White Matter Hemorrhage Research Articles

Unraveling the complex pathophysiology of white matter hemorrhage in intracerebral stroke: A single-cell RNA sequencing approach.

This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH). Using varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single-cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post-ICH were profiled using single-cell RNA sequencing (scRNA-seq). Gene Ontology (GO) and gene set variation analysis (GSVA) further interpreted the differentially expressed genes (DEGs). Following WMH induction, there was a notable increase in the percentage of myeloid cells and oligodendrocyte precursor cells (OPCs), alongside a reduction in the percentage of neurons, microglia, and oligodendrocytes (OLGs). Post-ICH WMH showed homeostatic microglia transitioning into pro-, anti-inflammatory, and proliferative states, influencing lipid metabolic pathways. Myeloid cells amplified chemokine expression, linked with ferroptosis pathways. Macrophages exhibited M1 and M2 phenotypes, and post-WMH, macrophages displayed a predominance of M2 phenotypes, characterized by their anti-inflammatory properties. A surge in OPC proliferation aligned with enhanced ribosomal signaling, suggesting potential reparative responses post-WMH. The study offers valuable insights into WMH's complex pathophysiology following ICH, highlighting the significance and utility of scRNA-seq in understanding the cellular dynamics and contributing to future cerebrovascular research.

Values of Sinogram Affirmed Iterative Reconstruction Algorithm-Based Low-Dose Computed Tomography Imaging in Clinical Diagnosis of Cerebral Hemorrhage

In this study, the sinogram affirmed iterative reconstruction (SAFIRE) technology combined with low-dose computed tomography (CT) scanning technology was applied to scan patients with cerebral hemorrhage to evaluate the application value of this combined technology in the diagnosis of patients with cerebral hemorrhage. 132 patients with cerebral hemorrhage admitted to the hospital were selected randomly as the research objects in this study. According to the patients’ wishes, all of them were rolled into an experimental group and a control group. Besides, patients who were willing to use low-dose CT imaging scanning technology based on the SAFIRE algorithm were classified into the experimental group, and those who received simple low-dose CT scans were classified into the control group. Subjective score, objective score (mean CT value), image noise (SD), signal-to-noise ratio (SNR), and contrast-noise ratio (CNR) were used to analyze and compare the two groups of detection methods. The results showed the following: (1) The average result of CT images was 4.05 ± 0.28 points for the control group and 4.43 ± 0.59 points for the experimental group. According to the classification, the excellent and good rates of the experimental group (89.9%) were markedly higher than the rates of the control group (65.8%), with a statistically obvious difference ( P < 0.05). (2) The standard deviation (SD), image signal-to-noise ratio (SNR), and contrast-noise ratio (CNR) results of gray matter, white matter, and cerebral hemorrhage lesions of patients from the experimental group were better than those of the control group, and the differences were statistically significant ( P < 0.05). In conclusion, the image quality of a low-dose CT scan reconstructed by the SAFIRE algorithm was superior to that of a simple low-dose CT scan. In other words, the image quality of CT images could be guaranteed by the SAFIRE technology under the condition of reducing radiation dose. It enabled patients with cerebral hemorrhage to carry out diagnostic examinations with guaranteed accuracy under the risk of low radiation and provided better imaging services for patients with cerebral hemorrhage.

Disseminated Multifocal Intracerebral Bleeding Events in Three Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation As Rescue Therapy.

To describe three coronavirus disease 2019 patients suffering from acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation therapy and tight anticoagulation monitoring presenting a novel pattern of multifocal brain hemorrhage in various degrees in all cerebral and cerebellar lobes. Clinical observation of three patients. Post mortem examinations. Two ICUs at the University Hospital Erlangen. Three patients (medium age 56.6 yr, two male with hypertension and diabetes, one female with no medical history) developed severe acute respiratory distress syndrome on the basis of a severe acute respiratory syndrome coronavirus 2 infection. All required mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Clinical observation, CT, data extraction from electronic medical records, and post mortem examinations. We report on an unusual multifocal bleeding pattern in the white matter in three cases with severe acute respiratory distress syndrome due to coronavirus disease 2019 undergoing venovenous extracorporeal membrane oxygenation therapy. Bleeding pattern with consecutive herniation was found in CT scans as well as in neuropathologic post mortem examinations. Frequency for this unusual brain hemorrhage in coronavirus disease 2019 patients with extracorporeal membrane oxygenation therapy at our hospital is currently 50%, whereas bleeding events in extracorporeal membrane oxygenation patients generally occur at 10-15%. Multifocality and high frequency of the unusual white matter hemorrhage pattern suggest a coherence to coronavirus disease 2019. Neuropathological analyses showed circumscribed thrombotic cerebrovascular occlusions, which eventually led to microvascular and later on macrovascular disseminated bleeding events. However, signs of cerebrovascular inflammation could not be detected. Polymerase chain reaction analyses of brain tissue or cerebrospinal fluid remained negative. Increased susceptibility for fatal bleeding events should be taken into consideration in terms of systemic anticoagulation strategies in coronavirus disease 2019.

Cerebral Small Vessel Disease

Diseases of the cerebral vasculature contribute to diverse forms of brain dysfunction, injury, and cell death. Small vessel disease (SVD) of the brain accounts for ≈25% to 30% of strokes and is a leading cause of age-related and hypertension-related cognitive decline and disability.1 Despite its impact on the brain, there are currently no specific treatments for SVD, and therapeutic options for secondary prevention are particularly limited compared with those for other common causes of stroke. Cerebral SVD refers to pathological processes that affect the structure or function of small vessels on the surface and within the brain, including arteries, arterioles, capillaries, venules, and veins.1 Clinically, the consequences of pathological changes of small vessels of the brain can be detected with neuroimaging. These consequences include white matter hyperintensities, small infarctions or hemorrhages in white or deep gray matter, enlargement of perivascular spaces, and brain atrophy.2,3 SVD can progress silently for many years before becoming clinically evident.2 Hence, medical scientists must not only address the clinical impact of SVD but also identify targets for prevention and early treatment. Both these tasks require a better understanding of the pathogenesis of SVD. The majority of SVD is sporadic and seems driven by a complex mix of genetic and cardiovascular risk factors, among which age and hypertension are deemed the most important.1,2 Rare monogenic forms of SVD have been identified and offer excellent opportunities for mechanistic studies using genetic models based on familial disease mutations.4 In some cases, genetic and sporadic forms of SVD may exhibit common underlying mechanisms. This article focuses on Mendelian forms of SVD, excluding the hereditary cerebral amyloid angiopathies, which have been the subject of recent reviews.5 Particularly, we review the pathogenesis of collagen type IV–related SVD and cerebral autosomal …

Severe Posterior Reversible Encephalopathy in Pheochromocytoma: Importance of Susceptibility-Weighted MRI

Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one of the common reasons of posterior reversible encephalopathy. Intracerebral hemorrhage is a serious and unexpected complication of hypertensive encephalopathy due to pheochromocytoma, and very rarely seen in the childhood. Intracerebral hemorrhages should be searched if there are hypertensive reversible signal changes on the brain. Susceptibility weighted imaging (SWI) is a more sensitive method than conventional MRI when demonstrating cerebral microhemorrhagic foci. This is the first report of SWI findings on intracerebral hemorrhages in basal ganglia, brain stem and periventricular white matter due to hypertensive encephalopathy in a child with pheochromocytoma.

OP16.06: Assessing acute fetal brain injury with US and MRI: antenatal imaging and associated risk factors

To identify patterns offetal brain injury with US and MRI, and to correlate findings with antenatal risk factors and postnatal outcome. Institutional ethical approval was obtained in order to review records to identify fetuses with evidence of brain injury. Postnatal imaging and postmortem findings were correlated with prenatal sonographic findings. Sonographic evidence of brain injury was documented antenatally in 54 fetuses and confirmed on fetal or postnatal MRI or at autopsy. There was intracranial hemorrhage in 24 (44%), hypoxia-ischemia in 9 (17%), fetal infection in 6 (11%), schizencephaly/stroke in 5 (9%), teratogen exposure in 5 (9%), and periventricular pseudocysts in 5 (9%) associated with other non-CNS anomalies. Aneuploidy was found in 2 fetuses (3.7%). Antenatal risk factors included multiple gestation in 26% of cases (3 dichorionic, 11 monochorionic gestation). Among monochorionic gestations, 3 were related to twin transfusion syndrome and 8 to IUFD. Intracranial hemorrhage was seen in 6 twins, 2 of which were dichorionic. Singletons with hemorrhage (18 cases) were associated with alloimmune thrombocytopenia in 4, metabolic disorder in 2, and CMV in 1; in the remainder, etiology was undetermined. A spectrum of imaging findings in brain hemorrhage included Grade 4 ICH in 6 fetuses, Grade 3 ICH in 7 including one with Dandy-Walker malformation, Grade 2 hemorrhage in 2, Grade 1 ICH in 3; and 3 fetuses with posterior fossa hemorrhage. Two fetuses had focal white matter hemorrhage. Fetal brain injury can be detected sonographically and confirmed with fetal MRI, postnatally, or at autopsy. Knowledge of risk factors and the spectrum of imaging findings can improve antenatal detection of prenatal insults. Specific maternal, fetal, or placental conditions are associated with a higher risk of fetal brain injury and a spectrum of causative pathological entities are involved (ischemia/infarction, hemorrhage, teratogens, infection).

Diffuse vascular injury: convergent-type hemorrhage in the supratentorial white matter on susceptibility-weighted image in cases of severe traumatic brain damage

Susceptibility-weighted image (SWI) is one of the most sensitive methods for detect microbleeding and useful for evaluation of traumatic brain damage. The purpose of this study is to delineate the characteristics and importance of supratentorial deep white matter hemorrhages detected by SWI in cases of traumatic brain damage. Twenty-one consecutive cases with severe traumatic head injury were included in the current study. MRI examinations were made within 1 month after injury. We evaluated the degree and distribution of the supratentorial hemorrhages on SWI retrospectively. We classified the degree of bleeding into four grades: "small hemorrhage," "single bead-like hemorrhage," "convergent-type hemorrhage," and "massive hemorrhage." We then correlated the degree and distribution of the hemorrhage to clinical outcomes. We also evaluated the apparent diffusion coefficient (ADC) image of lobes with "convergent-type hemorrhage." Existence of "massive hemorrhage" correlated with a poor outcome, that is, worse than "severely disabled" on the Glasgow Outcome Scale. The number of lobes affected by "convergent-type hemorrhage" also correlated with poor outcome. There were 45 lobes with "convergent-type hemorrhage" and 27 of them showed increased diffusivity on ADC images. Supratentorial massive hemorrhages and supratentorial convergent-type multiple hemorrhages were associated with poor prognosis after traumatic brain injury. The increased diffusivity in lobes with convergent-type hemorrhages may indicate that congestion of the proximal medullary vein may play some role for these hemorrhages.

Vaskuläre Demenz

Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

Cerebellar white matter injury following systemic endotoxemia in preterm fetal sheep

Injury to the cerebellum and brainstem is becoming increasingly recognized in prematurely born infants. The role of infection/inflammation in mediating damage to those structures in the preterm brain is largely unknown. Preterm fetal sheep (70% gestation) received either saline-vehicle (control group; n=11) or Escherichia coli lipopolysaccharide (100 ng intravenous [i.v.]; lipopolysaccharide [LPS] group; n=9), and were allowed to recover for 3 days before sacrifice. A diffuse pattern of cerebellar white matter damage was observed in all animals exposed to LPS, while focal cerebellar white matter lesions were observed in three out of nine animals, and an intragyral white matter hemorrhage in one animal. Cerebellar white matter injury was associated with a statistically significant loss of oligodendrocyte transcription factor-2–positive oligodendrocytes and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive cell counts. Ionized calcium binding adapter molecule 1 (Iba1)–positive cells which had the morphology of activated microglia were commonly observed in areas of injury. There was no obvious injury to the cerebellar cortex or to cerebellar Purkinje cells, and no obvious injury in any region of the brainstem. These data provide support for a role of infection/inflammation in selective white matter injury in the immature cerebellum, and demonstrate a differential vulnerability of the brainstem and cerebellar white matter to injury at this time.

OP04.11: MR diagnosis of ischemia/infarct in the fetal brain; spectrum of appearance and significance of findings

Objectives: Fetal stroke is defined as fetal intracranial hemorrhage that occurs between 14 weeks of gestation and the onset of labor. It has been associated with postnatal epilepsy, mental retardation, and cerebral palsy and may be caused by antenatal ischemic, thrombotic, or hemorrhagic injury. Maternal alloimmune thrombocytopenia and trauma are common predisposing conditions, but there are many unknown risk factors. MRI can depict intracranial hemorrhage, infarct, porencephaly, cystic encephalomalacia, and ischemia. Methods: This was a retrospective, chart review of cases performed between January 1, 2000 through February 2008. A comparison of CNS findings on prenatal ultrasound and fetal MRI was performed to assess potential differences in the two imaging modalities Results: Review of fetal MRI’s revealed 23 cases of diagnosed CNS hemorrhage, ischemia, and infarcts. MRI can delineate the features and extent of the cerebral injury and can define acute and chronic ischemic changes. This is extremely important for predicting prognosis and decision making. Prior studies have shown that major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilatation after intraventricular hemorrhage are associated with adverse outcomes, but punctate white matter lesions, hemorrhage, or ventricular dilatation without intraventricular hemorrhage are not necessarily correlated with unfavorable results. Conclusions: We present the spectrum of CNS injury diagnosed at our institution. Accurate diagnosis of CNS injury was valuable in prenatal counseling and decision making. It is hoped that additional studies will be performed with long term outcomes assessment to assist in prognostication of fetuses diagnosed with CNS ischemia/infarct.

Patterns of Cerebral Injury and Neurodevelopmental Outcomes After Symptomatic Neonatal Hypoglycemia

Symptomatic neonatal hypoglycemia may be associated with later neurodevelopmental impairment. Brain injury patterns identified on early MRI scans and their relationships to the nature of the hypoglycemic insult and neurodevelopmental outcomes are poorly defined. We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months. White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects. Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.

Coma With Diffuse White Matter Hemorrhages in Juvenile Diabetic Ketoacidosis

Cerebral edema is the most common neurologic complication of diabetic ketoacidosis in children. A minority of young patients with intracerebral crises in diabetic ketoacidosis present with cerebrovascular accidents. We report 2 adolescent patients with diabetic ketoacidosis who presented with coma and diffuse white matter hemorrhages in the absence of either cerebral edema or cerebrovascular accidents. These 2 cases illustrate a novel clinical and neuropathologic description of diffuse white matter hemorrhages, possibly related to a cytotoxic process as the underlying mechanism. These case descriptions emphasize that pediatric patients with diabetic ketoacidosis and coma can present with pathology not related to either cerebral edema or cerebrovascular accidents.

Blast-Related Traumatic Brain Injury: What Is Known?

Blast-Related Traumatic Brain Injury: What Is Known?

Leukoencephalomalacia and hemorrhage in the brain of rabbits gavaged with mycotoxin fumonisin B1

Two of five pregnant rabbits gavaged with purified fumonisin B1 at 1.75 mg/kg/day died, one after 9 and one after 13 doses. Microscopic examination revealed focal small hemorrhages in cerebral white matter in both animals, with malacia and hemorrhage also present in the hippocampus of one. The lesions were bilateral. Both animals also had marked degeneration of renal tubule epithelium and of hepatocytes. Apoptosis was the dominant degenerative change in kidney and liver. Fumonisin is known to cause leukoencephalomalacia and hemorrhage in equines, but CNS changes associated with exposure to fumonisins apparently have not been reported in other species. This preliminary observation in rabbits is reported to alert other investigators of a potential model of the disease in equines, as well as for investigation of potential mechanisms of toxicity to the CNS.

Effect of germinal matrix hemorrhage on terminal vein position and patency

Pathologic studies have suggested that periventricular intraparenchymal hemorrhages (IPH) occur as the result of compression and occlusion of terminal veins (TV) by germinal matrix hemorrhages (GMH). This study used color Doppler ultrasound techniques to test this hypothesis in vivo. Twenty-four infants with 32 intracranial hemorrhages (20 GMH, 12 GMH/IPH) were evaluated during routine sonography with color and duplex Doppler ultrasound using an ACUSON 128 XP unit with 7-MHz linear and vector transducers. Maximum transverse dimension was obtained for each GMH. On coronal color Doppler ultrasound images, TVs were evaluated for displacement, presence of flow, and time average velocity (TAV). Abnormalities of the TV were common with ipsilateral GMH. Of 48 terminal veins evaluated, no flow was identified in 13 (27 %), and flow in a displaced vein was seen in eight (17 %). TV abnormality occurred more frequently with GMH/IPH (90 %) than with GMH alone (52 %), and complete occlusion of the TV was more common in GMH/IPH (82 %) than in GMH alone (16 %, p < 0.002). GMH size correlated with increasing TV abnormality. Mean transverse GMH dimensions with unaffected TV, displaced TV, and occluded TV were 8.2 +/- 1 mm, 10.3 +/- 1 mm, and 12.6 +/- 1 mm, respectively (p = 0.008). A small but significant trend was observed between maximum GMH dimension and decreasing TV velocities (r = - 0.5, p < 0.01). Obstruction of terminal veins by germinal matrix hemorrhage may play an important role in the pathogenesis of periventricular white matter hemorrhage.

Acute post-traumatic intraventricular hemorrhage analysis of 25 patients with emphasis on final outcome

A series of 25 patients suffering acute post-traumatic intraventricular hemorrhage (IVH) after closed head injury is reviewed. Post-traumatic IVH was associated with other brain lesion in most cases; intracerebral lesions with contusion, subdural hematoma, and epidural hematoma coexisted with post-traumatic IVH in ten, three, and one instance, respectively. In six cases, no CT abnormality other than IVH was noted. The final outcome in this series is poor, only 10 (40%) patients made a functional survival. Four different groups of IVH were proposed according to the CT scan findings: deep nuclei hemorrhage, brain stem injury, white matter hemorrhage and isolated IVH. The group of isolated IVH usually got a good outcome. The abnormal motor response, abnormal pupil reaction and impaired oculocephalic response were reliable parameters for poor prognosis.

Magnetic resonance imaging in the CNS.

This article, aimed toward the nonneurologist specialist, presents current indications for MRI in the CNS. Primary and metastatic brain tumors, white matter disease, stroke and hemorrhage, hydrocephalus, and spinal disease are discussed. Emphasis is placed on the contribution of MRI to the evaluation of these major classes of disease. Because of its improved sensitivity and noninvasiveness, in most instances MRI is the initial imaging procedure of choice in the CNS.

Pathogenesis of periventricular white matter hemorrhages in preterm infants

Periventricular white matter hemorrhage (PWMH) was frequently found in very low-birth weight infants with perinatal asphyxia or respiratory distress. Primary PWMH with or without intraventricular rupture was found at the deep arterial borderzones of the frontal or occipital lobes. The ischemic tissue damage induced by hypoperfusion may be a predisposing factor for PWMH. However, the high incidence of visceral intravascular thrombi and the fan-shaped appearance of hemorrhage suggested venous hemorrhagic infarction. Venous thrombosis with coagulopathy may be an important factor for the pathogenesis of PWMH.

The encephalopathy of sepsis.

Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.

Responses to cortical injury: I. Methodology and local effects of contusions in the rat

In order to develop some understanding of the evolution of cortical contusions, interdisciplinary studies including behavior, morphology and histochemistry were conducted at varying intervals after standardized injuries. A method for producing graded and reproducible focal cortical contusions in the rat is described. When these impact injuries are made in the ‘hindpaw cortical area, ’ specific trauma dose dependent behavioral deficits can be readily observed in the contralateral hindlimb. While most functional recovery occurs in the first two weeks after trauma, with severe contusions, deficits persist beyond 90 days. Morphologically these injuries progress from hemorrhages in white matter directly under contused cortex during the first hours after injury to the development of a necrotic cavity by 24 hours. The cativation appears to expand over the subsequent two weeks and by 15 days is lined with fibroblast-like elements and macrophages. Intense acid phosphatase activity is seen on the borders of the area of necrosis. This lysosomal enzyme may participate in autolysis and development of focal cavitation following cortical contusion.