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.

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 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.

Gastrointestinal stromal tumors (GISTs) occur in ∼7% of neurofibromatosis type 1 (NF1) patients. Data about their natural history remain scarce and neither risk classifications, prognosis model nor adjuvant treatment have been validated in this population. This national retrospective study included consecutive operated NF1-GIST cases from 31 reference centers in France, mostly from the NETSARC+ network. Factors associated with relapse were used to build a new prognostic score (RECKGIST). To address potential bias between adjuvant group and follow-up group, a propensity score was used. A total of 119 patients were included between 2008 and 2023, of whom 61% were women. Median age was 53 years (range 20-78 years). The main primary location was the small bowel (86%) and the stomach (11%). Median size and mitotic count (mit) were 45 mm [95% confidence interval (CI) 45-58 mm] and 2 mit/5 mm² (95% CI 3-9 mit/5 mm²), respectively. The vast majority were KIT/PDGFRA wild type (mutation KIT 2%, PDGFRA 3%). The median follow-up was 6 years. For GISTs 30 mm (n = 84), 18 developed metastases (21%). There was no difference in relapse according to tumor location (P = 0.45) or tumor rupture (P = 0.11), whereas KIT/PDGFRA-mutated GISTs were at higher risk of relapse [recurrence-free survival (RFS) at 10 years of 30% versus 82.5% for wild type, P = 0.03]. Miettinen and Joensuu classification did not predict relapse accurately. For the RECKGIST score A (size ≤30 mm, n = 34) group, 10-year RFS was 100%; it was 78.5% in the RECKGIST B group (size >30 mm and 0 < mit ≤ 5, n = 60), and 45.5% in the RECKGIST C group (size >30 mm and mit >5, n = 20) (P < 0.0001). After matching, 10-year RFS was similar between adjuvant and surveillance groups (P = 0.34). For NF1-GISTs <30 mm, prognosis without relapse is excellent. RECKGIST score accurately predicts recurrence and needs to be validated in an external cohort, but it may help treatment decision making. No efficacy of adjuvant treatment was observed.

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.

The EWSR1::CREM rearranged intra-abdominal malignant epithelioid neoplasm is an emerging tumor, with only a few publications describing it to date. Here, we report two new cases of this highly aggressive tumor, primarily involving the peritoneal surface. The tumors presented as a widespread diffuse peritoneal lesion associated with a 4-cm pelvic mass in a 28-year-old woman (Case 1) and as a 10-cm intra-abdominal mass infiltrating the stomach with multiple hepatic metastases in a 53-year-old woman (Case 2). The tumors shared predominant epithelioid morphology with minimal nuclear polymorphism. One of them additionally harbored spindle and rhabdoid cell populations. Both tumors displayed immunoreactivity for pan-cytokeratins, EMA, and CD99, and variable positivity for MUC4, progesterone and estrogen receptors, pan-NTRK, and synaptophysin. This misleading histology and immunophenotype give rise to a wide spectrum of differential diagnoses and highlight the crucial role of RNA sequencing in diagnostic accuracy and thus in appropriate therapeutic approaches.