Search Results (34)

Background/Objectives: Septic cardiomyopathy (SC) is a frequent and clinically relevant complication of sepsis, characterized by acute, typically reversible myocardial dysfunction in the absence of primary coronary artery disease. Its clinical presentation is highly heterogeneous, and conventional diagnostic parameters frequently fail to capture the full extent of cardiac impairment. This narrative review aims to synthesize current evidence on the echocardiographic assessment of SC, with a focused emphasis on global longitudinal strain (GLS), right ventricular (RV) dysfunction, and diastolic impairment, and to discuss their prognostic and therapeutic implications. Methods: A comprehensive literature search was performed in PubMed/MEDLINE for publications between 2010 and March 2026, supplemented by seminal historical studies. A second, structured literature search was performed in PubMed/MEDLINE for publications between 2010 and April 2026, supplemented by seminal historical studies. Eligible study types included original research articles, systematic reviews, meta-analyses, and clinical guidelines. The search and selection workflow followed the principles of PRISMA-ScR. A qualitative narrative synthesis was performed. Results: SC encompasses distinct echocardiographic phenotypes—global hypokinesia, hyperdynamic function, RV dysfunction, and diastolic impairment—each carrying specific pathophysiological and prognostic implications. Left ventricular ejection fraction (LVEF) is highly load-dependent and may be misleading in vasoplegic states. GLS derived from speckle-tracking echocardiography defects may detect subclinical myocardial dysfunction earlier than LVEF, and provides independent prognostic information in observational studies. RV dysfunction occurs in 20–50% of sepsis patients and represents a powerful robust independent predictor of mortality. Diastolic dysfunction Grade ≥ 2 is independently associated with adverse outcomes through elevated filling pressures and reduced cardiac reserve. Conclusions: A multiparametric echocardiographic approach integrating LVEF, GLS, RV function indices, and diastolic parameters is essential and may improve the accurate phenotyping and hemodynamic management of SC. Structured diagnostic algorithms, expert-based diagnostic frameworks incorporating these tools which may facilitate phenotype-guided therapy and improve clinical outcomes, are proposed to facilitate phenotype-guided therapy; their impact on patient outcomes warrants confirmation in prospective multicenter studies. Full article

Background/Objectives: Although comprehensive transthoracic echocardiography (TTE) is part of the diagnostic workup in acute ischemic stroke, it is not cost-effective to use it for all patients. Guidelines recommend using it only for selected patients to guide secondary prevention. Neurologist-led, stroke-focused cardiac ultrasound (S-FoCUS) is an emerging bedside screening tool that optimizes cardiac evaluation in acute stroke care. We hypothesize that the implementation of S-FoCUS screening may reduce resource utilization in terms of hospital stay and TTE procedures. Methods: We conducted a retrospective before-and-after cohort study of patients with suspected acute ischemic stroke or TIA admitted to our comprehensive stroke center. We compared two 6-month periods: the pre-S-FoCUS period, during which patients underwent TTE as the initial cardiac imaging modality; and the post-S-FoCUS period, during which patients initially underwent S-FoCUS, with subsequent TTE performed only in the presence of abnormal findings or at the clinician’s discretion. We compared the time from admission to first cardiac ultrasound assessment, length of stay, relative reduction in TTE procedures and estimated in-hospital costs. Results: The pre-S-FoCUS period included 224 patients, and the post-S-FoCUS period included 229 patients. The S-FoCUS protocol reduced the median time to first cardiac ultrasound assessment by two days (median [IQR] 3 [2–5] vs. 1 [1–2], p < 0.001) and the median length of stay by one day (6 [4–9] vs. 5 [3–10], p = 0.014). Implementing the S-FoCUS protocol was associated with an exploratory estimate of lower in-hospital costs (approximately €716 per screened patient) driven mainly by a shorter length of stay. The distribution of the frequency of predefined cardioembolic sources was similar between both periods. There was a high agreement rate between the S-FoCUS and TTE findings in patients who underwent both tests: mitral stenosis (κ = 0.78), left atrial severe enlargement (κ = 0.74), left ventricular hypokinesia/akinesia (κ = 0.84), and depressed LVEF (κ = 0.88). Conclusions: Neurologist-led S-FoCUS is a feasible triage strategy to improve efficiency in the acute stroke pathway. Full article

Compensatory mechanisms are thought to maintain sufficient dopamine (DA) signaling to mitigate locomotor impairment during progressive nigrostriatal neuron loss in Parkinson’s disease (PD). Recent evidence indicated augmented DA tissue content in the substantia nigra (SN), not striatum, compensates for tyrosine hydroxylase (TH) and neuronal loss, and alleviates the severity of hypokinesia during neuronal loss. Here, we determined if increased extracellular DA in the SN may also be a compensatory mechanism to augment DA signaling. Following unilateral 6-hydroxydopamine (6-OHDA) lesion or sham-operation, we contemporaneously evaluated extracellular DA against both DA tissue and TH levels in striatum and SN at 7 and 28 days. At 7 days post-lesion, TH loss exceeded ~90% in striatum, and ~70% in the SN. The severity of DA tissue loss coincided with TH protein loss only in striatum (>90%) on both days after lesion, whereas in the SN, DA loss was absent on day 7 and significantly less than TH loss by day 28. Whereas there was a robust increase in extracellular DA in striatum in our sham-operation group, the severe TH and DA tissue loss in striatum practically abolished KCl (K⁺)-stimulated extracellular DA by day 7. In contrast, whereas striatal K⁺-stimulation had no effect on extracellular DA in the SN in sham-operation group, extracellular DA levels increased in the SN 7 days after nigrostriatal lesion: an increase no longer apparent by day 28. Thus, despite significant loss of TH protein loss in the SN, extracellular and tissue DA tissue levels were augmented during neuronal loss. These results build upon evidence that compensatory mechanisms to augment DA signaling are not engaged in striatum, and point to the SN as the locus of augmented DA signaling to offset loss of TH during nigrostriatal neuron loss. Full article

Background: Tremor-dominant Parkinson’s disease (TDPD) is the most common subtype of PD. Tremor is difficult to treat and less than 50% of patients respond to dopaminergic medications. Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an incisionless noninvasive method for treating pharmacoresistant tremor in PD patients, but its effect on progression of PD is unknown. In this study, we investigate the efficacy of MRgFUS thalamotomy on progression of motor and non-motor symptoms, using a levodopa equivalent daily dose (LEDD) requirement. Methods: A total of 21 PD patients with ineffective tremor correction by medical therapy underwent MRgFUS thalamotomy. Assessments of motor and non-motor symptoms, adverse events (AE), changes in LEDD, and evolution of FUS (focused ultrasound) lesion were performed on the day before surgery, and then 2 days, as well as 3, 6, and 12 months, after the procedure. Results: On the 2nd day after FUS thalamotomy, 11 patients were tremor-free and, in 10 patients, tremor decreased by 80–90% with a concomitant reduction in hypokinesia and rigidity. By the end of the 12th month, 5 patients remained tremor-free; in 11 patients, mild/moderate tremor re-emerged; and in 5 patients, there was a relapse of severe tremor. Quality of life (QoL) and activities of daily living (ADL) improved significantly at 3 months and remained stable thereafter. Cognitive function improved in patients with baseline MoCA score < 26 points at 3 months after FUS. Anxiety progressed between baseline and end of follow-up. By the end of the follow-up period, LEDD was lowered or stable in 9 patients. Four patients had persistent mild AE. Conclusions: This open label study suggests a beneficial effect of MRgFUS in reducing tremor, hypokinesia, and rigidity and improving QoL, ADL, and cognitive function in TDPD patients in the short term, although long-term data needs to be collected in further studies. Full article

Takotsubo Cardiomyopathy (TTC), often referred to as stress-induced or “broken heart” syndrome, is characterized by transient left ventricular dysfunction predominantly involving apical hypokinesia and basal hyperkinesia in the absence of obstructive coronary artery disease. Traditionally viewed as an acute and reversible phenomenon, accumulating evidence suggests that TTC may emerge from a preexisting myocardial substrate shaped by chronic stress and hemodynamic loading. Basal Septal Hypertrophy (BSH), a morphological finding commonly observed in elderly, hypertensive, or emotionally stressed individuals, has been increasingly recognized in patients with TTC. This hypertrophic pattern, often accompanied by dynamic contractile gradients and regional perfusion mismatch, reflects a broader adaptive remodeling process conceptualized as Stressed Heart Morphology (SHM). SHM encompasses the structural and functional myocardial responses to cumulative neurohormonal and mechanical stress, with BSH representing a key imaging marker within this spectrum. Advanced echocardiographic techniques, such as tissue Doppler imaging, speckle-tracking strain analysis, and stress echocardiography, consistently reveal overlapping features between SHM and TTC, including basal hyperkinesis, septal thickening, and inducible left ventricular outflow tract obstruction. These findings support a continuum in which SHM serves as a predisposing substrate for TTC, representing a stress-provoked clinical expression within a unified myocardial stress–response framework. Full article

Background/Objectives: Impaired balance and general mobility are common complications of Parkinson‘s disease (PD) and are largely caused by bradykinesia and hypokinesia. Although previous studies have shown that patients can increase the speed and amplitude of movement with training, apathy, which is also common among people with PD, reduces this prospect. Training with light pods was originally developed for athletes to enhance agility in a way that is motivating. However, this type of training could be ideal for individuals with PD and possibly reduce bradykinesia and its effects. This study used a longitudinal interventional design without a control group to explore the effects of a four-week agility training with light equipment on balance and general mobility in patients with PD, as well as to assess motivational properties. Methods: Seven individuals with PD of the motor subtype “akinetic–rigid” participated in this study. Each participant received training three times per week for four weeks. The training session consisted of five rounds; in each round, participants had to turn off 20 lights. Measurements were performed one and a half weeks before training, at the beginning of the program, and at the end of the program. Balance was assessed with Mini-BESTest, general mobility with Timed Up and Go (TUG), transfer skills with 5× Sit to Stand, walking speed with the 10 m walking test, and the ability to turn on a spot with the 360° Turn Test. Motivational aspects of training were assessed after each training session, with scoring on a scale of 0–10. Results: The training significantly improved overall balance (p < 0.001), especially reactive postural control, sensory orientation, and dynamic gait, while anticipatory balance remained unchanged. Turning ability improved, but mobility, transfer ability, and walking speed did not. Motivation remained consistently high across participants. Conclusions: A four-week light-based agility training program can improve balance and turning ability in people with PD and appears to be motivating. However, no clear effects were found for general mobility, transfer skills, or walking speed. Given the small sample size and absence of a control group, these findings should be interpreted with caution. Full article

Introduction: Twelve-lead electrocardiography (ECG) remains an essential diagnostic tool for patients presenting with chest pain. Timely recognition of specific electrocardiographic patterns is critical for guiding reperfusion strategies and predicting adverse outcomes. Among these, Wellens’ pattern is a high-risk marker of critical left anterior descending (LAD) artery stenosis and an impending anterior myocardial infarction. Although typically described in clinically stable patients without heart failure, its occurrence in the setting of acute decompensation is rare. Case Report: We report the case of a 66-year-old male with hypertension, obesity, and active smoking who presented with exertional chest pain, dyspnea, and signs of acute heart failure. Initial ECG revealed biphasic T waves in V2–V4, consistent with type A Wellens’ pattern. Laboratory evaluation demonstrated elevated troponin I, while point-of-care ultrasound (POCUS) identified systolic and diastolic dysfunction, lateral wall hypokinesia, pericardial effusion, and cardiogenic pulmonary edema. The patient received acute management with antiplatelet therapy, statins, diuretics, and anticoagulation, followed by referral for coronary angiography. This revealed critical stenosis (>90%) of the proximal LAD, successfully treated with percutaneous coronary intervention and drug-eluting stent implantation. The in-hospital course was uneventful, and guideline-directed medical therapy was optimized at discharge, including dual antiplatelet therapy, beta-blocker, renin–angiotensin system inhibitor, and SGLT2 inhibitor. Conclusions: This case highlights the need for early recognition of Wellens’ pattern, even in atypical contexts such as acute heart failure. Integrating ECG interpretation with bedside POCUS facilitated diagnostic accuracy and guided an early invasive strategy, preventing extensive myocardial infarction. In resource-limited settings, strengthening frontline diagnostic capabilities and referral networks is crucial to improving patient outcomes. Full article

Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson’s disease and related disorders—including mitochondrial dysfunction, oxidative stress, and synaptic impairment—which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 μM 1-methyl-4-phenylpyridinium (MPP⁺) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP⁺-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses—mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins—such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits—exhibited coordinated dysregulation, as visualized through protein–protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP⁺-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson’s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context. Full article

Background: Takotsubo syndrome (TS) mimics acute coronary syndrome in 1% to 3% of patients presenting with chest pain, ECG changes and echocardiographic transient apical wall hypokinesia. Objectives: This study aimed to validate a previously developed scoring system on a larger cohort size. Methods: Patients admitted to an intensive cardiovascular care unit were divided into three groups: (a) patients diagnosed with TS, (b) females with anterior MI, and (c) other all-comer STEMIs. A 10-point scoring system was used: stressful events (three points), female gender (two points), no history of diabetes mellitus (two points), estimated left ventricular ejection fraction (LVEF) ≤ 40% on admission echocardiography (one point), positive troponin on admission (one point), and no smoking (one point). A t-test was applied to the three study groups, sensitivity and specificity testing was performed using the ROC curve method. Results: A total of 1150 patients were included in our study: 54 with TS, 97 females with anterior MI and 999 other all-comer STEMIs. Patients in the TS group were predominantly females with a higher rate of stressful events prior to admission, lower rates of diabetes mellitus and smoking, and lower LVEF% systolic function compared to the STEMI cohort. In a multivariate logistic regression analysis, the average TS scoring system was significantly higher in the TS group compared with the anterior STEMI and all-comer STEMI groups (8.3 vs. 5.7 vs. 3.83, p < 0.001, respectively) with an AUC of 0.83 for TS score ≥ 8. Conclusions: The 10-point TS scoring system is an easy, reliable, and useful diagnostic tool that might help in distinguishing patients with TS and ACS. Full article

Parkinson’s disease (PD), the second most common neurodegenerative disorder, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been extensively used in different animal species to develop chemical models of PD. This study aimed to evaluate the effects of acute exposure to MPTP (3 × 150 mg/kg, intraperitoneally) on adult zebrafish by assessing the neurochemical, transcriptional, and motor changes associated with PD pathogenesis. MPTP treatment resulted in a significant decrease in brain catecholamines, including dopamine, norepinephrine, and normetanephrine. Additionally, a trend towards decreased levels of dopamine precursors (tyrosine and L-DOPA) and degradation products (3-MT and DOPAC) was also observed, although these changes were not statistically significant. Gene expression analysis showed the downregulation of dbh, while the expression of other genes involved in catecholamine metabolism (th1, th2, mao, comtb) and transport (slc6a3 and slc18a2) remained unaltered, suggesting a lack of dopaminergic neuron degeneration. Behavioral assessments revealed that MPTP-exposed zebrafish exhibited reduced motor activity, consistent with the observed decrease in dopamine levels. In contrast, the kinematic parameters of sharp turning were unaffected. A significant impairment in the sensorimotor gating of the ASR was detected in the MPTP-treated fish, consistent with psychosis. Despite dopamine depletion and behavioral impairments, the absence of neurodegeneration and some hallmark PD motor symptoms suggests limitations in the validity of this model for fully recapitulating PD pathology. Further studies are needed to refine the use of MPTP in zebrafish PD models. Full article

Epidemiological and eradication trial evidence indicates that Helicobacter pylori, a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson’s disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non-H. pylori Helicobacters (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis. In those occupationally at risk of NHPH infection, we address whether there is increased mortality with PD, or depression or suicide. Our systematic review gave evidence that occupational exposure to animals/their products is associated with excess mortality with PD. Indeed, whilst livestock farming increased the risk, crop farming decreased it. Moreover, excess mortality from non-Hodgkin lymphoma in livestock farmers is compatible with NHPH being causal. Our scoping review showed that farmers, veterinarians and abattoir workers have an increased risk of depression and suicide; whether their depression is associated with being down the pathway to PD and/or the presence of Helicobacter infection needs investigation. Regarding Helicobacter species specificity, the link between the presence of NHPH in gastric biopsy and PD was described using a ureA polymerase chain reaction (PCR) assay, targeting the most-commonly named NHPH, H. suis. We describe its redesign and optimisation as a probe-based PCR, confirming the exclusion of H. pylori but not H. suis specificity (additionally identifying 6 species of a 22-NHPH-species panel). The exploration of the zoonotic hypothesis requires a non-invasive pan-Helicobacter PCR screen, allowing the detection and molecular grouping of Helicobacter species. Full article

Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young male volunteers before and during a 10-day experimental bed rest. Additionally, we tracked changes in glutathione levels and specific metabolite ratios up to 21 days of bed rest. Using gas chromatography-mass spectrometry and the internal standard technique, we observed a 9 ± 9% decrease in glutathione levels during the first 5 days of bed rest, followed by an 11 ± 9% increase from the 5th to the 10th day, nearly returning to baseline ambulatory levels. The cysteinyl-glycine-to-glutathione ratio, reflecting γ-glutamyl cyclotransferase activity (a key enzyme in glutathione breakdown), rose by 14 ± 22% in the first 5 days and then fell by 10 ± 14% over the subsequent 5 days, again approaching baseline levels. Additionally, the γ-glutamyl cysteine-to-cysteine ratio, indicative of γ-glutamyl cysteine synthetase activity (crucial for glutathione synthesis), increased by 12 ± 30% on day 5 and by 29 ± 41% on day 10 of bed rest. The results observed on day 21 of bed rest confirm those seen on day 10. By calculating the ratio of product concentration to precursor concentration, we assessed the efficiency of these key enzymes in glutathione turnover. These results were corroborated by directly measuring glutathione synthesis and degradation rates in vivo using stable isotope techniques. Our findings reveal significant changes in glutathione kinetics during the initial days of bed rest and identify potential therapeutic targets for maintaining glutathione levels. Full article

(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02–1.12, p < 0.01), gait ataxia (OR 1.06, 95%-CI 1.00–1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00–1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01–1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms. Full article

Neuroscience applied to motor activity is a growing area that aims to understand the effects of motor activity on the structures and functions of the Central Nervous System. Attention has been paid to this multidisciplinary field of investigation by the scientific community both because it is of great importance in the treatment of many chronic diseases and because of its potential applications in the Movement Sciences. Motor activity during a developmental age is, in fact, an indispensable tool for the physical and mental growth of children, both able-bodied and disabled. Through movement, individuals can improve their physical efficiency and promote their own better health, establish relationships with the environment and others, express themselves and their emotions, form their identity and develop cognitive processes. This literature review aims, therefore, to highlight how an adequate practice of motor activity offers extraordinary possibilities for everyone in relation to learning, from the perspective of an integral development of the person, and, consequently, can raise the awareness of those involved in the training and growth, especially the youngest, towards the educational value of motor and sports activities. According to this review, and in line with the modern neuroscientific approach toward the relationships between motor activities and cognitive functions, it is possible to claim that hypokinesia tends to inhibit learning. Therefore, it now seems more topical than ever to draw attention to the need to introduce working proposals that integrate brain-based motor activity programs into the school curriculum. Full article

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare autosomal recessive neurometabolic disorder caused by AADC deficiency, an enzyme encoded by the DDC gene. Since the enzyme is involved in the biosynthesis of serotonin and dopamine, its deficiency determines the lack of these neurotransmitters, but also of norepinephrine and epinephrine. Onset is early and the key signs are hypotonia, movement disorders (oculogyric crises, dystonia and hypokinesia), developmental delay and autonomic dysfunction. Taiwan is the site of a potential founder variant (IVS6+4A>T) with a predicted incidence of 1/32,000 births, while only 261 patients with this deficit have been described worldwide. Actually, the number of affected persons could be greater, given that the spectrum of clinical manifestations is broad and still little known. In our study we selected 350 unrelated patients presenting with different neurological disorders including heterogeneous neuromuscular disorders, cognitive deficit, behavioral disorders and autism spectrum disorder, for which the underlying etiology had not yet been identified. Molecular investigation of the DDC gene was carried out with the aim of identifying affected patients and/or carriers. Our study shows a high frequency of carriers (2.57%) in Sicilian subjects with neurological deficits, with a higher concentration in northern and eastern Sicily. Assuming these data as representative of the general Sicilian population, the risk may be comparable to some rare diseases included in the newborn screening programs such as spinal muscular atrophy, cystic fibrosis and phenylketonuria. Full article