Rate of Infarct–Edema Growth on CT Predicts Need for Surgical Intervention and Clinical Outcome in Patients with Cerebellar Infarction

Background Up to 20% of patients with cerebellar infarcts will develop malignant edema and deteriorate clinically. Radiologic measures, such as initial infarct size, aid in identifying individuals at risk. Studies of anterior circulation stroke suggest that mapping early edema formation improves the ability to predict deterioration; however, the kinetics of edema in the posterior fossa have not been well characterized. We hypothesized that faster edema growth within the first hours after acute cerebellar stroke would be an indicator for individuals requiring surgical intervention and those with worse neurological outcomes. Methods Consecutive patients admitted to the neurological intensive care unit with acute cerebellar infarction were retrospectively identified. Hypodense regions of infarct and associated edema, “infarct–edema”, were delineated by using ABC/2 for all computed tomography (CT) scans up to 14 days from last known well. To examine how rate of infarct–edema growth varied across clinical variables and surgical intervention status, nonlinear and linear mixed-effect models were performed over 2 weeks and 2 days, respectively. In patients with at least two CT scans, multivariable logistic regression examined clinical and radiological predictors of surgical intervention (defined as extraventricular drainage and/or posterior fossa decompression) and poor clinical outcome (discharge to skilled nursing facility, long-term acute care facility, hospice, or morgue). Results Of 150 patients with acute cerebellar infarction, 38 (25%) received surgical intervention and 45 (30%) had poor clinical outcome. Age, admission National Institutes of Health Stroke Scale (NIHSS) score, and baseline infarct–edema volume did not differ, but bilateral/multiple vascular territory involvement was more frequent (87% vs. 50%, p < 0.001) in the surgical group than that in the medical intervention group. On 410 serial CTs, infarct–edema volume progressed rapidly over the first 2 days, followed by a subsequent plateau. Of 112 patients who presented within two days, infarct–edema growth rate was greater in the surgical group (20.1 ml/day vs. 8.01 ml/day, p = 0.002). Of 67 patients with at least two scans, after adjusting for baseline infarct–edema volume, vascular territory, and NIHSS, infarct–edema growth rate over the first 2 days (odds ratio 2.55; 95% confidence interval 1.40–4.65) was an independent, and the strongest, predictor of surgical intervention. Further, early infarct–edema growth rate predicted poor clinical outcome (odds ratio 2.20; 95% confidence interval 1.30–3.71), independent of baseline infarct–edema volume, brainstem infarct, and NIHSS. Conclusions Early infarct–edema growth rate, measured via ABC/2, is a promising biomarker for identifying the need for surgical intervention in patients with acute cerebellar infarction. Additionally, it may be used to facilitate discussions regarding patient prognosis.

Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm3). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm3) and lowest (1.6 mm3) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm3, respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm3), CFT (~386 µm), and TRV (~9.06 mm3), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning.

NIMG-65. RESTING-STATE FUNCTIONAL MRI DEMONSTRATES DAMAGE TO FUNCTIONAL CONNECTIVITY IN MENINGIOMA PATIENTS WITH PERIFOCAL EDEMA

BACKGROUND Meningiomas are common intracranial tumors which usually carry a benign prognosis. Some meningiomas cause perifocal edema which might indicate that this subset could interfere with normal brain function. Resting-state functional MRI (rsfMRI) can be used to assess whole brain functional connectivity (fc) which can be used as a marker for disease severity in patients with intracranial tumors, as was recently shown by our group in a cohort of glioma patients. In this study, we investigated whether the presence of perifocal edema in preoperative patients with meningioma leads to fc. METHODS Patients with suspected meningioma were prospectively included and functional resting state MRI scans were obtained. The resulting data was processed according to our recently published method and abnormality of fc was quantified for each individual patient. Abnormality of fc was then correlated with tumor and edema volume as well as WHO grade. RESULTS 26 patients (23 WHO grade I, 3 WHO grade II) were included. 13 patients had perifocal edema. There was a highly significant correlation between edema volume and higher abnormality of fc both in the lesional and the contra-lesional hemisphere (r=0.51, p=0.008 and r=0.61, p=0.001). Patients with no perifocal edema showed only very low abnormality of fc. Tumor volume was not correlated with abnormal fc in both the lesional and the contralesional hemispheres (r=0.23, p=0.27 and r=0.28, p=0.17). There was also no significant correlation between WHO grade and abnormality of fc. CONCLUSION RsfMRI showed significant abnormal fc in meningioma patients with perifocal edema in contrast to patients without edema, independent of tumor volume. This demonstrates that the presence of edema but not the tumor volume is relevant for disturbances of fc.

Large-Scale Multivariate Analysis to Interrogate an Animal Model of Stroke: Novel Insights Into Poststroke Pathology

Background and Purpose: Preclinical stroke studies endeavor to model the pathophysiology of clinical stroke, assessing a range of parameters of injury and impairment. However, poststroke pathology is complex and variable, and associations between diverse parameters may be difficult to identify within the usual small study designs that focus on infarct size. Methods: We have performed a retrospective large-scale big data analysis of records from 631 C57BL/6 mice of either sex in which the middle cerebral artery was occluded by 1 of 5 surgeons either transiently for 1 hour followed by 23-hour reperfusion (transient middle cerebral artery occlusion [MCAO]; n=435) or permanently for 24 hours without reperfusion (permanent MCAO; n=196). Analyses included a multivariate linear mixed model with random intercept for different surgeons as a random effect to reduce type I and type II errors and a generalized ordinal regression model for ordinal data when random effects are low. Results: Analyses indicated that brain edema volume was associated with infarct volume at 24 hours (β, 0.52 [95% CI, 0.45–0.59]) and was higher after permanent MCAO than after transient MCAO ( P <0.05). A more severe clinical score was associated with a greater infarct volume but not with the animal’s age or edema volume. Further, a more severe clinical score was observed for a given brain infarct volume after transient MCAO versus permanent MCAO. Remarkably the animal’s age, which corresponded with the period of young adulthood (6–40 weeks; equivalent to ≈18–35 years in humans), was positively associated with severity of lung infection (β, 0.65 [95% CI, 0.42–0.88]) and negatively with spleen weight (β, −0.36 [95% CI, −0.63 to −0.09]). Conclusions: Large-scale analysis of preclinical stroke data can provide researchers in our field with insight into relationships between variables not possible if individual studies are analyzed in isolation and has identified hypotheses for future study.

Factors Associated With Dysfunction of Glymphatic System in Patients With Glioma

ObjectivesRodent experiments have provided some insights into the changes of glymphatic function associated with glioma growth. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method offers an opportunity for the noninvasive investigation of the glymphatic system in patients with glioma. We aimed to investigate the factors associated with glymphatic function changes in patients with glioma.Materials and MethodsA total of 201 glioma patients (mean age = 47.4 years, 116 men; 86 grade II, 52 grade III, and 63 grade IV) who had preoperative diffusion tensor imaging for calculation of the ALPS index were retrospectively included. Information collected from each patient included sex, age, tumor grade, isocitrate dehydrogenase 1 (IDH1) mutation status, peritumoral brain edema volume, tumor volume, and ALPS index. Group differences in the ALPS index according to sex, tumor grade, and IDH1 mutation status were assessed using analysis of covariance with age adjustment. Linear regression analyses were performed to identify the factors associated with the ALPS index.ResultsGroup comparisons revealed that the ALPS index of grade II/III gliomas was significantly higher than that of grade IV gliomas (p &lt; 0.001). The ALPS index of IDH1 mutant gliomas was significantly higher than that of IDH1 wild-type gliomas (p &lt; 0.001). On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p &lt; 0.001) and peritumoral brain edema volume (β = −0.353, p &lt; 0.001) were the two independent factors associated with the ALPS index.ConclusionIDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.

Anti-Inflammatory Activity of Ethanol Extract of Marine Sponge Petrosia Sp. by Supression the Level of Tumor Necrosis Factor-alpha

Inflammation is the host's protective response to any stimulus that harms the body. Excessive inflammatory process causes tissue damage. Therefore, an anti-inflammatory agent is needed. The use of natural ingredients, especially sea sponges, is an option to reduce the side effects of anti-inflammatory agents. This utilization is related to the discovery of new agents. So, we tested the effect of the ethanol extract of Petrosia sp. as an anti-inflammatory agent. Animal induced with 1% carrageenan and left for 1 hour. After that the animals were divided into 6 groups (n = 4) and given oral treatment, namely: Group I (normal group); Group II (negative group); Group III (ethanol extract of Petrosia sp. Concentration of 0.05mg/ml); Group IV (ethanol extract of Petrosia sp. Concentration 0.1mg/ml); Group V (ethanol extract of Petrosia sp. Concentration 0.2mg/ml); and Group VI (positive group, Diclofenac Sodium). After 1 hour, the animals were measured for edema volume and plasma TNF-α levels. Based on the research conducted, the ethanol extract of Petrosia sp. decreased edema volume and plasma TNF-α levels in inflammatory mice. The concentration of 0.2mg/mL had a significant effect on the negative control used (p <0.05). On the other hand, Petrosia sp. indicates the presence of alkaloids, flavonoids, and steroids. They may play an important role in the anti-inflammatory process. Thus, it can be concluded that the ethanol extract of Petrosia sp. has anti-inflammatory activity.

Isolation and identification of leukocyte populations in intracranial blood collected during mechanical thrombectomy

Using standard techniques during mechanical thrombectomy, the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (NCT03153683) isolates intracranial arterial blood distal to the thrombus and proximal systemic blood in the carotid artery. We augmented the current protocol to study leukocyte subpopulations both distal and proximal to the thrombus during human stroke (n = 16 patients), and from patients with cerebrovascular disease (CVD) undergoing angiography for unrelated conditions (e.g. carotid artery stenosis; n = 12 patients). We isolated leukocytes for flow cytometry from small volume (<1 mL) intracranial blood and systemic blood (5–10 mL) to identify adaptive and innate leukocyte populations, in addition to platelets and endothelial cells (ECs). Intracranial blood exhibited significant increases in T cell representation and decreases in myeloid/macrophage representation compared to within-patient carotid artery samples. CD4+ T cells and classical dendritic cells were significantly lower than CVD controls and correlated to within-patient edema volume and last known normal. This novel protocol successfully isolates leukocytes from small volume intracranial blood samples of stroke patients at time of mechanical thrombectomy and can be used to confirm preclinical results, as well as identify novel targets for immunotherapies.

Synergistic Antinociceptive, Anti-inflammatory Interaction between Vitamin B12 and Ketorolac in Long Evans Rats

In certain painful disorders, B12 vitamins have been documented to be clinically useful alone or paired with non-steroidal anti-inflammatory drugs (NSAIDs). However, it has not been identified to equate these effects with related effects of ketorolac tromethamine (KT) and their combination. To test and compare the effects of vitamin B12 on pain with those of the combination of vitamin B12 with KT in rat models. This experimental research was performed at the Department of Physiology, BSMMU. The control (A, A1 with 5 ml/kg normal saline) and experimental (B1, B1a with 15 mg/kg B12; B2, B2a with 10 mg/kg KT; B3, B3a with B12+KT) groups of 5 rats in each group were divided into 40 (forty) long Evans rats (215±35 gm) of either sex. Both medications and vitamins were administered intraperitoneally in a single dose just one hour prior to the writhing and paw edema test caused by formalin. The statistical study was carried out by ANOVA, followed by the post-hoc Bonferroni test. In the interpretation of outcomes, p≤0.05 was regarded as significant. B12 lowered only the writhing count and KT lowered both writhing appearance latency time and writhing count significantly (p≤0.001) in the writhing test. However, the combination of B12 and KT significantly (p≤0.001) lowered both the study variables in the writhing test. In addition, KT lowered edema volume significantly (p≤0.01) in the paw edema test. The combination of B12 and KT, on the other hand, substantially (p≤0.001) decreased the amount of edema in the paw edema test. It can be concluded that vitamin B12 has analgesic and anti-inflammatory effects, and that the combination of B12 with KT is more effective than when administered individually.

Suppression of Proinflammatory Cytokines by Etlingera alba (A.D.) Poulsen Rhizome Extract and Its Antibacterial Properties

Etlingera alba is one of the Etlingera plants that has not been studied intensively. Plants that belong to the same genus have similar constituents and pharmacological activities. Thus, we aim to investigate the chemical composition and pharmacological activities, namely, anti-inflammatory and antibacterial properties, of E. alba rhizome extract (EA). The chemical constituent was detected using the test tube method. The inflammatory model rats were obtained by inducing them with 1% carrageenan, and their palm edema volume and cytokine levels, namely, IL-6, IL-12, and TNF-α, were measured. Antibacterial activity was performed with broth microdilution. The phytochemical screening of EA was detecting alkaloids, flavonoids, tannins, steroids, and phenols. The EA has anti-inflammatory activity by reducing the palms’ edema volume and cytokine levels (IL-6, IL-12, and TNF-α), and the optimal concentration was 400 mg/kg body weight (BW). On the other hand, EA also exhibited antibacterial properties against E. coli and S. enterica. In conclusion, similar to other Etlingera plants, EA also demonstrates pharmacological activities, namely, anti-inflammatory and antibacterial properties.

Optimizing Anti-inflammatory Activities of Arabica Coffee Ground (Coffea arabica L.) Nanoparticle Gel

Background: Arabica coffee ground nanoparticles gel is known to possess good physicochemical properties and high phenolic contents in which the phenolics are famous for their anti-inflammatory activities. Objectives: : This study aimed to investigate the anti-inflammatory activities of the arabica coffee ground nanoparticles gel on carrageenan-induced male mice for 6 h. The positive control was commercial medicine (Voltaren gel), and the control negative was base gel. Methods: The inflammatory inhibition of arabica coffee ground nanoparticles gel is determined by measuring the edema volume of the carrageenan-induced mice foot using a plethysmometer. Anti-inflammatory activities of arabica coffee ground nanoparticles gel were optimized using Box-Behnken Design of the response surface methodology. Results: The anti-inflammatory activities or inflammatory inhibition of arabica coffee ground nanoparticles gel was determined by measuring the edema volume of the carrageenan-induced mice foot. The increase of edema volume of the mice foot from the first to 180th min was caused by the release of inflammation mediator such as histamine, prostaglandins, bradykinins, and serotonin on the tissue; meanwhile, at the 240th min, the edema of the mice foot experienced a decrease due to the inhibition of prostaglandins synthesis to the tissue. The obtained results indicated that the arabica coffee ground nanoparticles gel has average value of anti-inflammatory activities of 27.75%. The obtained optimum formulation is 0.500% Carbopol 940, 0.400% triethanolamine, and 2.313% nanoparticle, giving 29.360% and 29.670% for the predicted and experimental inflammatory inhibition values, with 0.812 desirability value, respectively. Conclusions: The Box-Behnken design can be used to determine the optimal gel formulation of arabica coffee grounds for inflammatory inhibition.