Cytotoxic Edema Research Articles

Brain microbleeds resulting from presumed extensive fat emboli in a patient with bone marrow necrosis following a sickle cell disease vaso-occlusive crisis.

Acute manifestations of sickle cell disease (SCD) are numerous and multisystemic.Cerebral fat embolism (CFE) is a rare but serious complication of SCD caused by bone marrow necrosis (BMN) during vaso-occlusive crises (VOC). We present the case of a41-year-old man with SCD who developed severe VOC and multi-organ dysfunction.He subsequently experienced neurological deterioration with decreased consciousness and diffuse encephalopathy on serial electroencephalograms. Bone marrow aspiration confirmed BMN. Brain MRI revealed extensive diffuse leukoencephalopathy, vasogenic and cytotoxic edema in the white matter, patchy edema in the cranial vault bone marrow on fat-suppressed FLAIR sequence (a finding consistent with the confirmed BMN), and multiple cerebral microbleeds on susceptibility-weighted imaging consistent with CFE. The management of acute neurological complications of SCD varies depending on the specific complication. Brain MRI plays a crucial role in the accurate diagnosis of these complications to guide appropriate treatment.

Melatonin Improves Vasogenic Edema via Inhibition to Water Channel Aquaporin-4 (AQP4) and Metalloproteinase-9 (MMP-9) Following Permanent Focal Cerebral Ischemia.

Background: The efficacy of melatonin in reducing vasogenic and cytotoxic edema was investigated using a model of permanent middle cerebral artery occlusion (pMCAO). Methods: Rats underwent pMCAO, followed by intravenous administration of either melatonin (5 mg/kg) or a vehicle 10 min post-insult. Brain infarction and edema were assessed, and Western blot analyses were conducted to examine the expression levels of aquaporin-4 (AQP4), metalloproteinase-9 (MMP-9), and the neurovascular tight-junction protein ZO-1 upon sacrifice. The permeability of the blood-brain barrier (BBB) was measured using spectrophotometric quantification of Evans blue dye leakage. Results: Compared to controls, melatonin-treated rats exhibited a significant reduction in infarct volume by 26.9% and showed improved neurobehavioral outcomes (p < 0.05 for both). Melatonin treatment also led to decreased Evans blue dye extravasation and brain edema (p < 0.05 for both), along with lower expression levels of AQP4 and MMP-9 proteins and better preservation of ZO-1 protein (p < 0.05 for all). Conclusions: Therefore, melatonin offers neuroprotection against brain swelling induced by ischemia, possibly through its modulation of AQP4 and MMP-9 activities in glial cells and the extracellular matrix (ECM) during the early phase of ischemic injury.

Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.

Intraventricular haemorrhage is a common complication of premature birth. Survivors are often left with cerebral palsy, intellectual disability and/or hydrocephalus. Animal models suggest that brain tissue shrinkage, with subsequent vascular stretch and tear, is an important step in the pathophysiology, but the cause of this shrinkage is unknown. Clinical risk factors for intraventricular haemorrhage are biomarkers of hypoxic-ischaemic stress, which causes mature neurons to swell. However, immature neuronal volume might shift in the opposite direction in these conditions. This is because immature neurons express the chloride, salt and water transporter NKCC1, which subserves regulatory volume increases in non-neural cells, whereas mature neurons express KCC2, which subserves regulatory volume decreases. When hypoxic-ischaemic conditions reduce active ion transport and increase the cytoplasmic membrane permeability, the effects of these transporters are diminished. Consequentially, mature neurons swell (cytotoxic oedema), whereas immature neurons might shrink. After hypoxic-ischaemic stress, in vivo and in vitro multi-photon imaging of perinatal transgenic mice demonstrated shrinkage of viable immature neurons, bulk tissue shrinkage and blood vessel displacement. Neuronal shrinkage was correlated with age-dependent membrane salt and water transporter expression using immunohistochemistry. Shrinkage of immature neurons was prevented by prior genetic or pharmacological inhibition of NKCC1 transport. These findings open new avenues of investigation for the detection of acute brain injury by neuroimaging, in addition to prevention of neuronal shrinkage and the ensuing intraventricular haemorrhage, in premature infants.

Functional Changes in the Expression of the Aqp4 Gene in the Hypothalamus Under the Influence of Drinking Regimen and Arterial Hypertension in Rats

Aquaporin-4 (AQP4) is the main water channel in the central nervous system. AQP4 is densely expressed in brain structures suggesting a crucial role in water transport in normal conditions and in disease. The effect of changes in drinking regime (water-deprivation and hyperhydration) and inherited arterial hypertension on the expression of the AQP4 water channel gene in the hypothalamus, the center of regulation of visceral functions, was studied. It was shown that the level of the Aqp4 mRNA in hyperhydrated animals more than 1.5 times lower than in animals with water-deprivation. This decrease in the Aqp4 gene expression in the hypothalamus may be associated with the ability to prevent cytotoxic edema during increased fluid intake. Rats with inherited stress induced arterial hypertension (ISIAH) are characterized by an increased level of Aqp4 mRNA in the hypothalamus, which suggests the involvement of this channel in processes associated with the regulation of brain water balance during arterial hypertension and the prevention of vasogenic cerebral edema. Thus, the presence of the AQP4 water channel in the brain, associated with the protection of brain cells, is functionally determined by the state of the body. This may be evidenced by bidirectional changes in the Aqp4 gene expression during hyperhydration and arterial hypertension.

Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death.

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca2+-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca2+ imaging in vivo [Postnatal Day (P)12-17] and in acute brain slices (P8-12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca2+ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca2+-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Effects of apelin on neonatal brain neurogenesis in L-NAME-induced maternal preeclampsia

The aim of this study was to investigate the possible protective effects of apelin, which is known to have antioxidant and anti-inflammatory effects, on changes in neurogenesis in newborns of pregnant rats with L-NAME-induced preeclampsia. Wistar albino female rats were divided into four experimental groups: Control, Apelin, Preeclampsia and Preeclampsia + Apelin. Blood pressure was measured on the 5th, 11th and 17th days of gestation, urine protein was analyzed from urine samples collected for 24 h on the 6th, 12th and 18th days and serum creatinine was analyzed from serum samples. Maternal kidney and placenta tissues were obtained to establish the preeclampsia model, and neonatal brain tissues including the cortex, hippocampus and cerebellum regions were obtained to investigate neurogenesis and examined by histological and immunohistochemical methods. The number of newborns, body weight and brain weight of the newborns were measured. eNOS, IL-10, nNOS and NO levels in the brain analyzed via ELISA. Mean arterial pressure, urine protein and serum creatinine increased in the preeclampsia. Newborn weight decreased in the Preeclampsia group, the values in the Preeclampsia + Apelin group were closer to the Control and Apelin groups. In the Preeclampsia group, edema and dilatation in the proximal and distal tubules of kidneys, perivillous fibrin deposition and increase in syncytial nodules of placenta were observed. VEGF immunoreactivity decreased and iNOS immunoreactivity increased in both kidney and placenta. In neonatal brain tissue examinations, cytotoxic edema accompanied by thinning of cortex, delayed migration and lower cell counts in the hippocampus, and increase in intercellular spaces and EGL thickening in the cerebellum were observed in the preeclampsia. Expression of NeuN, GFAP, MBP, IL-10, eNOS, nNOS and NO levels decreased, whereas expression of Iba-1 increased in the preeclampsia. In the Preeclampsia + Apelin group, these findings were similar to the Control and Apelin groups. Apelin administration was found to be beneficial for preventing the adverse consequences of preeclampsia, but further experimental and clinical studies are needed to better understand these effects.

Dextromethorphan Associated Neurotoxicity with Cerebellar Edema (DANCE) Syndrome in Young Children: Neuroimaging Features.

Dextromethorphan toxicity in young children (especially those with age 4 years or younger) can have an extremely poor prognosis if untreated. However, if timely recognized and optimally managed, it can have a good clinical outcome despite significant initial insult. We present 3 pediatric cases (< 5 years old) with sudden unresponsiveness following ingestion of cough medications containing dextromethorphan. All these children showed cytotoxic edema in cerebellar hemispheres on MR brain, with diffusion restricting foci in supratentorial white matter in 2 patients. These features resemble the recently described acute opioid toxidrome in children, the POUNCE syndrome (Pediatric Opioid Use-associated Neurotoxicity with Cerebellar Edema). Hence, we name this entity "DANCE" (Dextromethorphan Associated Neurotoxicity with Cerebellar Edema) to increase the awareness of dextromethorphan toxicity in young children and the need to promptly recognize it to initiate optimal management.ABBREVIATIONS: POUNCE= Pediatric Opioid Use-associated Neurotoxicity with Cerebellar Edema; DANCE= Dextromethorphan Associated Neurotoxicity with Cerebellar Edema.

Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

Hypoxic ischemic encephalopathy (HIE).

The morbidity and mortality of acute ischemic hypoxic encephalopathy in newborns have not been dramatically modified over the last 20 years. The purpose of this review is to describe the use of hyperbaric oxygenation therapy (HBOT) in the management of acute ischemic hypoxic encephalopathy in newborns. A review of the medical literature was conducted on the use of HBOT in the pathophysiology of this condition and its impact on outcomes of patients treated at an early stage. When HBOT is administered promptly, it can promote the survival of the penumbra, modulate the cytokine storm, modify inflammatory cascades, restore mitochondrial function, inhibit apoptosis, reinstate cellular communication and cytoskeleton function, reinstall the functioning of the kinase system, reduce cytotoxic and tissue edema, promote microcirculation, and provide an antioxidant effect. All these secondary mechanisms aid in saving, rescuing, and protecting the marginal tissue. When used promptly, HBOT is a non-invasive adjunct treatment that can preserve the marginal tissue affected by ischemia, hypoxia, meet the metabolic needs of the penumbra, reduce inflammatory cascades, prevent the extension of the damaged tissue, and modulate ischemia-reperfusion injury.

Magnetic Resonance Imaging in Uremic Encephalopathy: Identifying Key Imaging Patterns and Clinical Correlations.

Background/Objectives: Magnetic Resonance Imaging (MRI) is essential in diagnosing neurological conditions, offering detailed insights into brain pathology. Uremic encephalopathy (UE) is a severe neurological disorder resulting from renal failure, characterized by cognitive impairments and brain abnormalities due to the accumulation of uremic toxins (UTs). Despite extensive research on UTs, there is a significant gap in the detailed characterization of MRI findings in UE patients. This study aims to bridge this gap by conducting a comprehensive literature review of cerebral MRI findings in UE. We hypothesize that specific MRI patterns correlate with the severity and clinical manifestations of UE, thereby enhancing diagnostic accuracy and improving patient outcomes. Methods: A literature review was performed using PubMed, Cochrane Library, and Google Scholar. The search terms included "uremic encephalopathy MRI", "uremia and kidney failure MRI", and "toxic and metabolic or acquired encephalopathies MRI". The inclusion criteria were original articles on UE and MRI findings published in English. Results: Common MRI sequences include T1-weighted, T2-weighted, FLAIR, and DWI. Frequent MRI findings in UE are cytotoxic and vasogenic brain edema in regions such as the basal ganglia and periventricular white matter. Patterns like the "lentiform fork sign" and basal ganglia involvement are key indicators of UE. Conclusions: MRI plays a crucial role in diagnosing UE by identifying characteristic brain edema and specific patterns. A comprehensive diagnostic approach, incorporating clinical, laboratory, and imaging data, is essential for accurate diagnosis and management. The study calls for larger well-designed cohorts with long-term follow-up to improve the understanding and treatment of UE.

Pathomorphology of severe Grade 3-4 hepatic encephalopathy in decompensated cirrhosis patients with acute-on-chronic liver failure

The study was aimed to determine of the most significant pathomorphological signs of severe hepatic encephalopathy (HE) in deceased cirrhotic patients with acute-on-chronic liver failure (ACLF) syndrome based on changes of the glioneuronal complex and the level of tissue ammonia. Using pathohistological, histochemical, and immunohistochemical methods, the cerebral cortex, thalamus, striatum, and cerebellum of 21 deceased patients with acutely decompensated liver cirrhosis with ACLF syndrome and HE Grade 3-4 were examined in comparison with control group, which included 30 deceased patients from acute cardiovascular failure. The study revealed that during HE Grade 3-4 as a component of ACLF, in all studied brain regions, there was a reliably (p&lt;0.05) higher histochemical level of tissue ammonia (up to 500%), increased numbers (up to 215.69%) of apoptotic neurons (according to caspase-3), reduced (up to 119.60%) level of synaptophysin, increased expression of glutamine synthetase (up to 253.02%) and aquaporin-4 (up to 481.81%) associated by reduced (up to 296.81%) expression of glial fibrillary acidic protein in astrocytes, increased (up to 11-fold) numbers of Alzheimer type 2-astrocytes, expansion of perivascular and pericellular «edematous» spaces (up to 890.81%), increased numbers of amyloid bodies (up to 5-fold), increased area of immunopositive material of CD68+ microgliocytes (up to 114.78%) with an increase (up to 71.91%) in the proportion of CD68+ amoeboid microglia. The above-mentioned changes confirm that the loss of consciousness and other psychoneurological manifestations of severe HE Grade 3-4 are due to compound am­monia-associated changes in the components of the glioneuronal complex, namely: adaptive remodeling and dystro­phic changes in astrocytes, reduced synaptic transmission and apoptotic neuronal death, reactive changes in microglia with a small proportion of microgliocytes involved in phagocytosis, cytotoxic brain edema and dysfunction of the glymphatic system

Unique presentation of acute neuro-Behçet's disease involving a cytotoxic edema core surrounded by vasogenic edema.

A 53-year-old woman with recurrent stomatitis, genital ulcers, and folliculitis was admitted to our hospital after experiencing visual disturbances for the past two weeks, and a non-throbbing headache for the past three days. She had also developed numbness in her left extremities. An ophthalmological examination revealed inflammatory changes in the eye. Cerebrospinal fluid analysis showed increased cell counts, protein, and interleukin-6 levels. Brain magnetic resonance imaging revealed multiple high signal intensities on T2-weighted (T2W)/fluid-attenuated inversion recovery (FLAIR) images of the pons and occipital and parietal lobes. The T2W/FLAIR high-signal-intensity lesion in the pons was hyperintense on diffusion-weighted imaging (DWI) and hypointense on apparent diffusion coefficient mapping (ADC), suggesting cytotoxic edema. Another high-signal-intensity lesion on T2W/FLAIR was isointense to hyperintense on DWI and hyperintense on ADC, indicating vasogenic edema. The vasogenic edema in the left occipital lobe contained a small core that was hyperintense on DWI and hypointense on ADC, suggesting cytotoxic edema. The patient was diagnosed with acute neuro-Behçet's disease (neuro-BD) and responded well to high-dose glucocorticoid and colchicine treatment. The present report emphasizes that patients with acute neuro-BD may present with cytotoxic edema in the pons and cerebral spheres. Further reports of similar cases would contribute to a better understanding of the role of cytotoxic edema in the pathophysiology of neuro-BD and help elucidate the mechanisms underlying a unique presentation characterized by a central cytotoxic edema core within vasogenic edema. (233 words).

Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia.

Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). Brain MRI studies of 83 term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) fourth and sixth days were retrospectively re-evaluated by 2 radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major, and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (P = .02 and P = .03, respectively) and ADCmin (P = .03 and P = .04, respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (P = .04) and normal development (P = .04) via cytotoxic oedema of the thalamus, corpus striatum, and diffuse cerebral cortical. The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimated similarly with volumetric ADC-HA and the conventional assessment of the ADC map. This study compares early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We could not find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

Microstructure and Perfusion Alterations of Globus Pallidus in Neonates with Hyperbilirubinemia.

Previous studies have indicated the abnormality of the globus pallidus in neonates with hyperbilirubinemia. This study aims to explore the microstructure and cerebral perfusion of globus pallidus in neonatal hyperbilirubinemia by using Diffusion Tensor Imaging (DTI) and Arterial Spin Labeling (ASL) approaches. Thirty-seven neonates were enrolled in this study, which were classified into Bilirubin-Induced Neurologic Dysfunction (BIND) group (hyperbilirubinemia with BIND, n=12), non-BIND group (hyperbilirubinemia without BIND, n=15), and healthy controls (HC) group (n=10). The quantitative values of globus pallidus were calculated from DTI, including the Apparent Diffusion Coefficient (ADC), the Fractional Anisotropy (FA), and Volume Ratio (VR) values. Additionally, the relative Cerebral Blood Flow (rCBF) values were obtained from ASL. It was observed that the mean DTI signal of globus pallidus was significantly different among the three groups (p < 0.05). However, there were no significant differences in the rCBF of globus pallidus among the three groups (p > 0.05). A positive correlation was also observed between the fractional anisotropy (FA) value and serum bilirubin level (r = 0.561, p = 0.002), while the VR value showed a negative correlation with serum bilirubin level (r=-0.484, p=0.011). The area under the curve (AUC) of FA, VR, and FA and VR combined was 0.897, 0.858, and 0.933, respectively. The alterations of microstructure in globus pallidus, especially FA and VR value, may be valuable and sensitive at the early stage of hyperbilirubinemia encephalopathy, suggesting that early hyperbilirubinemia may lead to cytotoxic edema and decreased permeability of the cell membrane.

Ultrahigh field diffusion magnetic resonance imaging uncovers intriguing microstructural changes in the adult zebrafish brain caused by Toll-like receptor 2 genomic deletion.

Toll-like receptor 2 (TLR2) belongs to the TLR protein family that plays an important role in the immune and inflammation response system. While TLR2 is predominantly expressed in immune cells, its expression has also been detected in the brain, specifically in microglia and astrocytes. Recent studies indicate that genomic deletion of TLR2 can result in impaired neurobehavioural function. It is currently not clear if the genomic deletion of TLR2 leads to any alterations in the microstructural features of the brain. In the current study, we noninvasively assess microstructural changes in the brain of TLR2-deficient (tlr2-/-) zebrafish using state-of-the art magnetic resonance imaging (MRI) methods at ultrahigh magnetic field strength (17.6 T). A significant increase in cortical thickness and an overall trend towards increased brain volumes were observed in young tlr2-/- zebrafish. An elevated T2 relaxation time and significantly reduced apparent diffusion coefficient (ADC) unveil brain-wide microstructural alterations, potentially indicative of cytotoxic oedema and astrogliosis in the tlr2-/- zebrafish. Multicomponent analysis of the ADC diffusivity signal by the phasor approach shows an increase in the slow ADC component associated with restricted diffusion. Diffusion tensor imaging and diffusion kurtosis imaging analysis revealed diminished diffusivity and enhanced kurtosis in various white matter tracks in tlr2-/- compared with control zebrafish, identifying the microstructural underpinnings associated with compromised white matter integrity and axonal degeneration. Taken together, our findings demonstrate that the genomic deletion of TLR2 results in severe alterations to the microstructural features of the zebrafish brain. This study also highlights the potential of ultrahigh field diffusion MRI techniques in discerning exceptionally fine microstructural details within the small zebrafish brain, offering potential for investigating microstructural changes in zebrafish models of various brain diseases.

Reversible Cytotoxic Edema in Patients with COVID-19 Associated Encephalitis Presenting Status Epilepticus

Coronavirus disease 2019 (COVID-19) is a serious infectious disease with multisystem alteration including neurological complications. COVID-19 associated encephalitis is a potentially fatal viral infection of the brain. Diffusion-weighted images (DWI) are a useful evaluation modality of cytotoxic edema in patients with encephalitis. We report on the reversible DWI change in a patient with COVID-19 associated encephalitis, who had diffused cytotoxic edema in the affected temporal lobe and accompanied status epilepticus. Sequential imaging showed that the cytotoxic edema in DWI confirmed recovery to normal after 12 days in the presence of cortical edema in fluid-attenuated inversion recovery image after aggressive neurocritical management. Thus, prompt, proper management is indispensable during the acute period and DWI may be a valuable tool for reflecting the clinical course of COVID-19 associated encephalitis.

Effects of d-allose on anti-brain edema effects and reduction of tumor necrosis factor-alpha and interleukin-6 in the water intoxication model

BackgroundRare sugars, which exist only in very small quantities in nature, have recently attracted attention for their various biological functions in medicine. Among them, d-allose is known to have cytoprotective effects by antioxidant effects. In this study, we investigated whether the antioxidant effects of d-allose reduce brain edema in a water intoxication model of cytotoxic brain edema. Methods: Mice were injected intraperitoneally with distilled water (10 % of body weight) to create a model of brain edema. d-allose was administered orally at 400 mg/kg 30 min before the model was created. Two hours later, the degree of brain edema was measured by the dry-weight method to determine whether d-allose reduced brain edema. As an index of antioxidant effects, we measured changes over time in inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) induced by the water intoxication model, and whether d-allose reduced inflammatory cytokines 4 h after model creation. Results: Administration of d-allose significantly suppressed brain edema formation of the water-intoxication model. And it significantly reduced inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6). These results suggest that the antioxidant effect of d-allose exerts an anti-inflammatory effect and reduces brain edema.

Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.

This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination. The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS2 score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO. Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema. This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.

Edema progression in proximity to traumatic microbleeds: Evolution of cytotoxic and vasogenic edema on serial MRI

IntroductionAlthough cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury. Researchers hypothesized that hypointense lesions on Apparent Diffusion Coefficient (ADC) detected acutely after injury would evolve into hyperintense Fluid Attenuated Inversion Recover (FLAIR) lesions. MethodsThis study analyzed the progression of cerebral edema after acute injury using multimodal MRI to classify TMBs as potential edema-related biomarkers. ADC and FLAIR MRI were utilized for edema classification at three different timepoints: ≤48 h, ∼1 week, and 30 days after injury. Hypointense lesions on ADC (ADC+) suggested the presence of cytotoxic edema while hyperintense lesions on FLAIR (FLAIR+) suggested vasogenic edema. Signal intensity Ratio (SIR) calculations were made using ADC and FLAIR to quantitatively confirm edema progression. ResultsOur results indicated the presence of ADC+ lesions ≤48 h and ∼1 week were associated with FLAIR + lesions at ∼1 week and 30 days, respectively, suggesting some progression of cytotoxic edema to vasogenic edema over time. Ten out of 15 FLAIR + lesions at 30 days (67%) were ADC+ ≤48 h. However, ADC + lesions ≤48 h were not associated with FLAIR + lesions at 30 days; 10 out of 25 (40%) ADC + lesions ≤48 h were FLAIR + at 30 days, which could indicate that some lesions resolved or were not visualized due to associated atrophy or tissue necrosis. Quantitative analysis confirmed the visual progression of some TMB lesions from ADC + to FLAIR+. FLAIR SIRs at ∼1 week were significantly higher when lesions were ADC+ ≤48 h (1.22 [1.08–1.32] vs 1.03 [0.97–1.11], p = 0.002). ConclusionAwareness of how cerebral edema can evolve in proximity to TMBs acutely after injury may facilitate identification and monitoring of patients with traumatic cerebrovascular injury and assist in development of novel therapeutic strategies.

Clinical relevance of reversible cerebral vasoconstriction syndrome in pregnant women with posterior reversible encephalopathy syndrome: review of case reports in Japan.

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.