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• This work enhances robustness and generalization in segmentation using uncertainty quantification and consistency loss. • It dynamically adjusts the consistency loss, enabling the model to focus on unlabeled data as training progresses gradually. • It adopts a weighted exponential moving average (wEMA) to influence different sources of information during training. • It provides an additional control layer and customization over the conventional exponential moving average. • It demonstrates the quantification of the hemorrhage volume in 3D, further elevating diagnostic and visualization abilities. Traumatic brain injury (TBI) is considered a critical neurological emergency with substantial morbidity and mortality rates across the world. Among significant neuropathological consequences of brain injuries, intracranial hemorrhage (ICH) stands out as a particularly urgent condition necessitating prompt diagnosis to avert life-threatening complications. However, the traditional manual approach to detecting and segmenting brain hemorrhages in CT scans is time-consuming and labor-intensive. This study proposes a fully automated uncertainty-guided framework for intracranial hemorrhage segmentation in brain CT scans. The framework is trained on a semi-supervised scheme that leverages both labeled and unlabeled data. Notably, when trained on 80% of labeled data, the semi-supervised framework yields an average Dice coefficient of 0.613 ± 0.01 and a Jaccard index of 0.441 ± 0.02. These metrics significantly exceed their supervised counterparts, which demonstrates the efficacy of the proposed methodology. Moreover, the proposed approach exhibits an overall accuracy of 89.03% in brain hemorrhage classification with a Cohen's Kappa value of 0.835, which indicates substantial agreement between the model's predictions and the ground truth labels. In addition to its capabilities in intracranial hemorrhage detection and localization, the proposed framework offers a robust estimation of hemorrhage volume and provides a comprehensive 3D volumetric view. The accuracy and reliability of the volume quantification approach are justified through a comprehensive qualitative and quantitative assessment, utilizing visualization techniques and a goodness-of-fit test ( R 2 = 0.837). In both instances, the method shows a notable alignment between the predicted hemorrhage volume and the actual hemorrhage volume. Thus, the proposed schemes of uncertainty-guided semi-supervised (UGSS) hemorrhage segmentation and volume quantification enhance model's applicability in clinical practice and research. [ABSTRACT FROM AUTHOR]

A definitive diagnosis of brain lesions not amenable to surgery is mainly made by stereotactic needle biopsy. The diagnostic yield and safety of the frameless versus frame-based image-guided stereotactic techniques is unclear. Our objective was to evaluate the safety and accuracy of frameless versus frame-based stereotactic brain biopsy techniques. A total of 278 patients (153 men; mean age: 65.5 years) with intra-axial brain lesions underwent frame-based (n = 148) or frameless image-guided stereotactic brain biopsy (n = 130) using a minimally invasive twist drill technique during 2010–2016 at Sheba Medical Center. Demographic, imaging, and clinical data were retrospectively analyzed. The diagnostic yield (>90%) did not differ significantly between groups. Overall morbidity (6.8% vs. 8.5%), incidence of permanent neurologic deficits (2.1% vs. 1.6%), mortality rate (0.7% vs. 0.8%), and postoperative computed tomography–detected asymptomatic (14.2% vs. 16.1%) and symptomatic (2.0% vs. 1.6%) bleeding also did not differ significantly between the frame-based and frameless cohorts, respectively. The diagnostic yield and complication rates related to the biopsy technique were not significantly associated with sex, age, entry angle to the skull and skull thickness, lesion location or depth, or radiologic characteristics. Diagnostic yield was significantly associated with the mean lesion volume. Smaller lesions were less diagnostic than larger lesions in both techniques (P = 0.043 frame-based and P = 0.048 frameless). The frameless biopsy technique is as efficient as the frame-based brain biopsy technique with a low complication rate. Lesion volume was the only predictive factor of diagnostic yield. The minimally invasive twist drill technique is safe and efficient. [ABSTRACT FROM AUTHOR]

Background: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban.Objective: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban.Methods: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration.Results: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159).Conclusion and Relevance: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is the most important obstacle to delivery of therapeutics to the central nervous system. Low-intensity pulsed focused ultrasound (FUS) in combination with microbubbles applied under magnetic resonance imaging (MRI) control provides a non-invasive and safe technique for BBB opening (BBBo). In rodent models, however, settings and application protocols differ significantly. Depending on the strain and size, important variables include ultrasound attenuation and sound field distortion caused by the skull. We examined the ultrasound attenuation of the skull of Wistar rats using a targeted FUS system. By modifying the transducer elements and by varying and simulating the acoustic field of the FUS system, we measured a skull attenuation of about 60%. To evaluate potential application of the targeted FUS system in genetically modified animals with increased sensitivity to brain hemorrhage caused by vascular dysfunction, we assessed safety in healthy animals. Histological and MRI analyses of the central nervous system revealed an increase in the number and severity of hyperacute bleeds with focal pressure. At a pressure of 0.4 MPa, no bleeds were induced, albeit at the cost of a weaker hyperintense MRI signal post BBBo. These results indicate a relationship between pressure and the dimension of permeabilization. [ABSTRACT FROM AUTHOR]

On April 7, 1498, Charles VIII, King of France, attended a game of palm in the ditches of the Château d'Amboise. The 27-year-old King suddenly collapsed and became comatose. He laid down, almost on his own, on a straw mat that was hastily arranged, and he died 9 hours later. His contemporaries perceived his death as a perfect reminder of fatality: a king could die alone in a miserable gallery. All who looked into this curious death had dwelled on the frontal blow to head that the king had sustained right before his demise and had not considered alternative scenarios. The present study, still with limited available evidence, aimed to reexamine the historical account of his death in light of modern medical knowledge. It is virtually impossible that a minor bump with low kinetic energy could kill a 27-year-old man. Many historical accounts of Charles VIII's life and death, including Italian ambassadors' letters, led us to reconsider the commonly held version and to propose an alternative hypothesis. We have concluded that Charles VIII had experienced an acute consciousness disorder with language impairment that could have been related to an epileptic condition secondary to neurosyphilis. We have discussed whether a more accurate diagnosis for the cause of death could be obtained by a pathological analysis of the King's remains. [ABSTRACT FROM AUTHOR]

The geriatric nutritional risk index (GNRI), which is calculated using the serum albumin level and body mass index, is a nutritional marker associated with an increased risk of cardiovascular events in patients who are receiving hemodialysis. However, no studies have examined the association between the GNRI level and the incidence of stroke in this population. Three thousand forty-five patients were registered in the Q-Cohort Study, which is a multicenter, observational cohort of hemodialysis patients. The main outcomes were brain infarction and brain hemorrhage. The main exposure was GNRI levels at baseline. Patients were divided into quartiles on the basis of baseline GNRI levels: Q1, <90.7; Q2, 90.7–95.5; Q3, 95.6–99.8; Q4, >99.8. The risk of brain infarction or hemorrhage was estimated using the multivariable-adjusted Cox proportional hazard risk models and restricted cubic spline analyses. During the 10-year follow-up period, 326 patients developed brain infarction and 149 patients developed brain hemorrhage. Cox proportional hazard risk models showed that the risk of brain infarction and hemorrhage in Q1 was significantly higher than that in Q4 group. The hazard ratios [95% confidence intervals] were 1.49 [1.05–2.12] and 1.89 [1.11–3.20], respectively. Restricted cubic spline curves showed that a lower GNRI was incrementally associated with an increased risk for both brain infarction and brain hemorrhage. Our results suggest that a lower GNRI is an independent risk factor for both brain infarction and hemorrhage in patients who are receiving maintenance hemodialysis. [Display omitted] • The present study is a longitudinal cohort study of 3045 hemodialysis patients. • The geriatric nutritional risk index (GNRI) is calculated by serum albumin and body mass index (BMI). • A lower GNRI is an independent risk factor for both brain infarction and hemorrhage. [ABSTRACT FROM AUTHOR]

The impact of interhospital transfer (IHT) on outcomes of patients with intracerebral hemorrhage (ICH) has not been well studied. We seek to describe the protocolized IHT and systems of care approach of a New York City hospital system, where ICH patients undergoing minimally invasive surgery (MIS) are transferred to a dedicated ICH center. We retrospectively reviewed 100 consecutively admitted patients with spontaneous ICH. We gathered information on demographics, variables related to IHT, clinical and radiographic characteristics, and details about the clinical course and outpatient follow-up. We grouped patients into 2 cohorts: those admitted through IHT and those directly admitted through the emergency department. Primary outcome was good functional outcome at 6 months, defined as modified Rankin Scale score 0–3. Of 100 patients, 89 underwent IHT and 11 were directly admitted. On multivariable analysis, there were no significant differences in 6-month functional outcome between the 2 cohorts. All transfers were managed by a system-wide transfer center and 24/7 hotline for neuroemergencies. An ICH-specific IHT protocol was followed, in which a neurointensivist provided recommendations for stabilizing patients for transfer. Average transfer time was 199.7 minutes and average distance travelled was 13.6 kilometers. In our hospital system, a centralized approach to ICH management and a dedicated ICH center increased access to specialist services, including MIS. Most patients undergoing MIS were transferred from outside hospitals, which highlights the need for additional studies and descriptions of experiences to further elucidate the impact of and best protocols for the IHT of ICH patients. [ABSTRACT FROM AUTHOR]

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder caused by antibody to aquaporin-4 (AQP4). NMOSD can infrequently present as a complication of posterior reversible encephalopathy syndrome (PRES). Moreover, few cases of NMOSD patients with brain hemorrhage have been reported. We report a rare case of PRES together with NMOSD recurrence, subsequent to pontine hemorrhage after intravenous methylprednisolone (IVMP) therapy. A 51-year-old Japanese woman, with a history of hypertension and dyslipidemia, and recurrent episodes of left visual acuity disorder related to AQP4-positive NMOSD, developed blindness in the left eye. Brain MRI showed a hyperintense lesion in pons. She was initially diagnosed with recurrence of NMOSD and 1000 mg of IVMP was administered for 3 days. After the 3rd course of IVMP, she developed left-sided sensory disturbance, and blood pressure was increased to 202/127 mmHg. Brain computed tomography (CT) showed pontine hemorrhage, and she was referred to our hospital again. We diagnosed PRES associated with NMOSD recurrence, along with development of pontine hemorrhage induced by the increase in blood pressure resulting from IVMP. The patient was treated with nicardipine to strictly control blood pressure, and tranexamic acid and glycerol for pontine hemorrhage and PRES. We also extended IVMP for 5 consecutive days in total, followed by plasmapheresis. After therapy, blindness in the left eye improved to light perception. Collectively, anti-AQP4 antibody could induce PRES together with recurrent NMOSD, and pontine hemorrhage could thus be induced by blood pressure increases resulting from IVMP. Graphical abstract Unlabelled Image Highlights • A patient with NMOSD developed PRES comorbid with pontine hemorrhage. • Anti-AQP4 antibody could induce PRES together with NMOSD recurrence. • Only 2 cases of NMOSD associated with brain hemorrhage have been reported. • IVMP increased BP, and induced pontine hemorrhage in active NMOSD in our case. [ABSTRACT FROM AUTHOR]

Background: Delirium is characterized by disturbances of attention and cognition that cause functional decline and complications. The predisposing factors of delirium are age, male gender, systemic or metabolic disorders, dementia, and stroke. This study aims to evaluate the prevalence of delirium and to identify risk factors.Methods: This is a retrospective study that includes patients admitted over 5 years with acute stroke. Patients with transient ischemic attack or venous thrombosis were excluded. Delirium was defined according the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Demographical characteristics, clinical-radiological profile, dependence on discharge (modified Rankin Scale score of ≥3 and Barthel Index < 65%), and mortality during hospitalization were compared between patients with and without delirium.Results: A total of 1161 patients were admitted (910 ischemic and 162 hemorrhagic). During hospitalization, 118 patients presented with delirium (10.2%) and 93 died (8%). On discharge, 517 patients were dependent (44.5%). Delirium was significantly associated with age, male gender, cortical infarcts in anterior circulation, higher leukocyte count, cholesterol and fibrinogen levels, lower albumin, atrial fibrillation, previous diagnosis of Alzheimer's disease, and hemorrhagic stroke. Logistic regression results showed that only previous Alzheimer's disease was related to delirium (odds ratio 21.68 [95% confidence interval 1.190-395.026, P = .038]). Dependence on discharge was associated with delirium.Conclusions: Ten percent of the patients presented with delirium associated with older age, Alzheimer's disease, and cortical anterior stroke. Patients with delirium had a higher risk of functional dependence on discharge. [ABSTRACT FROM AUTHOR]

To assess the association of maternal diabetes mellitus (DM) with intraventricular hemorrhage (IVH) and other intracranial hemorrhages (ICH) in newborns. We analyzed the National Inpatient Sample dataset and compared prevalence of IVH and other subtypes of ICH in infants of diabetic mothers (IDMs) vs. those born to mothers without DM. Regression models were used to control for demographic and clinical confounding variables. A total of 11,318,691 infants were included. Compared to controls, IDMs had increased prevalence of IVH (aOR = 1.18, CI: 1.12–1.23, p < 0.001) and other ICH (aOR = 1.18, CI: 1.07–1.31, p = 0.001). Severe IVH (grades 3 & 4) was encountered less frequently in IDMs (aOR = 0.75, CI: 0.66–0.85, p < 0.001) than controls. Gestational DM was not associated with increased IVH after controlling for the demographic, clinical and perinatal confounders in the logistic regression model (aOR = 1.04, CI: 0.98–1.11, p = 0.22). Chronic maternal DM is associated with increased neonatal IVH and other ICH but not severe IVH. This association needs to be confirmed in further studies. • Maternal chronic diabetes mellitus (DM) is associated with increased neonatal intracranial hemorrhages. • Maternal chronic DM is associated with intraventricular hemorrhages (IVH) but not severe IVH. • Gestational DM is not associated with increased neonatal ICH or IVH. [ABSTRACT FROM AUTHOR]

Brain arteriovenous malformations (AVM) are complex vascular lesions commonly associated with chronic headache. An occipital location appears to increase the risk of concurrent migraine-like headaches in AVM patients. We have experienced great success in treating these headaches through a multidisciplinary approach to eradicate cerebral AVM. However, the specific clinical characteristics of AVM-associated headaches and the most effective treatment strategies for these patients remain unclear. Here, we provide a comprehensive review of the literature on AVM-associated headaches. We detail the history, classification, epidemiology, presentation, pathophysiology, treatment options, and outcomes for this poorly described condition. Additionally, we illustrate our approach to the management of patients with occipital AVM and associated intractable headaches. [ABSTRACT FROM AUTHOR]

Background Is computed tomography (CT)–verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? Methods (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)–treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature. Results In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation ( P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, ( P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19). Conclusions LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA. [ABSTRACT FROM AUTHOR]

Objectives: To describe two patients who developed an intracranial hematoma as a complication of temporal lobe encephalitis due to herpes simplex type 1 virus, and to review the literature. Patients and methods: The first patient, a 45-year-old woman developed a brain hematoma in the location of the encephalitic lesion on day 9 after the onset of herpes simplex encephalitis (HSE) that required surgical evacuation. The second patient, a 53-year-old woman was being treated for HSE; on day 8 after admission a temporal lobe hematoma with midline shift was disclosed due to persistent headache. Both patients survived but were left with sequelae. We conducted a PubMed/MEDLINE search from 1986 to April 2013 on this topic. Results: We have found 20 additional cases reported in the literature and review their characteristics. Hemorrhage was present on admission in 35% of pooled patients, and consistently involved the area of encephalitis. Clinical presentation of intracranial hemorrhage overlapped the encephalitic symptoms in two-thirds of the patients. Half of patients underwent surgery. Overall, mortality rate was low (5.2%), and half of patients fully recovered. Conclusions: Intracranial bleeding, although infrequent, can complicate the evolution of herpes simplex encephalitis and should be borne in mind since its presence may require neurosurgery. Although its presentation may overlap the encephalitic features, the lack of improvement or the worsening of initial symptoms, particularly during the second week of admission, should lead to this suspicion and to perform a neuroimaging study. [ABSTRACT FROM AUTHOR]

Summary: Neonatal thrombocytopenia are common, they represent 20% of inpatients in neonatal units and intensive care. The causes are multiple; the main consequence of this condition is the risk of bleeding including intracranial hemorrhage. Objective: The objective of our work is to focus on the etiologic profile of thrombocytopenic hemorrhagic syndrome of origin and to emphasize the importance of having an accurate diagnostic approach to avoid late squealer or severe neurosensory deaths. Patients and methods: Our work is a retrospective study of 91 cases of infants with hemorrhagic syndrome of thrombotic origin, during a study period spanning 1st January 2009 to June 30, 2010. Results: During the study period, there were 91 cases of neonatal thrombocytopenic hemorrhagic syndrome, which represents 7.02% of hospitalized neonates. Premature infants had more thrombocytopenic hemorrhagic syndrome (68.13%) than in term newborns. The hypotrophy was encountered in 27 newborns (29.67%) including 17 of them were premature. Biologically, 37 cases or 40.65% had severe thrombocytopenia with a rate less than 13 cases or 30,000/mm3 and 14.28% had levels between 30,000/mm3 and 50,000/mm3. The etiologies of hemorrhagic syndrome of thrombotic origin were dominated by neonatal sepsis (74.72%) and périnatals asphyxia (13.18%). The outcome was favorable in 28 cases corresponding to 30.76% and 63 cases died or 69.23% in an array of severe hemorrhagic syndrome. Conclusion: We emphasize the interest of early treatment to prevent severe neurological squealer and mortality significant. [Copyright &y& Elsevier]

Abstract: We report the case of a 7-year-old boy with acute status asthmaticus requiring mechanic ventilation in the pediatric intensive care unit. He developed a brain hemorrhage during the course of his illness. We discuss the mechanisms that may have precipitated this neurological complication. [Copyright &y& Elsevier]

Abstract: Aim: To investigate the association between vasculopathy and survival during experimental cerebral malaria (ECM), and to determine whether targeting the endothelin-1 (ET-1) pathway alone or in combination with the anti-malaria drug artemether (a semi-synthetic derivative of artemisinin) will improve microvascular hemorrhage and survival. Main methods: C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were randomly assigned to four groups: no treatment, artemether treated, ETA receptor antagonist (HJP-272) treated, or HJP-272 and artemether treated. The uninfected control mice were treated with HJP-272 and artemether. We analyzed survival, cerebral hemorrhage, weight change, blood glucose levels and parasitemia. Key findings: Our studies demonstrated decreased brain hemorrhage in PbA-infected (ECM) mice treated when HJP-272, a 1,3,6-trisubstituted-2-carboxy-quinol-4-one novel ETA receptor antagonist synthesized by our group, is used in conjunction with artemether, an anti-malarial agent. In addition, despite adversely affecting parasitemia and weight in non-artemether treated infected mice, HJP-272, seemed to confer some survival benefit when used as adjunctive therapy, though this did not reach significance. Significance: Previous studies demonstrate that the endothelin pathway is associated with vasculopathy, neuronal injury and inflammation in ECM. As demonstrated here, components of the ET-1 pathway may be important targets for adjunctive therapy in ECM, and may help in preventing hemorrhage and in improving survival when used as adjunctive therapy during malaria infection. The data presented suggest that our novel agent, HJP-272, may ameliorate alterations in the vasculature which can potentially lead to inflammation, neurological dysfunction, and subsequent death in mice with ECM. [Copyright &y& Elsevier]

Abstract: We described a 7-year-old girl with reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage. She initially presented with high fever and pancytopenia, leading to a diagnosis of most severe type aplastic anemia. We treated her with cyclosporine, methylprednisolone and anti-thymocyte globulin. Thereafter she recurrently complained of a very severe headache called as thunderclap, and finally exhibited loss of consciousness. Brain imaging revealed massive parenchymal hemorrhage between the left occipital and parietal lobes on computed tomography, and diffuse cerebral vasoconstriction on magnetic resonance angiography. The cerebral vasoconstriction resolved within two months, and thus we diagnosed her as having reversible cerebral vasoconstriction syndrome associated with brain parenchymal hemorrhage. This syndrome has been frequently reported in adult females, but rarely in children. However, even in children, a so called thunderclap headache may become a clue for the diagnosis of reversible cerebral vasoconstriction syndrome, especially in cases taking immunosuppressive agents. Immediate magnetic resonance angiography is essential to diagnose this syndrome, and a prompt application of calcium channel inhibitors should be considered to resolve constriction of the vessels and to prevent subsequent brain damage. [Copyright &y& Elsevier]

The prevalence and implications of vertebrobasilar dolichoectasia (VBD), a causative arteriopathy of stroke are unclear in Asian stroke patients. Through a comparative study of VBD and non-VBD stroke patients, we aimed to elucidate the clinicoradiologic features of VBD patients in Japan. A total of 481 consecutive patients (302 men and 179 women) with acute stroke were admitted to our department between 2007 and 2008. Of these 481 inpatients, 374 (231 men and 143 women) had brain infarct (BI), and 107 (71 men and 36 women) had brain hemorrhage (BH). We reviewed medical records, and VBD was diagnosed by magnetic resonance angiography. Cardiovascular disease (CVD) risk profile, modified Rankin scale score at 30 days poststroke, and stroke lesions were compared among 4 groups: the VBD BI group, the VBD BH group, the non-VBD BI group, and the non-VBD BH group. The diameter, height, and lateral displacement of the basilar artery (BA) were analyzed in the VBD patients. Statistical analyses used multivariate logistic regression analysis. VBD was found in 37 patients (34 men and 3 women). Mean age (± SD) was 64.4 ± 14.7 years (63.4 ± 14.6 years in men and 65.3 ± 6.1 years in women). Twenty-four patients (21 men and 3 women) had BI, and 13 men had BH. There were significant male preferences in VBD BI (P < .01) and VBD BH patients (P < .01). Mean age (± SD) was 67.7 ± 14.3 years in BI patients and 56.7 ± 12.7 years in BH patients. The VBD BH men were significantly younger than the non-VBD BH men (P < .05) and VBD BI men (P < .01). Frequency of current smoking was significantly greater in VBD BI patients compared with non-VBD BI patients (P < .05). Other CVD risk factors did not differ among the 4 groups. Mean modified Rankin Scale score was significantly higher in VBD BH men compared with non-VBD BH men and VBD BI men (P < .01). The height and lateral displacement of the BA were scored more severely in BH patients than in BI patients (P < .01), but BA diameter did not differ between BH and BI patients. The frequency of pontine infarct and hemorrhage was 3-fold greater in VBD BI (P < .05) and VBD BH patients (P < .005) compared with non-VBD BI and BH patients. Our findings indicate a VBD prevalence of 7.7% in stroke patients, 6.4% in BI patients, and 12.1% in BH patients. Our clinicoradiologic analyses suggest male predominance, younger onset of BH, and higher frequency of pontine lesions in VBD patients. Significant BA changes and poor outcome of stroke were found in patients with hemorrhagic VBD rather than ischemic VBD. Thus, more attention should be paid to risk and care of BH in VBD patients, in addition to those of BI. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed the records of 44 patients with moyamoya disease evaluated and treated at our Institute from 1998 until 2007. Out of 44 patients, 18 (41%) were in the paediatric age group and 26 (59%) were adults. Presentation was ischemic in 14 (32%) and hemorrhagic in 30 patients (68%). Revascularization was performed in 11 patients (five patients with ischemic presentation and six with hemorrhagic presentation): nine patients underwent indirect revascularization procedures only and two patients underwent indirect revascularization procedures and a combined superficial temporal artery–middle cerebral artery bypass. Thirty-six patients (81.8%) were available for follow-up. Out of 11 patients who underwent revascularization procedures, none had further hemorrhagic or ischemic episodes. Out of the 19 conservatively managed patients who were followed-up, seven (36.8%) developed new episodes of ischemia (n =2) or hemorrhage (n =5). In-hospital mortality was 6.8% (three patients), all of whom were in the hemorrhagic presentation group. [Copyright &y& Elsevier]

Summary: Retinal photoreceptor and bipolar cell axon terminals possess synaptic ribbons (SR) that aid in the trafficking of synaptic vesicles at active zones. In rodents, besides SR, a number of other synaptic elements [e.g., synaptic spheres (SS)] are known to appear when exposed to altered ambient illumination. Here, we report changes of ribbon shape in photoreceptor and bipolar cell axon terminals in retinas of two persons at autopsy who suffered from brain hemorrhage. In both subjects, retinal hemorrhage was present in the outer and inner nuclear layers. SR were bent or swollen and transformed into SS. A count revealed that about 54–60% of the photoreceptor axon terminals over the nasal to temporal retina possessed SS. They were associated with synaptic triads or remained floating in cytoplasm. The bipolar cell axon terminals possessed either SR or sphere-like bodies. As these features were not seen in control retinas of donors who died of other causes, we assume that in hemorrhagic subjects, SR underwent transformation into SS, in which perhaps ischemia (caused due to vascular obstructions by hemorrhage) played a leading role. [Copyright &y& Elsevier]

Abstract: Inflammation following ischemic stroke is known to contribute to injury. NADPH oxidase (NOX) is a major enzyme system originally studied in immune cells that leads to superoxide (O·−) generation. Apocynin is a NOX inhibitor that has been studied as a potential treatment in experimental stroke. Here we explored the effect of different doses of apocynin in a mouse model of 2 h transient middle cerebral artery occlusion (tMCAO) followed by 22 h reperfusion. Apocynin, given i.v. at a dose of 2.5 mg/kg 30 min before reperfusion, improved neurological function (P<0.01), reduced infarct volume (P<0.05), and reduced the incidence of cerebral hemorrhage (P<0.05), but not at higher doses of 3.75 and 5 mg/kg, where it actually increased brain hemorrhage. Apocynin also tended to reduce mortality at the lower dose, but not at higher doses. Using hydroethine fluorescence to delineate O·− in the brain, neurons and some microglia/macrophages, but not vascular endothelial cells were found to contain O·−. Apocynin at protective doses markedly prevented ischemia-induced increases in O·−. Our data suggested that apocynin can protect against experimental stroke, but with a narrow therapeutic window. [Copyright &y& Elsevier]

Objective: Multiple sources document a higher proportion of intraparenchymal hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We sought an explanation for this phenomenon through analysis of multiple variables in our hospital-based stroke population. Methods: We performed univariate and multivariate analysis of risk factors in our HIS and WHI patients with stroke to identify differences that might account for a greater propensity for HEM in HIS patients. Results: Multivariate analysis disclosed that the risk of HEM correlated significantly with untreated hypertension (HTN), HIS ethnicity, and heavy alcohol intake. A negative correlation was found for hyperlipidemia and diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN and heavy alcohol intake, with HIS men being at greatest risk. Conclusions: HIS patients with stroke in our hospital-based population appear relatively more prone to HEM than do WHI patients. This risk correlates with a greater likelihood of having untreated HTN and heavy alcohol intake, more so for HIS men. The explanation appears to be a relative lack of health awareness and involvement in our health care system. The possibility that HIS ethnicity itself constitutes a biological risk factor for HEM remains a matter of speculation. Validation of this work with community data should lead to remediation through a community-based effort. [Copyright &y& Elsevier]

Rationale and Objectives: To determine the sensitivity of susceptibility-weighted imaging (SWI) for depicting hemorrhagic hypointense foci of the brain in comparison with gradient-recalled echo (GRE)- and GRE-type single-shot echo-planar imaging (GREI, GRE-EPI), and to assess the basic characteristics of the susceptibility effect by using a phantom. Materials and Methods: We prospectively examined 16 patients (9 males, 7 females, aged 10–74 years, mean 43 years) with hypointense foci using SWI, GREI, and GRE-EPI at a 1.5-T magnetic resonance (MR) unit. The contrast-to-noise ratio (CNR), sensitivity to small hypointese foci, and artifacts were evaluated. To assess the basic characteristics of SWI, we performed a phantom study using different concentrations of superparamagnetic iron oxide (SPIO). Results: The CNR of lesions was significantly greater for SWI than the other images (P < .0001). SWI detected the greatest number of small hypointense foci, even in the near-skull-base and infratentorial regions. Quantitative and qualitative analyses in our clinical and phantom studies demonstrated that the degree of artifacts was similar with SWI and GREI. Conclusion: SWI was best for detecting small hemorrhagic hypointense foci. Artifacts of SWI were similar to GREI. [Copyright &y& Elsevier]

Objective: This article reviews the mechanisms and pathophysiology of traumatic brain injury (TBI).Methods: Research on the pathophysiology of diffuse and focal TBI is reviewed with an emphasis on damage that occurs at the cellular level. The mechanisms of injury are discussed in detail including the factors and time course associated with mild to severe diffuse injury as well as the pathophysiology of focal injuries. Examples of electrophysiologic procedures consistent with recent theory and research evidence are presented.Results: Acceleration/deceleration (A/D) forces rarely cause shearing of nervous tissue, but instead, initiate a pathophysiologic process with a well defined temporal progression. The injury foci are considered to be diffuse trauma to white matter with damage occurring at the superficial layers of the brain, and extending inward as A/D forces increase. Focal injuries result in primary injuries to neurons and the surrounding cerebrovasculature, with secondary damage occurring due to ischemia and a cytotoxic cascade. A subset of electrophysiologic procedures consistent with current TBI research is briefly reviewed.Conclusions: The pathophysiology of TBI occurs over time, in a pattern consistent with the physics of injury. The development of electrophysiologic procedures designed to detect specific patterns of change related to TBI may be of most use to the neurophysiologist.Significance: This article provides an up-to-date review of the mechanisms and pathophysiology of TBI and attempts to address misconceptions in the existing literature. [Copyright &y& Elsevier]

Objective: to report an unusual pattern of brain petechial hemorrhages in 2 patients after veno-arterial extracorporeal membrane oxygenation support (VA-ECMO) CASE 1: a 28-year-old man (Marfan disease) presented in the early post-operative period a multi-organ failure associated with a disseminated intravascular coagulation (DIC). He was placed on continuous veno-venous hemofiltration and VA-ECMO. He was weaned from ECMO 4 days later. He then developed bacterial pneumoniae leading to respiratory failure and requiring mechanical ventilation. MRI 30 days later showed widespread petechial hemorrhages in the subcortical and deep white matter (WM) (optic radiations, corpus callosum, predominantly in the splenium, internal and external capsules), caudate nuclei, basal ganglia, frontal and parietal cortex and in infratentorial structures. These hemorrhages were bilateral and almost symmetric and marked at the border zones of the carotid arteries territories. CASE 2: a 60-year-old man presented an out-of-hospital refractory hypothermic cardiac arrest. At arrival, cardiopulmonary resuscitation was continued; he presented bleeding at the puncture sites related to DIC and associated with multi-organ failure. VA-ECMO was implanted. After ECMO removal (day 7) he presented a severe spatial orientation deficit. MRI showed petechial hemorrhages in both hippocampi and microbleeds at the cerebral cortex and the juxta-cortical WM. Both patients had good functional outcome.Conclusion: Two unusual presentations of brain hemorrhages in patients who underwent VA-ECMO are reported. If their specific cause remains unclear, there seems to be a relationship in time between DIC and microhemorrhages in these cases, even if in case 1 brain hemorrhages seem to have a multifactorial cause. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The relationship between antithrombotic therapy and the anatomical location of acute brain hematoma remains disputed. The current study was therefore designed to address this issue. Methods: The medical records and CT images were retrospectively reviewed in 484 consecutive patients with an acute brain hemorrhage (291 men, 193 women; mean age, 67.2±12.3 years) who were admitted to the hospital within 7 days of stroke onset from January 1999 through October 2003. Antithrombotic therapy had been performed in 116 patients (AT Group): warfarin (n =38), antiplatelet therapy (n =70), or both (n =8). The other 368 patients had not received antithrombotic therapy (non-AT Group). The hematoma location was compared among the groups. Results: The location of the hematoma was significantly different between the two groups (p <0.0001). The following locations were seen more frequently in the AT Group than in the non-AT Group: thalamic hemorrhage (44.8% vs. 30.7%), cerebellar hemorrhage (7.8% vs. 2.7%), and lobar hemorrhage (18.1% vs. 11.4%). The clinical characteristics in patients with thalamic, cerebellar, or lobar hemorrhage were compared with those with putaminal hemorrhage. A multivariate analysis using the logistic regression model showed that antithrombotic therapy was an independent factor for cerebellar hemorrhage (OR 3.66, 95%CI 1.31–10.18), lobar hemorrhage (OR 2.27, 95%CI 1.12–4.57), and thalamic hemorrhage (OR 2.20, 95%CI 1.06–4.54) in comparison to putaminal hemorrhage. Conclusions: It therefore appears that antithrombotic therapy is independently associated with thalamic, cerebellar, and lobar hemorrhage. [Copyright &y& Elsevier]

Aims: We prospectively investigated the incidence of stroke and its subtypes, risk factors and prognosis in Japanese patients with type 2 diabetes.Methods: A total of 4,875 participants with type 2 diabetes (mean age 65.4 years, male 57%, previous stroke 10%) were investigated for the development of stroke for 5 years. Risk factors were evaluated using multivariable adjusted Cox proportional models.Results: The incidence rates per 1,000 person-years were 6.7 for new-onset stroke (ischemic 5.5, hemorrhagic 1.2) and 22.7 for recurrent stroke (ischemic 18.8, hemorrhagic 3.8), respectively. Ischemic stroke was significantly associated with age, male, reduced regular physical activity, HbA1c, diabetic kidney disease and previous stroke. Lacunar infarction was significantly associated with obesity, reduced regular physical activity, HbA1c and diabetic kidney disease, whereas atherothrombotic stroke was significantly associated with age, reduced intake of dietary fiber, reduced regular physical activity, HbA1c and previous stroke. Recurrent stroke was significantly associated with depressive symptom. Thirty-day and one-year survival was 76% and 64% for hemorrhagic stroke, and 96% and 91% for ischemic stroke, respectively.Conclusions: The current study reemphasized the importance of glycemic control and lifestyle modification such as regular physical exercise for stroke prevention in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background/objective: Infratentorial intracerebral hemorrhage (ICH) is associated with worse prognosis than supratentorial ICH; however, infratentorial ICH is often excluded or underrepresented in clinical trials of ICH. We sought to evaluate the natural history of infratentorial ICH stratified by brainstem or cerebellar location using a prospective observational study inclusive of all spontaneous ICH.Methods: Using a prospective, single center cohort of patients with spontaneous ICH between 2008-2019, we conducted a descriptive analysis of baseline demographics, severity of injury scores, and long-term functional outcomes of infratentorial ICH stratified by cerebellar or brainstem location.Results: Infratentorial ICH occurred in 82 (13%) of 632 patients in our ICH cohort. Among infratentorial ICH, cerebellar ICH occurred in 45 (55%) and brainstem ICH occurred in 37 (45%). Compared to cerebellar ICH, patients with brainstem ICH had significantly worse severity of injury scores, including lower admission Glasgow Coma Scale (median 14 [7.0 - 15.0] versus 4 [3.0 - 8.0], respectively; P < 0.001) and higher ICH Score (median 2 [1.0 - 3.0] versus 3 [2.75 - 4.0], respectively; P =  0.02). Patients with cerebellar ICH were more likely to be discharged home or to acute rehabilitation (OR 4.8, 95% CI 1.8 - 12.8) but there was no difference in in-hospital mortality (OR 0.4, 95% CI 0.1 - 1.1, P =  0.08) or cause of death (P =  0.5). Modified Rankin Scale scores at 3 months were significantly better in patients with cerebellar ICH compared to brainstem ICH (median 3.5 [1.8 - 6.0] versus median 6 [5.0 - 6.0], P =  0.03).Conclusions: Location of infratentorial ICH is an important determinant of admission severity and clinical outcome in unselected patients with ICH. Patients with cerebellar ICH have less severe symptoms at presentation and more favorable functional outcomes compared to patients with brainstem ICH. [ABSTRACT FROM AUTHOR]

Background A bibliometric uses the citation count of an article to determine its impact on the clinical world. There is a paucity of literature concerning top article citations on spontaneous intracerebral hemorrhage (ICH). The main objective of this investigation was to bridge this gap and to provide understanding of the trends on the most influential articles written on this subject. Methods The Scopus Library database was searched to determine the citations of all articles published on spontaneous ICH. Articles that focused on other forms of ICH, such as trauma-related hemorrhages, subarachnoid hemorrhages, or hemorrhages caused by anticoagulation, vascular malformations, or cavernomas, were excluded from our list. The articles were divided into 2 groups: “specific” articles, which focused specifically on spontaneous ICH, and “generalized” articles, which were about ICH in general, including spontaneous as well as other forms of ICH. We did not apply any time or study-type restriction in our search. The top 100 cited articles were selected and analyzed by 2 independent investigators. Results J. Broderick was the author with most publications in the list ( n = 21). The largest subset of spontaneous ICH articles was published in the 5-year periods from 1996 to 2000 and 2001 to 2005 ( n = 27 each). The United States had the highest number of articles ( n = 49). The journal with the highest number of top 100 cited articles was Stroke , with 39, followed by Neurology with 16. Conclusions Our study identifies the trends related to spontaneous ICH by analyzing the citation frequency of the most-cited articles in the field. [ABSTRACT FROM AUTHOR]

Cowden syndrome is a rare autosomal dominant disease. It is characterized by multiple noncancerous tumorlike growths called hamartomas, which typically are found in the skin, oral mucosa, thyroid, breast, and gastrointestinal tract. It carries with it a potential risk of malignant transformation, especially of the breast and thyroid. In 80% of the cases, the human tumor suppressor gene, phosphatase and tensin homolog (PTEN), is mutated in the germ line. We report a patient with Cowden syndrome who presented with generalized seizure and left anterior temporal hemorrhage and a nontraumatic subarachnoid hemorrhage due to multiple intracranial arteriovenous fistulas (AVFs). We discuss previous reports about vascular malformations in patients with Cowden syndrome and PTEN mutations. Importantly, we hypothesize that the production of multiple AVFs in our patient was associated with PTEN mutation. [ABSTRACT FROM AUTHOR]