Intrathecal IgG Research Articles

Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF

We investigated the correlation of antimyelin oligodendrocyte glycoprotein-(anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested,the incidence of more frequent and rapid progression to clinically definite MS (CDMS). 133CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count(p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01,respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076).Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti-MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reported.

Isoelectric focusing is superior to immunofixation electrophoresis in diagnosing CNS inflammation

A sensitive method to detect intrathecal IgG production is important in diagnosing inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). To compare cerebrospinal fluid (CSF) electrophoresis with isoelectric focusing (IEF), immunofixation-peroxidase electrophoresis (IFPE) and high-resolution agarose electrophoresis with protein-staining (HRAGE). Paired serum and CSF samples from 307 consecutive patients attending a general neurology clinic were examined with IEF, IFPE and HRAGE. Clinical diagnosis was based on review of the patients' medical records after an average of 4 years. The sensitivity for detecting any inflammatory (autoimmune or infectious) CNS disease (52 patients) was 67% for IEF, 50% for IFPE and 29% for HRAGE. The sensitivity for detecting MS (14 patients) was 93%, 86% and 29% respectively. The sensitivity for detecting clinically isolated syndrome (eight patients) was 75%, 25% and 13% respectively. The number of oligoclonal bands in IEF was higher in inflammatory than in non-inflammatory neurological diseases or symptoms, but similar in MS and other inflammatory diseases. IEF is the method of choice in diagnosing intrathecal IgG synthesis.

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.

IL-6 and CCL2 levels in CSF are associated with the clinical course of MS: Implications for their possible immunopathogenic roles

Biological markers would provide valuable tools for tracking disease activity, immunopathological processes or therapeutic efficacy in MS. In this study we analysed a panel of Th 1/Th 2 cytokines and the chemokine CCL2 in serum and CSF from MS patients and healthy controls. Increased levels of IL-6 ( p < 0.05) and decreased levels of CCL2 ( p < 0.001), with the lowest levels during acute relapses, was found in CSF from patients with relapsing–remitting MS. CSF levels of CCL2 correlated with indices for intrathecal IgG production and the CSF level of the neurofilament light protein, a marker for axonal damage, indicating a immunopathogenic role for CCL2.

Cytokines and intrathecal IgG synthesis in multiple sclerosis patients during clinical remission

Cytokines and intrathecal IgG synthesis were determined in the cerebrospinal fluid (CSF) and sera to evaluate inflammatory activity in multiple sclerosis (MS) patients during clinical remission. Although the disease was stable, there had been a significant increase of proinflammatory cytokines such as TNFalpha and IFNgamma in the CSF and serum, with no significant changes of IL12 and IL10 production. The changes in the cytokine production patterns were associated with an increase of leukocytes in the CSF, as well as the presence of oligoclonal bands suggesting intrathecal IgG synthesis. These results suggest that even when the disease is clinically silent, one can observe inflammatory activity in these MS patients.

Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) with an unknown etiology. Although intrathecal IgG synthesis is a key feature of the disease, little is still known about the B cell response in the CNS of MS patients. Here, we analyzed the phenotype and kinetics of different B cell subsets in patients with MS, infectious (IND) and non-inflammatory neurological diseases (NIND). B cells were detected in the CSF of MS and IND patients, but were largely absent in NIND patients. In the CSF the majority of B cells had a phenotype of memory B cells and short-lived plasma blast (PB), plasma cells were absent from the compartment. The proportion of PB was highest in MS patients and patients with acute CNS infection. While PB rapidly disappeared from the CSF after resolution of infection in IND patients, these cells were present at high numbers throughout the disease course in MS patients. CSF PB numbers in MS patients strongly correlated with intrathecal IgG synthesis and inflammatory parenchymal disease activity as disclosed by MRI. This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in MS patients.

Tau protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo. We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing-remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus 152.0 pg/mL; P = 0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P = 0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.

Early Differential Diagnosis of Multiple Sclerosis Using a New Oligoclonal Band Test

Intrathecal IgG synthesis (ITGS), in conjunction with magnetic resonance imaging, can help in the early diagnosis of multiple sclerosis (MS). Recently, we developed a new oligoclonal IgG band (OCGB) test for ITGS detection that is more sensitive and easier to interpret than previously described methods. To assess the accuracy of a new OCGB detection test in the diagnosis of MS. Prospective observational study. A hospital neurology department. Patients A total of 385 patients with various neurologic disorders. The sensitivity and specificity of the OCGB detection test for MS diagnosis. Intrathecal IgG synthesis was found in 127 patients with MS (96.2%), 18 (35.3%) with central nervous system infections, and 1 with motor neuron disease. Two patterns reflected ITGS. One pattern, showing OCGBs restricted to cerebrospinal fluid, was predominantly found in MS. The other pattern, with OCGBs in serum and additional bands in cerebrospinal fluid, was mostly found in central nervous system infections. No patients with other inflammatory neurologic diseases showed ITGS. These patients frequently displayed a mirror pattern, with identical bands in serum and cerebrospinal fluid. Considering all patients, the sensitivity for the diagnosis of MS was 96.2%, and the specificity was 92.5%. Excluding infections, which usually do not present a differential diagnosis problem with MS, the sensitivity was still 96.2%, and the specificity increased to 99.5%. The accuracy of this OCGB method reinforces the value of cerebrospinal fluid studies in the early differential diagnosis of MS.

HIV?induced chorea

Sirs: Neurological disorders cooccur with the acquired immunodeficiency syndrome (AIDS) in approximately 30–50 % of AIDS patients [1], e. g. HIV-1-associated dementia (HAD) [2]. Movement disorders, mostly due to Toxoplasmosis abscesses but also with other rare causes, appear in 2–3 % of these patients [2, 3]. We describe a 32-year-old HIV-infected patient with chorea, which in all probability was caused by HAD. The generalized, but asymmetric (left > right) involuntary movements of the trunk and the extremities in our patient had progressed over the preceding 6 months. The CD4 cell count was 310 cells/μl and the patient received highly active antiretroviral treatment and also pyrimethamine as a secondary prophylaxis for cerebral toxoplasmosis, which had occurred 3 years before. At that time minor cognitive deficits had suggested mild HAD, but all symptoms had improved during closely monitored treatment. The current brain MRI showed marked frontal atrophy with white matter hyperintensities in the T2and proton-density (PD) weighted images (see Fig. 1 A and B). Compared with an MRI examination 2 years previously, these findings had worsened. However, the structure and signaling of the basal ganglia were not pathological. The SPECT binding study with 187 MBq 123Iodine-IBZM (binding to postsynaptic dopamine-D2 receptor) revealed a significant reduction on the right and a slight reduction on the left in the striatum (Fig. 1 C). The SPECT binding study with 188 MBq 123Iodine-DaTSCAN (binding on presynaptic dopamine transporter) showed a bilateral (right > left) reduction that was pronounced in the posterior striatum (Fig. 1 D). The PET examination with 132 MBq 18F-FDG (FDG PET) indicated that glucose utilization had significantly decreased in the right temporal, frontomesial, parietal, and central cortex as well as bilaterally in the hippocampus (right > left). The striati showed no abnormalities, but the FDG uptake in the left thalamus was slightly reduced (Fig. 1 E). CSF analysis revealed only a mildly increased CSF WBC count (7 cells/μl) and increased intrathecal IgG production. PCRs for varicella zoster virus, JC virus, and cytomegalovirus were negative. Huntington’s chorea was excluded by genetic examination. The chorea in our patient was associated with an asymmetric (right > left) dysfunction of the dopaminergic system, which is compatible with the asymmetric clinical presentation and comparable to patients with Huntington’s disease [4]. MRI and FDG PET examination, however, revealed no clear pathologies in the region of the basal ganglia. The SPECT findings suggest an asymmetric encephalopathic involvement of the basal ganglia, most probably the anatomo-clinical correlate of chorea in our patient. Interestingly, HAD worsened clinically with the appearance of chorea, but the patient’s mental status did not obviously deteriorate. FDG PET showed reduced glucose metabolism bilaterally in the hippocampus, frontomesially, parietally, and centrally, and MRI revealed an increase of white matter hyperintensities that conformed with slowly progressive HAD. HAD [5, 6] typically presents with subcortical dementia combined with slight motor disturbances, but a significant involvement of the basal ganglia during HAD has also been documented in immunohistochemical [7–9], neuroradiological [10, 11], MRI spectroscopic [12], and CSF studies [9, 13]. Ours is the first report of a dedicated SPECT study of the nigrostriatal dopaminergic system. Although a rare clinical manifestation of HAD, HIV-associated chorea should be considered in young patients who present with chorea but lack a family history of movement disorders. Dedicated SPECT studies of the nigrostriatal dopaminergic system may help establish the diagnosis of HAD-associated chorea and also provide a more detailed documentation of basal ganglia involvement. The reported SPECT abnormalities are, however, not specific for HAD-associated chorea.

Diagnostic value of CSF proteins assay in differential diagnosis of CNS disease

The differential diagnosis between inflammatory and noninflammatory diseases of CNS includes CSF quantitative measurements of immunoglobulin and albumin concentrations and their comparison to the serum. For that purpose we estimated the concentrations of albumin and immunoglobulin G both in CSF and serum of patients with inflammatory and noninflammatory diseases of CNS. Parallely, these parameters were determined in the control group composed of patients having the values of investigated parameters within reference ranges. The obtained data were statistically evaluated by nonparametric Mann-Whitney test. The values of calculated CSF/albumin ratio have shown significant differences between the both patient groups and the control one (p &lt; 0.001). It proves that in each examined group the blood brain barrier is damaged. For the assessment of intrathecal IgG synthesis we have calculated both IgG/albumin index and Schuller index. The comparison of the values obtained for patients with noninflammatory diseases to the control one, revealed no statistically significant differences (p &gt; 0.05). On the contrary, significant difference have been observed between the group with inflammatory diseases and the control (p &lt; 0.05), proving the existence of IgG intrathecal synthesis. Values of both indexes were much higher in patients with inflammatory than noninflamatory diseases, meaning that they can be used in differential diagnosis.

Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer's disease patients

It was previously shown that herpes simplex virus type 1 (HSV1) DNA resides latently in a high proportion of aged brains and that in carriers of the type 4 allele of the apolipoprotein E gene (APOE-epsilon4), it confers a strong risk of Alzheimer's disease. It was suggested that initial entry of brain by HSV1 and any subsequent reactivation(s) would cause a type of limited encephalitis, the resulting damage being more harmful in APOE-epsilon4 carriers. Reactivation(s) would induce synthesis of intrathecal antibodies; these are long-lived after herpes simplex encephalitis so they were sought in cerebrospinal fluid (CSF) of Alzheimer's disease patients and age-matched normal subjects. Intrathecal antibodies to human herpesvirus 6 (HHV6) were also sought as DNA of this virus has been detected previously in a high proportion of Alzheimer's disease brains. Antibody indices for HSV and HHV6 were measured using indirect ELISA for IgG antibody, and single radial immunodiffusion was used for albumin, in serum and CSF. A raised antibody index (>1.5) indicative of virus-specific intrathecal HSV1 IgG synthesis was found in 14/27 (52%) Alzheimer's disease patients and 9/13 (69%) age-matched normals (difference non-significant). A raised antibody index to HHV6 was detected in 22% of the Alzheimer's disease patients and in no normals, so presumably this virus either did not reactivate in brain or it elicited only short-lived intrathecal antibodies. The HSV1 results confirm the original PCR findings that show the presence of HSV1 DNA sequences in many elderly brains, and indicate also that the whole functional HSV1 genome is present, and that the virus has replicated.

Le profil cytoimmunologique du LCR lors du diagnostic précoce de la sclérose en plaques

The purpose of this paper is to report cerebrospinal fluid (CSF) findings in multiple sclerosis (MS) from our laboratory, to discuss the implications of CSF abnormalities in terms of diagnosis. Paired CSF-serum samples from of 1533 on 3893 patients with suspected neurological diseases over a 10 year period were analysed by routine laboratory microscopy and assays of immunoglobulin G by isoelectric focusing for the detection of intrathecal oligoclonal IgG. Patients were grouped further into four headings according to their disorders: MS (625 cases), definite (246 cases) probable (123 cases) and possible (256 cases) according to Poser, others inflammatory neurological diseases (91 cases), various non-inflammatory neurological disorders (732 cases) and uncertain neurological disorders (85 cases). Definite MS group (16%) was compared to non-inflammatory neurological disorders (48%). Important signs for activity of multiple sclerosis are observed. Cell counts were 10/μl in 71% ( N ≤ 2/μl). Inflammatory cytology is observed after concentration and cytocentrifugation on slides with activated B-lymphocytes, lymphoplasmocytes and/or plasmocytes (76%), total protein concentration is increased in 37% ( N < 0.40g/l), CSF/serum albumin quotient with age dependent references for the blood-CSF barrier dysfunction is increased in 26% ( N < 0.65 × 10 –2), IgG index for intrathecal synthesis of IgG is increased in 69% ( N < 0.70), sensitive detection of oligoclonal IgG restricted to CSF by isoelectric focusing is positive in 91% (86–96%) with a specificity of 96% (93–99%).

Place de l'immunofixation des IgG du LCR dans le diagnostic de sclérose en plaques (SEP)

We presented the analytical and diagnostic performances of immunofixation for detection of oligoclonal IgG bands in native unconcentrated cerebrospinal fluid (CSF) and diluted serum samples analysed in the same run on Hydragel 6 CSF Sebia on Hydrasys ® Sebia, an alternative to the manual technique of IgG isoelectric focusing (IEF). Pairs of CSF and serum of 124 patients studied over a 2 year period were classified in: 29 definite multiple sclerosis (MS) 35 possible MS, 11 inflammatory neurological diseases other than MS, and 49 non-inflammatory diseases of the central nervous system. Pairs of CSF and serum of 98 patients were tested by isoelectric focusing for control of intrathecal IgG synthesis. The analytical performances of the two techniques to reveal IgG oligoclonal bands are practically identical. The sensivity of immunofixation is 96%, of isoelectric focusing is 93%. Their specificity is 93% and 96%, respectively. The positive predictive value to establish diagnosis of MS is 90% with immunofixation and 92% with isoelectric focusing. The negative predictive value to exclude diagnosis is 97% with immunofixation and 96% with isoelectric focusing. The interpretation of IgG immunofixation is in practice more difficult than IgG isoelectric focusing, the procedure is easy and quick to perform.

Neurosarcoidosis: Clinical Experience and Diagnostic Pitfalls

Objective: To describe a group of patients with neurosarcoidosis and to highlight diagnostic difficulties based on current diagnostic criteria. Methods: The patient database of a general neurological department was searched for patients with established or suspected diagnosis of neurosarcoidosis. Twenty-four patients were identified with definite (n = 3), probable (n = 10) and possible neurosarcoidosis (n = 10). History and clinical, laboratory and imaging data of patients with definite and probable neurosarcoidosis were analyzed. Results: Cranial nerve symptoms were a dominant clinical feature, with the optic nerve being affected most frequently. Cerebrospinal fluid pleocytosis was found in more than half of the patients. Intrathecal IgG synthesis and oligoclonal bands were less frequent. There was a wide array of MRI lesions in both groups. Chest X-ray was false negative in 2 of 5 patients who also underwent a thoracic CT. Therapy with prednisolone was initiated in all patients. After a median of 36 months, 6 of 8 patients with follow-up data of >24 months were still in remission. Aggravation of symptoms required therapy escalation in 2 patients. Conclusion: There is a wide range of clinical symptoms and test results in patients with ‘definite’ or ‘probable’ neurosarcoidosis. Because systemic involvement is a crucial diagnostic criterion, extensive medical work-up may be necessary. Prognosis under corticosteroid treatment may be better than previously thought.

Intrathecal production of Chlamydia pneumoniae-specific high-affinity antibodies is significantly associated to a subset of multiple sclerosis patients with progressive forms

The purpose of this study was to provide further insight into the effective relevance of the association between Chlamydia pneumoniae and MS. We evaluated by ELISA technique cerebrospinal fluid (CSF) and serum levels of anti- C. pneumoniae IgG in 46 relapsing–remitting (RR), 14 secondary progressive (SP) and 11 primary progressive (PP) MS patients grouped according to clinical and Magnetic Resonance Imaging (MRI) evidence of disease activity. Fifty-one patients with other inflammatory neurological disorders (OIND) and 52 with non-inflammatory neurological disorders (NIND) were used as controls. A C. pneumoniae-specific intrathecal IgG synthesis as detected by the relative specific index was present in a small proportion of MS (17%), OIND (22%) and NIND (2%) patients and was significantly more frequent in MS and in OIND than in NIND ( p<0.001) and in SP and PP MS than in RR MS patients ( p<0.02). Among the patients with C. pneumoniae-specific intratecally produced antibodies, CSF high-affinity anti- C. pneumoniae IgG were found in the majority of SP or PP MS, occasionally in OIND, but not in RR MS and NIND patients. These findings confirm that the presence of a humoral immune response to C. pneumoniae within the central nervous system (CNS) is not selectively restricted to MS, but is shared by several inflammatory neurological conditions. In addition, our results suggest that an intrathecal production of C. pneumoniae-specific high-affinity IgG can occur in a subset of patients with MS progressive forms in which a C. pneumoniae brain chronic persistent infection may play an important pathogenetic role.

Viliuisk encephalomyelitis: intrathecal synthesis of oligoclonal IgG

Viliuisk encephalomyelitis (VE) is a neurodegenerative disorder expressed as subacute meningo-encephalitis progressing to a more prolonged pan-encephalitic syndrome with a fatal outcome within 1 to 10 years. Some patients survive to a steady state of global dementia and severe spasticity that may last for over 20 years. Multiple micronecrotic foci surrounded by inflammatory infiltrates are observed throughout the cerebral cortex and other gray matter areas. Infectious etiology of VE is strongly suspected, but the causative agent has not been identified. We conducted a search for assays that might be helpful for VE diagnosis and established for the first time that the majority of patients with definite VE show evidence for intrathecal IgG synthesis correlating with the clinical manifestations of the disease. This indicates that the detection of oligoclonal IgG banding in the cerebrospinal fluid is a valuable diagnostic assay for VE. Implications of these findings for a possible etiology of VE are discussed.

Distinct heterogeneity of IgG immune response in cerebrospinal fluid (CSF) detected by isoelectric focusing (IEF) with extended immunofixation

An optimized automated IEF procedure in polyacrylamide micro gels and immunofixation with 10 monospecific antibodies against some fragments of the IgG molecule and against the whole IgG isotypes IgG 1, IgG 2, IgG 3, IgG 4, respectively, detected oligoclonal bands (OBs) within acid, neutral, and alkaline ranges of the gels. Accuracy and reliability of the OB assay for detection of an intrathecal IgG synthesis proved to be higher with immunofixation than with silver staining of bands precipitated by trichloroacetic acid. CSF OBs were specified as lambda or kappa IgG subfractions, respectively, duplex IgGs precipitated with anti-lambda, anti-kappa, and anti-Fc antibodies at the same p I. Most of OBs were classified as belonging to either IgG 1, IgG 2, IgG 3, or IgG 4 isotypes in CSF. The IEF procedure additionally allowed the discrimination of both free light chains and possible “free” heavy gamma chain fragments in CSF, when immunofixation was done with monospecific antibodies against both light chains and gamma chain fragments (e.g. anti-F(ab′) 2, anti-Fd, anti-Fc, anti-C H2). The results pointed out a distinct heterogeneity of the IgG immune response in human CSF. The IEF procedure with extended immunofixation is recommended for completion of the basic laboratory procedures used in neuroimmunology in order to discriminate inflammatory processes in human CNS.

Approach to discriminate subgroups in multiple sclerosis with cerebrospinal fluid (CSF) basic inflammation indices and TNF-α, IL-1β, IL-6, IL-8

Lumbar CSF and serum pairs of untreated multiple sclerosis patients (MS; n=47) were analyzed on admission. On average, higher CSF leukocyte (lymphocyte and monocyte) counts, IgG index, CSF IgG contents, but not of TNF-α, IL-1β, IL-6, IL-8 in CSF and serum, were revealed in all MS or patients with long disease course (LO-MS) compared with controls. In primary progressive MS (PP-MS) cell counts were low, but IgG contents were high, when compared to relapsing-remitting MS (RR-MS). In clinically probable MS (CP-MS) both contents were low, in clinically definite MS (CD-MS) high. Spearman’s correlation with the four monokines and the basic indices in CSF revealed activation patterns known for microglia/macrophages in the four MS subgroups, for astrocytes in CP-MS and RR-MS, for CSF lymphocytes in CP-MS and PP-MS, for cells of blood–brain barrier (BBB) in CP-MS, for intrathecal IgG synthesis in PP-MS and for lymphocyte transfer in CD-MS. Correlations between CSF and serum parameters indicated CNS disease processes to be associated with systemic processes of inflammation (acute, chronic) in CD-MS, RR-MS, and PP-MS in different ways. CSF IgG content, IgG index and systemic markers of inflammation correlated with overall disability scores in LO-MS; increasing levels may indicate a bad outcome.

Étude biochimique du liquide céphalorachidien dans le cadre de la sclérose en plaques

The aim of the biochemical analysis of cerebrospinal fluid in support to clinical diagnosis of multiple sclerosis and inflammatory disorders of the central nervous system is the detection of intrathecal IgG synthesis. According to the European consensus report, we have developed a sensitive and specific iso-electric focusing method for detection of oligoclonal immunoglobulin banding in CSF and serum, and performed evaluation of blood-brain barrier and quantification of humoral immune response by albumin and immunoglobulin determination. We present a retrospective study of 537 patients having a CSF and serum pair analysed for intrathecal IgG synthesis study, 140 of them being suspected of multiple sclerosis according to Poser criteria. Quantitative and qualitative methods for IgG intrathecal detection are compared in the area of multiple sclerosis diagnosis contribution. This study confirms the interest to search IgG oligoclonal banding by the most sensible method (iso-electric focusing of oligoclonal IgG, according to the European consensus).

Clinical characteristics and neurophysiologic findings in patients with multiple sclerosis without oligoclonal IgG in cerebrospinal fluid

Besides magnetic resonance imaging, the presence of locally produced oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) is the most consistent laboratory abnormality in patients with multiple sclerosis (MS). The most sensitive method for the detection of CSF OCB is isoelectric focusing (IEF) [6]. Occasional patients with clinically definite MS lack evidence for intrathecal IgG synthesis [7, 8]. This study was designed to compare clinical data and evoked potential (EP) findings between CSF OCB positive and OCB negative MS patients. The study comprised 22 OCB negative patients with clinically definite MS [11] and 22 OCB positive controls matched for age, disease duration, activity and course of MS. In both groups clinical assessment was performed by using Expanded Disability Status Scale (EDSS) score [12] and progression rate (PR). All patients underwent multimodal EP: visual (VEPs), brainstem auditory (BAEPs) and median somatosensory (mSEPs). The VEPa were considered abnormal if the P100 latency exceeded 117 ms or inter-ocular difference greater than 8 ms was detected. The BAEPs were considered abnormal if waves III or V were absent or the interpeak latencies I-III, III-V, or I-V were increased. The mSEPs were considered abnormal when N9, N13 and N20 potentials were absent or when increased interpeak latencies were recorded. The severity of the neurophysiological abnormalities was scored for each modality as follows: normal EP score 0; every other EP abnormality except the absence of one of the main waves, score 1; absence of one or more of the main waves, score 2 [13]. Both mean EDSS score (4.0 vs. 3.5) and PR (0.6 vs. 0.5) were similar in OCB positive and OCB negative group, (p > 0.05). In the first group males were predominant, but without statistical significance (Table 1). Disease started more often with the brainstem symptoms in the OCB positive than in OCB negative MS group (p = 0.028), while there was no differences in other initial symptoms between the groups (Graph 2). The frequency of (multimodal) EP abnormalities was higher in the OCB positive group but the differences were not statistically significant, except for bilateral SEP abnormalities (p = 0.012). The severity of the AEPs abnormalities was similar in both groups while for the VEPs and SEPs abnormalities were more pronounced in the OCB positive group but not significantly (Table 2). The male preponderance of OCB negative MS patients in our study is in accordance with previous studies [14, 15]. This finding could be potentially ascribed to the well known gender-related differences in both humoral and cellular immune responses [17]. We found no statistically significant differences in either disability or PR between the two patient groups, although OCB negative MS patients had lower EDSS score and PR than OCB positive cases. In accordance with these findings, Fukazawa et al. also failed to show differences in disability between OCB negative and positive MS patients. On the other hand, few studies reported that OCB negative MS patients have a better prognosis [16, 18]. The only clinical difference between two groups of patients that we found was that the disease more often started with brainstem symptoms in OCB positive MS patients (p = 0.028). OCB positive MS patients had more often bilateral SEPs abnormalities (p = 0.012). There was no statistically significant differences between two groups of patients in the severity of trimodal EPs abnormalities and the frequency of BAEPs and VEPs abnormalities although OCB negative patients had trend towards less pronounced EP disturbancies. Our results did not reveal significant difference in clinical and neurophysiological(y) parameters between two groups of patients. However, they indicate a trend towards better prognosis of the disease in OCB negative MS patients.