not subjective symptoms, were associated with pre-treatment symptom duration >or=6 weeks. No difference in outcome was observed between patients treated with IV ceftriaxone and patients treated with oral doxycycline. Remaining complaints are common after neuroborreliosis. The majority of the complaints are subjective. Pre-treatment symptom duration >or=6 weeks, high pre-treatment CSF cell count, and female gender seem to be risk factors for remaining complaints. Presence of CSF OCBs may also predict a non-favorable outcome, but this should be further studied. Whether subjective and objective complaints are associated with different risk factors is also an issue for future studies.

Chlamydia pneumoniae–specific intrathecal oligoclonal antibody response is predominantly detected in a subset of multiple sclerosis patients with progressive forms

The purpose of this study was to verify the actual involvement of Chlamydia pneumoniae in multiple sclerosis (MS) by the evaluation of its specific intrathecal humoral immune response in MS. We measured by enzyme-linked immunosorbent assay (ELISA) technique cerebrospinal fluid (CSF) and serum levels of anti-C. pneumoniae immunoglobulin G (IgG) in 27 relapsing-remitting (RR), 9 secondary progressive (SP), and 5 primary progressive (PP) MS patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Twenty-one patients with other inflammatory neurological disorders (OIND) and 21 with noninflammatory neurological disorders (NIND) were used as controls. Quantitative intrathecal synthesis of anti-C. pneumoniae IgG was determined by antibody-specific index (ASI), whereas the presence of C. pneumoniae-specific CSF oligoclonal IgG bands was assessed by antigen-specific immunoblotting. ASI values indicative of C. pneumoniae-specific intrathecal IgG synthesis were present in a small proportion of MS (29.3%), OIND (33.3%), and NIND (4.8%) patients and were significantly more frequent (P < .05) in total MS and in OIND than in NIND and in SP (P < .01) and PP MS (P < .05) than in RR MS. C. pneumoniae-specific CSF-restricted OCB were detected only in three SP, one PP, and one RR MS patients. These findings suggest that an intrathecal production of anti-C. pneumoniae IgG is part of humoral polyreactivity driven by MS chronic brain inflammation. However, an intrathecal release of C. pneumoniae-specific oligoclonal IgG can occur in a subset of patients with MS progressive forms in whom a C. pneumoniae-persistent brain infection may play a pathogenetic role.

Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo

The frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) varies widely in different populations. The objective of this study was to determine the frequency of these OCB in a group of MS patients in the city of São Paulo. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. Oligoclonal bands were found in 49 (54.4%) out of 90 patients with clinically definite MS; in (31.2%) of the 16 patients with clinically isolated syndrome; in 7 (17.9%) of 39 patients with inflammatory disorders of the central nervous system (IDCNS), and in none of the individuals with no neurological condition (control group). The specificity of the method was 100% when compared to the control group and 82.1% when compared to the IDCNS group. These results suggest that the frequency of CSF OCB is much lower in Brazilian MS patients from São Paulo city than that reported in MS series from Caucasian populations.

CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis

Oligoclonal IgG bands (OCGB) are characteristic of multiple sclerosis (MS). Most patients show OCGB exclusively in cerebrospinal fluid (CSF). Others have serum bands with additional ones in CSF. Moreover, IgM bands against myelin lipids (LS-OCMB) associate with aggressive relapsing–remitting MS (RRMS). We studied oligoclonal bands in 424 MS patients. Most primary progressive (PPMS) patients showed serum OCGB with additional bands in CSF. Conversely, most RRMS and secondary progressive (SPMS) patients showed OCGB exclusively in CSF ( p < 0.0001). Moreover, no PPMS patient presented LS-OCMB, while 31% of RRMS and 60% of SPMS groups showed these antibodies ( p < 0.0001). This suggests heterogeneous autoimmune mechanisms in MS.

Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long‐term follow‐up: comparison of presenting features

The aim of this study was to compare the characteristics of the first demyelinating event between acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). Children with acute demyelinating disease of the central nervous system and an abnormal brain magnetic resonance image (MRI) were studied. Patients were assigned a final diagnosis after long-term follow-up. Comparisons were made between the MS and ADEM groups. Proposed definitions by the Pediatric MS Study Group were applied to our cohort in retrospect and are discussed. Fifty-two children and adolescents with a documented abnormal brain MRI were identified (24 females, 28 males; mean age 10y 11mo [SD 5y 4mo] range 1y 10mo-19y 7mo). To date, 26 children have been diagnosed with MS, and 24 with ADEM. One child has relapsing neuromyelitis optica and one child has clinically isolated optic neuritis. Follow-up duration was 6 years 8 months in monophasic patients, and 5 years 6 months in relapsing patients. None of the patients with MS had encephalopathy while encephalopathy was present in 42% of patients with ADEM. Cerebrospinal fluid oligoclonal bands, an elevated immunoglobulin and the periventricular perpendicular ovoid lesions correlated with MS outcome. Several clinical characteristics differ between ADEM and MS at first presentation; encephalopathy, when present, strongly suggests the diagnosis of ADEM.

Isoelectric focusing herpes simplex virus-gB overlay study in brainstem encephalitis

We report a case of herpetic brainstem encephalitis (HBE) retrospectively diagnosed in adult patient. Conventional immunovirological studies failed to disclose the etiology of this patient's affection. An isoelectric focusing-antigen overlay (IEF-O) technique showed that the target of one of the four cerebrospinal fluid oligoclonal bands was herpes simplex virus (HSV)-1 glycoprotein B, indicating a specific anti-HSV immunoresponse restricted to the CNS. IEF-O may represent a useful support for in vivo diagnosis of HBE.

The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis of multiple sclerosis

Background McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. Objective To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. Methods We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). Results We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. Conclusion OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

Demyelinating Optic Neuritis in Children

Acute demyelinating optic neuritis in children can occur in isolation or be associated with acute disseminated encephalomyelitis, multiple sclerosis, or neuromyelitis optica. Clinical features, neuroimaging, cerebrospinal fluid findings, and long-term prognosis were reviewed in 26 children diagnosed with optic neuritis at the first presentation of demyelinating disease. The risk factors for the subsequent diagnosis of multiple sclerosis were analyzed. The mean duration of follow-up was 6.2 years. To date, 6 children have been diagnosed with multiple sclerosis (23%). An abnormal brain magnetic resonance imaging, older age, oligoclonal bands in cerebrospinal fluid, and elevated immunoglobulin G index were associated with multiple sclerosis outcome. Children with monosymptomatic optic neuritis and an abnormal brain magnetic resonance imaging had a higher risk for multiple sclerosis. These children should be monitored closely for the subsequent diagnosis of multiple sclerosis and can be considered for early preventive therapy.

Optic Neuritis: An Update. II. Optic Neuritis and Multiple Sclerosis

Demyelinating optic neuritis (DON) is an acute inflammatory demyelinating disorder affecting the optic nerve. The risk of having a subsequent clinical episode elsewhere in the central nervous system leading to a diagnosis of clinically definite multiple sclerosis (CDMS) varies in different parts of the world. In countries with a high prevalence of MS, most patients with DON will eventually develop CDMS. The presence of oligoclonal bands in cerebrospinal fluid and asymptomatic lesions on magnetic resonance imaging (MRI) of the brain at presentation are strong predictors of progression to CDMS. The Optic Neuritis Treatment Trial reported that DON patients treated with intravenous methylprednisolone had a delay in progression to CDMS, but only up to two years. Interferon-β and glatiramer actetate have now been shown to reduce the risk of developing CDMS after two to three years when compared with placebo. The BENEFIT study has demonstrated that delaying interferon-β1b therapy in patients presenting with a clinically isolated syndrome (CIS) such as optic neuritis leads to a slightly higher risk for sustained disability progression compared with patients who started interferon-β1b after a CIS. Controversy remains if these small benefits of reducing conversion to CDMS from CIS and slowing disability with interferon-β treatment outweigh the adverse effects of the medication and its costs as the overall disability progression off treatment is mild, at least in the short-term, and particularly in patients in whom optic neuritis is the initial event.

CNS demyelination after treatment with bupropion

We present a case of presumed inflammatory central nervous system demyelination in association with the use of bupropion for smoking cessation. The patient developed paraesesthesia and Lhermitte's phenomenon shortly after starting the drug. There were oligoclonal bands in cerebrospinal fluid and white matter lesions in the cerebral hemispheres and cervical spinal cord. The case is discussed in the light of the known side effects of the drug.

Unusual findings in Leigh syndrome caused by T8993C mutation

The pathological nature of Leigh syndrome is highly variable and depends on the underlying mitochondrial or nuclear genome defect. Mitochondrial m.8993T>G and m.8993T>C mutations are responsible for both NARP (neurogenic weakness, ataxia and retinitis pigmentosa) and Leigh syndrome depending on the amount of mutant mtDNA. The clinical findings of Leigh syndrome caused by the m.8993T>C mutation are less severe than those associated with the m.8993T>G mutation, and ragged red fibers, oligoclonal bands in cerebrospinal fluid, and additional deficiencies of respiratory enzyme complexes are usually not found. This report presents a two year old girl with Leigh syndrome caused by a m.8993T>C mutation. Interestingly she had ragged red fibers in muscle tissue, oligoclonal bands in CSF and focal deficient histochemical staining for complexes I and IV.

Brain-specific Proteins Decline in the Cerebrospinal Fluid of Humans with Huntington Disease

We integrated five sets of proteomics data profiling the constituents of cerebrospinal fluid (CSF) derived from Huntington disease (HD)-affected and -unaffected individuals with genomics data profiling various human and mouse tissues, including the human HD brain. Based on an integrated analysis, we found that brain-specific proteins are 1.8 times more likely to be observed in CSF than in plasma, that brain-specific proteins tend to decrease in HD CSF compared with unaffected CSF, and that 81% of brain-specific proteins have quantitative changes concordant with transcriptional changes identified in different regions of HD brain. The proteins found to increase in HD CSF tend to be liver-associated. These protein changes are consistent with neurodegeneration, microgliosis, and astrocytosis known to occur in HD. We also discuss concordance between laboratories and find that ratios of individual proteins can vary greatly, but the overall trends with respect to brain or liver specificity were consistent. Concordance is highest between the two laboratories observing the largest numbers of proteins.

Detection of oligoclonal bands in cerebrospinal fluid from German Shepherd dogs with degenerative myelopathy by isoelectric focusing and immunofixation

Detection of intrathecal IgG synthesis is important in evaluating inflammatory diseases in the central nervous system. Isoelectric focusing (IEF) is currently the most sensitive method to demonstrate intrathecal IgG synthesis and may have diagnostic value for German Shepherd degenerative myelopathy (GSDM). The objective of this study was to adapt a modified IEF and immunofixation method for the detection of oligoclonal bands in cerebrospinal fluid (CSF) from dogs with GSDM. Serum and lumbar CSF samples were collected from 6 German Shepherd dogs clinically diagnosed with GSDM. Samples were also collected from 6 clinically healthy dogs for comparison. The concentration of IgG was measured by quantitative ELISA and the concentration of total protein was measured by the Bradford protein assay. The presence of oligoclonal bands was evaluated by use of modified IEF followed by immunofixation. The concentrations of total protein and IgG, and the IgG/total protein ratio in CSF samples, were not significantly different between GSDM patients and control dogs. Four GSDM patients had oligoclonal bands in their CSF based on IEF-immunofixation. No oligoclonal bands were found in CSF from control dogs. The results suggest that the detection of oligoclonal bands by IEF-immunofixation may have diagnostic value for GSDM, and support the idea that humoral immune responses may play a role in the pathogenesis of GSDM.

Cerebrospinal fluid oligoclonal bands and progression of disability of multiple sclerosis

European Journal of NeurologyVolume 15, Issue 4 p. e23-e23 Cerebrospinal fluid oligoclonal bands and progression of disability of multiple sclerosis D. Deleu, D. Deleu Neurology (Medicine), Hamad Medical Corporation, Doha, QatarSearch for more papers by this author D. Deleu, D. Deleu Neurology (Medicine), Hamad Medical Corporation, Doha, QatarSearch for more papers by this author First published: 18 March 2008 https://doi.org/10.1111/j.1468-1331.2008.02072.xCitations: 1 Dirk Deleu MD, PhD, FAAN, FRCP, Senior Consultant Neurologist, A/Head Neurology & Neurophysiology, Hamad Medical Corporation, Professor of Clinical Neurology and Neuroscience, Weill Cornell Medical College – Qatar, PO Box 3050, Doha - State of Qatar (e-mail: ddeleu@hmc.org.qa) Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume15, Issue4April 2008Pages e23-e23 RelatedInformation

Neurosyphilis révélée par une atteinte multiple des nerfs crâniens : apport de l’imagerie par résonance magnétique nucléaire

Introduction We report the magnetic resonance imaging (MRI) findings in a case of neurosyphilis revealed by the involvement of two cranial nerves. Case report A 41-year-old man developed a right cochleovestibular and left trigeminal neuropathy, associated with high serum titers of VDRL and TPHA, high titers of TPHA in the cerebrospinal fluid (CSF) and several CSF oligoclonal IgG bands. On MRI, hypertrophy and gadolinium contrast enhancement of these cranial nerves were associated with several supratentorial cortical nodules surrounded by marked cerebral edema, corresponding to syphilitic gummas. One of these cortical nodules was biopsied. Microscopic examination showed lesions of meningoencephalitis with necrosis and granulomatous vasculitis. After penicillin therapy, the serum VDRL titers and the MRI abnormalities disappeared, a partial clinical recovery was observed and a significant reduction of the serum TPHA titers was found. Discussion Such MRI abnormalities are not specific and can be observed in various tumoral, auto-immune and infectious diseases. They can also mimic neurofibromatosis type II. Cranial nerve involvements in neurosyphilis can result from nerve inflammation in basal meningitis, nerve ischemia in meningovasculitis or from compression by an adjacent gumma. In our case, the cranial neuropathy was related to a mixed meningovascular and parenchymatous form of neurosyphilis.

Progressive myoclonic ataxia with intrathecal immune activation in six patients

In six patients with slowly progressive sporadic cerebellar ataxia and cortical multifocal action myoclonus, cerebrospinal fluid (CSF) IgG index was persistently very high (1.2-6.7) and numerous oligoclonal bands were detected. Progressive cognitive impairment and MRI cerebellar and cerebral atrophy were observed. No serum antibodies were found. Various degenerative, metabolic, inflammatory and systemic diseases were excluded. The cerebellum may be the main target of a degenerative or immune process and releases antigens that, enhancing a compartmentalised (auto)immune response, as suggested by the persistent intrathecal activation, could lead to further cerebellar damage. As the frequency of CSF oligoclonal banding in myoclonic ataxia is unknown, our patients' disease might represent a hitherto unreported entity or a subset of progressive myoclonic ataxia.

Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis

Antibody-mediated inflammation is believed to contribute to tissue injury in multiple sclerosis (MS). The majority of patients with MS have oligoclonal bands (OCB), corresponding to antibodies against a variety of antigens, in their cerebrospinal fluid (CSF). The relation of CSF OCB and disease progression in MS is uncertain. To investigate whether there is a relation between CSF OCB and a more aggressive disease course of MS, 143 patients with definite MS according to the Poser diagnostic criteria and CSF analysis at time of diagnosis were followed over a period of 5 years. There were no differences in presence or number of CSF OCB between patients with significant worsening of disability and stable patients. There were no differences in presence or number of CSF OCB between patients with stable relapsing-remitting MS and patients developing secondary progression during follow-up. The presence or number of CSF OCB does not seem to influence early disease progression in MS.

Antigen-specific oligoclonal bands in cerebrospinal fluid and serum from patients with anti-amphiphysin- and anti-CV2/CRMP5 associated paraneoplastic neurological syndromes

Using isoelectric focusing and affinity blotting employing paraneoplastic recombinant antigens, we investigated cerebrospinal fluid (CSF) and sera from three patients with positive anti-CV2/CRMP5- and one patient with positive anti-amphiphysin serology. CSF and sera were previously adjusted to total IgG concentrations of 20 mg/l. All patients suffered from paraneoplastic neurological syndromes (PNS) with predominant involvement of the central nervous system (CNS). Using affinity blot preloaded with paraneoplastic antigen, we detected in three of four patients more or stronger specific oligoclonal bands (OCB) in the CSF than in the corresponding serum, providing qualitative evidence of antigen specific intrathecal antibody synthesis. These results are in line with previous studies demonstrating specific OCB predominantly in CSF from patients with anti-Hu-, anti-Yo- and anti-Ri-associated PNS, supporting the hypothesis of autoimmunity in the pathogenesis of PNS. One patient harboured extensive anti-amphiphysin specific OCB, although OCB of total IgG could not be detected, indicating a higher sensitivity for detection of intrathecal antibody synthesis of the affinity blot preloaded with the paraneoplastic antigen, compared with investigation of total IgG OCB. These results could have implications concerning pathophysiological autoimmune aspects in other inflammatory diseases of CNS associated with total IgG OCB, provided that the target antigen is known.

Cerebrospinal fluid IgG profiles and oligoclonal bands in Chinese patients with multiple sclerosis

To investigate the significance of oligoclonal bands (OCBs) and intrathecal IgG fractions (IgGIF) for the diagnosis of multiple sclerosis (MS) in northern China. OCBs in cerebrospinal fluid from 30 patients with MS, 34 with other inflammatory neurological diseases (IND) and 22 with non-inflammatory neurological diseases (NIND) were detected using isoelectric focusing. IgGIF was calculated based on corresponding formula. There was no significant difference in the frequencies of positive OCBs and elevated IgGIF between the MS group and the IND group. Compared with NIND, the MS and IND groups had a significantly higher incidence of OCBs and elevated IgGIF. The sensitivity, specificity and positive result likelihood ratio of OCBs for the diagnosis of MS were 63.3%, 74.2% and 2.5 respectively; those of IgGIF were 36.7%, 84.5% and 2.4. The two parameters, OCBs and IgGIF are of less diagnostic value for MS in China.

B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation

B cells have long played an enigmatic role in the scenario of multiple sclerosis pathogenesis. This review summarizes recent progress in our understanding of B-cell trafficking, survival, and differentiation in the central nervous system (CNS). We propose four possible routes of intrathecal immunoglobulin-producing cells. The inflammatory CNS provides a unique, B-cell-friendly environment, in which B lineage cells, notably long-lived plasma cells, can survive for many years, perhaps even for a lifetime. These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands. Furthermore, we highlight similarities and differences of intrathecal immunoglobulin production in multiple sclerosis patients and patients with other CNS inflammatory conditions. Finally, we outline the possibly double-edged effects of B cells and immunoglobulin in the CNS and discuss various therapeutic strategies for targeting the B-cell response.