Neurological disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), may be associated with alterations in blood cell composition and phenotype. Here, we focused our ...attention on circulating mucosal-associated invariant T (MAIT) cells, a CD8 + T cell memory population expressing the invariant Vα7.2 region in the T cell receptor and high surface levels of the CD161 marker. Transcriptomics data relative to peripheral blood mononuclear cells (PBMC) highlighted downregulation of CD161 and other MAIT-associated markers in progressive MS and not relapsing remitting (RR)-MS when gene expressions relative to each disease course were compared to those from healthy controls. Multiparametric flow cytometry of freshly isolated PBMC samples from untreated RR-MS, primary or secondary progressive MS (PP- or SP-MS), ALS and age- and sex-matched healthy controls revealed specific loss of circulating CD8 + MAIT cells in PP-MS and no other MS courses or another neurological disorder such as ALS. Overall, these observations point to the existence of immunological changes in blood specific for the primary progressive course of MS that may support clinical definition of disease.
Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; ...occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients.
OBJECTIVE:To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in skin nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and ...(2) small fiber neuropathy (SFN) is associated with DLB.
METHODS:We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein.
RESULTS:No p-syn was detected in any skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of skin was more severe in patients with autonomic dysfunctions.
CONCLUSIONS:(1) In autonomic skin nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that p-syn in skin nerve fibers on skin biopsy accurately distinguishes DLB from other forms of dementia.
Dopo un’analisi del clima politico nell’Unione europea, e delle sue premesse economiche e sociali, l’intervista prosegue con una disamina dei principali problemi irrisolti regione balcanica con ...speciale riferimento alla Croazia. Si tratta di una situazione paradossale, dal momento che, “l’Europa sudorientale non si riesce a riprendere dai propri problemi senza un maggiore aiuto da parte dell’Europa. Allo stesso tempo, la UE vincola l’erogazione di ulteriori aiuti ad un miglioramento proprio in quei settori”. Infine, viene proposta una riflessione sul ruolo degli intellettuali e la loro importanza nel presente.
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