Search Results (707)

Background: Intracranial hemorrhage (ICH) is a life-threatening medical condition that needs early detection and treatment. In this systematic review and meta-analysis, we aimed to update our knowledge of the performance of deep learning (DL) models in detecting ICH on non-contrast computed tomography (NCCT). Methods: The study protocol was registered with PROSPERO (CRD420250654071). PubMed/MEDLINE and Google Scholar databases and the reference section of included studies were searched for eligible studies. The risk of bias in the included studies was assessed using the QUADAS-2 tool. Required data was collected to calculate pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with the corresponding 95% CI using the random effects model. Results: Seventy-three studies were included in our qualitative synthesis, and fifty-eight studies were selected for our meta-analysis. A pooled sensitivity of 0.92 (95% CI 0.90–0.94) and a pooled specificity of 0.94 (95% CI 0.92–0.95) were achieved. Pooled PPV was 0.84 (95% CI 0.78–0.89) and pooled NPV was 0.97 (95% CI 0.96–0.98). A bivariate model showed a pooled AUC of 0.96 (95% CI 0.95–0.97). Conclusions: This meta-analysis demonstrates that DL performs well in detecting ICH from NCCTs, highlighting a promising potential for the use of AI tools in various practice settings. More prospective studies are needed to confirm the potential clinical benefit of implementing DL-based tools and reveal the limitations of such tools for automated ICH detection and their impact on clinical workflow and outcomes of patients. Full article

Background/Objectives: The Munich Oktoberfest is the largest Volksfest in the world, attracting more than 6 million visitors every year to the city of Munich and surroundings, posing challenges to healthcare providers. Since 2022, a CT has been installed on the festival site to decrease patient transport to emergency departments (EDs) and relieve EDs of a significant number of patients. The aim of our studies was to determine the economic impact of on-site CT on the healthcare system, both from a German and a U.S. perspective. Methods: A decision model was built using patient data from the Munich Oktoberfest. Two scenarios were investigated where patients with mild traumatic brain injuries were either scanned for intracranial hemorrhage (ICH) with CT on-site or brought directly to an ED for further investigation. Costs for patient transportation and CT scans were derived from German national reimbursement rates as well as U.S. Medicare data. Costs were calculated by diagnosis in the national currency. Results: In all scenarios, on-site CT scans were associated with reduced costs per patient (EUR 243 vs. EUR 908 in the German setting and EUR 438 vs. EUR 1635 in the international setting, as well as USD 160 vs. USD 403 in the U.S. setting). For the U.S. scenario, the proportion of ICH in the patient group, as well as the transport distance, had the strongest impact on average costs per patient. Conclusions: On-site CT scanning is a cost-reducing as well as clinically beneficial method for triaging patients at the Munich Oktoberfest. Full article

Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is a pressing need to develop novel therapeutic approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention as a potential alternative to stem cell therapy. Because of their ability to cross the blood–brain barrier and exert neuroprotective effects in cerebral ischemia and hemorrhage, the exploration of EVs for clinical application in stroke treatment is expanding. EVs are characterized by high heterogeneity, with their composition closely mirroring that of their parent cells. This property enables EVs to distinguish between cerebral ischemia and hemorrhage, thus facilitating a more rapid and accurate diagnosis. Additionally, EVs can be engineered to carry specific molecules, such as miRNAs, targeting them to specific cells, potentially enhancing the therapeutic outcome and improving stroke prognosis. In this review, we will also explore the methodologies for the isolation and extraction of EVs, critically evaluating the advantages and disadvantages of various commonly employed separation techniques. Furthermore, we will briefly address current EV preservation and administration methods, providing a comprehensive overview of the state of EV-based therapies in stroke treatment. Full article

Cells respond to external mechanical cues and transduce these forces into biological signals. This process is known as mechanotransduction and requires a group of proteins called mechanosensors. This peculiar class of receptors include extracellular matrix proteins, plasma membrane proteins, the cytoskeleton and the nuclear envelope. These cell components are responsive to a wide spectrum of physical cues including stiffness, tensile force, hydrostatic pressure and shear stress. Among mechanotransducers, the Transient Receptor Potential (TRP) and the PIEZO family members are mechanosensitive ion channels, coupling force transduction with intracellular cation transport. Their activity contributes to embryo development, tissue remodeling and repair, and cell homeostasis. In particular, vessel development is driven by hemodynamic cues such as flow direction and shear stress. Perturbed mechanotransduction is involved in several pathological vascular phenotypes including hereditary hemorrhagic telangiectasia. This review is conceived to summarize the most recent findings of mechanotransduction in development. We first collected main features of mechanosensitive proteins. However, we focused on the role of mechanical cues during development. Mechanosensitive ion channels and their function in vascular development are also discussed, with a focus on brain vessel morphogenesis. Full article

Background/Objectives: Cerebral palsy (CP), often caused by early brain injury such as perinatal stroke or hemorrhage, is the most common lifelong motor disability. Early identification of at-risk infants and timely access to rehabilitation interventions are essential for improving long-term outcomes. The General Movements Assessment (GMA), performed in the first months of life, has high sensitivity and specificity to predict CP; however, the neurological correlates of general movements remain unclear. This analysis aimed to investigate the relationship between white matter integrity and general movements in infants with perinatal brain injury using advanced neuroimaging techniques. Methods: Diffusion-weighted MRI data were analyzed in 17 infants, 12 with perinatal brain injury and 5 typically developing infants. Tractography was used to identify the corticospinal tract, a key motor pathway often affected by perinatal brain injury, and tract-based spatial statistics (TBSS) were used to examine broader white matter networks. Diffusion parameters from the diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models were compared between infants with and without typical general movements. Results: Corticospinal tract integrity did not differ between groups when averaged across hemispheres. However, infants with asymmetric general movements exhibited greater corticospinal tract asymmetries. A subset of infants with atypical general movement trajectories at <6 weeks and 3–5 months of age showed reduced corticospinal tract integrity compared to those with typical general movements. TBSS revealed significant differences in white matter integrity between infants with typical and atypical general movements in several white matter pathways, including the corpus callosum, the right posterior corona radiata, bilateral posterior thalamic radiations, the left fornix/stria terminalis, and bilateral tapetum. Conclusions: These findings support and expand upon previous research suggesting that white matter integrity across multiple brain regions plays a role in the formation of general movements. Corticospinal integrity alone was not strongly associated with general movements; interhemispheric and cortical-subcortical connectivity appear critical. These findings underscore the need for further research in larger, diverse populations to refine early biomarkers of neurodevelopmental impairment and guide targeted interventions. Full article

Background/Objectives: This study aimed to research the potential association between brain atrophy and hematoma expansion (HE) in intracerebral hemorrhage (ICH). Methods: A retrospective analysis was conducted using data from patients with primary ICH in our stroke database. ICH volumes from initial and follow-up CT scans were manually segmented. Total brain and intracranial volumes were quantified using an automated head CT segmentation method. Normalized brain volume (NBV) was calculated by dividing the total brain volume by the total intracranial volume to account for individual head size differences. The relationship between the NBV and hematoma expansion was assessed using linear regression, adjusting for other variables influencing hematoma expansion. Results: Our final analysis included 420 patients. Brain atrophy (lower NBV) was associated with hematoma growth (>0 mL) in patients not on oral anticoagulants (β = −0.159, p = 0.032). A strong association was observed in patients using vitamin K antagonists (β = −0.667, p = 0.006) but not in those on direct oral anticoagulants (DOACs; (β = −0.159, p = 0.436)). Results remained significant in patients not on oral anticoagulants and in those on VKAs when hematoma expansion was defined as a volume increase >6 mL or >33%. Conclusions: This research provides initial evidence that brain atrophy is a risk factor for hematoma expansion, depending on the patient’s coagulation status. These findings could enhance risk stratification for acute clinical management and deepen understanding of the biological mechanisms behind hematoma expansion. Full article

In the history of yellow fever (YF) outbreaks in Brazil, howler monkeys (Alouatta sp.) and marmosets (Callithrix sp.) have been among the most affected genera, exhibiting significant hepatic injuries similar to those seen in humans. However, limited information exists regarding yellow fever virus (YFV) infection in their central nervous system (CNS). To address this gap, an epidemiological study was conducted to assess tissue changes, viral detection, and cytokine profiles in the brains of both neotropical primate species when they are naturally infected with YFV. A total of 22 brain samples from these species (8 from Alouatta sp. and 14 from Callithrix sp.) showing infection with YFV in the liver via immunohistochemistry (IHC) were selected. From them, YFV antigen detection occurred in 35.7% (5/14) of Callithrix sp. brain samples and 87.5% (7/8) of Alouatta sp. samples, with a higher frequency of viral antigen quantification in Callithrix sp. Both species exhibited similar CNS lesions, characterized by congestion, low hemorrhage, limited inflammatory infiltration interstitial and perivascular edema associated with neuronal degeneration, neurophagy, and higher cell death (necrosis and apoptosis) quantification. Pro- and anti-inflammatory cytokine profiles were balanced, with TNF-α and IL-1β playing a key role in inflammation, while IL-10 and IL-13 exhibited a prominent role in immunomodulation, suggesting an anti-inflammatory modulation typical of flaviviruses occurs. This study demonstrates that YFV can induce CNS lesions in neotropical primates, establishing it as a secondary target of viral tropism. These findings highlight the importance of collecting nervous tissue during epizootics, particularly in Callithrix sp., as such tissue is often overlooked despite its critical role in disease monitoring. Full article

Background/Objectives: Growing evidence is underscoring the neuroprotective properties of melatonin, particularly its anti-inflammatory, anti-apoptotic, and antioxidant effects. Preliminary findings suggest that it has the potential to attenuate secondary brain injury following intracerebral hemorrhage (ICH). This observational study aimed to investigate the effect of melatonin on post-ICH mortality and functional outcomes. Methods: We conducted an exploratory analysis of data from a single-center, non-randomized, prospective cohort study involving 177 non-ventilated patients with spontaneous ICH consecutively admitted to the Stroke Unit at the University Hospital of Tübingen, Germany, between December 2015 and December 2020. Patients received either the best standard of care (control group) or the best standard of care plus melatonin (2 mg nightly), initiated within 24 h of symptom onset and continued until discharge. The primary endpoint was mortality at discharge, while secondary endpoints included mortality at 90 days and favorable outcomes (modified Rankin Scale [mRS] ≤ 2) at both discharge and a 90-day follow-up. To minimize baseline differences, propensity score matching (PSM) was employed in the secondary analysis. Additionally, ordinal mRS shift analysis was performed to assess the patients’ functional status at discharge. Results: In the full cohort (84 melatonin-treated patients vs. 93 controls), melatonin was not associated with any of the primary or secondary outcomes. In the PSM cohort (38 melatonin-treated patients vs. 38 controls), mortality at discharge was three times lower in the melatonin group compared to the control group (2.6% vs. 7.9%), although this trend did not reach statistical significance (ORadj: 0.372; 95% CI: 0.036–3.843; p = 0.407). Ordinal mRS analysis revealed no significant association between melatonin and functional status at discharge (common OR: 0.762; 95% CI: 0.327–1.773; p = 0.527). Similarly, the melatonin treatment was not associated with 90-day mortality (ORadj: 1.519; 95% CI: 0.295–7.826; p = 0.617) or the functional outcome at 90 days (ORadj: 0.626; 95% CI: 0.198–1.983; p = 0.426). Conclusions: Although 2 mg of melatonin daily did not significantly reduce mortality or improve functional outcomes in ICH patients, robust preclinical evidence and the favorable safety profile of melatonin warrant its further exploration in adequately powered, randomized-controlled clinical trials to evaluate optimized dosing regimens. Full article

Background: Stroke and traumatic brain injury (TBI) represent two major health concerns worldwide. There is growing evidence suggesting a potential association between TBI and stroke. In this systematic review and meta-analysis, we aim to explore the association between TBI and stroke risk, with a specific focus on overall stroke risk and subgroup variations based on stroke type, severity, and the post-TBI time period. Methods: PubMed, Web of Science (WOS), Scopus, and Cochrane Library were systematically searched for studies exploring the link between stroke and TBI. The pooled hazard ratios (HRs) with a 95% confidence interval (CI) were calculated. The Comprehensive Meta-Analysis (CMA) software was used for the analysis. Subgroup analyses were conducted based on stroke type, TBI severity, and post-TBI phase. The Newcastle–Ottawa Scale (NOS) was utilized for the quality assessment. Results: We included a total of 13 observational studies, with data from 8 studies used for quantitative analysis. A history of TBI was associated with a significantly higher odds of stroke compared to controls (HR = 2.3, 95% CI (1.79 to 2.958), p < 0.001). The risk was greater for hemorrhagic stroke (HR = 4.8, 95% CI (3.336 to 6.942), p < 0.001) than for ischemic stroke (HR = 1.56, 95% CI (1.28 to 1.9), p < 0.001). Both moderate-to-severe TBI (HR = 3.64, 95% CI (2.158 to 6.142), p < 0.001) and mild TBI (HR = 1.81, 95% CI (1.17 to 2.8), p = 0.007) were associated with a significantly higher risk of stroke. The risk was also higher in the early post-TBI phase (1–30 days) (HR = 4.155, 95% CI (2.25 to 7.67), p < 0.001) compared to later phases (HR = 1.68, 95% CI (1.089 to 2.59), p = 0.019) from 30 days to 1 year and (HR = 1.87, 95% CI (1.375 to 2.544), p < 0.001) after 1 year. Conclusions: This systematic review confirms a significant association between TBI and an increased risk of stroke, regardless of TBI severity, type, or timing of stroke. The findings highlight the need for early monitoring and advocating preventive strategies for stroke in patients with a history of TBI. Full article

Background: Disorders of Consciousness (DoC) following acute brain injuries, such as intracerebral hemorrhage, present significant clinical challenges in intensive care and rehabilitation settings. Early multidisciplinary interventions, including physiatric care, are critical in optimizing recovery trajectories. However, evidence regarding the timing and intensity of rehabilitation interventions remains limited. This case report highlights the role of physiatrists in managing a critically ill patient with a DoC in an Intensive Care Unit (ICU), focusing on early rehabilitation strategies and individualized care planning. Case presentation: A 63-year-old male with a history of hypertension and cardiac disease presented with a left hemispheric hemorrhage and quadriventricular intraventricular hemorrhage. The patient was admitted to the ICU in a comatose state (Glasgow Coma Scale [GCS] 5). Initial physiatric evaluation revealed a critical condition precluding immediate initiation of an Individual Rehabilitation Project (IRP). Over subsequent weeks, clinical improvements were observed, including an increased GCS and Coma Recovery Scale-Revised (CRS-R) score. A tailored IRP was implemented, emphasizing passive mobilization to prevent complications such as muscle atrophy, joint contractures, and pressure ulcers. The patient demonstrated gradual progress, transitioning to a Minimally Conscious State (MCS) and achieving improved joint mobility and reduced peripheral edema. Discussion and Conclusions: This case underscores the pivotal role of physiatrists in ICU settings, particularly for patients with DoC. Early physiatric interventions, even in critically ill patients, can prevent secondary complications and facilitate functional recovery. Close collaboration with ICU teams and infectious disease specialists ensured the safe implementation of rehabilitation strategies despite the patient’s severe condition. The observed clinical improvements highlight the potential benefits of early mobilization and individualized care plans, both in terms of survival (quoad vitam) and quality of life (quoad valetudinem). This report emphasizes the need for further research to refine rehabilitation practices for patients with DoC, bridging gaps between acute care and neurorehabilitation. Full article

The diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) is most difficult in patients who are in good clinical condition with a small hemorrhage, especially when a ruptured aneurysm might not be considered, or if a computed tomographic (CT) scan is not obtained, or if when a CT is obtained, the findings are subtle and missed by an inexperienced reviewer. All acute onset (thunderclap) headaches should be considered ruptured aneurysms until proven otherwise. Treatment begins with immediate control of pain and blood pressure, placement of an external ventricular drain (EVD) in poor-grade patients and those with acute hydrocephalus on CT scanning, administration of antifibrinolytic tranexamic acid, and then repair of the aneurysm with either surgical clipping or endovascular techniques as soon as the appropriate treatment team can be assembled. After securing the aneurysm, aSAH patient treatment is focused on maintaining euvolemia and a favorable systemic metabolic state for brain repair. A significant and aneurysm-specific threat after aSAH is delayed arterial vasospasm and resulting cerebral ischemia, which is detected by vigilant bedside examinations for new-onset focal deficits or neurological decline, assisted with daily transcranial Doppler examinations and the judicious use of vascular imaging and cerebral perfusion studies with CT. The management of diagnosed symptomatic vasospasm is the prompt induction of hypertension with vasopressors, but if this fails to reverse deficits quickly after reaching a target systolic blood pressure of 200 mmHg, endovascular angioplasty is indicated, providing CT scanning rules out an established cerebral infarction. Balloon angioplasty should be considered early for all patients found to have severe angiographic vasospasm, with or without detectable signs of ischemic neurological deterioration due to either sedation or a pre-existing deficit. Full article

Pediatric stroke, a significant cause of long-term neurological deficits in children, often arises from disruptions within neurovascular unit (NVU) components. The NVU, a dynamic ensemble of astrocytes, endothelial cells, pericytes, and microglia, is vital for maintaining cerebral homeostasis and regulating vascular brain development. Its structural integrity, particularly at the blood–brain barrier (BBB), depends on intercellular junctions and the basement membrane, which together restrict paracellular transport and shield the brain from systemic insults. Dysfunction in this intricate system is increasingly linked to pediatric stroke and related cerebrovascular conditions. Mutations disrupting endothelial cell adhesion or pericyte–endothelial interactions can compromise BBB stability, leading to pathological outcomes such as intraventricular hemorrhage in the germinal matrix, a hallmark of vascular brain immaturity. Additionally, inflammation, ferroptosis, necroptosis, and autophagy are key cellular processes influencing brain damage and repair. Excessive activation of these mechanisms can exacerbate NVU injury, whereas targeted therapeutic modulation offers potential pathways to mitigate damage and support recovery. This review explores the cellular and molecular mechanisms underlying NVU dysfunction, BBB disruption, and subsequent brain injury in pediatric stroke. Understanding the interplay between genetic mutations, environmental stressors, and NVU dynamics provides new insights into stroke pathogenesis. The susceptibility of the germinal matrix to vascular rupture further emphasizes the critical role of NVU integrity in early brain development. Targeting inflammatory pathways and cell death mechanisms presents promising strategies to preserve NVU function and improve outcomes for affected neonates. Full article

Background: Quality improvement (QI) interventions may reduce the incidence and severity of Intraventricular Hemorrhage (IVH) in the population of inborn micropremature infants (born at ≤26 weeks’ gestation) with the goal of improving outcomes in this high-risk population. Methods: A multidisciplinary team reviewed the current literature to develop a site-specific brain protective bundle. Baseline data were collected from June 2014 to February 2015, with interventions occurring from March 2015 to December 2015. The period of sustainability was assessed from January 2016 to December 2023. Control charts were used to analyze the effect of the interventions. Outcome measures included all grades of IVH, periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), and spontaneous intestinal perforations (SIP). Results: Brain care initiatives decrease the rate of severe IVH in the inborn micropremature infant population from a baseline of 21% to 6.45% with a sustained rate of 4.5% with no change to balancing measures. Conclusions: Brain-protective initiatives such as midline head positioning and minimal handling are associated with a significant and sustained reduction in severe IVH among inborn micropremature infants. Full article

Objective: This study aimed to investigate potential specific molecular and neuroimaging biomarkers for stroke subtype recurrence to improve secondary stroke prevention. Methods: A retrospective analysis was conducted on a prospective stroke biobank. The main endpoint was to evaluate the association between different biomarkers and the recurrence of stroke subtypes. Serum levels of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) were analyzed as inflammation biomarkers; N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and microalbuminuria were used as atrial/endothelial dysfunction biomarkers, while leukoaraiosis (LA) and soluble TNF-like inducers of apoptosis (sTWEAK) were used as biomarkers for blood–brain barrier dysfunction. Demographic and clinical variables were also included. Results: A total of 5038 stroke patients were included, with a mean follow-up of 4.9 years (±3.3). Stroke recurrences were observed in 18.4% of patients (927 individuals). The main results found were as follows: LA was independently associated with lacunar stroke recurrence (adjusted OR 9.50; 95% CI: 3.12–28.93). NT-pro-BNP levels higher than >1000 pg/mL were independently associated with cardioembolic stroke recurrence (adjusted OR 1.80; 95% CI: 1.23–2.61). Persistently elevated TNF-a levels (>24 pg/mL) after stroke recurrence showed an adjusted OR of 21.26 (95% CI: 12.42–37.59) for atherothrombotic subtype, whereas persistently high sTWEAK levels (>7000 pg/mL) after a second hemorrhagic stroke showed an adjusted OR of 4.81 (95% CI: 2.86–8.07) for hemorrhagic subtype. Conclusions: The presence of LA and high levels of NT-pro-BNP, TNF-a, and sTWEAK were associated with an increased risk for lacunar, cardioembolic, atherothrombotic, and hemorrhagic stroke recurrences, respectively. Full article

Severe injuries and some pathologies associated with massive bleeding, such as maternal hemorrhage, gastrointestinal and perioperative bleeding, and rupture of an aneurysm, often lead to major blood loss and the development of hemorrhagic shock. A sharp decrease in circulating blood volume triggers a vicious cycle of vasoconstriction and coagulopathy leading to ischemia of all internal organs and, in severe decompensated states, ischemia of the brain and heart. The basis of tissue damage and dysfunction in hemorrhagic shock is an interruption in the supply of oxygen and substrates for energy production to the cells, making the mitochondria a source and target of oxidative stress and proapoptotic signaling. Based on these mechanisms, different strategies are proposed to treat the multiple organ failure that occurs in shock. The main direction of such treatment is to provide the cells with a sufficient amount of substrates that utilize oxidative phosphorylation at different stages and increase the efficiency of energy production by the mitochondria. These strategies include restoring the efficiency of mitochondrial complexes, for example, by restoring the nicotinamide adenine dinucleotide (NAD) pool. Another direction is approaches to minimize oxidative stress as well as apoptosis, which are primarily dependent on the mitochondria. There are also a number of other methods to reduce mitochondrial dysfunction and improve the quality of the mitochondrial population. In this review, we consider such strategies for the treatment of hemorrhagic shock and show the promise of therapeutic approaches aimed at restoring the bioenergetic functions of the cell and protecting mitochondria. Full article