In the past few years evidence that atherosclerotic disease of the aortic arch is probably an underestimate source of emboli, particularly moving thrombi in the lumen, has accumulated. Pathological ...studies, and more recently transesophageal echocardiographic studies, have shown that atherosclerotic disease of the aortic arch is an independent risk factor for ischemic stroke and carries a high risk of recurrent vascular events. It could account for a more or less part of brain infarcts of unknown cause, with no carotid or cardiac source of emboli. This location of atherosclerotic disease is rare under 60 years of age. It mainly involves patients older than 60 years of age, and is frequent in patients in their eighties. Transesophageal echocardiography is accurate, safe and well tolerated for the examination of the aortic arch, even in elderly patients. Practical implications for patients and future clinical trials are important. As it is a strong marker for recurrent vascular events, the risks and benefits of different therapeutic options should now be evaluated in randomised trials.
To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French ...follow-up cohort Observatoire of Multiple Sclerosis.
Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0-5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting).
The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation.
Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years.
This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod.
Les facteurs de risque de mortalité modifiables sont peu étudiés dans la SEP. La défavorisation socioéconomique et une mauvaise accessibilité aux soins sont deux facteurs de risque avérés dans ...d’autres pathologies.
L’objectif était d’examiner l’influence de la défavorisation socioéconomique ainsi que de l’accessibilité aux soins primaires et neurologiques spécialisés sur la mortalité en excès de patients atteints de SEP.
Les patients de 18 centres experts participant à l’OFSEP ont été recrutés entre 1960 et 2015. La défavorisation mesurée grâce à l’EDI (European Deprivation Index), le temps de trajet au centre expert et l’accessibilité aux soins primaires (mesurée par l’indice SCALE (Spatial accessibility multiscalar)) ont été intégrés afin d’estimer la mortalité en excès (mortalité uniquement liée à la SEP). L’utilisation de splines pénalisées a permis de modéliser des effets non-proportionnels et non-linéaires.
La population d’étude incluait 33 697 patients (88 % de forme rémittente et 12 % de forme progressive). Pour les formes rémittentes, la défavorisation socioéconomique et le temps de trajet au centre spécialisé étaient associés à une augmentation de la mortalité en excès, alors qu’un déficit d’accès aux soins primaire n’était associé à aucune surmortalité. Pour les formes progressives, aucune variable mesurant les inégalités socio-territoriales n’était associée à la mortalité en excès (Fig. 1 et Fig. 2).
La défavorisation socioéconomique est associée à un risque de mortalité liée à la SEP plus élevé pour les formes rémittentes et ce dès le début de la maladie. La diminution de la mortalité en excès avec l’augmentation du temps de trajet au centre expert suggère une sélection potentielle de patients suivis en centre expert, plus motivés et/ou en meilleure santé et de ce fait une perte de chance pour les patients les plus isolés géographiquement.
Nos résultats suggèrent que l’environnement socioterritorial doit être considéré comme un facteur potentiellement péjoratif pour la survie des patients et devrait être considéré dans la prise en charge.
New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients’ ...quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain.
A consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up.
The French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re-baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences.
To establish recommendations on immunization for patients with multiple sclerosis (MS).
Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive ...treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients.
The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain.
Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs.
Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.
Background: Interferon beta-1b (IFNB-1b; Betaferon registered )has demonstrated efficacy and safety in relapsing-remitting MS (RRMS). It was the first approved interferon in France for RRMS with ...greater than or equal to 2 relapses in the last 2 years. Impact of IFNB-1b on very active MS (VAMS) has not been studied. The 12-year long-term follow-up (LTF) French cohort ATU of IFNB-1b will evaluate the long-term effect of IFNB-1b on clinical parameters in a cohort of patients with VAMS. Objective: To assess the clinical status MS patients included in the French cohort ATU of IFNB-1b after 12-year follow-up. Methods: This study is a multi-center, open-label, observational study that evaluates outcomes in patients included in the French cohort of ATU between July 1995 and June 1996. ATU is an administrative procedure aimed to propose treatment to patients before definite agreement by the French health regulatory agency. During this period, inclusion criteria for IFNB-1b were: 1) RR clinically definite MS; 2) greater than or equal to 3 relapses with objective sequellae confirmed by a neurologist in the last 12 months; 3) Expanded Disability Status Scale (EDSS) score: 3.0 less than or equal to EDSS less than or equal to 6.0; 4) Age: 18-50 years; 5) MS onset <10 years; 6) Abnormal magnetic resonce imaging (MRI). When a neurologist wanted to treat a patient he sent the medical record to a selection comittee of 12 members, who checked the inclusion criteria and allowed the delivery of IFNB-1b. All the patients were followed by a neurologist for safety end efficacy every month for the first 3 months and then every 3 months. The procedure of the ATU ended when IFNB-1b was marketed in August 1996. All the patients included in the cohort ATU were identified. Their medical history was reviewed to collect the following information: duration of treatment, reason for treatment interruption, survival, course of the disease (relapsing-remitting or secondary progressive), relapse rate, EDSS score. Results: Two hundred and thirty seven MS patients were included in the cohort. At inclusion, mean age was 34 years, mean MS duration was 5 years, mean relapse rate was 3.5; median EDSS was 4.0. Follow-up data will be presented at the meeting. Conclusions: The French cohort ATU is the first LTF of VAMS patients under IFNB-1b.
Evidence for a genetic susceptibility to systemic lupus erythematosus (SLE) in humans is based on the high concordance rate observed in identical twins and on the relatively high incidence of ...familial cases. Although recent genetic studies have lead to significant advances in the identification of new susceptibility genes in SLE, no large clinico-pathologic study of familial SLE has been reported to date. In the present study, we describe the main clinical and immunologic features of 125 lupus multiplex families including at least 2 cases of SLE and/or discoid lupus erythematosus (DLE), recruited through a French national survey starting in July 1997. Medical records of all affected members were reviewed by the same investigator, all available family members were interviewed using the same standardized procedure, and blood was drawn for autoantibodies typing. Clinical and immunologic features of 90 probands from multiplex SLE families were compared with those of 100 sporadic SLE patients sharing the same French Caucasian origin. The 125 lupus multiplex families included 282 affected members (2.3 patients per family); of the 125 families, 96 were of French Caucasian origin. One hundred multiplex families included 2 affected relatives, while 25 included 3 or more affected individuals. The relationship between affected members was sibs (45%), parent-offspring (31%), and second-degree (24%). An autosomal dominant mode of inheritance was strongly suggested in 1 extended pedigree with 6 clinically affected members, and a recessive pattern was suspected in 5 other families. No obvious mode of inheritance could be suspected in most of the remainder. Among French Caucasians, sex ratio, mean age at onset, and clinical and biologic SLE-related manifestations were not significantly different in multiplex compared with sporadic SLE cases. The analysis of these 125 multiplex families suggests a genetic heterogeneity that should be considered for ongoing genomic screening.
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