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Biomedical subjects

M Chofflon

Publications and source records attributed to M Chofflon.

At least 19 recordsLinked to original sources
PubMed2006

[Immunity and neurodegeneration: new concepts in multiple sclerosis].

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system that leads to a progressive deterioration of the neurological functions. The concept of primary myelin and oligodendrocyte damage with axon sparing (axon-myelin dissociation) has been recently reconsidered with the demonstration that neuro-axonal lesions are an early phenomenon, linked to the inflammatory process, observed outside demyelinated areas, and correlated with the progression of the disease. Neurodegeneration in MS, long considered as a late process following recurrent episodes of demyelination, is now accepted as an early and major trigger of MS pathogenesis on which research should focus in the

Humans↗
PubMed2006

A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting.

An International Working Group for Treatment Optimization in MS met to recommend evidence-based therapeutic options for the management of suboptimal responses or intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side-effects on their current therapy.

Algorithms↗
PubMed2005

[Immunomodulatory/suppressive treatments in neurology].

Immunomodulatory/suppressive treatments are frequently used in neurological disorders affecting the central and peripheral nervous system. Demyelinating disorders are a good example of a wide application of the various types of existing therapies. Although these therapies are still mostly not disease specific, their combination with more targeted molecules appears most relevant for diseases with multiple pathogenic mechanisms.

Adjuvants, Immunologic↗
PubMed2005

Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

BACKGROUND: The simultaneous occurrence of bullous pemphigoid (BP) and multiple sclerosis (MS), two autoimmune diseases involving the skin and the central nervous system (CNS), respectively, has been described. OBJECTIVES: As the BPAG1 gene encodes the epithelial isoform of BP antigen 1 (BPAG1-e), a major autoantigen of BP, as well as additional variants expressed in the neurones of the CNS and peripheral nervous system and in Schwann cells, we tested the hypothesis that products of the BPAG1 gene act as shared autoantigens in both BP and MS. METHODS: The reactivity of cerebrospinal fluid (CSF) obtained from 18 patients with MS, 10 patients with other inflammatory CNS diseases and 20 normal controls was assayed by immunoblotting against two recombinant fragments of BPAG1-e encompassing regions that are also found in the neuronal variants BPAG1-n and BPAG1-a. RESULTS: The recombinant protein glutathione-S-transferase (GST)-BPAG1-e1-887 was recognized by five of 18 (27%) CSF samples obtained from patients with MS, two of 10 (20%) samples from patients with other inflammatory neurological diseases and five of 20 (25%) samples from normal controls. Furthermore, two of 18 (11%) CSF samples from patients with MS bound to GST-BPAG1-e1880-2649, whereas none of the samples obtained from patients with other inflammatory neurological diseases or from control subjects showed reactivity. CONCLUSIONS: These results raise the possibility that a subset of patients with MS develops an autoantibody response to the neuronal variants of BPAG1. These findings potentially open the avenue of neuronal BPAG1 variants being novel targets of autoantibodies in neurological diseases.

Autoantibodies↗
PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗
PubMed2001

Beneficial effect of co-polymer 1 on cytokine production by CD4 T cells in multiple sclerosis.

Multiple sclerosis (MS) has been associated with an imbalance in the T helper type 1 (Th1) and Th2 subsets. We investigated, at the single-cell level, the synthesis of pro-inflammatory cytokines by CD4 and CD8 T cells from MS patients. We report the relationship between priming of CD4 and CD8 T cells for interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) and disease evolution in MS patients, clinically subdivided into relapsing-remitting MS (RRMS) in remission, RRMS in relapse, or chronic progressive MS (CPMS). Moreover, we report the in vivo influence of co-polymer 1 (COP) treatment on the pattern of cytokine producers in RRMS patients. We show that the frequency of CD4 T cells primed for TNF-alpha synthesis increased in all stages of MS, including RRMS remitting, and was normalized to control values in COP-treated patients (43.2 +/- 11.8% in treated patients versus 47 +/- 7.3% in RRMS remitting versus 40.3 +/- 8% in controls). In addition, a significant decrease in the frequency of CD4 T cells primed for IL-2 was found in COP-treated patients as compared to the other groups of patients, reaching values below that of controls (59.1 +/- 9.9% in treated patients versus 70 +/- 11.6% in RRMS remitting versus 67.1 +/- 7.4% in controls). Unexpectedly, COP-treated patients also showed a significantly decreased priming for IFN-gamma at the CD4 T-cell level (9.1 +/- 3.4% in treated patients versus 18.8 +/- 0.6.4% in RRMS remitting versus 15.4 +/- 4.7% in controls), but not at the CD8 T-cell level. This bystander suppression on the inflammatory cells should be considered in the monitoring of MS patients submitted to COP treatment, in order to evaluate better its clinical efficacy.

Adult↗
PubMed2000

Recombinant human interferon beta in relapsing-remitting multiple sclerosis: a review of the major clinical trials.

The beneficial effects of interferon beta (IFN-beta) on disease activity in relapsing-remitting multiple sclerosis (RRMS) have been confirmed in several clinical trials. Three IFN-beta products are currently available and licensed for use in RRMS at different dosages and with different routes of administration. For the prescribing physician, therefore, questions remain about the effect these differences may have on the success of therapy. This paper reviews the four large placebo-controlled clinical trials that have been conducted with IFN-beta in patients with RRMS. The evidence available indicates that optimal results are likely to be achieved with the highest tolerable dosage of IFN-beta. Furthermore, as inflammatory brain lesions in MS have been shown to exhibit more extensive and early axonal damage than previously suspected, early treatment may be advisable in order to delay disease progression in RRMS.

Clinical Trials as Topic↗
PubMed1999

Cerebrospinal fluid in acute peripheral facial palsy.

Cerebrospinal fluid (CSF) is rarely analyzed in peripheral facial palsy, and reports in the literature are scarce. We report the CSF findings in 265 patients with acute isolated peripheral facial palsy. The CSF findings were abnormal in 11% of 230 patients with idiopathic peripheral facial palsy, in 60% of 17 patients with Ramsay Hunt syndrome (pleocytosis), in 25% of 8 patients with Lyme disease, in all of 8 patients with HIV infection, and in 2 other patients (sarcoidosis and herpes simplex). We conclude from this large series that the CSF is usually normal in idiopathic peripheral facial palsy. If the CSF is abnormal, a specific cause should be sought.

Adolescent↗
PubMed1998

Corticosteroid-responsive postmalaria encephalopathy characterized by motor aphasia, myoclonus, and postural tremor.

OBJECTIVES: To study the clinical spectrum of an acute severe encephalopathy occurring in 2 patients after recovery from falciparum malaria infection and to compare it with the reported clinical features of the postmalaria neurological syndrome. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: Two patients presented with acute onset of fluctuating motor aphasia, severe generalized myoclonus, and postural tremor. Additional signs were cerebellar ataxia, and in 1 patient, generalized epileptic seizures. Magnetic resonance imaging of the brain revealed patchy white matter lesions in 1 patient. Clinically, the patients' conditions continued to worsen until corticosteroids were introduced, the use of which induced a rapid, albeit incomplete, recovery. CONCLUSIONS: We describe a new, severe variant of the still poorly defined postmalaria neurological syndrome. We propose a preliminary classification of this syndrome, according to its clinical characteristics, as follows: a mild or localized form, characterized by isolated cerebellar ataxia or postural tremor; a diffuse, but relatively mild encephalopathic form, characterized by acute confusion or epileptic seizures; and a severe, corticosteroid-responsive encephalopathy that is characterized by motor aphasia, generalized myoclonus, postural tremor, and cerebellar ataxia.

Adrenal Cortex Hormones↗
PubMed1998

[Brown-Vialetto-Van Laere syndrome: a case with anti-ganglioside GM1 antibodies and literature review].

We report the case of a woman suffering from progressive bulbopontine paralysis in whose the first symptom, bilateral hypoacousia, began in childhood. This clinical picture is that of the Brown-Vialetto-Van Laere (BVVL) syndrome. Anti-ganglioside GM1 antibodies were moderately elevated in this patient. Intravenous immunoglobulins produced little benefit. The main clinical characteristics of 29 BVVL patients reported in literature are reviewed, and the pathological significance of anti-GM1 antibodies is discussed in the context of this disorder.

Adult↗
PubMed1997

Brain microvascular endothelial cells and leukocytes derived from patients with multiple sclerosis exhibit increased adhesion capacity.

The adhesion properties of brain microvascular endothelial cells (MVEC) and leukocytes derived from patients with multiple sclerosis (MS) were investigated. Leukocytes and brain MVEC from MS patients exhibited significantly higher adhesion capacity than the same cells isolated from normal donors. Flow cytometry showed that MS-derived brain MVEC constitutively expressed higher levels of ICAM-1 and contained an increased proportion of MHC class II positive cells than normal brain MVEC. In contrast, no difference was seen for vascular cell adhesion molecule-1 and endothelial cell leukocyte adhesion molecule-1. Circulating leukocytes from MS patients expressed higher levels of LFA-1, a ligand of intercellular adhesion molecule-1 (ICAM-1), than did normal leukocytes. The data presented here suggest that the ICAM-1/LFA-1 interaction may determine cytoadherence of leukocytes to brain MVEC in MS.

Brain↗
PubMed1997

Early high-dose intravenous methylprednisolone in acute disseminated encephalomyelitis: a successful recovery.

We describe a patient with acute disseminated encephalomyelitis (ADEM) who was treated with high-dose intravenous methylprednisolone 2 days after onset of neurologic symptoms. Despite poor prognostic factors and extensive white matter lesions, the patient recovered dramatically with no need for maintenance steroid therapy. This case report of fulminant ADEM treated successfully with early high-dose intravenous methylprednisolone, although uncontrolled, suggests that this agent should be studied in other cases.

Adult↗
PubMed1997

Tumor necrosis factor production capacity as a potentially useful parameter to monitor disease activity in multiple sclerosis.

The aim of this study was to develop a test allowing to monitor disease activity in patients with multiple sclerosis (MS). A simple, fast and reliable test was used to assess the cytokine production capacity of blood leucocytes. The whole blood test (WBT) involved in vitro stimulation of a whole blood sample with either the mitogen phytohaemagglutinin (PHA), or specific antigens. We focused our attention on the production of tumor necrosis factor alpha (TNF), because of the possible involvement of this cytokine in MS pathogenesis. Under in vitro stimulation with PHA or MBP, TNF production was found to be significantly higher in patients during the clinical relapses than during remissions. The increment of TNF production correlated with the severity of the relapses, as determined by the modification of Kurtzke EDSS scale. Moreover, each clinical relapse appeared to be preceded by a peak of TNF production. We then retrospectively analysed 21 patients with the relapsing-remitting form of the disease, in whom the WBT was performed every 2-4 weeks, for periods ranging from 16 to 52 months. Seventy-three peaks of TNF production (defined as the doubling or more of the individual baseline value, which was found to be stable for each patient during remissions), and 47 relapses, including 36 objective and 11 subjective, were observed. Forty-seven out of the 73 TNF peaks were followed by or concomitant with a clinical relapse. In 10 out of the 26 cases where no relapse followed the TNF peak, another cause (mainly infections) of increased TNF production was found. Thus, by excluding other causes, the specificity of the WBT, i.e., the probability to develop a relapse when a TNF peak was found to be 74.6% (47/63). The sensitivity of the WBT was 100%, since all the 47 relapses were preceded by a TNF peak. Assessment of TNF production capacity by the WBT may thus be useful in the follow-up of MS patients, particularly for the follow-up of various treatments. Information provided by the WBT may also be useful to orientate the therapeutic decision for an incipient relapse. Earlier treatment is likely to result in an improved prevention of neurological damage.

Case-Control Studies↗
PubMed1995

[Isolated peripheral facial paralysis and HIV infection: 7 cases].

Human immunodeficiency virus infection frequently involves the peripheral or central nervous system. Seven cases of isolated peripheral facial palsy that occurred at various stages of the disease are reported. The palsy was the first manifestation of the disease in 5 patients, and revealed it in 3 of them. The palsy involved the right side in 6 cases (complete N = 2; incomplete N = 4); it was bilateral in one (complete on both sides). Abnormalities of the cerebrospinal fluid were present in all patients but differed depending on the stage of the retroviral infection. Electroneuromyography defined the type of the palsy, principally due to axonotmesis in 4 patients (including the bilateral one) and principally to neurapraxia in 3 patients. The outcome was good in most cases. The physiopathology remains undetermined.

Adult↗
PubMed1994

Central nervous system involvement in systemic lupus erythematosus: a new therapeutic approach with intrathecal dexamethasone and methotrexate.

In systemic lupus erythematosus (SLE), neurological involvement has been reported to occur with frequencies ranging from 14% (severe cases) to 83% (mild forms included). In spite of early diagnosis and aggressive treatment, neuropsychiatric SLE may represent a serious problem of management. We describe three cases, one with acute transverse myelitis, one with hemiparesis, and one with signs of focal and diffuse cerebral dysfunction, in whom improvement following intrathecal therapy with methotrexate and dexamethasone was observed.

Adolescent↗