Evolution of structural neuroimaging biomarkers in a series of adult patients with Niemann-Pick type C under treatment

International audienceBackground: Niemann-Pick type C (NPC) disease is a lysosomal storage disorder characterized by a wide clinical spectrum and non-specific conventional magnetic resonance imaging (MRI) signs. As substrate reduction therapy with miglustat is now used in almost all patients, its efficacy and the course of the disease are sometimes difficult to evaluate. Neuroimaging biomarkers could prove useful in this matter. We first performed a retrospective analysis of volumetric and diffusion tensor imaging (DTI) data on 13 adult NPC patients compared to 13 controls of similar age and sex. Eleven NPC patients were then studied using the same neuroimaging modalities over a mean of 5 years. The NPC composite score was used to evaluate disease severity.ResultsNPC patients showed atrophy in basal ganglia – pallidum (p = 0.029), caudate nucleus (p = 0.022), putamen (p = 0.002) and thalamus (p < 0.001) – cerebral peduncles (p = 0.003) and corpus callosum (p = 0.006), compared to controls. NPC patients also displayed decreased fractional anisotropy (FA) in several regions of interest – corona radiata (p = 0.015), internal capsule (p = 0.007), corpus callosum (p = 0.032) and cingulate gyrus (p = 0.002) – as well as a broad increase in radial diffusivity (p < 0.001), compared to controls. Over time, 3 patients worsened clinically, including 2 patients who interrupted treatment, while 8 patients remained stable. With miglustat, no significant volumetric change was observed but FA improved after 2 years in the corpus callosum and the corona radiata of NPC patients (n = 4; p = 0.029) – although that was no longer observed at further time points.ConclusionThis is the first study conducted on a series of adult NPC patients using two neuroimaging modalities and followed under treatment. It confirmed that NPC patients displayed cerebral atrophy in several regions of interest compared to controls. Furthermore, miglustat showed an early effect on diffusion metrics in treated patients. DTI can detect brain microstructure alterations caused by neurometabolic dysfunction. Its potential as a biomarker in NPC shall be further evaluated in upcoming therapeutic trials

Pseudocinchona africana A. Chev.

Le pseudocinchona africana A. Chev. est présent dans une région particulière d'Afrique, dans la grande forêt tropicale de la Côte d'Ivoire. Bien connue localement, cette espèce a été étudiée par les botanistes français au début du XXe siècle. Cet arbre de 15 à 20 m de hauteur et large de 15 à 35 cm possède une écorce relativement mince d'un blanc jaunâtre, des feuilles de 15 à 20 cm de long et de 5 à 7 cm de large, ainsi que des fleurs formant une inflorescence pyramidale. De cet arbre ont été extraits et identifiés six alcaloïdes : la corynanthine et la corynanthidine dont les études ont montré que ces deux molécules sont des isomères de la yohimbine ; la corynanthéïne et la corynanthéïdine qui sont de même formule brute mais possède un sens rotatoire différent ; et deux alcaloïdes oxyndoliques, la corynoxéïne et la corynoxine. Le pseudocinchona africana A. Chev. possède de par ses alcaloïdes une action sympatholytique ainsi qu'une action érective deux fois plus active que la yohimbine. Des études en toxicologie ont également été réalisées sur des cobayes afin de déterminer leur seuil de toxicitéPARIS-BIUP (751062107) / SudocSudocFranceF

Natural history of cerebrotendinous xanthomatosis: a paediatric disease diagnosed in adulthood

International audienceCerebrotendinous xanthomatosis (CTX) is among the few inherited neurometabolic disorders amenable to specific treatment. It is easily diagnosed using plasma cholestanol. We wished to delineate the natural history of the most common neurological and non-neurological symptoms in thirteen patients with CTX. Diarrhea almost always developed within the first year of life. Cataract and school difficulties usually occurred between 5 and 15 years of age preceding by years the onset of motor or psychiatric symptoms. The median age at diagnosis was 24.5 years old. It appears critical to raise awareness about CTX among paediatricians in order to initiate treatment before irreversible damage occurs

Omega-3 polyunsaturated fatty acids and brain health: Preclinical evidence for the prevention of neurodegenerative diseases

Background As the prevalence of neurodegenerative diseases increases steadily, the need to develop new treatment approaches intensifies and the possibility of targeting risk and protective factors to delay onset of these diseases is attracting more interest. Dietary habits stand as one of the most promising modifiable risk factors for both Alzheimer's (AD) and Parkinson's (PD) diseases. Scope and approach Over the last 30 years, several groups have generated data indicating that concentrations of specific brain lipids highly depend on dietary intake. Preclinical results show that treatments with omega-3 polyunsaturated fatty acids (n-3 PUFA) improve cognition, provide neuroprotection (and even neurorestoration), reduce neuroinflammation and influence neuronal function, while high-fat diets exert deleterious effects. Preclinical experiments have been conducted in well-recognized animal models of AD, PD, and ischemic stroke. Key findings and conclusions These studies have shown that dietary n-3 PUFA treatments consistently improve cognitive performance in animal models and may also exert disease-modifying actions. N-3 PUFA also provide protection to dopaminergic neurons in animal models of PD and possibly recovery after lesion. Furthermore, some of these effects might depend on specific diet formulations to protect long-chain fatty acids from oxidation or synergies with other nutrients. More generally, this review aims at providing evidence that adjustments in the consumption of dietary lipids alone or combined with other nutrients may be a cost-effective intervention to optimize brain function and prevent AD or PD