Background: Distinguishing between distal myopathies (DMs) and distal hereditary motor neuropathies (dHMNs) can be challenging because clinical, EMG and biopsy findings sometimes overlap. This study aims to identify distinctive muscle MRI features that can guide the diagnosis. Methods: We collected clinical, genetic and muscle MRI data from patients with a confirmed diagnosis of DM and dHMN. We analyzed potential MRI characteristics to distinguish these conditions and to guide molecular diagnosis, such as the texture and pattern of infiltration. Results: Seventy-eight (71.5%) patients diagnosed with DMs and thirty-one (28.4%) with dHMNs were included. A length-dependent pattern of muscle involvement, a distal to proximal gradient of fat replacement along the length of the muscles and severe and widespread involvement of foot muscles were more common in patients with dHMNs. Muscle hypertrophy and asymmetry were more frequently observed in the DMs. A reticular pattern of fat infiltration was exclusive to patients with dHMNs, while the moth-eaten pattern predominated in DMs. Muscle islands were more commonly identified in dHMNs (54.8%) but were also observed in 32% of patients with DMs. Conclusions: Analysis of MRI features can help distinguish between DMs and dHMNs. A reticular pattern is an early feature of dHMNs while muscle islands are identified in advanced stages and in some forms of DMs, though not specific to neurogenic conditions. We recommend including foot muscles in the MRI protocol as they show extensive involvement in most dHMNs, while in DMs their involvement correlates with greater fatty infiltration of lower leg muscles.
Huntington’s disease (HD) is a neurodegenerative disorder caused by mutations in the huntingtin gene resulting in an extended polyglutamine (polyQ) stretch in the protein, which is prone to aggregation and toxicity. In addition to a proteostasis imbalance, growing evidence highlights the role of mitochondrial dysfunction in HD progression. Here we explore the role of SIR-2.3/SIRT4, a mitochondrial sirtuin, in polyQ-expanded peptides and mutant huntingtin (mHTT) toxicity using C. elegans and mammalian models. Notably, loss of sir-2.3 function results in neuronal protection mediated by AMPK activation and enhanced autophagy. These neuroprotective effects require the transcription factors DAF-16/FOXO and NHR-49, which regulate autophagy and metabolism. To explore the translational potential of these findings, we used soft ATP synthase inhibitors to mimic sir-2.3 ablation, successfully reducing mHTT-induced neuronal toxicity. These results identify the SIRT4-AMPK axis as a critical regulator linking mitochondrial metabolism, autophagy, and neuronal homeostasis in HD. These findings not only advance our understanding of HD pathogenesis but also offer promising therapeutic targets for restoring proteostasis and neuronal resilience capacity against neurodegenerative diseases.
Parkinson's disease and other synucleinopathies are neurodegenerative disorders defined by the pathological aggregation of alpha-synuclein (α-syn). The alpha-synuclein Seed Amplification Assay (α-syn SAA), also known as real-time quaking-induced conversion (RT-QuIC), has gained recognition as a high-sensitivity, high-specificity diagnostic tool capable of detecting misfolded α-syn seeds in biological samples through cyclic amplification and thioflavin T-based fluorescence readout. Despite its diagnostic promise, the lack of standardized protocols across laboratories remains a critical obstacle to clinical implementation. This systematic review, conducted following PRISMA guidelines, analysed 78 studies published between 2019 and 2025 to comprehensively characterize the methodological parameters employed in α-syn SAA. Data extraction encompassed equipment settings (fluorescence reader model, incubation temperature, shaking speed and ratio, bead configuration), reaction mixture components (recombinant α-syn concentration and type, buffer composition, NaCl and SDS concentrations, thioflavin T concentration), sample types, investigated pathologies, and positivity criteria. Findings revealed relative consensus in certain parameters. First, 73% of studies used the same equipment, 0.1 mg/mL recombinant α-syn, and 10 μmol/L thioflavin T; while substantial heterogeneity persisted in incubation temperature, buffer composition, and diagnostic thresholds. Cerebrospinal fluid was the predominant sample type, and Parkinson's disease the most frequently studied condition. Positivity criteria varied widely, with no universally validated standard. These results underscore the urgent need for harmonized protocols to ensure reproducibility and facilitate the clinical translation of α-syn SAA as a reliable biomarker tool to detect synucleinopathies.
AIMS AND METHODS:The yeast community in the hospital environment (surface and air samples from two tertiary and one secondary hospitals) was assessed by selective cultivation, DNA metabarcoding and a novel duplex qPCR assay. RESULTS:Two WHO priority opportunistic pathogens, Candida parapsilosis and Candida albicans, were dominant in this survey. C. parapsilopsis showed a wider distribution covering all hospital zones, from outside to indoor admission halls, patient rooms and intensive care units (ICUs) protected by HEPA filters; while C. albicans was especially associated with patient rooms and ICUs. Other clinically relevant yeasts are reported, such as Candida tropicalis, Nakaseomyces glabratus (formerly Candida glabrata), Pichia kudriavzevii (formerly Candida krusei), Clavispora lusitaniae (formerly Candida lusitaniae), Meyerozyma guilliermondii (formerly Candida guilliermondii) and Lodderomyces elongisporus. CONCLUSION:This study provides relevant insights to improve the environmental microbial assessments in healthcare settings, which are vital for guaranteeing proper indoor conditions and preventing the nosocomial infections.
Introduction Lumbar puncture (LP) is a standard procedure in neurology units for the detection of Alzheimer disease and other neurodegenerative disorders. Several side effects associated with this procedure have been described, along with strategies to prevent them. Methods The data for this observational study were obtained by telephone (24h and 7 days after LP), using a structured interview, from patients who underwent a diagnostic LP for the evaluation of cognitive impairment (n=348). Participants were recruited from clinical practice, without comparison with other age groups or a non-LP control group. Results Some 31% of patients (108/348) reported headache 24h after LP, with duration up to 24h in 82%, and longer than 24h in 32.2% of those followed up at one week. After 7 days, 19% reported other types of pain or discomfort. In 16% of patients, these problems affected their daily activities, requiring interruption of the activity in more than 50% of cases. No relationship was observed between either the volume of water or the amount of caffeine consumed, and the percentage of patients with pain. Age was associated with higher headache incidence and greater intensity. However, in a multivariate model including baseline characteristics, no independent predictors of post-LP headache were identified. Similarly, patients with other complications were younger (median [IQR]: 67 [61–72] years) than those without other complications (P=.012). There were no sex differences in the presence/absence of headache. Weight, height, and BMI were not related to headache nor other self-reported complications. Conclusion Approximately one-third of patients at risk of dementia experienced post-LP complications, with headache being the most common. No baseline patient characteristics or commonly recommended modifiable factors reliably predicted these events. Younger age and certain CSF biomarkers showed weak associations with headache in univariate analyses but were not predictive in the multivariate analysis. Although post-LP complications cannot be robustly anticipated, careful monitoring and supportive care are recommended for all patients.
