Despite recent advances in treatment options, stroke remains a highly prevalent and devastating condition with significant socioeconomic impact. Recanalization therapies, including intravenous thrombolysis and endovascular treatments, have revolutionized stroke management and prognosis, providing a promising framework for exploring new therapeutic strategies. Endothelial dysfunction plays a critical role in the pathophysiology, progression, and prognosis of stroke. This review aims to synthesize the current evidence regarding the involvement of the nitric oxide (NO)/endothelium pathway in ischemic stroke, with a particular focus on aging, response to recanalization therapies, and therapeutic approaches. While significant progress has been made in recent years in understanding the relationship between endothelial dysfunction and stroke, many uncertainties persist, and although treatments targeting this pathway are promising, they have yet to demonstrate clear clinical benefits.

Spinocerebellar ataxia type 17 or ATX‐TBP is a CAG/CAA repeat expansion disorder characterized by marked clinical heterogeneity. Reports of affected carriers with subthreshold repeat expansions and of patients with Parkinson's disease (PD) with expanded repeats have cast doubt on the established cutoff values of the expansions and the phenotypic spectrum of this disorder. The objective of this systematic review was to explore the genotype–phenotype relationships for repeat expansions in TBP to delineate the ATX‐TBP phenotype and reevaluate the pathological range of repeat expansions. The International Parkinson and Movement Disorder Society Genetic Mutation Database (MDSGene) standardized data extraction protocol was followed. Clinically affected carriers of reported ATX‐TBP expansions were included. Publications that contained repeat sizes in screened cohorts of patients with PD and/or healthy individuals were included for a separate evaluation of cutoff values. Phenotypic and genotypic data for 346 ATX‐TBP patients were curated. Overall, 97.7% of the patients had ≥41 repeats, while 99.6% of patients with PD and 99.9% of healthy individuals had ≤42 repeats, with a gray zone of reduced penetrance between 41 and 45 repeats. Pure parkinsonism was more common in ATX‐TBP patients with 41 to 45 repeats than in the group with ≥46 repeats, which conversely more often presented with a complex phenotype with mixed movement disorders. An updated genotype–phenotype assessment for ATX‐TBP is provided, and new repeat expansion cutoff values of reduced penetrance (41–45 expanded repeats) and full penetrance (46–66 expanded repeats) are proposed. These adjusted cutoff values will have diagnostic and counseling implications and may guide future clinical trial protocol. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neuropsychiatric symptoms in Parkinson’s disease (PD) are highly prevalent and profoundly disabling, often emerging even before the onset of motor symptoms. As the disease progresses, these symptoms usually become increasingly impairing and are now recognized as having the greatest impact on quality of life not only for patients but also for caregivers. In recent years, there have been significant advances in the diagnosis and management of neuropsychiatric symptoms. However, there are still substantial gaps in therapeutic approaches and algorithms, with limited pharmacological and nonpharmacological treatment options currently available. One of the main reasons for this is the complex molecular and neural bases of these symptoms, which involve both dopaminergic and nondopaminergic neurotransmission systems and extend far beyond the nigrostriatal pathway. As a result, the drugs currently recommended for treating neuropsychiatric symptoms in PD are few and supported by limited evidence. In this context, the experience of the treating neurologist remains critical in selecting the most appropriate individualized therapy. The aim of this paper is to review the available therapeutic options and provide an overview of current research efforts, particularly those focusing on pharmacological treatments.