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PubMed1983

Lymphocyte populations in the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis and optic neuritis.

The cerebrospinal fluid (CSF) and peripheral blood (PB) of patients with multiple sclerosis (MS), optic neuritis (ON), and aseptic meningitis (AM) were studied with respect to the percentage of B cells (using membrane Ig fluorescence), T cells, and T-cell subpopulations (using a rosetting technique or monoclonal antibodies). In the PB of all three patient groups there were normal B-cell levels but a significant decrease in T cells compared with PB of normal individuals. In the CSF the B cells were reduced but the T cells elevated when compared with the PB of the patients, and these differences were statistically significant. The level of total T cells was not influenced by disease activity in MS or ON, but there was a significant reduction of suppressor cells in PB during disease activity in MS patients. In CSF there were also fewer suppressor cells during active disease, but the reduction was not statistically significant. Differences in B and T cells in CSF and PB indicate that the immune reactions within the central nervous system are at least partially isolated from the rest of the immune system. The changes in the T-cell subpopulations in MS support the evidence for an immunoregulatory defect in this disease.

B-Lymphocytes↗
PubMed1983

Ia-expressing cells and T lymphocytes of different subsets in peripheral nerve tissue during experimental allergic neuritis in Lewis rats.

Inflammatory infiltrates in sciatic nerves during the acute phase of experimental allergic neuritis in the Lewis rat have been characterized with regard to occurrence and distribution of Ia-expressing cells and T-lymphocyte subsets by the help of an immunohistochemical double-staining technique, enabling the simultaneous visualization of T lymphocytes and Ia-expressing non-T cells. Large numbers of Ia-expressing irregular macrophage-like/dendritic cells were seen both within inflammatory infiltrates and within afflicted nervous tissue. Many W3/13-reactive T lymphocytes of both 'helper' and 'suppressor/cytoxic' phenotypes appeared in close contact with these Ia-expressing non-T cells, particularly within the infiltrates. B lymphocytes and plasma cells were relatively few and mainly found close to endoneurial vessels.

Animals↗
PubMed1985

In vivo treatment of rats with monoclonal anti-T-cell antibodies. Immunohistochemical and functional analysis in normal rats and in experimental allergic neuritis.

The effects of intraperitoneal injection of monoclonal anti-rat T-lymphocyte antibodies were evaluated immunohistochemically and functionally in normal rats and in rats with experimental allergic neuritis. In the normal animals a single injection of OX8 antibodies, reactive with suppressor/cytotoxic T cells, completely eliminated OX8-reactive cells from peripheral lymphoid organs and from circulation, whereas the 'pan' T-cell-reactive W3/13 antibodies and the helper T-cell-reactive W3/25 antibodies only caused a partial elimination of their respective target cells. Injection of the W3/13 and W3/25 antibodies but not of OX8 antibodies led to a diminished responsiveness to allogeneic stimulation in vitro for spleen cells obtained from the treated rats, whereas the OX8 injection caused a complete elimination of the in vitro cytotoxic response to allogeneic cells in the mixed lymphocyte reaction-activated spleen cell population. When Lewis rats were injected with peripheral nerve myelin and Freund's adjuvant for the induction of EAN, treatment with W3/13 antibodies completely prevented the onset of disease, whereas treatment with the OX8 antibodies exaggerated the disease symptoms.

Animals↗
PubMed1988

Elimination of CD8+ T cells in vivo does not break induced immunospecific tolerance to experimental allergic neuritis in rats.

The role of CD8+ T 'cytotoxic/suppressor' T cells in induced immunospecific tolerance and during recovery after actively induced disease was examined by means of elimination of CD8+ cells from Lewis rats using in vivo treatment by Ox8 monoclonal antibodies, in experimental allergic neuritis (EAN). Animals depleted of CD8+ T cells after recovery from EAN did not show any clinical signs of relapse. Other animals were pretreated with the peripheral nerve basic protein P2 and thereby rendered resistant to disease induction with a potentially neuritogenic emulsion. The elimination of CD8+ T cells did not result in EAN here either. Thus, the CD8+ T-cell population does not seem to participate in the suppression of this autoimmune disease under these experimental conditions.

Animals↗
PubMed1993

T cells recognizing multiple peptides of myelin basic protein are found in blood and enriched in cerebrospinal fluid in optic neuritis and multiple sclerosis.

The cause of multiple sclerosis (MS) is unknown. Recently reported abnormal T-cell responses to several myelin proteins and myelin basic protein (MBP) peptides in peripheral blood constitute one line of evidence that autoimmune mechanisms could be involved in the pathogenesis of the disease. Monosymptomatic unilateral optic neuritis (ON) is a common first manifestation of MS and important to examine for a possible restriction of the T-cell repertoire early in the disease. T-cell activities to MBP and the MBP amino acid sequences 63-88, 110-128 and 148-165 were examined by short-term cultures of mononuclear cells from cerebrospinal fluid (CSF) and blood in the presence of these antigens, and subsequent detection and counting of antigen-specific T cells that responded by interferon-gamma (IFN-gamma) secretion. Most patients with MS and ON had MBP and MBP peptide-reactive T cells in CSF, amounting to mean values of between about 1 per 2000 and 1 per 7000 CSF cells and without immunodominance for any of the peptides. Numbers were 10-fold to 100-fold lower in the patients' blood. Values were similar in ON and MS, and no evidence was obtained for a more restricted T-cell repertoire in ON. The MBP peptide-recognizing T-cell repertoire was different in CSF than in blood in individual patients with ON and MS, thereby giving further evidence for an autonomy of the autoimmune T-cell response in the CSF compartment. No relations were observed between numbers of autoreactive T cells and presence of oligoclonal IgG bands in CSF or abnormalities on magnetic resonance imaging of the brain in ON or clinical variables of MS. The high numbers of MBP and MBP peptide-reactive T cells could play a role in the pathogenesis of ON via secretion of effector molecules, one of them being IFN-gamma, as well as in the transfer of ON to MS.

Adult↗
PubMed1994

Peptide specificity of anti-myelin basic protein antibodies in patients with acute optic neuritis and the HLA system.

Multiple sclerosis (MS) may be an autoimmune disease, partially caused by autoreactivity to myelin basic protein (MBP) and other central nervous system proteins. Acute optic neuritis (ON) is a frequent first symptom of MS. The role of the HLA system in anti-MBP antibody production in ON was investigated employing a restriction fragment length polymorphism system for genomic HLA-DQ and -DR typing and an immunospot assay for the detection of individual cells secreting antibodies to three different synthetic MBP peptides. Thirty-two out of 40 patients (80%) with ON had cells in cerebrospinal fluid secreting anti-MBP peptide antibodies while this occurred in 10/19 patients with other neurological diseases (53%; mainly in patients with inflammatory diseases in the central nervous system). This difference was statistically significant (P = 0.03). None of the three examined peptides were immunodominant in any patient group. It was found, however, that presence of HLA DR15, which is associated with MS, may be associated further with predominant production of antibodies to the MBP amino acids 63-88 in patients with ON (P = 0.002, corrected for multiple comparisons).

Adult↗
PubMed1995

Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of immunoregulatory cytokines, including the Th2 related IL-10. We describe the use of in situ hybridization with cDNA oligonucleotide probes to detect and enumerate mononuclear cells (MNC) expressing mRNA for IL-10, which is known to down-regulate Th1 cell related cytokines such as interferon-gamma. Expression of IL-10 was studied in blood MNC of MS and blood and cerebrospinal fluid (CSF) MNC of optic neuritis (ON) patients without culture and after culture in the presence of myelin basic protein (MBP), the control antigen acetylcholine receptor (AChR), and without antigen. Numbers of IL-10 mRNA expressing MNC were elevated in the MS patients' blood both when enumerated without culture and after culture with MBP. Control patients with myasthenia gravis had elevated numbers of AChR-reactive IL-10 mRNA expressing cells, while numbers of MBP-reactive IL-10 positive cells did not differ from numbers registered in cells without antigen. Patients with ON, in many instances representing early MS, had IL-10 positive blood MNC that were elevated to the same extent as in clinically definite MS, and further increased in the CSF. ON patients examined within 1 month after onset had lower numbers of MBP induced IL-10 mRNA expressing blood MNC compared with patients examined later suggesting that IL-10 is related to the degree of inflammation and outcome in ON.

Adolescent↗
PubMed1990

Plasma serotonergic activation in rats during the course of experimental allergic neuritis.

The plasma serotonin (5-HT) levels in Lewis rats were measured during the course of experimental allergic neuritis (EAN) induced by use of purified bovine myelin. The plasma 5-HT levels in EAN rats were significantly higher than those in control rats 15 days (day 15) and 20 days (day 20) after the inoculation. On day 15 and day 20, the 5-hydroxytryptophan levels in the EAN rats were higher than those in the control rats. It is suggested that 5-HT plays a role in the clinical course of EAN.

5-Hydroxytryptophan↗
PubMed2006

Multifocal objective perimetry compared with Humphrey full-threshold perimetry in patients with optic neuritis.

BACKGROUND: The aim of the study is to compare multifocal visual evoked potential (mfVEP) objective perimetry with Humphrey full-threshold visual field (HVF) perimetry, in the assessment of patients with optic neuritis (ON). METHODS: We assessed 16 patients with clinically diagnosed ON. A comparison was made between the HVF and mfVEP, based on the global severity indices of both tests and number and topography of significant abnormalities detected. The latency data and inter-eye asymmetry findings on the mfVEP were also evaluated. RESULTS: From a total of 128 quadrants analysed in the 16 patients (100 affected, 28 unaffected eyes), HVF perimetry identified a scotoma in 39/128 (30.5%) quadrants, all of which were in affected eyes; the mfVEP detected a scotoma in 68/128 (53.1%) quadrants using amplitude and/or asymmetry data (XV2=7.2485, P=0.0071). Latency plots on the mfVEP identified a significant latency deviation cluster in 20/25 (80%) affected eyes. Abnormalities were also detected in 4/7 (57%) unaffected eyes. The global severity indices in the affected eyes showed a high correlation between the two tests (r=0.73). CONCLUSIONS: The mfVEP detected more abnormalities in patients with ON than HVF perimetry. The use of latency recordings as well as combined amplitude and asymmetry plots is advantageous and has the potential to detect abnormalities not otherwise detected on HVF perimetry.

Adolescent↗
PubMed1986

Paraneoplastic optic neuritis and external ophthalmoplegia.

A 58 year old man developed bilateral optic neuritis and external ophthalmoplegia nine months before presentation with a small cell carcinoma of the lung. There was no evidence of central nervous system metastases and his ocular symptoms responded to corticosteroid therapy.

Carcinoma, Small Cell↗
PubMed2005

Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study.

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.

Adolescent↗
PubMed2004

Chromatic and luminance losses with multiple sclerosis and optic neuritis measured using dynamic random luminance contrast noise.

We measured thresholds for detecting changes in colour and in luminance contrast in observers with multiple sclerosis (MS) and/or optic neuritis (ON) to determine whether reduced sensitivity occurs principally in red-green or blue-yellow second-stage chromatic channels or in an achromatic channel. Colour thresholds for the observers with MS/ON were higher in the red-green direction than in the blue-yellow direction, indicating greater levels of red-green loss than blue-yellow loss. Achromatic thresholds were raised less than either red-green or blue-yellow thresholds, showing less luminance-contrast loss than chromatic loss. With the MS/ON observers, blue-yellow and red-green thresholds were positively correlated but increasing impairment was associated with more rapid changes in red-green thresholds than blue-yellow thresholds. These findings indicate that demyelinating disease selectively reduces sensitivity to colour vision over luminance vision and red-green colours over blue-yellow colours.

Adult↗
PubMed2005

Spatio-temporal selectivity of loss of colour and luminance contrast sensitivity with multiple sclerosis and optic neuritis.

Colour and luminance-contrast thresholds were measured in the presence of dynamic Random Luminance-contrast Masking (RLM) in individuals who had had past diagnoses of optic neuritis (ON) some of whom have progressed to a diagnosis of multiple sclerosis (MS). To explore the spatio-temporal selectivity of chromatic and luminance losses in MS/ON, thresholds were measured using three different sizes and modulation rates of the RLM displays: small checks modulating slowly, medium-sized checks with moderate modulation and large checks modulating rapidly. The colour of the chromatic stimuli used were specified in a cone-excitation space to measure relative impairments in red-green and blue-yellow chromatic channels. These observers showed chromatic thresholds along the L/(L+M) axis that were higher than those along the S-cone axis for all display sizes/modulation rates and both red-green and blue-yellow colour thresholds were higher than luminance-contrast thresholds. The principal change in thresholds with spatio-temporal changes in the display was a reduction in thresholds for L/(L+M) and S-cones with increasing check size and modulation rate. However, luminance contrast thresholds did not change with display size/rate. These results are consistent with MS/ON selectively affecting processing in colour pathways rather than in the magnocellular pathway, and that within the colour pathways neurones with opposed L- and M-cone inputs are more damaged than colour-opponent neurons with input from S-cones.

Adult↗
PubMed2002

Functional magnetic resonance imaging in acute unilateral optic neuritis.

Despite good clinical criteria for diagnosing optic neuritis (ON), only a few techniques can precisely assess its impact on visual brain function. The authors studied whether functional magnetic resonance imaging (fMRI) of visual activation reliably reflects the cerebral consequences of acute unilateral ON, and how fMRI correlates with clinical function and visual evoked potentials (VEPs). Twenty ON patients, before and after steroid treatment, were compared to 20 controls. Each eye was stimulated separately with a checkerboard pattern reversing at 1, 2, 4, and 8 Hz. VEPs were recorded the same day. Initially, affected eye responses differed significantly from those of unaffected counterparts and controls in 12 patients. Post hoc classification by fMRI criteria was correct in approximately 85%. fMRI and VEP response parameters (as well as visual acuity) correlated significantly. The higher stimulation frequencies yielded greater fMRI responses from unaffected eyes, but not from affected eyes, in controls. The fMRI responses were quantifiable in every subject, whereas in 11 ON eyes, no VEPs were obtained during the acute stage. The authors conclude that fMRI is sensitive to the cerebral response alteration during ON and might therefore contribute to evaluating the temporal evolution of the visual functional deficit during recovery or therapy.

Acute Disease↗
PubMed1975

HL-A histocompatibility antigens in optic neuritis.

HL-A and MLC typing in 54 patients with optic neruitis showed increased frequencies of the HL-A3, 7 and LD-7a determinants of approximately the same magnitude as in patients with multiple sclerosis. The frequencies of the same three determinants were not different in the 11 patients who developed multiple sclerosis during the period of follow-up compared to the remaining patients. There was a significant increase in the frequency of the HL-A3 determinant in patients with oligoclonal IgG of the cerebrospinal fluid at the onset of disease. The connection between this determinant and the occurrence of cerebrospinal fluid changes is not clear. The results suggest that optic neuritis and multiple sclerosis represent different aspects of the same disease entity, rather than two distinct diseases. HL-A and MLC typing did not seem to offer prognostic information as to the later development of multiple sclerosis in these patients, but the observation period is still short.

Adolescent↗
PubMed1975

Optic neuritis: studies on the cerebrospinal fluid in relation to clinical course in 61 patients.

A prospective study on 61 previously healthy patients with acute mono-symptomatic optic neuritis is reported. Interest was focused on changes in the cerebrospinal fluid and the clinical course with possible development of multiple sclerosis. At the beginning of the disease, a mononuclear pleocytosis was noted in 51 per cent of the patients, an elevated IgG level in 18 per cent, and an oligoclonal IgG distribution in 41 per cent. These results are in sharp contrast to those in multiple sclerosis. Eleven patients have so far developed definite multiple sclerosis. At onset only five of these had cerebrospinal fluid findings indistinguishable from those in multiple sclerosis, with pleocytosis and bands on electrophoresis. In five more patients, who subsequently developed multiple sclerosis, the cerebrospinal fluid IgG was normal at onset, but an oligoclonal IgG appeared during the follow-up; there was no correlation in time between the appearance of new symptoms and cerebrospinal fluid changes. In six patients with normal cerebrospinal fluid and four patients with only mononuclear pleocytosis at the onset of disease, the IgG pattern became oligoclonal on electrophoresis during the follow-up period, although the patients had no further symptoms or signs of disease. It was concluded, therefore, that the cerebrospinal fluid was often normal in the first attack of what later proved to be multiple sclerosis, and that a normal fluid did not preclude a development into definite multiple sclerosis. Sometimes IgG bands appeared in previously normal cerebrospinal fluid, although the patients had not experienced new symptoms.

Adolescent↗
PubMed1978

B and T lymphocytes in cerebrospinal fluid and blood in multiple sclerosis, optic neuritis and mumps meningitis.

B and T cells were defined in cerebrospinal fluid (CSF) and blood of 18 multiple sclerosis (MS), five optic neuritis, and 17 mumps meningitis patients by counting immunoglobulin-bearing lymphocytes for B cells, and the capacity of rosette formation with sheep erythrocytes of T-cell determination. Patients with MS and mumps meningitis had significantly higher T-cell values in CSF compared to blood, while the B cell value was significantly lower in CSF in mumps meningitis only. MS patients also displayed significantly lower B-cell values in blood compared to mumps meningitis patients and blood donors. No significant differences were observed between MS patients in exacerbation and in remission.

Adolescent↗
PubMed1979

Optic neuritis: local synthesis in the central nervous system of oligoclonal antibodies to measles, mumps, rubella, and herpes simplex viruses.

Antibodies to measles, mumps, rubella and herpes simplex type 1 viruses in serum and CSF of 10 patients with acute monosymptomatic optic neuritis were characterized by imprint electro-immunofixation (IEIF). Comparisons of the IEIF antibody patterns in serum and CSF indicated that a local synthesis in the central nervous system of oligoclonal virus antibodies took place in five of the 10 patients. Three of the five patients had a local synthesis of antibody to more than one type of virus. Oligoclonal IgG was detected by agarose electrophoresis of the CSF in four of the five patients with a local synthesis of virus antibodies. There was, however, no association between the locally synthesized antibodies and the oligoclonal CSF IgG, indicating that they account for only a minor fraction of the locally synthesized IgG in these patients. In the fifth patient, distinct fractions of locally synthesized virus-specific oligoclonal Ig were detected by the IEIF method, although the agarose electrophoresis showed a normal pattern of CSF IgG.

Adult↗