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OBJECTIVE: This study aims to compare the outcomes of robot-assisted drainage and conservative treatment in minor basal ganglia hemorrhage (10ml< hemorrhage volume ≤ 30 ml) patients with neurological dysfunction, and analyze patients treated with robot-assisted drainage in order to optimize this treatment strategy. METHODS: In a retrospective study conducted in December 2021 to December 2023, minor basal ganglia cerebral hemorrhage patients with neurological dysfunction were enrolled from the Department of Neurosurgery, Shanghai Ninth People's Hospital. The patients included both the surgical (robot-assisted drainage) and conservative groups. The efficacy of robot-assisted drainage compared with conservative treatment in patients with minor cerebral hemorrhage and neurological dysfunction was evaluated by modified Rankin Scale (mRS) score after 3 months, muscle strength (grade 1 to 5) and cost of hospitalization. RESULTS: Of the patients included, 23 received robot-assisted drainage and 20 received conservative treatment. There were no significant differences in gender, age, history of hypertension and diabetes, muscle strength and mRS score at admission. Female patients accounted for 32.6%, and male patients accounted for 67.4%. About 90% of the patients enrolled had a pre-existing hypertension history. The mRS score after 3 months indicated that prognosis of the patients was significantly better in the surgical treatment group than the conservative treatment group (favorable prognosis 69.57% VS. 35%, P = 0.034) while the patients underwent surgery paid higher hospital bills than patients treated conservatively. CONCLUSION: Compared with traditional conservative treatment, robot-assisted drainage surgery is more helpful to improve the prognosis of patients with minor basal ganglia hemorrhage (volume ≤ 30mL) accompanied by neurological dysfunction. Robot assisted surgery can safely and effectively remove the hematoma of minor basal ganglia hemorrhage, and there were 69.6% of surgery group patients had a good prognosis in this study.
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Hemorragia de los Ganglios Basales , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemorragia de los Ganglios Basales/cirugía , Hemorragia de los Ganglios Basales/complicaciones , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Anciano , Adulto , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/métodos , Enfermedades del Sistema Nervioso/cirugía , Drenaje/métodos , Hemorragia Cerebral/cirugía , Hemorragia Cerebral/complicacionesRESUMEN
OBJECTIVE: The primary objective of this study was to explore the clinical characteristics of apoplectic intratumoral hemorrhage in gliomas and offer insights for improving the diagnosis and treatment of this disease. METHODS: We analyzed the clinical data of 35 patients with glioma and hemorrhage. There were eight cases of multiple cerebral lobe involvement, and 22 cases involved a single lobe. Twenty-one patients had a preoperative Glasgow Coma Scale (GCS) score of ≥ 9 and had a craniotomy with tumor resection and hematoma evacuation after undergoing preoperative preparation. A total of 14 patients with GCS < 9, including one with thalamic hemorrhage breaking into the ventricles and acute obstructive hydrocephalus, underwent craniotomy for tumor resection after external ventricular drainage (EVD). One patient had combined thrombocytopenia, which was surgically treated after platelet levels were normalized through transfusion. The remaining 12 patients received immediate intervention in the form of craniotomy hematoma evacuation and tumor resection. RESULTS: We performed subtotal resection on three tumors of thalamic origin and two tumors of corpus callosum origin, but we were able to successfully resect all the tumors in other locations that were gross total resection Pathology results showed that 71.43% of cases accounted for WHO-grade 4 tumors. Among the 21 patients with a GCS score of ≥ 9, two died perioperatively. Fourteen patients had a GCS score < 9, of which eight patients died perioperatively. CONCLUSIONS: Patients with a preoperative GCS score ≥ 9 who underwent subemergency surgery and received aggressive treatment showed a reasonable prognosis. We found their long-term outcomes to be correlated with the pathology findings. On the other hand, patients with a preoperative GCS score < 9 required emergency treatment and had a high perioperative mortality rate.
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Neoplasias Encefálicas , Glioma , Humanos , Glioma/complicaciones , Glioma/cirugía , Masculino , Femenino , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/complicaciones , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Adolescente , Hemorragia Cerebral/cirugía , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/complicaciones , Niño , Craneotomía/métodos , Escala de Coma de Glasgow , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.
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Hemorragia Cerebral , Leucemia , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Adulto , Tomografía Computarizada por Rayos X/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/complicaciones , Leucemia/complicaciones , Leucemia/diagnóstico por imagen , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Anciano , AdolescenteRESUMEN
AIMS: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL-10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood. METHODS: Recombinant IL-10 was administered to ICH model mice via caudal vein injection, an IL-10-inhibiting adeno-associated virus and an IL-10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated. RESULTS: Our study demonstrated that the peripheral cytokine IL-10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL-10 deficiency reversed these effects, likely through the IL-10R/JAK1/STAT3 signaling pathway. CONCLUSIONS: Peripheral IL-10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis.
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Edema Encefálico , Hemorragia Cerebral , Interleucina-10 , Janus Quinasa 1 , Receptores de Interleucina-10 , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Factor de Transcripción STAT3/metabolismo , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Edema Encefálico/etiología , Edema Encefálico/tratamiento farmacológico , Janus Quinasa 1/metabolismo , Janus Quinasa 1/antagonistas & inhibidores , Interleucina-10/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismoRESUMEN
BACKGROUND: The treatment of patients with infective endocarditis (IE) who have preoperative cerebral complications remains less understood. Therefore, this study aimed to retrospectively evaluate the clinical outcomes of patients with acute IE based on preoperative intracranial findings. METHODS: Of 32 patients with acute IE treated at our hospital between August 2015 and March 2022, 31 patients of whom preoperative intracranial imaging evaluation was available were included in our analysis and compared with those with and without intracranial findings. We controlled the mean arterial blood pressure and activated clotting time (ACT) to prevent abnormally high perfusion pressures and ACTs during cardiopulmonary bypass (CPB). The preoperative background, and postoperative courses focusing on postoperative brain complications were reviewed. RESULTS: Among the 31 patients, 20 (65%) had preoperative imaging findings. The group with intracranial findings was significantly older, with more embolisms in other organs, positive intraoperative pathology findings, and longer CPB times. A new cerebral hemorrhage developed postoperatively in one patient without intracranial findings. There were no early deaths; two patients had recurrent infections in each group, and one died because of sepsis in the late phase in the group with intracranial findings. CONCLUSIONS: Positive intracranial findings indicated significantly active infectious conditions preoperatively but did not affect the postoperative course. Patients without preoperative cerebral complications can develop serious cerebral hemorrhage. Although meticulous examination of preoperative cerebral complications in all patients with IE is essential, a strategy should be adopted to prevent cerebral hemorrhage, even in patients without intracranial findings.
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Endocarditis Bacteriana , Endocarditis , Humanos , Estudios Retrospectivos , Endocarditis Bacteriana/cirugía , Endocarditis/complicaciones , Endocarditis/cirugía , Endocarditis/diagnóstico , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.
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Apatía , Angiopatía Amiloide Cerebral Familiar , Angiopatía Amiloide Cerebral , Masculino , Humanos , Femenino , Anciano , Niño , Angiopatía Amiloide Cerebral Familiar/complicaciones , Estudios Prospectivos , Angiopatía Amiloide Cerebral/complicaciones , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Imagen por Resonancia MagnéticaRESUMEN
Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.
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Hemorragia Cerebral , Electroacupuntura , Glutamato-Cisteína Ligasa , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , PPAR gamma , Ratas Sprague-Dawley , Animales , PPAR gamma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Electroacupuntura/métodos , Estrés Oxidativo/fisiología , Estrés Oxidativo/efectos de los fármacos , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/complicaciones , Ratas , Masculino , Glutamato-Cisteína Ligasa/metabolismo , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This review article discusses the role of MR imaging-based biomarkers in understanding and managing hemorrhagic strokes, focusing on intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage. ICH is a severe type of stroke with high mortality and morbidity rates, primarily caused by the rupture of small blood vessels in the brain, resulting in hematoma formation. MR imaging-based biomarkers, including brain iron quantification, ultra-early erythrolysis detection, and diffusion tensor imaging, offer valuable insights for hemorrhagic stroke management. These biomarkers could improve early diagnosis, risk stratification, treatment monitoring, and patient outcomes in the future, revolutionizing our approach to hemorrhagic strokes.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Humanos , Imagen de Difusión Tensora , Hierro , Encéfalo/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Biomarcadores , Imagen por Resonancia MagnéticaRESUMEN
Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague-Dawley rats were used, subjected to a collagenase-induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test. Results indicated a significant improvement in neurological functions in loganin-treated groups, evident from the mNSS and rotarod tests, suggesting dose-dependent neuroprotection. Loganin also effectively reduced the blood-brain barrier (BBB) permeability and cerebral oedema. Additionally, it mitigated cellular pyroptosis, as shown by terminal deoxynucleotidyl transferase dUTP nick-end labelling staining and western blot analysis, which indicated reduced levels of pyroptosis markers in treated rats. Furthermore, loganin's regulatory effects on the adenosine A2A receptor and myosin light chain kinase pathways were observed, potentially underpinning its protective mechanism against ICH. The study concludes that loganin exhibits significant neuroprotective properties in a rat ICH model, highlighting its potential as a novel therapeutic strategy. Despite promising results, the study needs further research to determine loganin's therapeutic potential in human ICH patients. This research paves the way for further exploration into loganin's clinical applications, potentially revolutionizing treatment strategies for patients suffering from intracerebral haemorrhage.
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Iridoides , Fármacos Neuroprotectores , Humanos , Ratas , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas Sprague-Dawley , Piroptosis , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamenteRESUMEN
AIMS: Intracerebral hemorrhage (ICH) is a disease with high rates of disability and mortality. The role of epidermal growth factor receptor 1 (ERBB1) in ICH was elucidated in this study. METHODS: ICH model was constructed by injecting autologous arterial blood into the right basal ganglia. The protein level of ERBB1 was detected by western blot analysis. To up- and downregulation of ERBB1 in rats, intraventricular injection of a lentivirus overexpression vector of ERBB1 and AG1478 (a specific inhibitor of ERBB1) was used. The cell apoptosis, neuronal loss, and pro-inflammatory cytokines were assessed by TUNEL, Nissl staining, and ELISA. Meanwhile, behavioral cognitive impairment of ICH rats was evaluated after ERBB1-targeted interventions. RESULTS: ERBB1 increased significantly in brain tissue of ICH rats. Overexpression of ERBB1 remarkably reduced cell apoptosis and neuronal loss induced by ICH, as well as pro-inflammatory cytokines and oxidative stress. Meanwhile, the behavioral and cognitive impairment of ICH rats were alleviated after upregulation of ERBB1; however, the secondary brain injury (SBI) was aggravated by AG1478 treatment. Furthermore, the upregulation of PLC-γ and PKC in ICH rats was reversed by AG1478 treatment. CONCLUSIONS: ERBB1 can improve SBI and has a neuroprotective effect in experimental ICH rats via PLC-γ/PKC pathway.
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Lesiones Encefálicas , Hemorragia Cerebral , Receptores ErbB , Quinazolinas , Animales , Ratas , Apoptosis , Lesiones Encefálicas/metabolismo , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/metabolismo , Citocinas/metabolismo , Fosfolipasa C gamma/metabolismo , Ratas Sprague-Dawley , Tirfostinos , Receptores ErbB/metabolismo , Proteína Quinasa C/metabolismoRESUMEN
OBJECTIVE: In contrast to high-grade dural arteriovenous fistula (dAVF), low-grade dAVF is mainly associated with tinnitus and carries a low risk of morbidity and mortality. It remains unclear whether the benefits of active interventions outweigh the associated risk of complications in low-grade dAVF. METHODS: The authors conducted a retrospective single-center study that included all consecutive patients diagnosed with an intracranial low-grade dAVF (Cognard type I and IIa) during 2012-2022 with DSA. The authors analyzed symptom relief, symptomatic angiographic cure, treatment-related complications, risk for intracerebral hemorrhage (ICH), and mortality. All patients were followed up until the end of 2022. RESULTS: A total of 81 patients were diagnosed with a low-grade dAVF. Of these, 48 patients (59%) underwent treatment (all primary endovascular treatments), and 33 patients (41%) did not undergo treatment. Nine patients (19%) underwent retreatments. Angiographic follow-up was performed after median (IQR) 7.7 (6.1-24.1) months by means of DSA (mean 15.0, median 6.4 months, range 4.5-83.4 months) or MRA (mean 29.3, median 24.7 months, range 5.9-62.1 months). Symptom control was achieved in 98% of treated patients after final treatment. On final angiographic follow-up, 73% of patients had a completely occluded dAVF. There were 2 treatment-related complications resulting in 1 transient (2%) and 1 permanent (2%) neurological complication. One patient showed recurrence and progression of a completely occluded low-grade dAVF to an asymptomatic high-grade dAVF. No cases of ICH- or dAVF-related mortality were found in either treated patients (median [IQR] follow-up 5.1 [2.0-6.8] years) or untreated patients (median [IQR] follow-up 5.7 [3.2-9.0] years). CONCLUSIONS: Treatment of low-grade dAVF provides a high rate of symptom relief with small risks for complications with neurological sequela. The risks of ICH and mortality in patients with untreated low-grade dAVF are minimal. Symptoms may not reveal high-grade recurrence, and radiological follow-up may be warranted in selected patients with treated low-grade dAVF. An optimal radiographic follow-up regimen should be developed by a future prospective multicenter registry.
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Malformaciones Vasculares del Sistema Nervioso Central , Embolización Terapéutica , Enfermedades del Sistema Nervioso , Humanos , Angiografía , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Hemorragia Cerebral/complicaciones , Embolización Terapéutica/métodos , Enfermedades del Sistema Nervioso/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antihipertensivos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/complicaciones , Hematoma/diagnóstico por imagen , Hematoma/epidemiología , Hematoma/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
Hemorrhagic stroke, specifically intracerebral hemorrhage (ICH), has been implicated in the development of persistent cognitive impairment, significantly compromising the quality of life for affected individuals. Nevertheless, the precise underlying mechanism remains elusive. Here, we report for the first time that the accumulation of iron within the hippocampus, distal to the site of ICH in the striatum, is causally linked to the observed cognitive impairment with both clinical patient data and animal model. Both susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) demonstrated significant iron accumulation in the hippocampus of ICH patients, which is far from the actual hematoma. Logistical regression analysis and multiple linear regression analysis identified iron level as an independent risk factor with a negative correlation with post-ICH cognitive impairment. Using a mouse model of ICH, we demonstrated that iron accumulation triggers an excessive activation of neural stem cells (NSCs). This overactivation subsequently leads to the depletion of the NSC pool, diminished neurogenesis, and the onset of progressive cognitive dysfunction. Mechanistically, iron accumulation elevated the levels of reactive oxygen species (ROS), which downregulated the expression of Itga3. Notably, pharmacological chelation of iron accumulation or scavenger of aberrant ROS levels, as well as conditionally overexpressed Itga3 in NSCs, remarkably attenuated the exhaustion of NSC pool, abnormal neurogenesis and cognitive decline in the mouse model of ICH. Together, these results provide molecular insights into ICH-induced cognitive impairment, shedding light on the value of maintaining NSC pool in preventing cognitive dysfunction in patients with hemorrhagic stroke or related conditions.
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Disfunción Cognitiva , Accidente Cerebrovascular Hemorrágico , Células-Madre Neurales , Animales , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Accidente Cerebrovascular Hemorrágico/metabolismo , Hipocampo/metabolismo , Hierro/metabolismo , Células-Madre Neurales/metabolismo , Calidad de Vida , Especies Reactivas de Oxígeno/metabolismo , RatonesRESUMEN
There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India-CTRI/2019/05/019305.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Activador de Tejido Plasminógeno/efectos adversos , Acetilcisteína/efectos adversos , Proyectos Piloto , Accidente Cerebrovascular Isquémico/etiología , Resultado del Tratamiento , Fibrinolíticos/efectos adversos , Hemorragia Cerebral/complicaciones , Isquemia Encefálica/complicaciones , Terapia Trombolítica/efectos adversosRESUMEN
OBJECTIVES: This study aimed to investigate factors associated with undergoing dysphagia screening (DS) and developing pneumonia, as well as the relationship between DS and pneumonia in patients with intracerebral haemorrhage (ICH). DESIGN: Our study was a cross-sectional hospital-based retrospective study. STUDY DESIGN AND SETTINGS: We derived data from the China Stroke Centre Alliance, a nationwide clinical registry of ICH from 1476 participating hospitals in mainland China. To identify predictors for pneumonia, multivariable logistic regression models were used to identify patient characteristics that were independently associated with DS and pneumonia. PARTICIPANTS: We included 31 546 patients in this study with patient characteristics, admission location, medical history, hospital characteristics and hospital grade from August 2015 to July 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were DS and pneumonia during acute hospitalisation. RESULTS: In total, 25 749 (81.6%) and 7257 (23.0%) patients with ICH underwent DS and developed pneumonia. Compared with patients without pneumonia, those who developed pneumonia were older and had severe strokes (Glasgow Coma Scale 9-13: 52.7% vs 26.9%). Multivariable analyses revealed that a higher pneumonia risk was associated with dysphagia (OR, 4.34; 95% CI, 4.02 to 4.68), heart failure (OR, 1.85; 95% CI, 1.24 to 2.77) and smoking (OR, 1.12; 95% CI, 1.12 to 0.20). DS was associated with lower odds of pneumonia (OR, 0.65; 95% CI, 0.44 to 0.95). CONCLUSION: Our findings further confirm that dysphagia is an independent risk factor for pneumonia; one-fifth of patients with ICH did not undergo DS. However, comprehensive dysphagia evaluation and effective management are crucial. Nursing processes ensure the collection of complete and accurate information during evaluation of patients. There is a need to increase the rate of DS in patients with ICH, especially those with severe stroke or older. Further, randomised controlled trials are warranted to determine the effectiveness of DS on clinical outcomes.
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Trastornos de Deglución , Neumonía , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Estudios Transversales , Hemorragia Cerebral/complicaciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Neumonía/complicaciones , Neumonía/epidemiología , Neumonía/diagnóstico , Hospitales , China/epidemiologíaRESUMEN
BACKGROUND: The stress hyperglycemia ratio (SHR), a newly developed metric, is used to assess adverse outcomes in patients with acute ischemic stroke (AIS). However, the relationship between SHR and fatal outcomes (in-hospital mortality [IHM], malignant cerebral edema [MCE], symptomatic intracerebral hemorrhage [sICH], 3-month mortality, and poor functional outcome) in AIS patients receiving recombinant tissue plasminogen activator (rt-PA) treatment is unclear, and determining the optimal threshold remains incomplete. MATERIALS AND METHODS: We retrospectively enrolled a total of 345 AIS patients treated with rt-PA during 2015-2022 and collected data on various glucose metrics, including different types of SHR, glycemic gap (GG), random plasma glucose (RPG), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). SHR and GG were calculated using these equations: SHR1, [FPG]/[HbA1c]; SHR2, [admission RPG]/[HbA1c]; SHR3, FPG/[(1.59 × HbA1c)-2.59]; SHR4, [admission RPG]/[(1.59 × HbA1c)-2.59]; GG, admission RPG - [(1.59 × HbA1c)-2.59]. We used multivariable logistic regression analysis (MVLR) to identify the association between different glucose metrics and outcomes while comparing their predictive values. RESULTS: SHR1 had the greatest predictive power and a more significant correlation with fatal outcomes than other continuous glucose metrics. The area under the curve of the SHR1 for IHM, MCE, and sICH, 3-month mortality, and poor functional outcome were 0.75, 0.77, 0.77, 0.76, and 0.73, respectively. SHR1 (per 1-point increases) was independently associated with IHM (Odds ratios [ORs] = 5.80; 95% CI [1.96, 17.17]; p = 0.001), MCE (ORs = 4.73; 95% CI [1.71, 13.04]; p = 0.003), sICH (ORs = 4.68, 95% CI [1.48-14.82]; p = 0.009), 3-month mortality (ORs = 10.87; 95% CI [3.56, 33.21]; p<0.001), and 3-month poor functional outcome (ORs = 8.05; 95% CI [2.77, 23.39]; p<0.001) after adjustment in MVLR. In subgroup analysis, elevated SHR1 was associated with fatal outcomes in patients with non-diabetes, SBP≥ 180 mmHg, and NIHSS <16. CONCLUSION: SHR1 demonstrates an independent association with fatal outcomes in AIS patients treated with rt-PA, exhibiting superior predictive ability over other glucose metrics.
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Isquemia Encefálica , Hiperglucemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Activador de Tejido Plasminógeno/uso terapéutico , Accidente Cerebrovascular Isquémico/complicaciones , Glucemia , Hemoglobina Glucada , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Riesgo , Hiperglucemia/complicaciones , Hiperglucemia/inducido químicamente , Hemorragia Cerebral/complicaciones , Glucosa , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/complicacionesRESUMEN
Germinal matrix hemorrhage (GMH) is a devasting neurological disease in premature newborns. After GMH, brain iron overload associated with hemoglobin degradation contributed to oxidative stress, causing disruption of the already vulnerable blood-brain barrier (BBB). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, is crucial in maintaining cellular iron homeostasis. We aimed to investigate the effect of FTMT upregulation on oxidative stress and BBB disruption associated with brain iron overload in rats. A total of 222 Sprague-Dawley neonatal rat pups (7 days old) were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. Deferiprone was administered via gastric lavage 1 h after GMH and given daily until euthanasia. FTMT CRISPR Knockout and adenovirus (Ad)-FTMT were administered intracerebroventricularly 48 h before GMH and FeCl2 injection, respectively. Neurobehavioral tests, immunofluorescence, Western blot, Malondialdehyde measurement, and brain water content were performed to evaluate neurobehavior deficits, oxidative stress, and BBB disruption, respectively. The results demonstrated that brain expressions of iron exporter Ferroportin (FPN) and antioxidant glutathione peroxidase 4 (GPX4) as well as BBB tight junction proteins including Claudin-5 and Zona Occulta (ZO)-1 were found to be decreased at 72 h after GMH. FTMT agonist Deferiprone attenuated oxidative stress and preserved BBB tight junction proteins after GMH. These effects were partially reversed by FTMT CRISPR Knockout. Iron overload by FeCl2 injection resulted in oxidative stress and BBB disruption, which were improved by Ad-FTMT mediated FTMT overexpression. Collectively, FTMT upregulation is neuroprotective against brain injury associated with iron overload. Deferiprone reduced oxidative stress and BBB disruption by maintaining cellular iron homeostasis partially by the upregulating of FTMT after GMH. Deferiprone may be an effective treatment for patients with GMH.
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Barrera Hematoencefálica , Sobrecarga de Hierro , Humanos , Recién Nacido , Ratas , Animales , Barrera Hematoencefálica/metabolismo , Animales Recién Nacidos , Ratas Sprague-Dawley , Regulación hacia Arriba , Deferiprona/metabolismo , Deferiprona/farmacología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/metabolismo , Estrés Oxidativo , Hierro/metabolismo , Sobrecarga de Hierro/metabolismo , Homeostasis , Ferritinas/metabolismo , Proteínas de Uniones Estrechas/metabolismoRESUMEN
BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Hemorrágico/complicaciones , Imagen de Difusión Tensora , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Hemorragia Cerebral/complicaciones , Imagen por Resonancia Magnética/métodos , Hematoma/complicaciones , Coagulación Sanguínea , Hemoglobinas , FibrinaAsunto(s)
Hemorragia Cerebral , Parálisis Facial , Puente , Humanos , Parálisis Facial/etiología , Puente/irrigación sanguínea , Puente/diagnóstico por imagen , Hemorragia Cerebral/etiología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Masculino , Femenino , Terapia Combinada , Persona de Mediana Edad , Enfermedades del Nervio Facial/etiologíaRESUMEN
Pink1 (PTEN-induced putative kinase 1) is a protein associated with maintaining mitochondrial function and integrity and has been reported to mediate neurodegeneration and neuroinflammation. While the role of Pink1 in intracerebral hemorrhage (ICH)-related neurological deficits and inflammatory responses is not deciphered. Congenic blood was transfused into the left corpus striatum to construct the ICH model in C57/BL6 wild-type (WT) and Pink1-/- mice. The relative expression of Pink1, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, Cd86, nitric oxide synthase 2 (Nos2), Cd206, arginase 1 (Arg-1), and IL-10 was detected with qRT-PCR, Western blotting, or ELISA. Mouse neurological deficit scores (mNSS) and water content were detected, and an open-field test was performed to assay anxiety-like behavior. Remarkably decreased Pink1 expression and increased MIP-2, IL-1ß, MCP-1, and TNF-α expression were observed after 12 âh, 24 âh, 48 âh, 72 âh, and 7 âd post-ICH induction in the ipsilateral injury hemispheres. Pink1 deficiency could further up-regulate mNSS scores, brain water content, MIP-2, MCP-1, IL-1ß, and TNF-α in the ipsilateral injury hemispheres. On the other hand, Pink1 deficiency could decrease the number of center cross, the velocity, and the total distance traveled in open field test. Pink1 deficiency could further up-regulate the mRNA levels of pro-inflammatory (M1) molecules (Cd86, Nos2), and down-regulate the relative expression of anti-inflammatory (M2) molecules (Cd206, Arg-1, and IL-10). Pink1 deficiency deteriorates neurological deficits and inflammatory responses after ICH, which can be considered as a treatment target.