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J Oger

Publications and source records attributed to J Oger.

At least 19 recordsLinked to original sources
PubMed2006

Acetylcholine receptor antibodies in myasthenia gravis are associated with greater risk of diabetes and thyroid disease.

OBJECTIVE: Myasthenia gravis (MG) may be associated with the presence of acetylcholine receptor antibodies (AChRAb) [seropositive MG (SPMG)] or their absence [seronegative MG (SNMG)]. Along with features of MG, the presence of the AChRAb may relate to the existence of other immune-mediated diseases. We sought to determine the association of SPMG with other potential autoimmune diseases. METHODS: A retrospective evaluation of prospectively identified MG patients at a tertiary care center was performed, with patients separated into SPMG and SNMG. Prevalence of other immune-mediated disorders, as well as the epidemiology, sensitivity of diagnostic testing, and thymic pathology, was contrasted between both patient groups. RESULTS: Of the 109 MG patients identified, 66% were SPMG. SPMG was associated with a greater likelihood of significant repetitive stimulation decrement, the presence of either thymoma or thymic hyperplasia, and the presence of thyroid disease. In addition, all patients with a diagnosis of diabetes, concurrent with MG, were found to be SPMG. CONCLUSIONS: AChRAb and SPMG impart not only a distinctive clinical and electrophysiological phenotype of MG, but are also associated with the heightened presence of endocrinological disease.

Adolescent↗
PubMed2005

Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study.

The efficacy of interferon (IFN) beta has been shown in several placebo-controlled, parallel-group studies in relapsing-remitting multiple sclerosis (RRMS). PRISMS, the largest such study to date, clearly demonstrated the efficacy of IFN beta-1a on all outcome measures over 2 years during the placebo-controlled, parallel-group phase. However, this study's placebo-crossover design also provided us with a unique opportunity to conduct a prospective within-group assessment, eliminating the impact of inter-patient variability. At the start of year 3, patients receiving placebo during years 1-2 were re-randomized in a dose-blinded fashion to receive IFN beta-1a, 22 or 44 mcg subcutaneously three times weekly, during years 3 and 4. Clinic visits occurred 3-6 monthly and T2 MRI scans were obtained after 1 and 2 years on therapy. Comparison of the mean relapse count per patient over 2 years (the primary outcome measure) during time on placebo (years 1 and 2) with that during active treatment (years 3 and 4) revealed a decrease from 2.6 to 1.2 in both dose groups (54% relative reduction; p<0.001). Disability progression, T2 MRI lesion activity and accumulation of T2 lesion burden were also significantly improved with therapy (p<0.01). No new safety issues were noted. These data provide further support for IFN beta-1a's efficacy in RRMS. The ability to detect significant treatment effects with reduced patient numbers in this type of before/after analysis, may be due to the reduction in inter-patient variability.

Adult↗
PubMed2004

Water content and myelin water fraction in multiple sclerosis. A T2 relaxation study.

BACKGROUND: Measurements of the T2 decay curve provide estimates of total water content and myelin water fraction in white matter in-vivo, which may help in understanding the pathological progression of multiple sclerosis (MS). METHODS: Thirty-three MS patients (24 relapsing remitting, 8 secondary progressive, 1 primary progressive) and 18 controls underwent MR examinations. T2 relaxation data were acquired using a 32-echo measurement. All controls and 18 of the 33 MS patients were scanned in the transverse plane through the genu and splenium of the corpus callosum. Five white matter and 6 grey matter structures were outlined in each of these subjects. The remaining 15 MS patients were scanned in other transverse planes. A total of 189 lesions were outlined in the MS patients. Water content and myelin water fraction were calculated for all regions of interest and all lesions. RESULTS: The normal appearing white matter (NAWM) water content was, on average, 2.2% greater than that from controls, with significant differences occurring in the posterior internal capsules, genu and splenium of the corpus callosum, minor forceps and major forceps (p<0.0006). On average, MS lesions had 6.3% higher water content than contralateral NAWM (p<0.0001). Myelin water fraction was 16% lower in NAWM than for controls, with significant differences in the major and minor forceps, internal capsules, and splenium (p<0.05). The myelin water fraction of MS lesions averaged 52 % that of NAWM. CONCLUSIONS: NAWM in MS has a higher water content and lower myelin water fraction than control white matter. The cause of the myelin water fraction decrease in NAWM could potentially be due to either diffuse edema, inflammation, demyelination or any combination of these features. We present a simple model which suggests that myelin loss is the dominant feature of NAWM pathology.

Adult↗
PubMed2003

A sensitive radioimmunoprecipitation assay for assessing the clinical relevance of antibodies to IFN beta.

BACKGROUND: Some multiple sclerosis (MS) patients treated with interferon beta (IFN beta) develop antibodies to the drug. Neutralising antibody (NAB) assays for IFN beta are expensive and the clinical relevance of the results has been debated. OBJECTIVE: To establish a cheap, sensitive, and reliable assay for antibodies to (125)I-IFN beta, and to correlate levels of antibodies with clinical response to IFN beta treatment. METHODS: We established a radioimmunoprecipitation assay (RIPA) using (125)I-IFN beta. We tested NAB positive sera, healthy control sera, and serial samples of 33 IFN beta-1b treated MS patients from the Vancouver cohort of the Berlex pivotal trial who had a high incidence of NABs. RESULTS: We found that the RIPA was highly sensitive for the detection of antibodies to IFN beta-1a and -1b, and that there was a strong correlation between reactivity of NAB positive sera for (125)I-IFN beta-1b and for (125)I-IFN beta-1a. The RIPA was more sensitive and consistent than the NAB. Moreover, there was a trend towards poorer MRI outcomes in RIPA positive patients, but not in NAB-positive patients. CONCLUSIONS: The RIPA assay is sensitive and easy to perform. It should be of value in assessing the clinical impact of IFN beta antibodies, and its use could help target expensive INF beta treatments to those who will respond best.

Antibodies↗
PubMed2003

Clinical presentation of primary progressive multiple sclerosis 10 years after the incidental finding of typical magnetic resonance imaging brain lesions: the subclinical stage of primary progressive multiple sclerosis may last 10 years.

BACKGROUND: Subclinical multiple sclerosis (MS) has been identified incidentally at autopsy; apparently unaffected individuals with an affected twin have demonstrated magnetic resonance imaging (MRI) changes consistent with MS, and 'MRI relapses' are several times more common than clinical relapses. CASE DESCRIPTION: A 39-year-old, right-handed man underwent MRI and PET scanning in 1986 as a 'normal' control in a Parkinson's disease study, where his father was the proband. MRI indicated multiple areas of abnormal signal intensity in a periventricular and grey-white matter junction distribution. Repeated clinical evaluations over the next 10 years were unchanged until 1996, when he complained of progressive weakness of the right foot and clumsiness in the right hand. MRI now indicated a further area of high signal intensity in the right posterior cord at the level of C5/C6. There was mild pyramidal distribution weakness in the right leg with an extensor plantar response on the same side. Over the next five years there has been mild progression in weakness and fatigue and intermittent Lhermitte's phenomenon. At no stage has there been a history of relapse, cerebrospinal fluid examination was normal and evoked responses (visual and somatosensory) are normal. CONCLUSION: This case demonstrates the phenomenon of subclinical MS, unusually supported by prolonged clinical and MRI follow-up. The patient eventually became symptomatic nine years after MRI diagnosis and is following a primary progressive course. Although MRI is known to be sensitive in identifying subclinical 'attacks', the pattern illustrated here may actually be quite typical of primary progressive MS and is compatible with the later onset seen in this subgroup of patients.

Adult↗
PubMed2003

Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia.

We describe eight patients with associated multiple sclerosis (MS) and myasthenia gravis (MG). Patients were less than 50 years old at the time of onset, and seven were female. The clinical course of both MS and MG was mild in most patients. To our knowledge, this represents the largest reported series. We provide further evidence for a nonrandom association of these two diseases and discuss common mechanisms of pathogenesis.

Adult↗
PubMed2001

Potassium channel antibodies in two patients with reversible limbic encephalitis.

Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage-gated potassium channels (VGKC) were detected retrospectively in serial serum samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been detected in the years following presentation. Plasma exchange was effective in reducing VGKC antibody levels, with substantial improvement in mental symptoms in patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years, with almost complete recovery of mental function. Although neither patient had obvious neuromyotonia at presentation, both showed excessive secretions. We suggest that patients with limbic symptoms and excessive secretions should be tested for VGKC antibodies, and, if they are present, prompt and effective immunosuppressive treatment should be considered.

Aged↗
PubMed2001

Genetic susceptibility to MS: a second stage analysis in Canadian MS families.

Four published genome screens have identified a number of markers with increased sharing in multiple sclerosis (MS) families, although none has reached statistical significance. One hundred and five markers previously identified as showing increased sharing in Canadian, British, Finnish, and American genome screens were genotyped in 219 sibling pairs ascertained from the database of the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No markers examined met criteria for significant linkage. Markers located at 5p14 and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS was confirmed (P<0.0001). Significant transmission disequilibrium was also observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of searching for genes with only mild-to-moderate effects on susceptibility, although large effects of specific loci may still be present in individual families. Future progress in the genetics of this complex trait may be helped by (1) focussing on more ethnically homogeneous samples, (2) using an increased number of MS families, and (3) using transmission disequilibrium analysis in candidate regions rather than the affected relative pair linkage analysis.

Canada↗
PubMed2000

A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain.

OBJECTIVE: To determine the pathologic basis of areas not exhibiting signal of the short-T2 component of the T2 relaxation distribution in MS, as studied in formalin-fixed brain. BACKGROUND: A myelin-specific MRI signal would be of great importance in assessing demyelination in patients with MS. Evidence indicates that the short-T2 (10 to 50 millisecond) component of the T2 relaxation distribution originates from water in myelin sheaths. The authors present two cases of MS in which the anatomic distribution of the short-T2 component was correlated with the pathologic findings in postmortem formalin-fixed brain. METHOD: One half of the formalin-fixed brain was suspended in a gelatin-albumin mixture cross-linked with glutaraldehyde, and scanned with a 32-echo MRI sequence. The brain was then cut along the center of the 5-mm slices scanned, photographed, dehydrated, and embedded in paraffin. Paraffin sections, stained with Luxol fast blue and immunocytochemically for 2',3'-cyclic nucleotide 3'-phosphohydrolase for myelin and by the Bielschowsky technique for axons, were compared with the distribution of the amplitude of the short-T2 component of the comparable image slices. RESULTS: The anatomic distribution of the short-T2 component signal corresponded to the myelin distribution. Chronic, silent MS plaques with myelin loss correlated with areas of absence of short-T2 signal. The numbers of axons within lesions were reduced, but many surviving axons were also seen in these areas of complete loss of myelin. CONCLUSION: In formalin-fixed MS brains the short-T2 component of the T2 relaxation distribution corresponds to the anatomic distribution of myelin. Chronic, silent demyelinated MS plaques show absence of the short-T2 component signal. These results support the hypothesis that the short-T2 component originates from water related to myelin.-1510

Aged↗
PubMed2000

Analysis of effector CD4 (OX-40+) and CD8 (CD45RA+CD27-) T lymphocytes in active multiple sclerosis.

OBJECTIVE: Recently, effector T-cell subpopulations have been identified that can be distinguished by expression of members of the TNF-R family: CD4+OX-40+ cells are CD4 helper-effector cells CD8+CD45RA+CD27 cells are CD8-killer-effector cells. We investigated whether these lymphocyte subsets were increased in the active phase of multiple sclerosis (MS). MATERIAL AND METHODS: Multiple colour immunofluorescence staining was performed on peripheral blood lymphocytes of 28 patients with active MS and of 29 healthy controls, followed by FACS analysis. RESULTS: Frequencies of CD8-killer-effector cells showed a wide interindividual range in both groups and percentages of CD4 helper-effector cells were low. No significant difference between the groups was observed for these subsets, but CD8+CD45RA-CD27 were increased in MS. In healthy individuals, CD4 helper-effector cells correlated with the total percentages of memory cells. Moreover, CD4+ and CD8 memory cells were strongly correlated. CONCLUSION: The here described recently identified effector CD4 and CD8 lymphocyte subpopulations were not increased in clinically active MS. It is however still possible that in MS, myelin-specific encephalitogenic cells reside within these subsets.

Adult↗
PubMed2000

Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group.

In this 'double-blind', randomized, placebo-controlled phase II trial, we compared an altered peptide ligand of myelin basic protein with placebo, evaluating their safety and influence on magnetic resonance imaging in relapsing-remitting multiple sclerosis. A safety board suspended the trial because of hypersensitivity reactions in 9% of the patients. There were no increases in either clinical relapses or in new enhancing lesions in any patient, even those with hypersensitivity reactions. Secondary analysis of those patients completing the study showed that the volume and number of enhancing lesions were reduced at a dose of 5 mg. There was also a regulatory type 2 T helper-cell response to altered peptide ligand that cross-reacted with the native peptide.

Dose-Response Relationship, Drug↗
PubMed1999

Blood mononuclear cells in patients with HTLV-I-associated myelopathy: lymphocytes are highly activated and adhesion to endothelial cells is increased.

We have investigated lymphocyte subpopulations and blood mononuclear cell (MNC) adhesion to activated endothelial monolayers in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy (HAM), in HTLV-I asymptomatic carriers (carriers), and in seronegative controls. HAM patients and carriers had higher levels of CD4(+)CD29(+) "memory cells" than controls (P < 0.05). The percentage of CD3(+)CD27(-) "primed T cell" was elevated in patients with HAM (P < 0.05), but not in carriers. HAM patients had higher levels of CD8(+)CD57(+) "cytotoxic cells" (P < 0.05) than controls and carriers. The percentages of CD4(+) cells coexpressing activation markers HLA-DR and CD25, and of CD8(+) cells expressing HLA-DR, were significantly higher in HAM patients and carriers than in controls. Functional experiments indicated that MNC from HAM patients adhered more to activated endothelial monolayers than MNC from carriers or controls. Blocking studies demonstrated that the adhesion molecules VLA-4 and ICAM-1 and also L-selectin all contributed to increased binding. Analysis of expression of molecules involved in adhesion indicated that in HAM patients, L-selectin (CD62L) expression on CD4(+) and CD8(+) subsets was lower than in controls. Interestingly, HAM patients had a lower percentage of CD4(+) subsets expressing L-selectin than carriers (P < 0.05). In contrast, the percentage of CD4(+) and CD8(+) cells expressing VLA-4 (CD49d) was found to be higher in both HAM patients and carriers compared with controls. After 2 days in culture without mitogen, the percentage of T cells expressing ICAM-1 (CD54) increased in culture in carriers and more profoundly in HAM, but not in controls (P < 0. 05). After culture, T cells expressing the early activation antigen CD69 were also increased in HAM and carriers (P < 0.05) but not in controls. Interestingly, the levels of CD8(+) cells coexpressing activation antigen HLA-DR and CD38 were higher in HAM patients compared with both carriers and controls (P < 0.05) after culture. These findings are consistent with the observations that HTLV-I produces chronic lymphocyte activation with increased adhesion. This may be sufficient to initiate events leading to central nervous system inflammation and ultimately to HAM.

Adult↗
PubMed1999

The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b.

The fate of the neutralizing antibody (NAB) in MS patients treated with interferons remains unclear. We conducted a follow-up survey of NAB titers in 59 long-term treated patients from the London and Vancouver cohorts of the pivotal trial of interferon alpha-1b. NAB were measured with the myxovirus protein A assay and an ELISA, at a mean follow-up that exceeded 8 years. NAB disappeared in the majority of patients.

Antigen-Antibody Reactions↗
PubMed1999

Treatment with interferon beta-1b improves quality of life in multiple sclerosis.

BACKGROUND: The Canadian Burden of Illness Study Group reported that the quality of life (QoL) of multiple sclerosis (MS) patients falls drastically, early in the disease. With disability progression, the physical functioning scales of the Short Form 36 (SF-36) showed further decreases in QoL. The objective of this study is to describe the QoL of MS patients treated with interferon beta-1b (IFNB-1b) and to compare it to the QoL observed in a group of patients who had not been treated with IFNB-1b. METHODS: Treated patients were prospectively recruited and were seen at their regular visit to the MS clinic. They self-completed the SF-36 questionnaire and their QoL was described and retrospectively compared to that of historical controls. RESULTS: When IFNB-1b treated patients were compared to historical control patients with the same relapsing forms of MS, the treated patients with an Expanded Disability Status Scale (EDSS) score lower than 3.0 had a significantly better QoL. This was significant for four of the eight SF-36 domains: Physical Function (+22%, p = 0.0102), Role-Physical (+100%, p = 0.0022), General Health (+27%, p = 0.0070) and Social Function (+19%, p = 0.0287). The average QoL difference was 8% in the EDSS 3.0-6.0 group and 10% in the EDSS > 6 group. CONCLUSION: Patients with relapsing forms of MS treated with IFNB-1b have better QoL than patients who are not treated, especially those with an EDSS < 3.0.

Adolescent↗
PubMed1999

Clinical evaluation of a staphylococcal protein A immunoadsorption system in the treatment of myasthenia gravis patients.

BACKGROUND: The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Plasma antibody removal by conventional means, however, is nonselective and uses replacement fluids (chiefly, albumin solution) derived from human plasma. STUDY DESIGN AND METHODS: The Canadian Apheresis Group undertook a study at two Canadian apheresis centers to clinically evaluate a staphylococcal protein A immunoadsorption system (EXCORIM) in myasthenia gravis patients. RESULTS: The immunoadsorption system was safe and well tolerated. Ten of 12 patients had improvement in their neurologic status, as measured by a 20-point scoring system. The mean improvement in the weakness score was significant for the group (p = 0.0013). CONCLUSION: Patients with myasthenia gravis respond to treatment with plasma immunoadsorption. Further studies are required for a cost-benefit analysis.

Adult↗
PubMed1999

Cerebrospinal fluid concentrations of soluble CD27 in HTLV-I associated myelopathy and multiple sclerosis.

OBJECTIVES: Stimulation of T lymphocytes via the T cell receptor strongly enhances CD27 membrane expression and induces the release of a soluble 32 kDa form of CD27 (sCD27). CD27 is a member of the TNF receptor family, a group of molecules that have important roles in lymphocyte differentiation and survival. Raised concentrations of sCD27 have been reported in various immunopathological conditions and there is evidence that this molecule can serve as a marker of T cell activation in vivo. Concentrations of sCD27 in CSF were compared between patients with T cell mediated neurological disease and non-inflammatory controls. Also, the relation of CSF-sCD27 concentrations with clinical disease activity was investigated in patients with multiple sclerosis. METHODS: Four groups were studied: (1) eight patients with HTLV-1 associated myelopathy/ tropical spastic paraparisis (HAM)/TSP), (2) eight HTLV-I carriers, (3) 41 patients with multiple sclerosis, and (4) 43 patients with other neurological disease (OND). Concentrations of CSF-sCD27 were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Quantification of CSF-sCD27 differentiates patients with HAM/TSP from HTLV-I carriers (p<0.01) and from patients with OND (p<0.001). Moreover, the multiple sclerosis patient group was different from the OND group (p<0.0001). In patients with multiple sclerosis, CSF-sCD27 concentrations were higher in 24 patients with clinically active disease than in 17 with clinically stable disease. In addition, most of the patients with multiple sclerosis with high sCD27 concentrations showed an increase in EDSS, whereas none of the patients with low sCD27 had an EDSS increase. CONCLUSIONS: As a reliable marker of immunological disease activity in inflammatory white matter disease is still not available, it is proposed that quantification of CSF-sCD27 concentrations is a good candidate. Also, it may serve as a tool to stratify neurological diseases in inflammatory and non-inflammatory states.

Adult↗