No abstract

In this review, we draw attention to the roles of calcitriol (1,25-dihydroxyvitamin D3) in the trophicity of the peripheral nervous system. Calcitriol has long been known to be crucial in phosphocalcium homeostasis. However, recent discoveries concerning its involvement in the immune system, anti-cancer defenses, and central nervous system development suggest a more pleiotropic role than previously thought. Several studies have highlighted the impact of calcitriol deficiency as a promoting factor of various central neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Based on these findings and recent publications, a greater role for calcitriol may be envisioned in the peripheral nervous system. Indeed, calcitriol is involved in myelination, axonal homogeneity of peripheral nerves, and neuronal-cell differentiation. This may have useful clinical consequences, as calcitriol supplementation may be a simple means to avoid the onset and/or development of peripheral nervous-system disorders.

The relationships between psychological stress and cognitive functions are still to be defined despite some recent progress. Clinically, we noticed that patients with Down syndrome (DS) may develop rapid neurocognitive decline and Alzheimer's disease (AD) earlier than expected, often shortly after a traumatic life event (bereavement over the leave of a primary caregiver, an assault, modification of lifestyle, or the loss of parents). Of course, individuals with DS are naturally prone to develop AD, given the triplication of chromosome 21. However, the relatively weak intensity of the stressful event and the rapid pace of cognitive decline after stress in these patients have to be noticed. It seems DS patients react to stress in a similar manner normal persons react to a very intense stress, and thereafter develop a state very much alike post-traumatic stress disorders. Unfortunately, only a few studies have studied stress-induced regression in patients with DS. Thus, we reviewed the biochemical events involved in psychological stress and found some possible links with cognitive impairment and AD. Interestingly, these links could probably be also applied to non-DS persons submitted to an intense stress. We believe these links should be further explored as a better understanding of the relationships between stress and cognition could help in many situations including individuals of the general population.

Cerebral folate deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF). The prevalence of this autosomal recessive disorder is estimated to be <1/1,000,000. Fifteen different pathogenic variants in the folate receptor 1 gene (FOLR1) encoding the receptor of folate α (FRα) have already been described. We present a new pathogenic variation in the FOLR1 in a childhood-stage patient. We aim to establish the core structure of the FRα protein mandatory for its activity. A three-year-old child was admitted at hospital for a first febrile convulsions episode. Recurrent seizures without fever also occurred a few months later, associated with motor and cognitive impairment. Various antiepileptic drugs failed to control seizures. Magnetic resonance imaging (MRI) showed central hypomyelination and biological analysis revealed markedly low levels of 5-MTHF in CSF. Next generation sequencing (NGS) confirmed a CFD with a FOLR1 homozygous variation (c.197 G > A, p.Cys66Tyr). This variation induces an altered folate receptor α protein and underlines the role of a disulfide bond: Cys66-Cys109, essential to transport 5-MTHF into the central nervous system. Fortunately, this severe form of CFD had remarkably responded to high doses of oral folinic acid combined with intravenous administrations.

A corrigendum onSevere toxic rhabdomyolysis under combined palbociclib and simvastatin treatment: A case report