Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

[Brain MRI associated with chronic hepatic failure and hypermanganism]. / Hypersignal T1 bipallidal dans le cadre d'une cirrhose avec hypermanganésémie.

INTRODUCTION: Hypermanganism is primarily linked to inhalation exposure. Several observations of exogenous manganese poisoning have been reported associating neuropsychiatric symptoms, parkinsonian syndrome and hyperintensities of the two pallida on T1 weighted sequences on brain MRI. Recently, similar neurological and radiological signs have been described without exogenous exposure to manganese but in the framework of endogenous poisoning particularly in chronic hepatic failure. CASE REPORT: We report the case of a 41-year-old HIV-positive and HVC-positive man who presented psychomotor impairment associated with bipallidal T1 hyperintensities on the brain MRI. The diagnosis of a hypermanganesemia was made on blood samples. We present a literature review on exogenous and endogenous hypermanganesemia and discuss differential diagnosis in the radiological setting of bipallidal T1 hyperintensities. CONCLUSION: Bipallidal T1 hyperintensities on brain MRI may suggest hypermanganism even in the clinical setting of a non-specific neurological disorder such as psychomotor impairment.

[Multiple sclerosis and familial Mediterranean fever: a case report]. / Sclérose en plaques et fièvre méditerranéenne familiale : un cas et revue de la littérature.

INTRODUCTION: Few cases of patients with both Familial Mediterranean Fever (FMF) and Multiple Sclerosis (MS) have been reported, mainly from Turkey. Central nervous system manifestations are rare in FMF. CASE REPORT: We report the case of a 37-year-old right-handed man with FMF diagnosed at 17 the age of years and successfully treated with colchicine. The patient was born in Algeria and lived in France since he was four years old. He had a brother who had multiple sclerosis. When the patient was 23 years old, he experienced diplopia and leg numbness that resolved spontaneously without treatment. Ten years later, new neurological events appeared every six months and were treated with corticoid-steroids. The diagnosis of MS was made. In 2006, he was hospitalized for new explorations in order to search for neuro-Behçet's disease, because of the development of a canker sore. There was no argument for neuro-Behçet's disease. DISCUSSION: Neurological complications of FMF are rare. It is important to rule out a neuro-Behçet disease in a FMF patient with neurological disorders. Previous studies and case reports on the association between FMF and MS have failed to draw a clear conclusion as to whether this is a true association or a simple coincidence. In our patient's clinical situation, we found no argument for changing the treatment of MS and FMF.

[Transient high-intensity T2 signal in the splenium of the corpus callosum in a non-epileptic patient]. / Hypersignal T2 transitoire du splenium du corps calleux chez une patiente non épileptique.

Transient splenial lesions of the corpus callosum have been mainly reported in epileptic patients. We report the case of a non-epileptic woman with bipolar affective disorder treated by oxcarbazepine which was withdrawn because of a mild hyponatremia (128 mmol/l). A confusional state followed withdrawal and the electroencephalogram was free of spike or sharp waves. Brain MRI showed a single splenial lesion of the corpus callosum revealed by a high intensity T2 signal on FLAIR and diffusion sequences. Because of a major depressive episode, twelve sessions of electroconvulsive therapy were performed and yielded clinical improvement. A second brain MRI performed 5 weeks later was normal. The relevances of this cases are the non-epileptic status of the patient, the drug incriminated (oxcarbazepine), and the normalisation of brain MRI despite electroconvulsive therapy. Different mechanisms of this brain MRI abnormality are discussed including the sudden withdraw of oxcarbazepine. Prognosis of transient splenial lesions of the corpus callosum is good. Clinicians should search for recent metabolic disorders and therapeutic modifications.