Conference Report: International Symposium on Multiple Sclerosis University of Western Ontario May 3-5, 1981
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An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.Multiple sclerosis is a multifactorial and heterogeneous neurological disease; hence, several experimental animal models had to be developed to mimic the different features of human pathology. Three main classes of animal models have been developed: experimental autoimmune encephalomyelitis (EAE), cuprizone intoxication, and Theiler's murine encephalomyelitis virus (TMEV) infection. The EAE model is the most versatile as it allows the reproduction of different patterns of multiple sclerosis; it is mostly relevant for relapsing-remitting multiple sclerosis and has allowed the development of several first-line, disease-modifying drugs for the treatment of multiple sclerosis. The other two models are less flexible than the EAE model and, to date, have not led to the discovery of any clinically relevant therapies. The cuprizone model mostly mimics the acute and chronic courses of multiple sclerosis, and it may represent a useful tool to develop novel therapies to protect oligodendrocytes and stimulate remyelination. Finally, the TMEV infection is the reference model to specifically study viral-mediated mechanisms of acute and primary progressive multiple sclerosis.
Remyelination
Encephalomyelitis
Demyelinating disease
Animal model
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One single center study has provided support for a home-based approach to the therapeutic management of multiple sclerosis (MS) relapse.To report a multicenter series of patients with MS who were treated at home for a relapse with a 3-day course of intravenous methylprednisolone.The home administration of intravenous methylprednisolone was coordinated by four MS networks in France; patients with MS with a relapse were referred by their neurologists, and treatment was administered by a local nurse. We analyzed the safety and efficiency of this approach and estimated the related cost savings. Patients completed a patient satisfaction questionnaire.Eight hundred and seven patients received intravenous methylprednisolone at home. The mean disease duration was 10.3 +/- 7.9 years. Treatment was often prescribed by community-based neurologists. The delay between prescription and treatment was 2.8 +/- 0.5 days if treatment was initiated at home and 1.9 +/- 3.0 days if treatment was initiated in hospital (the subsequent two injections were always administered at home). Home treatment was well tolerated; three serious side effects requiring hospital transfer were observed (anxiety, thoracic oppression, and arrhythmia), which were fully reversible. Overall, 93.8% of patients were satisfied with the treatment approach, and 98% wished to receive future treatment courses at home. The overall cost savings of home-based treatment versus hospital-based treatment were evaluated at EUR1,091,482.Safety data, patient satisfaction, and economic considerations support home-based treatment of MS relapses with intravenous methylprednisolone, provided strict patient selection criteria are observed and the process is coordinated and closely monitored by an MS network.
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Objective: To investigate the association between apolipoprotein E (Apo E) genotype in multiple sclerosis (MS) and acute monosymptomatic optic neuritis (ON) in a genetically homogeneous population with a high frequency of the Apo o4 allele. Background: The association between heterozygosity of Apo o4 and the development of MS is thoroughly investigated, while the association between homozygosity of Apo o4 and the development of MS is insufficiently studied. The association between Apo E genotype and disease progression remains controversial. Methods: 475 patients were included, 385 with MS and 90 with ON, consecutively seen in the MS clinic in the County of Copenhagen. Clinical data were obtained from medical records and degree of disability was determined prospectively using the Kurtzke expanded disability status scale (EDSS). Blood samples were used for Apo E genotyping. Disease progression was evaluated by the progression index (PI=EDSS/disease duration). Apo E genotype distribution was compared with 361 healthy controls. Results: The Apo o genotype distribution in the MS and ON groups was similar to the controls. The rate of disease progression in the group of MS patients with a disease duration of 10 years or less was significantly faster in the Apo o4 positive group (heterozygosity and homozygosity for Apo o4) (PI=1.41) compared to the Apo o4 negative group (PI=0.92) (P=0.009). Observing the MS subgroups, we found that the group of patients with RRMS had a faster rate of disease progression in the Apo o4 positive group (PI=1.12) compared to the Apo o4 negative group (PI=0.77) (P=0.024). Conclusions: Apo E genotypes do not influence the development of MS and ON. The Apo o4 allele seems to predispose carriers with MS to a faster progression of disease.
Optic neuritis
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Background: There is a growing need for biomarkers that can help in early diagnosis of multiple sclerosis (MS) and in recognizing patients with MS activity.Moreover, many studies are recently focusing on biomarkers that may help in diagnosis of the transition from relapsing remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS).Circulating microRNAs (miRNAs) are now considered promising biomarkers.Objectives: Studying the role of plasma miRNA-145 and miRNA-484 in the diagnosis of MS, disease activity and in diagnosing the transition from RRMS to SPMS.Patients and Methods: Forty-six subjects of both sexes were included, 31 patients with MS )21 with RRMS, 8 with SPMS and Two patients with primary progressive multiple sclerosis (PPMS)) and 15 healthy controls.Expression analysis of plasma miRNAs; miR-145 and miR-484 were assessed by real-time quantitative polymerase chain reaction (PCR) after miRNA extraction.Results: MicroRNAs 145 and 484 could significantly discriminate between MS cases and controls, with best cut-off values > 0.6 and > 1.7 respectively.They could also significantly discriminate between active and inactive MS cases, with best cut-off values > 0.8 and > 2 respectively.Plasma miRNA-145 could discriminate between RRMS and SPMS cases, with best cut-off value ≤1.4.Conclusion: Plasma miRNAs 145 and 484 might be used as promising biomarkers for early diagnosis of MS and in diagnosis of disease activity.Plasma miRNA-145 could be also helpful in diagnosis of the transition from RRMS to SPMS.
Relapsing remitting
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Multiple sclerosis is a disorder of the immune system that is caused by a malfunction of our body defenses. In multiple sclerosis, healthy cells of the nervous system are destroyed, and this leads to many health problems, like paralysis. Multiple sclerosis affects a lot of people worldwide. Treatments exist but are still not entirely efficient and do not work for all patients. Many researchers are studying this disease and our group is focusing on specific cells of the immune system that might be playing a role in multiple sclerosis.
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多発性硬化症（multiple sclerosis：MS）は，本邦の指定難病の一つに定められる中枢神経系の炎症性脱髄疾患である．時間的および空間的に多発する組織硬化を特徴とし，病変部に応じた症状を示す．典型的には再発と寛解を繰り返しながら神経症状が進行し，根治療法は未だ存在しない．MS患者検体やMS動物モデルである実験的自己免疫性脳脊髄炎（experimental autoimmune encephalomyelitis：EAE）を用いた多くの研究により，その本態は中枢神経系の髄鞘タンパク質を標的とした自己免疫疾患であることが明らかとなっている．病態形成には獲得免疫である自己反応性T細胞が中心的な役割を果たしており，近年の研究成果によりB細胞の役割も注目を集めている．MSは再発寛解型MSと進行型MSに分類され，再発寛解型MSに対してはこれらの獲得免疫を標的とする多くの疾患修飾薬が開発されている．進行型MSに対する治療薬はここ数年で承認が始まったばかりであり，神経障害が蓄積する進行期に有効な治療法の確立が待ち望まれている．進行型MSの病態では，獲得免疫だけでなく自然免疫やグリア細胞が免疫病態の重要な構成要素として認知されつつあるが，免疫細胞と神経細胞，グリア細胞間のクロストークの分子機序には未だ不明な点を多く残している．本稿では，MSの病態，および免疫細胞を標的する疾患修飾薬について概説するとともに，EAEを用いた我々の研究成果を交えてアストロサイトによるMS病態の制御機構について紹介する．
Pathogenesis
Encephalomyelitis
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Demyelinating disease
Relapsing remitting
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Neuroradiology
Clinical neurology
Optic neuritis
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Reports on fatty acids levels in multiple sclerosis remain inconclusive.To determine the erythrocyte membrane fatty acid levels in multiple sclerosis patients and correlate with Kurtzke Expanded Disability Status Scale.Fatty acid composition of 31 multiple sclerosis and 30 control individuals were measured by gas chromatography.The membrane phosphatidylcholine C20:4n - 6 concentration was lower in the multiple sclerosis patients when compared to that of the control group, P = 0.04 and it correlated inversely with the EDSS and FSS.Decrease in C20:4n - 6 in the erythrocyte membrane could be an indication of depleted plasma stores, and a reflection of disease severity.
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