Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration within the central nervous system (CNS). While the inflammatory components of MS have been extensively studied, the progressive neurodegenerative aspect remains a critical factor contributing to long-term disability. Therefore, the identification and validation of biomarkers associated with neurodegenerative processes are essential for improved diagnosis, prognosis, and treatment monitoring. This review explores cerebrospinal fluid (CSF) and blood-based biomarkers, including neurofilaments, lipid markers, kynurenines, and other molecular indicators that provide insights into neurodegeneration in MS.

Zilebesiran represents an innovative antihypertensive therapy employing small interfering RNA (siRNA) to inhibit hepatic angiotensinogen, a key regulator of the renin–angiotensin–aldosterone system. By directly targeting the source of angiotensin II production, zilebesiran offers a novel mechanism distinct from conventional antihypertensive treatments. In the clinical studies KARDIA-1 and KARDIA-2, zilebesiran demonstrated clinically significant reductions in systolic blood pressure, with effects lasting up to 24 weeks after a single subcutaneous injection. In KARDIA-1, doses of 300 mg and 600 mg administered every 6 months resulted in reductions of over 15 mmHg in systolic blood pressure at 3 months compared with placebo. KARDIA-2 further showed an additional reduction of up to 12.1 mmHg at 3 months when zilebesiran was used as an adjunct to standard antihypertensive therapy. KARDIA-3 is currently evaluating the therapy in a larger global population to assess its impact on major cardiovascular outcomes. Zilebesiran has demonstrated a favorable safety profile with minimal adverse events, offering potential advantages for patients with resistant or uncontrolled hypertension and those at high cardiovascular risk, especially where adherence to daily oral medications is challenging. Beyond blood pressure reduction, zilebesiran may protect target organs, including the heart, kidneys, and retina. In conclusion, zilebesiran represents a promising siRNA-based therapy that may redefine the management of difficult-to-control hypertension, offering durable, targeted, and patient-friendly treatment with broad cardiovascular benefits. Future studies will clarify its long-term safety, efficacy across diverse populations, and integration into personalized hypertension management strategies.

Secondary Progressive Multiple Sclerosis (SPMS) represents a challenging phase of multiple sclerosis, marked by gradual neurological decline and reduced inflammatory activity. In recent years, magnetic resonance imaging (MRI) has become essential for characterizing the neurodegenerative changes underlying SPMS, including white and gray matter damage, brain atrophy, slowly expanding lesions, and iron rim lesions. This narrative review aims to synthesize the current knowledge on established and emerging MRI biomarkers relevant to SPMS, with a particular focus on their diagnostic, prognostic, and therapeutic implications. This review discusses key themes, such as the shift from inflammatory to neurodegenerative mechanisms, the role of advanced imaging techniques, and the limitations of conventional MRI in detecting smoldering disease. In doing so, it identifies current gaps in evidence, including the need for standardized imaging protocols and large-scale longitudinal studies. A clearer understanding and application of MRI biomarkers may facilitate earlier diagnosis, more tailored treatment strategies, and improved outcomes in patients with SPMS.

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood–brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research.

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies.

Background: Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist administered subcutaneously once a week, developed through recombinant DNA technology, and prescribed as an add-on to diet and exercise for managing type 2 diabetes mellitus in adults. In several clinical trials, once-weekly dulaglutide has demonstrated reductions in cardiovascular risk associated with diabetes, as well as improvements in glycemic control and weight reduction. The scope of this study was to evaluate the effect of dulaglutide 1.5 mg on glycemic control, weight management, and LDL-cholesterol levels in patients with uncontrolled type 2 diabetes mellitus. Methods: We retrospectively reviewed the medical records of 55 patients with inadequately controlled type 2 diabetes mellitus who were on oral antidiabetic agents and insulin, and who were additionally treated with dulaglutide 1.5 mg. We monitored fasting plasma glucose and glycated hemoglobin (HbA1c) at baseline and at 6, 12, and 24 months after initiating dulaglutide treatment. Weight, body mass index, and LDL-cholesterol were assessed at baseline and after 24 months of dulaglutide therapy. Results: Treatment with dulaglutide resulted in significant improvements in fasting plasma glucose and HbA1c after 6 months (p < 0.001), 12 months (p < 0.001), and 24 months (p < 0.001). A significant weight reduction was observed after 24 months of dulaglutide therapy (−3.3 kg; p < 0.001). In addition, we observed a significant reduction in LDL-cholesterol after 24 months (p < 0.001). Conclusions: Our data demonstrate that dulaglutide 1.5 mg significantly improves glycemic control, reduces body weight, and lowers LDL-cholesterol in Romanian patients with inadequately controlled type 2 diabetes.