Hereditary spastic paraplegias proteome: common pathways and pathogenetic mechanisms.

INTRODUCTION: Hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness of the lower limbs. These conditions are caused by lesions in the neuronal pyramidal tract and exhibit clinical and genetic variability. Ongoing research focuses on understanding the underlying mechanisms of HSP onset, which ultimately lead to neuronal degeneration. Key molecular mechanisms involved include axonal transport, cytoskeleton dynamics, myelination abnormalities, membrane trafficking, organelle morphogenesis, ER homeostasis, mitochondrial dysfunction, and autophagy deregulation. AREAS COVERED: This review aims to provide an overview of the shared pathogenetic mechanisms in various forms of HSPs. By examining disease-causing gene products and their associated functional pathways, this understanding could lead to the discovery of new therapeutic targets and the development of treatments to modify the progression of the disease. EXPERT OPINION: Investigating gene functionality is crucial for identifying shared pathogenetic pathways underlying different HSP subtypes. Categorizing protein function and identifying pathways aids in finding biomarkers, predicting early onset, and guiding treatment for a better quality of life. Targeting shared mechanisms enables efficient and cost-effective therapies. Prospects involve identifying new disease-causing genes, refining molecular processes, and implementing findings in diagnosis, key for advancing HSP understanding and developing effective treatments.

Prevalence of Incidental Findings Suspicious for Transthyretin Cardiac Amyloidosis among Patients Undergoing Bone Scintigraphy: A Systematic Review and a Meta-Analysis.

BACKGROUND: The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. METHODS: A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. RESULTS: Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7-1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. CONCLUSIONS: The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted.