Emerging evidence suggests that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have long-term deleterious effects on the central nervous system and even contribute to post-COVID neurological syndromes. Interestingly, inflammation-induced proteolytic processing of the Spike protein of SARS-CoV-2 leads to the generation of peptides capable of aggregating into amyloid fibrils in vitro. Herein, we investigate the in vitro effect of a fibrillogenic fragment of the Spike protein [Spike 194-203 (S194)] on the aggregation and toxicity of the Parkinson's disease (PD) protein α-synuclein (αSyn). Our results indicate that S194 fibrils stimulate in a concentration-dependent manner the fibrillation of αSyn monomer, resulting in aggregates with increased capacity of inducing lipid vesicle leakage and toxicity to neuroblastoma cells, in comparison with either αSyn or S194 alone. Bidimensional NMR (1H-15N-HSQC) suggests that S194 fibrils cause a higher perturbation in both the N-terminal region (sequence: 19-68) and the hydrophobic central domain of the αSyn monomer (sequence: 71-95), which is corroborated by protein-peptide docking and molecular dynamics simulations. In contrast with fibrils from wild-type αSyn, aggregates from the PD variant A30P exhibited a remarkable accelerative effect on S194 fibrillation. Similarly, fibrils from amyloid-β peptides, which are linked to Alzheimer's disease, exhibited a pro-aggregating effect on the S194 monomer. Taken together, these findings might contribute to a broader understanding of the potential connections between SARS-CoV-2 infection and amyloid-related neurodegenerative disorders, highlighting areas that may warrant further investigation.

We describe the case of a 54-year-old patient, who was admitted to our Rehabilitation Unit with diagnosis of Guillain-Barré Syndrome (GBS). Neurophysiological investigation revealed an axonal polyneuropathy, with impairment of the motor component and preserved sensory function. Despite rapid diagnosis, therapeutic treatment and customized progressive rehabilitation program, nine months after the onset of the disease he presented severe motor sequelae and functional impairment. Patient's hospitalization lasted about two months, while he performed a conventional rehabilitation training. Besides, he underwent a 4-week comprehensive rehabilitation treatment, including both conventional and robotic multidimensional trainings, for 5 1-h sessions per week. Despite the residual global impairment, this treatment, specifically tailored on patient's skills and progress, promoted improvements in functional abilities such as motricity, trunk control, and activities of daily living. Therefore, this case report evidenced the feasibility and efficacy of a multidimensional robotic therapeutic approach along with conventional treatment in the post-acute phase of GBS.

About 20% of adults and between 6% and 13% of children experience mild to moderate anxiety and stress-related symptoms. Benzodiazepines (BZDs) are considered the referring medications for early-stage anxiety and stress-related symptoms management. Nevertheless, BZDs must be managed carefully because their use, especially chronic, could be linked with some adverse effects, and can promote the onset of psychological and physical dependence. They also often show progressive tolerance, necessitating an increase in dosage, and therefore their use should be discouraged. In the clinical management of patients with pathological/dysfunctional anxiety, one of the main issues related to the discontinuation of BZDs treatment is the occurrence of rebound effects and withdrawal syndrome, especially in subjects with certain personality disorders and poly-drug users. The deprescription of BZDs is advisable with the availability of other therapies and interventions, especially in elderly subjects. Therefore, an effective and safe alternative pharmacological tool for mild to moderate anxiety and stress-related symptoms is needed. After the identification of potentially new medications to flank BZDs, it is mandatory to revise and improve good clinical practices even through a consensus process. Taking into consideration all the above-mentioned premises, the present Delphi Consensus Study has explored whether there is agreement about the use of the low-dose multicomponent natural medication Ignatia-Heel in overlapping with BZDs is appropriate for the reduction and potential discontinuation of BZDs intake in patients on chronic BZDs treatment. The Consensus Study also explored the possibility to maintain symptom remission or low disease activity with the long-term use of Ignatia-Heel in patients with pathological/dysfunctional anxiety, after clinical remission achieved with BZDs. For each questionnaire statement, consensus was achieved (being based on the agreement of at least 66.6% of the Consensus Panel and the acceptance of the scientific committee). Ignatia-Heel can be considered a valid opportunity for the treatment of pathological anxiety favoring the deprescription of BZDs in patients under chronic BZDs treatment and the maintenance of a good control of symptomatology, i.e., a good low disease activity.

Charcot-Marie-Tooth disease (CMT) rarely presents with painful symptoms, which mainly occur in association with myelin protein zero (MPZ) gene mutations. We aimed to further characterize the features of painful neuropathic phenotypes in MPZ-related CMT. We report on a 58-year-old woman with a longstanding history of intermittent migrant pain and dysesthesias. Examination showed minimal clinical signs of neuropathy along with mild changes upon electroneurographic examination, consistent with an intermediate pattern, and small-fiber loss upon skin biopsy. Genetic testing identified the heterozygous variant p.Trp101Ter in MPZ. We identified another 20 CMT patients in the literature who presented with neuropathic pain as a main feature in association with MPZ mutations, mostly in the extracellular MPZ domain; the majority of these patients showed late onset (14/20), with motor-nerve-conduction velocities predominantly in the intermediate range (12/20). It is hypothesized that some MPZ mutations could manifest with, or predispose to, neuropathic pain. However, the mechanisms linking MPZ mutations and pain-generating nerve changes are unclear, as are the possible role of modifier factors. This peculiar CMT presentation may be diagnostically misleading, as it is suggestive of an acquired pain syndrome rather than of an inherited neuropathy.

Problematic Internet uUse (PIU) is a multifaceted syndrome characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding Internet use leading to significant impairments in daily life and mental health. Previous research has separately related PIU to loneliness and dissociation, both in adults and adolescents. The aim of the present study is to analyze the mutual relationship between PIU, loneliness, and dissociation in an adolescent sample, in particular evaluating the indirect effect of dissociation on the relationship between loneliness and PIU. A cross-sectional design was used with 243 Italian high school students (69.1% females), from year 9 to 13 (age: M = 17.1, SD = 1.4 years), who participated in the study from January to June 2020. They completed measures of PIU (Generalized Problematic Internet Use Scale-2), loneliness (UCLA Loneliness Scale), and dissociation (Adolescent Dissociative Experiences Scale). Socio-demographic and contextual variables were also collected (i.e., age, gender, type of school, school year, sport practice, hobby engagement, assessment before/during the COVID-19 pandemic). Data were analyzed using regression, Pearson's correlation, and mediation analysis. Severe PIU was observed in 8.6% of the sample. None of the socio-demographic and contextual variables had a significant effect on PIU. Positive medium-sized correlations were observed between PIU, loneliness, and dissociation. Mediation analyses showed an indirect effect of loneliness on PIU through dissociation. Feelings of loneliness may significantly exacerbate adolescents' PIU by increasing their dissociative tendency. Understanding this dynamic is crucial for developing targeted interventions to address both loneliness and dissociation in efforts to mitigate PIU among adolescents.