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BACKGROUND: Cerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Structural changes of brain arterioles cannot be visualized with routine imaging techniques in vivo. However, optical coherence tomography (OCT) is thought to be a "window to the brain". Thus, retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage. METHODS: We applied OCT-based assessment of retinal vessels, magnetic resonance imaging (MRI), and CSF biomarker analysis in a monocentric prospective cohort of 24 patients with sporadic CSVD related stroke and cognitive impairment. MRI lesions were defined according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Biomarkers were assessed using commercially available ELISA kits. Owing to the unavailability of an age-matched control-group lacking MRI-characteristics of CSVD, we compared the retinal vessel parameters in CSVD patients (73.8 ± 8.5 years) with a younger group of healthy controls (51.0 ± 16.0 years) by using an age- and sex-adjusted multiple linear regression analysis model. RESULTS: Among the parameters measured with OCT, the Wall to Lumen Ratio (WLR) but not Mean Wall Thickness (MWT) of the superior branch of the retinal artery correlated significantly with the volume of white matter hyperintensities on MRI (rs = - 0.5) and with CSF-levels of Chitinase 3 like 1 protein (rs = - 0.6), zona occludens 1 protein (rs = - 0.5) and GFAP (rs = - 0.4). MWT and WLR were higher in CSVD than in controls (28.9 µm vs. 23.9 µm, p = 0.001 and 0.32 vs. 0.25, p = 0.001). CONCLUSIONS: In this exploratory study, WLR correlated with the volume of white matter hyperintensities, and markers of vascular integrity, microglial activation, and neuroaxonal damage in CSVD. Further prospective studies should clarify whether retinal vessel parameters and CSF biomarkers may serve to monitor the natural course and treatment effects in clinical studies on CSVD.
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INTRODUCTION: Cerebrospinal fluid (CSF) analysis is important for detecting inflammation of the nervous system and the meninges, bleeding in the area of the subarachnoid space that may not be visualized by imaging, and the spread of malignant diseases to the CSF space. In the diagnosis and differential diagnosis of neurodegenerative diseases, the importance of CSF analysis is increasing. Measuring the opening pressure of CSF in idiopathic intracranial hypertension and at spinal tap in normal pressure hydrocephalus constitute diagnostic examination procedures with therapeutic benefits.Recommendations (most important 3-5 recommendations on a glimpse): The indications and contraindications must be checked before lumbar puncture (LP) is performed, and sampling CSF requires the consent of the patient.Puncture with an atraumatic needle is associated with a lower incidence of postpuncture discomfort. The frequency of postpuncture syndrome correlates inversely with age and body mass index, and it is more common in women and patients with a history of headache. The sharp needle is preferably used in older or obese patients, also in punctures expected to be difficult.In order to avoid repeating LP, a sufficient quantity of CSF (at least 10 ml) should be collected. The CSF sample and the serum sample taken at the same time should be sent to a specialized laboratory immediately so that the emergency and basic CSF analysis program can be carried out within 2 h.The indication for LP in anticoagulant therapy should always be decided on an individual basis. The risk of interrupting anticoagulant therapy must be weighed against the increased bleeding risk of LP with anticoagulant therapy.As a quality assurance measure in CSF analysis, it is recommended that all cytological, clinical-chemical, and microbiological findings are combined in an integrated summary report and evaluated by an expert in CSF analysis. CONCLUSIONS: In view of the importance and developments in CSF analysis, the S1 guideline "Lumbar puncture and cerebrospinal fluid analysis" was recently prepared by the German Society for CSF analysis and clinical neurochemistry (DGLN) and published in German in accordance with the guidelines of the AWMF (https://www.awmf.org). /uploads/tx_szleitlinien/030-141l_S1_Lumbalpunktion_und_Liquordiagnostik_2019-08.pdf). The present article is an abridged translation of the above cited guideline. The guideline has been jointly edited by the DGLN and DGN.
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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While neurofilament light chain (NfL) measurement in serum is a well-established marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial markers in serum are missing. In our study, glial fibrillary acid protein (GFAP) and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and patients with other non-inflammatory neurological diseases (OND) using the Simoa technology. Clinical data like age, gender, expanded disability status scale (EDSS) and MRI findings were correlated to neurochemical markers. We included 80 MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p < 0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups). Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p = 0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p = 0.01). in summary, we report elevated levels of GFAP in the serum of MS patients. Since serum levels of GFAP correlate with the clinical severity scores and MRI lesion count, especially in PMS patients, it might be a suitable disease progression marker.
Subject(s)
Biomarkers/blood , Glial Fibrillary Acidic Protein/blood , Multiple Sclerosis/diagnosis , Serum/chemistry , Adult , Biomarkers/cerebrospinal fluid , Cerebrospinal Fluid/chemistry , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Humans , Middle Aged , Neurofilament Proteins/blood , Neurofilament Proteins/cerebrospinal fluid , Young AdultABSTRACT
BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. OBJECTIVE: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. METHODS: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. RESULTS: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. CONCLUSION: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.
Subject(s)
Immunoglobulin G/blood , Multiple Sclerosis, Chronic Progressive/immunology , Multiple Sclerosis, Chronic Progressive/metabolism , Myelin-Oligodendrocyte Glycoprotein/immunology , Adolescent , Adult , Aged , Cohort Studies , Databases, Bibliographic , Female , HEK293 Cells , Humans , Male , Middle Aged , Transfection , Young AdultABSTRACT
BACKGROUND AND PURPOSE: To compare the frequency of intrathecal immunoglobulin (Ig) synthesis in patients with symptomatic epilepsy and epilepsy of unknown etiology ('cryptogenic'). METHODS: Patients with epileptic (n = 301) and non-epileptic (n = 10) seizures were retrospectively screened for autochthonous intrathecal Ig synthesis and oligoclonal bands (OCBs) in the cerebrospinal fluid. RESULTS: Intrathecal IgG/OCBs were detected in 8% of patients with epilepsies of unknown etiology, 5% of patients with first seizures of unknown cause and 0-4% of patients with epilepsy due to brain tumors, cerebrovascular disease or other etiologies. Intrathecal IgG/OCBs were not seen in patients with psychogenic seizures. Identical OCBs in serum and cerebrospinal fluid were more common in all patient groups (10-40% depending on underlying etiology). CONCLUSIONS: Intrathecal IgG synthesis/OCBs were observed slightly more frequently in patients with 'cryptogenic' epilepsy and with first seizures of unknown etiology than in other patient groups. However, this remained an infrequent finding and thus we could not confirm humoral immunity as a leading disease mechanism in patients with epilepsy in general or with unknown etiology in particular.
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Epilepsy/cerebrospinal fluid , Immunoglobulins/cerebrospinal fluid , Spinal Cord/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Epilepsy/etiology , Epilepsy/immunology , Female , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/cerebrospinal fluid , Immunoglobulin G/biosynthesis , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/biosynthesis , Immunoglobulin M/cerebrospinal fluid , Immunoglobulins/biosynthesis , Male , Middle Aged , Oligoclonal Bands/cerebrospinal fluid , Oligoclonal Bands/immunology , Retrospective Studies , Seizures/cerebrospinal fluid , Seizures/immunology , Seizures/metabolism , Young AdultSubject(s)
Biomarkers/cerebrospinal fluid , Brain Diseases/cerebrospinal fluid , Brain Diseases/diagnosis , Diagnostic Techniques, Neurological , Mental Disorders/cerebrospinal fluid , Mental Disorders/diagnosis , Brain Diseases/complications , Cerebrospinal Fluid/cytology , Cerebrospinal Fluid/metabolism , Humans , Mental Disorders/etiologyABSTRACT
Cerebrospinal fluid (CSF) analysis requires a combined assessment of all individual test findings in an integrated total report in order to achieve a reliable and specific diagnostic conclusion. Such a standard assessment strategy allows the identification of disease-typical result patterns and plausibility checks to avoid analytical errors. The integrated total report consists of 1) a basic CSF program with cytological and protein chemical parameters, 2) an expanded CSF program with special parameters for detection of pathogens and markers of neurodegeneration and 3) a final contextual interpretation considering methodological and clinical aspects.
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Blood Proteins/analysis , Cerebrospinal Fluid/chemistry , Cerebrospinal Fluid/microbiology , Clinical Laboratory Techniques/methods , Diagnostic Techniques, Neurological , Neurodegenerative Diseases/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Humans , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/microbiologyABSTRACT
As a chronic inflammatory disease of the central nervous system (CNS), multiple sclerosis (MS) is associated with characteristic abnormalities in cerebrospinal fluid (CSF). Thus, in addition to magnetic resonance imaging, CSF examination is a central diagnostic procedure in patients with MS, which can corroborate a diagnosis of MS and may also help to discern differential diagnoses. The most important CSF finding in MS is the detection of persistent polyspecific intrathecal immunoglobulin synthesis. This review summarizes CSF findings of patients with MS and addresses issues of relevance for clinical practice, potential diagnostic pitfalls as well as new developments in CSF diagnostics of MS.
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Biomarkers/cerebrospinal fluid , Cerebrospinal Fluid/chemistry , Diagnostic Techniques, Neurological , Immunoglobulins/analysis , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , HumansABSTRACT
With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.
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Immunotherapy/adverse effects , Immunotherapy/methods , Monitoring, Immunologic/methods , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , Humans , Immunocompetence/drug effects , Immunocompetence/immunology , Multiple Sclerosis/classificationSubject(s)
Brain Ischemia/pathology , Central Nervous System Diseases/pathology , Dendritic Cells/pathology , Encephalitis/pathology , Adolescent , Adult , Aged , Amino Sugars/metabolism , Brain Ischemia/complications , Central Nervous System Diseases/complications , Dendritic Cells/metabolism , Encephalitis/complications , Female , Humans , Inflammation Mediators/metabolism , Macrophages/pathology , Male , Middle Aged , Young AdultABSTRACT
In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.
Subject(s)
Allergy and Immunology/standards , Immunosuppressive Agents/administration & dosage , Immunotherapy/standards , Multiple Sclerosis/drug therapy , Neurology/standards , Practice Guidelines as Topic , Dose-Response Relationship, Drug , Drug Administration Schedule , Germany , Humans , Immunosuppressive Agents/standards , Multiple Sclerosis/immunologyABSTRACT
BACKGROUND: The chemokine CXCL13 has been discussed as a diagnostic parameter with high specificity for Lyme neuroborreliosis (LNB) and as a marker of disease activity. Neurosyphilis and LNB share similar characteristics. We investigated retrospectively CXCL13 levels in the cerebrospinal fluid (CSF) of patients with neurosyphilis at initial diagnosis and during treatment. RESULTS: Five patients with neurosyphilis were identified retrospectively using an electronic database in a tertiary care hospital from 2005 to 2012. CXCL13 levels were measured using an ELISA. Five patients with definite LNB and 10 patients with multiple sclerosis (MS) served as controls. Median CXCL13 levels at baseline were 972 pg/mL for neurosyphilis patients, 8,000 pg/mL for LNB patients, and 7.8 pg/mL for MS patients. Patients with LNB and neurosyphilis showed significantly higher CXCL13 levels in their CSF compared to MS patients (p < 0.05, p < 0.001, respectively). CXCL13 levels in the CSF declined during treatment. CONCLUSION: CXCL13 levels in the CSF of patients with neurosyphilis can be as high as in patients with LNB, exceeding the proposed threshold of 250 pg/mL for the diagnosis of LNB. Patients with encephalitic/myelitic syndromes appear to have especially high levels of CXCL13. Clinicians should be aware that high levels of CXCL13 are not found exclusively in LNB but also in other infectious diseases of the CNS.
Subject(s)
Chemokine CXCL13/analysis , Neurosyphilis/cerebrospinal fluid , Neurosyphilis/diagnosis , Adult , Aged , Female , Humans , Lyme Neuroborreliosis/cerebrospinal fluid , Lyme Neuroborreliosis/diagnosis , Male , Middle Aged , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , Retrospective StudiesSubject(s)
Cerebellar Diseases/chemically induced , Immune Reconstitution Inflammatory Syndrome/etiology , Immunologic Factors/adverse effects , Leukoencephalopathy, Progressive Multifocal/chemically induced , Multiple Sclerosis/drug therapy , Natalizumab/adverse effects , Adult , Female , Humans , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immunoglobulins/administration & dosage , Immunologic Factors/administration & dosage , Natalizumab/administration & dosageABSTRACT
BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults. Over time, the disease progresses and, with accumulating disability, symptoms such as spasticity may occur. Although several treatment options are available, some patients may not respond to first-line therapeutics. However, some of these patients may benefit from intrathecally administered triamcinolone-acetonide (TCA), a derivative of glucocorticosteroids (GCS). GCS may have neurotoxic effects, and cell apoptosis may occur. The aim of this study was to investigate the effects of TCA on biomarkers in the cerebrospinal fluid (CSF) suggestive of neurodegeneration. METHODS: In order to assess neurotoxic effects of TCA, neurofilament heavy-chain (NfH)(SMI35), tau protein, and S-100B protein levels were determined before and during treatment with TCA in 54 patients with primary progressive MS, as well as relapsing MS (relapsing-remitting and secondary progressive MS). RESULTS: NfH(SMI35) levels in the CSF of patients treated with TCA intrathecally did not increase significantly during the treatment cycle (p = 0.068). After application of TCA, tau protein levels were increased significantly at day 4 (p = 0.03) and at day 8 (p ≤ 0.001). S-100B protein levels decreased significantly (p ≤ 0.05) during treatment with TCA. CONCLUSION: NfH(SMI35) levels did not change significantly; however, tau protein levels did increase significantly within the reference range. Taking these findings together, the long-term effects of TCA on NfH(SMI35) and tau protein levels need to be investigated further to understand whether levels of both biomarkers will change over repeated TCA applications. Interestingly, S-100B protein levels decreased significantly during the first applications, which may have represented reduced astrocytic activity during TCA treatment.
Subject(s)
Biomarkers/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Neurofilament Proteins/cerebrospinal fluid , S100 Calcium Binding Protein beta Subunit/cerebrospinal fluid , Triamcinolone Acetonide/administration & dosage , tau Proteins/cerebrospinal fluid , Adult , Anti-Inflammatory Agents/administration & dosage , Axons/drug effects , Axons/metabolism , Axons/pathology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Injections, Spinal , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/pathology , Neuroglia/drug effects , Neuroglia/metabolism , Neuroglia/pathology , Prognosis , Prospective StudiesABSTRACT
BACKGROUND: The level of CXCL13 is a cerebrospinal fluid (CSF) biomarker for acute Lyme neuroborreliosis (LNB) with a high sensitivity. As the concentration rapidly declines during antibiotic therapy CXCL13 can also be used as a follow-up parameter. However, CXCL13 is not yet in use as a routine parameter due to concerns about the specificity. OBJECTIVES: The sensitivity, specificity and predictive value of CXCL13 in the clinical routine work-up of suspected LNB was analyzed. MATERIAL AND METHODS: Since July 2010 the CSF of all patients (n = 204) with suspected acute LNB was not only analyzed for the routine parameters (i.e. pleocytosis and intrathecal production of Borrelia-specific antibodies, AI) but also for CXCL13. In cases of incongruent findings, a follow-up puncture after antibiotic therapy was carried out. The cut-off level for acute LNB was set at 250 pg/ml. RESULTS: This study included 179 patients who were not pretreated with antibiotics. Of these patients 15 suffered from definite LNB, 3 had a probable LNB and all had a CXCL13 value above the cut-off level. Only 2 of the 161 patients with a non-LNB diagnosis (both with a lymphoma) had a CXCL13 value in the CSF higher than 250 pg/ml. Especially noteworthy were two patients without pleocytosis in the CSF but with CXCL13 levels above the cut-off level in whom LNB could be confirmed in the follow-up CSF analysis. CONCLUSIONS: The biomarker CXCL13 has a higher sensitivity (100 % vs. 87 %) with a specificity (99 %) comparable with the established diagnostic markers for LNB, e.g. CSF pleocytosis and Borrelia-AI in the investigated patient population. The negative predictive value of CXCL13 is 100 %. Therefore, a normal CXCL13 level virtually excludes LNB. In the clinical routine CXCL13 is a valuable and practical diagnostic marker for LNB and can even detect an acute LNB in patients without CSF pleocytosis.
Subject(s)
Biomarkers/cerebrospinal fluid , Chemokine CXCL13/cerebrospinal fluid , Lyme Neuroborreliosis/cerebrospinal fluid , Lyme Neuroborreliosis/diagnosis , Acute Disease , Adult , Aged , Aged, 80 and over , Cerebrospinal Fluid/cytology , Cerebrospinal Fluid/immunology , Female , Humans , Leukocytosis/diagnosis , Male , Middle Aged , Predictive Value of Tests , Reference ValuesABSTRACT
BACKGROUND AND PURPOSE: In recent years a possible non-motor involvement of the nervous system in amyotrophic lateral sclerosis (ALS) has come into the focus of research and has been investigated by numerous techniques. Optical coherence tomography (OCT) - with its potential to reveal neuroaxonal retinal damage - may be an appropriate tool to investigate whether the anterior visual pathway is involved. Our aim was to determine whether OCT-based measures of retinal nerve fiber layer, ganglion cell layer, inner nuclear layer and outer nuclear layer thickness are abnormal in ALS, or correlated with disease severity. METHODS: Seventy-six ALS patients (144 eyes) and 54 healthy controls (108 eyes; HCs) were examined with OCT, including automated intraretinal macular segmentation. ALS disease severity was determined with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. RESULTS: There was no significant difference between ALS patients and HCs in any of the examined OCT measures. Moreover, OCT parameters showed no correlation with clinical measures of disease severity. CONCLUSIONS: These findings indicate that involvement of the anterior visual pathway is not one of the non-motor manifestations of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Optic Nerve/pathology , Tomography, Optical Coherence/methods , Adult , Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Retinal Ganglion Cells/pathology , Retinal Neurons/pathology , Retinal Photoreceptor Cell Inner Segment/pathology , Retinal Photoreceptor Cell Outer Segment/pathologyABSTRACT
Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis.
Subject(s)
Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/diagnosis , Antibodies/cerebrospinal fluid , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Cerebrospinal Fluid/cytology , Cerebrospinal Fluid Proteins/cerebrospinal fluid , Cooperative Behavior , Diagnosis, Differential , Encephalitis/cerebrospinal fluid , Encephalitis/diagnosis , Humans , Immunoglobulins/cerebrospinal fluid , Interdisciplinary Communication , Lactic Acid/cerebrospinal fluid , Leukocyte Count , Lyme Neuroborreliosis/cerebrospinal fluid , Lyme Neuroborreliosis/diagnosis , Meningitis/cerebrospinal fluid , Meningitis/diagnosis , Polymerase Chain Reaction , Predictive Value of Tests , Spinal Puncture , Tuberculosis, Central Nervous System/cerebrospinal fluid , Tuberculosis, Central Nervous System/diagnosisABSTRACT
Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.