Tardive Reactivation of Progressive Multiple Sclerosis During Treatment with Biotin

International audienceMultiple sclerosis (MS) is a common autoimmune disease of the central nervous system, causing neurological disability in young adults. A growing understanding of its immunopathogenesis has led to an expanding array of therapies. Notable new advances in disease-modifying therapies for relapsing forms of multiple sclerosis that are based on anti-inflammatory activity have recently been developed. Management of progressive MS is still challenging. Data published in 2014 suggested that daily high doses of biotin, a vitamin involved in myelin synthesis, might have a beneficial impact on disability and progression in progressive MS. However, some patients worsened while on biotin without any clear explanation for this effect. We report the case of a 41-year-old patient suffering from primary progressive (PP) MS who presented after 16 months of treatment with high doses of biotin (QIZENDAY) with worsening of his Expanding Disability Status Scale (EDSS) score and the appearance of a symptomatic new T2 pseudo-tumoural lesion on brain magnetic resonance imaging (MRI), suggestive of tardive inflammatory reactivation possibly due to the biotin. The newer and more effective therapies for MS are, however, associated with risks that necessitate an active management strategy and continuous vigilance. Physicians should be aware of iatrogenic neurological complications and the possible paradoxical effects of biotin. Future treatment approaches to progressive MS must include identification of a biomarker of disease activity. The study of neurofilaments in the cerebrospinal fluid (CSF) and the serum could be of interest when determining the optimal treatment strategy

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

International audienceIdiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: 60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression

More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke

International audienceBACKGROUND: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol 50% from baseline rather than 50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had 50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43–0.88]; P =0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73–1.26]; P =0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu ; Unique identifier: EUDRACT2009-A01280-57.gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.URL: https://www