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Joel Oger

Publications and source records attributed to Joel Oger.

14 recordsLinked to original sources
PubMed2006

During 3 years treatment of primary progressive multiple sclerosis with glatiramer acetate, specific antibodies switch from IgG1 to IgG4.

In this study we analyzed the humoral immune response to glatiramer acetate in 16 GA-treated primary progressive MS patients and 9 placebo patients from the PROMiSe study. We have demonstrated that all multiple sclerosis patients (n=16) continuously treated with GA for 3 years developed anti-GA antibodies that peaked at month 3 and remained elevated during the whole study. We have also demonstrated that initially GA-reactive antibodies of the IgG1 subclass predominate, peaking at month 9 of therapy, but after 9 months IgG1 decreases while anti-GA antibodies of the IgG4 subclass increase and remain high for the 3 years of follow-up. These results support a shift from Th1 to Th2 in the antibody response to glatiramer acetate treatment.

Antibody Specificity↗
PubMed2006

Neuromyelitis optica in patients with myasthenia gravis who underwent thymectomy.

BACKGROUND: Myasthenia gravis (MG) and neuromyelitis optica (NMO, also known as Devic disease) are rare autoimmune disorders, with upper-limit prevalence estimates in the general population of 15 per 100,000 and 5 per 100,000, respectively. To our knowledge, an association between these diseases has not been previously reported. OBJECTIVES: To describe 4 patients with MG who developed NMO after thymectomy and to analyze possible causes of apparent increased prevalence of NMO among patients with MG. DESIGN: Case series. PATIENTS: Four patients with MG who underwent thymectomy. INTERVENTIONS: None. RESULTS: The prevalence of MG within the published cohort of patients with NMO is more than 150 times higher than that in the general population. CONCLUSION: Dysregulation of B-cell autoimmunity in myasthenia, possibly exacerbated by loss of control over autoreactive cells as a result of thymectomy, may predispose patients to the development of NMO.

Adolescent↗
PubMed2006

Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM).

After the first description of TSP/HAM in 1985 and the elaboration of WHO's diagnostic criteria in 1988, the experience of the professionals in this field has increased so that a critical reappraisal of these diagnostic guidelines was considered timely. Brazilian neurologists and observers from other countries met recently to discuss and propose a modified model for diagnosing TSP/HAM with levels of ascertainment as definite, probable, and possible, according to myelopathic symptoms, serological findings, and/or detection of HTLV-I DNA and exclusion of other disorders.

Adult↗
PubMed2005

Reappraisal of Lhermitte's sign in multiple sclerosis.

Lhermitte's sign (LS) is strongly linked to multiple sclerosis (MS). Our aim is to reassess its frequency, natural history, various characteristics and neuroradiological correlation in a cohort of MS patients attending our specialized MS clinic and to propose a working definition. Consecutive patients with CDMS and normal controls were interviewed using a structured questionnaire. Cervical MRIs were reviewed when available. There were 300 MS patients and 100 normal controls. Forty-one per cent of the patients and none of the controls reported having LS during the course of their illness. In 53% of those who reported LS, it started in the first three years of the illness and began as an isolated symptom in 64% and was polysymptomatic in 36%. In all patients LS was a short-lasting sensation in all patient who experienced it and was mostly stereotyped in individual patients. Characteristics varied widely between patients. Forty-three patients had cervical MRIs; 17 out of 18 patients who reported LS had abnormalities, whereas only 13 out of the 25 with no LS had abnormalities. The results indicate that LS is highly prevalent in MS, is commonly stereotyped in individual patients, has a variable natural course and correlates significantly with cervical MRI abnormalities. A working definition is proposed.

Adult↗
PubMed2004

Liver injury associated with the beta-interferons for MS: a comparison between the three products.

A population-based retrospective chart review of the biochemical liver tests of 844 patients with multiple sclerosis prescribed a beta-interferon (IFNbeta) product in British Columbia, Canada was performed between 1995 and 2001. Overall, 36.9% (243/659) of patients developed new elevations of alanine aminotransferase. All the IFNbetas caused elevated aminotransferase levels compared with pretreatment levels (p < 0.005) and were higher than reported in clinical trials. Their relative effect on aminotransferases can be approximated as IFNbeta-1b(subcutaneous [SC]) = IFNbeta-1a(SC) > IFNbeta-1a(IM).

Adult↗
PubMed2004

Hepatic injury, liver monitoring and the beta-interferons for multiple sclerosis.

This review explores the salient issues surrounding liver injury and liver monitoring associated with beta-interferon (IFNB) treatment for multiple sclerosis (MS). Post-marketing studies have found a higher proportion of IFNB-treated MS patients with elevated aminotransferases than reported in the pivotal clinical trials. Although the risk of severe liver injury appears small, the true incidence is unknown. Post-marketing studies have shown that the greatest period of risk for the development of liver test abnormalities appears to be in the first year of IFNB treatment. The risk also increases with the more frequently administered, higher-dosage IFNBs. Males are more likely than females to develop elevated aminotransferases (> upper normal limit), although females appear at a greater risk of severe liver injury. Of the commonly used biochemical liver tests, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP) and bilirubin appear the most useful for routine monitoring of IFNB treatment. Whilst many other factors can affect liver test results, including obesity, alcohol, concomitant medications, co-morbidities and theoretically even MS itself, regular liver testing both prior and during IFNB therapy might help minimise Type A or dose/frequency dependent aminotransferase elevations. However, testing will probably not prevent the Type B idiosyncratic reactions which can result in severe hepatic injury; hence patients need to be aware, and to report hepatic side effects promptly.

Aspartate Aminotransferases↗
PubMed2004

A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis.

BACKGROUND: A new liquid formulation of Avonex (interferon beta-1a [IFNbeta-1a]) in a prefilled syringe has been developed to make administration of the drug easier for patients with multiple sclerosis (MS). This formulation does not contain human serum albumin (HSA), often added to interferon (IFN) products for stabilization. However, formulation changes may alter the secondary, tertiary, and quaternary structures of IFNbeta products. These kinds of structural changes could lead to the formation of antibodies directed against IFNbeta. Some of these anti-IFN antibodies may neutralize the biologic activity of IFNbeta. OBJECTIVE: This study was designed to determine the immunogenicity and safety of the new prefilled syringe (liquid) HSA-free formulation of Avonex in patients with relapsing MS. METHODS: This was a multicenter, single-arm, open-label study. Patients with relapsing MS received liquid, HSA-free Avonex 30 microg by IM injection from a prefilled syringe once weekly for up to 24 months. Immunogenicity and safety were assessed every 3 months. Serum levels of neutralizing antibodies (NAbs) were measured at baseline and every 3 months using a 2-step enzyme-linked immunosorbent assay and antiviral cytopathic effect assay. RESULTS: A total of 153 patients (121 women, 32 men; mean [SD] age, 39.6 [9.9] years; age range, 19.0-59.0 years) were enrolled in the study. Sera were available for analysis from 125 and 119 patients after 18 and 24 months of treatment, respectively. By 18 months, 1 patient (1%) had > or =2 consecutive titers of > or =20, a level at which the persistent presence of NAbs has been shown in some studies to have clinical consequences. By 24 months, 1 additional patient (total 2%) had > or =2 consecutive titers of > or =20. At 18 months, 5 patients (4%) had > or =1 NAb titer of > or =5; at 24 months, 6 patients (5%) had > or =1 NAb titer of > or =5. The safety profile of liquid Avonex was comparable to the lyophilized form containing HSA. CONCLUSIONS: The prefilled syringe (liquid) HSA-free formulation of Avonex was well tolerated and showed a low level of immunogenicity. Over 24 months, 2% of patients developed persistent NAbs (> or =2 consecutive titers of > or =20).

Adjuvants, Immunologic↗
PubMed2004

Elevated aminotransferases during treatment with interferon-beta for multiple sclerosis: actions and outcomes.

The authors report further analysis of a six-year retrospective chart review of multiple sclerosis (MS) patients prescribed interferon-beta (IFNB) in British Columbia, Canada. Actions and outcomes taken when 284/835 (34%) of the patients developed de novo elevated aminotransferases are presented; 239/284 (84%) of patients were continued on treatment despite these elevations; 216/246 (88%) of patients reaching grade 1 toxicity (greater than the upper limit of normal) continued IFNB treatment; of these, 167/216 (77%) returned to within normal limits. Of the 22/29 (76%) reaching grade 2 toxicity (> 2.5 times the upper limit of normal) and continuing treatment, 14/22 (64%) returned to within the normal range. One of the nine patients reaching grade 3 toxicity ( > 5 times the upper limit of normal) was allowed continue treatment and their aminotransferase levels returned to within normal limits. However, one patient reaching grade 3 toxicity went on to develop liver failure (previously reported).

Adjuvants, Immunologic↗
PubMed2003

Interrupted therapy: stopping and switching of the beta-interferons prescribed for MS.

A retrospective chart review of patients in British Columbia with multiple sclerosis prescribed beta-interferon (IFNbeta) between 1995 and 2001 was carried out to investigate reasons for the interruption of therapy. The highest proportion of interruptions (76/281; 27%) occurred in the first 6 months. The single most common reason was perceived lack of efficacy, cited by 84 of 281 (30%). Gender, disability, and disease duration were identified as factors influencing interruption of IFNbeta therapy.

Adjuvants, Immunologic↗
PubMed2003

Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis.

Magnetisation transfer (MT) imaging provides indirect information on tissue structure abnormalities in areas that otherwise may appear normal on conventional MRI. We determined the evolution of MT changes in normal appearing white matter (NAWM) and lesion on serial examination of 9 multiple sclerosis (MS) patients and age matched controls. The mean NAWM MT ratio (MTR) was found to correlate strongly (R = 0.93) with the length of time since the patient's first clinical presentation and was well characterized by a linear decrease of -0.16%/year (p < 0.0001). The time zero intercept of the NAWM MTR regression was 30.7 +/- 0.2%, not different from the average MTR of white matter from controls (30.4 +/- 0.2 %). An additional gradual decrease in NAWM MTR was observed 6 to 12 months before the appearance of a new lesion on conventional MRI, while a more precipitous decrease in MTR was seen 2 to 6 months before the lesion appeared. Those lesions that exhibited pre-lesion MTR decreases showed less MTR recovery than lesions which had no pre-lesion MTR decrease. The data suggest that the MTR of NAWM in MS undergoes a slow progressive decrease that starts at disease onset and accelerates rapidly in focal areas just prior to lesion appearance on conventional MRI.

Adult↗
PubMed2002

In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes.

In myasthenia gravis (MG), presence of pathogenic acetylcholine receptor antibodies (AchRAb) and thymic pathology are related. Our study assesses the long-term clinical outcome of thymectomy as a function of thymic pathologies, AchRAb levels in blood and the ability of immunocytes to secrete AchRAb ex vivo. We found that those patients who have thymocytes that secrete AchRAb in vitro have a greater decrease in their need for Mestinon over the 60 months of follow-up than the non-secretors (p = 0.04). Those patients whose cultured peripheral blood mononuclear cells (PBMC) secreted AchRAb also had a greater decrease in Mestinon requirements over the 60 months of follow-up than the non-secretors (p = 0.05), however, differences between the two groups at each individual assessment were not statistically significant. Serial post-op AchRAb measurements in sera of thymocyte and PBMC non-secretors showed no change from pre-op levels (< 10 nmol/l), while secretors had a reduction of more than 80% from pre-op levels, starting 6 months post-op. We also found that results of PBMC culture at time of thymectomy is a better predictor of response to thymectomy than serum AchRAb levels but inferior to results of thymocytes cultures. Patients with thymoma had the highest proportion of individuals secreting AchRAb from thymocytes in culture (78%), the shortest duration of disease (9 months) and showed the greatest trend toward improvement in clinical signs and symptoms post-op. We have thus demonstrated the long held suspicion that removal of actively secreting cells from the thymus at an early time in the disease confers the greatest benefit.

Adult↗