Search Results (2,165)

Lipodystrophy is a rare group of metabolic disorders characterized by the abnormal distribution of body fat, which can lead to various metabolic complications due to the body’s inability to adequately process carbohydrates and fat. We report the case of a female, aged 53 years, who was admitted as an outpatient for progressive weight loss of the upper part of the body (face, neck, arms, and chest), dyspeptic complaints, fatigue, mild insomnia, and anxious behavior. Her medical history was characterized by the presence of dyslipidemia, hypertension, and a minor stroke episode. However, she denied any family-relevant medical history. Although the clinical perspective suggested a possible late onset of partial acquired lipodystrophy, due to the imaging exam that revealed an enlarged liver with inhomogeneous structure with multiple nodular lesions, scattered over both lobes, a lot of lab work-ups and complementary studies were performed. Eventually, a liver biopsy was performed by a laparoscopic approach during cholecystectomy, the histology consistent with metabolic disease-associated steatohepatitis (MASH). In conclusion, given their heterogeneity and rarity, lipodystrophies may be either overlooked or misdiagnosed for other entities. Barraquer–Simons syndrome (BSS) may be associated with liver disease, including cirrhosis and liver failure. Liver lipodystrophy in BSS may sometimes feature steatosis with a focal, multi-nodular aspect, multiplying the diagnostic burden. Liver lipodystrophy may manifest as asymptomatic fat accumulation but may progress to severe conditions, representing one of the major causes of mortality in BSS, apart from the cardio-vascular comorbidities. Given the potential of severe outcomes, it is mandatory to correctly assess the stage of liver disease since the first diagnosis. Full article

Background and Objectives: Although several meta-analyses have evaluated the effects of motor imagery (MI) on upper-limb recovery using the Fugl-Meyer Assessment for the Upper Extremity (FM-UE), evidence based on more specific (Action Research Arm Test, ARAT) and functional (Barthel Index, BI) outcomes remains scarce. This study examined the effect of MI combined with conventional rehabilitation therapy (CRT), which translates into meaningful improvements in upper-limb performance and functional independence after stroke, accounting for methodological quality and publication bias. Materials and Methods: A systematic review and meta-analysis were carried out in accordance with PRISMA recommendations, with prior registration in PROSPERO (CRD420251120044). Comprehensive searches were conducted across six electronic databases up to July 2025. The methodological rigor of the included studies was evaluated using the PEDro scale, and risk of bias was appraised with the Cochrane RoB 2 instrument. Random-effects models estimated pooled effect sizes (ESs) for the ARAT and BI, alongside analyses of heterogeneity, publication bias, and moderators. Results: Eleven RCTs (n = 425) were included. A small pooled improvement in ARAT was observed (ES = 0.25; 95% CI: 0.13–0.37; p < 0.001); however, this effect was rendered non-significant after correction for publication bias (ES = 0.08; 95% CI: −0.14–0.31). No significant differences were found for the BI (ES = 0.41; 95% CI: −0.35–1.18; p = 0.268), with substantial heterogeneity (I² = 96.6%). The mean PEDro score was 6.6, indicating moderate methodological quality. Conclusions: MI combined with CRT yields small and inconsistent effects on upper-limb recovery and no improvement in functional independence. Current evidence does not support its routine use in stroke rehabilitation. Well-designed, adequately powered randomized controlled trials employing standardized MI protocols are required to determine its true clinical relevance. Full article

Background: Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin’s association with neurological diseases and its underlying mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle–Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. Results: Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher α-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-β pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin αVβ5/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. Conclusions: Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation. Full article

Background: Chagas disease, caused by Trypanosoma cruzi, remains endemic throughout Latin America but is increasingly reported in urban areas due to migration and vector adaptation. The cardiac form is the most severe manifestation, associated with arrhythmia, mural thrombus formation, and a high risk of cardioembolic events. Stroke secondary to Chagas cardiomyopathy is uncommon and poses diagnostic and therapeutic challenges. Case Presentation: A 58-year-old woman with serologic evidence of T. cruzi infection presented with sudden-onset dyspnea, oppressive chest pain, and left-sided weakness. Neurological examination revealed left brachiocrural hemiparesis and mild dysarthria (NIHSS = 9). Non-contrast cranial CT showed an acute infarct in the right middle cerebral artery territory (ASPECTS = 7). Electrocardiography demonstrated typical atrial flutter with variable conduction, and transthoracic echocardiography revealed a markedly dilated left atrium containing a mural thrombus and a left ventricular ejection fraction of 45%. Intravenous thrombolysis with alteplase (0.9 mg/kg) was administered within 4.5 h of symptom onset. Pharmacologic rhythm control was achieved using intravenous and oral amiodarone, followed by oral anticoagulation with warfarin (target INR 2.0–3.0) after excluding hemorrhagic transformation. The patient showed rapid neurological improvement (NIHSS reduction from 9 to 2) and was discharged on day 10 with minimal residual deficit (mRS = 1), sinus rhythm, and stable hemodynamics. Conclusions: This case highlights the rare coexistence of Chagas cardiomyopathy, atrial flutter, and cardioembolic stroke due to left atrial thrombus. Early recognition, adherence to evidence-based guidelines, and multidisciplinary management were key to achieving a favorable outcome. Timely diagnosis and intervention remain crucial to preventing severe complications in patients with Chagas disease. Full article

COVID-19 has raised significant concern regarding its neurological impact, particularly during the early pandemic waves when severe systemic inflammation and neuroimmune dysregulation were more common. Although SARS-CoV-2 has been extensively studied, the precise mechanisms underlying its neurological effects remain incompletely understood, and much of the available evidence is derived from early variants with higher pathogenicity. Current research indicates that neuroinflammatory processes—driven primarily by systemic cytokine elevation, microglial activation, and blood–brain barrier dysfunction—contribute to a wide range of neurological symptoms. Severe complications such as encephalopathy, stroke, and cognitive impairment were predominantly reported in critically ill patients infected with the Wuhan, Alpha, or Delta variants, while such manifestations are considerably less frequent in the Omicron era. Most proposed mechanisms, including ACE2-mediated viral entry into the central nervous system, are supported mainly by experimental or preclinical studies rather than definitive human evidence. Biomarkers such as IL-6 and TNF-α, along with neuroimaging modalities including MRI and PET, offer useful but indirect indicators of neuroinflammation. Therapeutic approaches continue to focus on controlling systemic inflammation through immunomodulatory agents, complemented by targeted non-pharmacological strategies—such as physical rehabilitation, cognitive support, and psychological interventions—for the minority of patients with persistent neurological deficits. Overall, current evidence supports a variant-dependent neuroinflammatory profile and underscores the need for longitudinal, mechanism-focused studies to better characterize long-term neurological outcomes and refine therapeutic strategies. Full article

Objective: This study investigated the efficacy and neural mechanisms of robot-assisted mirror therapy (RMT) for post-stroke upper limb rehabilitation. RMT integrates the multimodal feedback of mirror therapy with robotic precision and repetition to enhance cortical activation and neuroplasticity. Methods: Seventy-eight stroke patients were randomly assigned to control, mirror therapy (MT), or RMT groups. All received conventional rehabilitation; the MT group additionally underwent mirror therapy, and the RMT group received robot-assisted mirror therapy combined with functional electrical stimulation. The primary outcome was the Fugl–Meyer Assessment for Upper Extremity (FMA-UE), with secondary measures including spasticity, dexterity, daily living, and quality of life. Functional near-infrared spectroscopy (fNIRS) was applied to assess cortical activation and connectivity at baseline, post-intervention, and one-month follow-up. Results: All groups showed significant time effects, though between-group differences were limited. Subgroup analysis revealed that patients at Brunnstrom stages I–II in the MT group achieved greater improvements in upper limb function, dexterity, and daily living ability. fNIRS findings showed enhanced activation in the right sensory association cortex and increased prefrontal–sensory connectivity. Conclusions: While all interventions improved motor outcomes, MT yielded slightly superior recovery associated with neuroplastic changes. RMT demonstrated high safety, compliance, and potential benefit for patients with severe motor deficits. Full article

Growth Differentiation Factor-15 (GDF-15) is a stress-responsive cytokine belonging to the Transforming Growth Factor-beta (TGF-β) superfamily. Initially identified as macrophage inhibitory cytokine-1 (MIC-1), GDF-15 is expressed in various tissues and markedly upregulated under pathological conditions involving inflammation, oxidative stress, and tissue injury. Notably, GDF-15 upregulation has been associated with several cardiovascular events, such as heart failure, atrial fibrillation, atherosclerosis, coronary artery disease, and stroke. Furthermore, it has been observed that GDF-15, either alone or in combination with other cardiac biomarkers, can provide valuable complementary information enhancing risk assessment, early detection of cardiovascular events, and prediction of adverse outcomes. GDF-15 can be measured in various body fluids, using different methods. Immunoassays are widely employed and offer good sensitivity and reproducibility; however, variability between methods and potential interference from genetic variants highlight the need for standardization. This review summarizes current insights into GDF-15, with emphasis on its quantification methods, biological functions in cardiovascular diseases, and its emerging role as a diagnostic and prognostic biomarker. Full article

Background and Objectives: We aimed to evaluate the effectiveness of virtual reality (VR) therapy compared with conventional rehabilitation on static postural control and dynamic balance in patients with stroke. Design: A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted in accordance with the PRISMA 2020 guidelines. Materials and Methods: RCTs involving adults with stroke who received VR-based interventions, alone or combined with conventional therapy, were included. Outcomes were static postural control measured by center of pressure (COP) and dynamic balance assessed by the Berg Balance Scale (BBS) and Timed Up-and-Go Test (TUG). Results: Thirty-six RCTs (1118 participants) were analyzed. Pooled estimates favored VR-based interventions for several measures of static postural control, with standardized mean differences ranging from −0.59 to −0.38 (p < 0.05), whereas no clear difference was observed for COP sway speed under eyes-closed conditions (standardized mean difference (SMD) = –0.13, p = 0.43). For dynamic balance outcomes, pooled mean differences favored the VR group compared with conventional rehabilitation (BBS: mean difference (MD) = 3.29, 95% CI 2.76–3.83; TUG: MD = −3.43, 95% CI −4.03 to −2.82; both p < 0.0001). However, substantial heterogeneity and a high risk of bias were observed across several outcomes, which may affect the certainty of these findings. Conclusions: VR-based interventions may offer potential benefits for improving static postural control and dynamic balance in individuals with stroke, particularly when used as an adjunct to conventional rehabilitation. Nevertheless, given the substantial heterogeneity and risk of bias among included studies, the findings should be interpreted cautiously, and further well-designed, large-scale trials are required to confirm the magnitude and clinical relevance of these effects. Full article

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations. Full article

Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain’s vulnerability to ischemic and reperfusion injury. This review integrates recent insights into how these intrinsic modulators govern the transition from adaptive physiological redox signaling to pathological oxidative stress during stroke. Aging compromises mitochondrial quality control and blunts NRF2-driven antioxidant responses, heightening susceptibility to ROS-driven damage. Metabolic dysfunction, as seen in obesity and diabetes, amplifies oxidative burden through NADPH oxidase activation, lipid peroxidation, and impaired glutathione recycling, further aggravating post-ischemic inflammation. Circadian misalignment, meanwhile, disrupts the rhythmic expression of antioxidant enzymes and metabolic regulators such as BMAL1, REV-ERBα, and SIRT1, constricting the brain’s temporal window of resilience. We highlight convergent signaling hubs, NRF2/KEAP1, SIRT–PGC1α, and AMPK pathways, as integrators of these physiological inputs that collectively calibrate redox homeostasis. Recognizing oxidative stress as a dynamic, context-dependent process reframes it from a static pathological state to a dynamic outcome of systemic and temporal imbalance, offering new opportunities for time-sensitive and metabolism-informed redox interventions in stroke. Full article

Stroke often results in lasting cognitive impairments that severely reduce independence and quality of life. Traditional neuropsychological assessments rely on mean scores that provide an average estimate of overall cognitive function but neglect the fluctuations in performance. The variability in performance can be captured as inconsistency, i.e., fluctuations across multiple trials within a single task or as dispersion, i.e., fluctuations across multiple tasks. While inconsistency has been extensively studied, the impact of post-stroke cognitive impairment on cognitive dispersion is unknown. In this study, ninety-five stroke survivors (41 cognitively impaired and 54 cognitively normal) completed a neuropsychological battery that captured performance across five cognitive domains: executive function, attention, memory, language, and processing speed. We compared the stroke groups on across- and within-domain cognitive dispersion. Cognitively impaired stroke individuals showed elevated dispersion within executive function compared to cognitively normal individuals. The two groups did not differ on any other within-domain or across-domain cognitive dispersion. Post-stroke cognitive impairment increased variability within executive functioning. Incorporating cognitive dispersion into routine post-stroke assessment can advance clinical practice by identifying subtle cognitive instability, anticipate supportive needs, and tailor rehabilitation plans for improving stroke care. Full article

Background/Objectives: Diaschisis, reduced neural activity, perfusion, and metabolism in structurally intact but anatomically connected regions, is a network-level consequence of focal brain injury. Despite the extensive literature, its prevalence across imaging modalities and diaschisis subtypes has not been systematically synthesized. This review aims to identify convergent evidence for diaschisis after ischemic stroke and clarify how its detection relates to neuroanatomical disconnection, clinical factors, and imaging methods. (PROSPERO: CRD420251017909). Methods: PubMed and Embase were searched through February 2025 for studies reporting quantitative measures of diaschisis using perfusion, metabolic, or functional imaging. Pooled prevalence and modality-specific estimates were calculated. Subgroup analyses examined diaschisis subtypes, stroke severity, age, and study quality. Results: Sixty-six studies (3021 patients) were included. Overall pooled prevalence was 53% (95% CI: 47–58%). Crossed cerebellar diaschisis was most frequently studied (49%), while thalamic and other remote patterns showed comparable or higher effect sizes. Detection varied primarily by imaging modality: ASL MRI (67%) and PET (58%) showed the highest sensitivity; SPECT (53%) and CTP (49%) were intermediate; DSC-PWI had the lowest (28%). In contrast, age had no measurable effect and stroke severity only modestly increased detection, suggesting that diaschisis is driven predominantly by neuroanatomical disconnection rather than demographic or clinical variables. Egger’s tests indicated minimal publication bias. Conclusions: Diaschisis is a common manifestation of network vulnerability after ischemic stroke, determined chiefly by lesion topology and long-range anatomical connectivity. Detection depends more on imaging physiology than patient characteristics. Standardized definitions and longitudinal multimodal studies are needed to clarify its temporal evolution and clinical significance. Full article

Introduction: Stroke is a severe neurological condition associated with high rates of mortality and disability. Objective: This systematic review aimed to analyze the efficacy of early mobilization (EM) on the quality of life and the dependency levels in stroke patients. Additionally, the impact on anxiety and depression, the occurrence of adverse effects, and length of hospital stay were assessed. Methods: A systematic search was conducted in PubMed, Web of Science, and Scopus databases. The search was restricted to randomized controlled trials published within the last 10 years that included EM as an intervention in the experimental group. The Cochrane tools were used to assess risk of bias, and the PEDro scale was applied to evaluate the methodological quality of the included studies. Results: Nine studies were included in this review. Findings indicated that EM performed within 24–48 h post-stroke reduces dependency levels; however, no significant improvement in quality of life was observed. Evidence regarding anxiety and depression was inconclusive, and no significant differences were reported between groups concerning adverse events or reduction in hospital stay duration. Conclusions: This review demonstrates that EM is beneficial for reducing dependency after stroke, but there is no evidence of a significant improvement in quality of life. Further research is needed to establish clear protocols and appropriate intervention doses. Full article

Background/Objectives: Aspiration pneumonia is among the most frequent medical complications after intracerebral hemorrhage (ICH), yet its role during the ultra-early emergency department (ED) phase remains poorly understood. This study aimed to identify clinical and neurological factors independently associated with radiologically confirmed aspiration pneumonia in patients presenting with acute spontaneous ICH and to evaluate its association with early clinical outcomes. Methods: A retrospective observational cohort study was conducted in the neuro-emergency department of a large tertiary university hospital. All consecutive adults with spontaneous ICH confirmed by neuroimaging between January 2020 and December 2023 were included. Univariable and multivariable logistic regression models were used to identify independent predictors of pneumonia. Results: A total of 184 patients were analyzed (median age 74 years; 46% female). Radiologically confirmed aspiration pneumonia occurred in 37 patients (22.0%). Pneumonia was significantly associated with lower GCS, higher National Institutes of Health Stroke Scale (NIHSS) and ICH scores, shorter ED stay, and more frequent endotracheal intubation (ETI). In multivariable analysis, ETI (OR 5.42, 95% CI 1.57–18.63, p = 0.007), higher NIHSS score (OR 1.09, 95% CI 1.01–1.20, p = 0.047), and shorter ED stay (OR 0.97, 95% CI 0.95–0.99, p = 0.035) were independently associated with pneumonia. Aspiration pneumonia was not independently associated with neurosurgical referral (p = 0.082) or low GCS at discharge (p = 0.650). Conclusions: In this neuro-emergency cohort, aspiration pneumonia was common and strongly associated with neurological severity, particularly with endotracheal intubation and higher NIHSS scores. Although it did not independently predict early neurological deterioration or neurosurgical transfer, it identifies a critical period in which preventive measures—such as dysphagia screening, oral hygiene, and careful airway management—should be systematically applied. Larger multicenter studies with longer follow-up are needed to better define its long-term clinical consequences after ICH. Full article

Background/Objectives: Limited information exists on the burden of major cardiovascular morbidity in elderly patients with chronic coronary syndrome (CCS). Our objective was to investigate the cumulative incidence of lifetime hospitalizations for major cardiovascular events (MCE) in patients aged 75 years or older with CCS and to identify clinical predictors of these events. Methods: All consecutive outpatients aged 75 years or older with CCS seen in two consultations at a tertiary hospital between 2000 and 2008 were included in a prospective study and followed until death. All MCEs requiring admission (hospitalizations for heart failure (HF), acute myocardial infarction, and stroke) were recorded, and the cumulative incidence of each event and the combination of all events was calculated, considering death without admission as a competing event. Results: A total of 414 patients were selected (mean age was 79 ± 4 years, 36% women). After a 22-year follow-up (median 7 years, p25–75 4–11), 198 patients (48%) experienced at least one MCE, the most common being hospitalization for HF (122 patients had 209 hospitalizations). The 10 and 20-year cumulative incidence was 41% (95% CI 36–46%) and 48% (43–53%) for any event. In multivariate analysis, independent predictors of hospitalization for MCE were hypertension (HR 1.58 [95% CI:1.15–2.18], p = 0.005), diabetes (HR 1.38 [1.03–1.85], p = 0.031), prior HF (HR 2.52 [1.59–4.01], p < 0.0005), and atrial fibrillation (HR:1.68 [1.13–2.50], p = 0.011). Conclusions: Nearly half of elderly patients with CCS were hospitalized for MCE during their lifetime. HF was the most common event. Several clinical variables could be useful to stratify the risk of events. Full article