OBJECTIVE: The optic nerve sheath diameter (ONSD) is a commonly used estimate of intracranial pressure (ICP). The rationale behind this is that pressure changes in the cerebrospinal fluid affect the optic nerve subarachnoid space (ONSAS) thickness. Still, possible effects on other compartments of the optic nerve sheath (ONS) have not been studied. This is the first study ever to analyze all measurable compartments of the ONS for associations with elevated ICP.
METHODS: We measured changes in ICP and changes in ONS compartments in 75 patients treated with invasive ICP monitoring at the Karolinska University Hospital. Associations between changes in ICP and changes in ONS compartments were estimated with generalized estimating equations. The potential to identify elevated ICP was assessed with the area under the receiver operating characteristic curve (AUROC) for ONS compartments associated with ICP changes.
RESULTS: Both ONSAS and perioptic dura mater thickness were significantly associated with changes in ICP in multivariable modeling. ONSAS was the only compartment that independently predicted changes in ICP, with an AUROC of 0.69 for predicting ICP increase. Still, both the perioptic dura mater thickness and the optic nerve diameter added value in predicting ICP changes in multivariable modeling.
CONCLUSIONS: The results from this study challenge the current understanding of the mechanism behind the association between ICP and ONSD. Contrary to the common opinion that ONSAS is the only affected compartment, this study shows a more complex picture. It suggests that all ONS compartments may add value in predicting changes in ICP.

Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.

UNASSIGNED: Liver cirrhosis patients commonly progress to minimal hepatic encephalopathy (MHE) with cognitive impairment and raised blood ammonia and proinflammatory cytokines levels. This study aims to identify the subjects of MHE in patients with liver cirrhosis by hydrogen 1 magnetic resonance (1H-MR) spectroscopy of the brain, serum proinflammatory cytokines, and neuropsychiatric tests.
UNASSIGNED: This prospective was carried out on 100 patients of liver cirrhosis without overt hepatic encephalopathy (HE) and compared with 100 healthy controls in a tertiary care hospital in Northeast India between September 2017 and October 2019. The psychometric hepatic encephalopathy score (PHES) neuropsychological tests, cranial MRIwith 1H-MR spectroscopy, and estimation of serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were done. The PHES scores and serum proinflammatory markers levels were correlated with the conventional and 1H-MR spectroscopy findings of the brain.
UNASSIGNED: The mean PHES score in the case group was -7.58±3.43 (standard deviation [SD]) and the control group was -3.41 ± 3.87 (SD). Patients with Child-Pugh class A (n = 8) had a PHES score of -8.7 ± 2.5 (SD), class B (n = 42) -7.62 ± 3.7 (SD), and class C (n = 50) had a score of -7.36 ± 3.3 (SD). The mean value of IL-6 and TNF-α in the case group was 219 ± 180 (SD) pg/mL and 99 ± 118 (SD) pg/mL and the control group was 67.4 ± 77 (SD) pg/mL and 57.5 ± 76 (SD) pg/mL. Globus pallidus T1-weighted hyperintensities on the visibility scale with a visibility score of 0 were observed in 39 cases, a score of 1 in 38 cases, and a score of 2 in 23 cases. Increased glutamate/glutamine/creatine (Glx/Cr) ratio was identified in the case group on MR spectroscopy as compared to the control (0.95 ± 0.24 vs. 0.31 ± 0.19, P < 0.0005), a decrease of myoinositol/creatine (mI/Cr) ratio (0.11 ± 0.13 vs. 0.30 ± 0.12, P < 0.0005), and increase choline/creatine (Cho/Cr) ratio (0.69 ± 0.26 vs. 0.61 ± 0.20, P < 0.0005). There was a statistically significant difference in Glx/Cr, mI/Cr and Cho/Cr ratio between the case and control groups with P < 0.0005.
UNASSIGNED: Predicting the development of MHE in established cases of liver cirrhosis using non-invasive modalities like PHES, IL-6, TNF-α levels, and 1H-MR spectroscopy plays an important role in further progression to overt HE and coma.

OBJECTIVE: The outcomes of patients with large ischemic core who fail to recanalize with endovascular therapy (EVT) compared to medical management (MM) are uncertain. The objective was to evaluate the clinical and safety outcomes of patients who underwent EVT in patients with large ischemic core and unsuccessful recanalization.
METHODS: This was a post hoc analysis of the ANGEL-ASPECT randomized trial. Unsuccessful recanalization was defined as patients who underwent EVT with eTICI 0-2a. The primary endpoint was 90-day very poor outcome (mRS 5-6). Multivariable logistic regression was conducted controlling for ASPECTS, occlusion location, intravenous thrombolysis, and time to treatment.
RESULTS: Of 455 patients 225 were treated with MM. Of 230 treated with EVT, 43 (19%) patients had unsuccessful recanalization. There was no difference in 90-day very poor outcomes (39.5% vs. 40%, aOR 0.93, 95% confidence interval, CI 0.47-1.85, p = 0.95), sICH (7.0% vs. 2.7%, aOR 2.81, 95% CI 0.6-13.29, p = 0.19), or mortality (30% vs. 20%, aOR 1.65, 95% CI 0.89-3.06, p = 0.11) between the unsuccessful EVT and MM groups, respectively. There were higher rates of ICH (55.8% vs. 17.3%, p < 0.001), infarct core volume growth (142.7 ml vs. 90.5 ml, β = 47.77, 95% CI 20.97-74.57 ml, p < 0.001), and decompressive craniectomy (18.6% vs. 3.6%, p < 0.001) in the unsuccessful EVT versus MM groups.
CONCLUSIONS: In a randomized trial of patients with large ischemic core undergoing EVT with unsuccessful recanalization, there was no difference in very poor outcomes, sICH or death versus medically managed patients. In the unsuccessful EVT group, there were higher rates of any ICH, volume of infarct core growth, and decompressive craniectomy.

We assessed the effectiveness and safety of target temperature management (TTM) in treating patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). The primary objective was to evaluate the neurological outcome at 3 months. Secondary objectives were to assess mortality, delayed cerebral ischemia, cerebral edema, hydrocephalus, midline shift, and laboratory indicators related to TTM.
A single-blind, nonrandomized controlled trial was conducted. After admission, patients with poor-grade aSAH (Hunt-Hess scores IV ∼ V) were assigned to a TTM group or a control group in a 1:1 ratio. TTM with core temperatures ranging from 36°C to 37°C was performed immediately and maintained until microclipping or endovascular embolization. Subsequently, rapid induction to 33°C ∼ 35°C was carried out and maintained for 3 to 5 days. Then, the patients underwent slow rewarming to 36°C ∼ 37°C and maintained at that temperature for a minimum of 48 hours.
Sixty patients (30 treated with TTM and 30 with standard treatment) were included in the study. At 3 months, a favorable prognosis (modified Rankin scale score 0 to 3) was significantly higher in the TTM group than in the control group (n = 14, 46.7% vs. n = 6, 20.0%, P = 0.028). Adjusted multivariate logistics regression analysis indicated that TTM (odds ratio = 0.20, 95% confidence interval: 0.05-0.77, P = 0.019) reduced the number of unfavorable prognoses 3 months after admission.
This study demonstrated the effectiveness and safety of TTM in patients with poor-grade aSAH, and its implementation improved neurological outcomes. Multicenter randomized controlled studies with a large number of patients are needed to confirm these observations.

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a \"worst-case\" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.

UNASSIGNED: To analyze the brain imaging features of high-altitude cerebral edema (HACE) using computed tomography (CT) and multi-sequence magnetic resonance imaging (MRI) and to explore its injury characteristics.
UNASSIGNED: We selected 30 patients with HACE diagnosed between January 2012 to August 2022 as the experimental group and 60 patients with dizziness on traveling from the plain to the plateau or from lower altitude to higher altitude in a short period of time as the control group. We collected general clinical data from the experimental group and classified it according to clinical symptoms. In both groups, we then performed a head CT and multi-sequence MRI (T1WI, T2WI, FLAIR, and DWI). Among them, nine patients with HACE were also scanned using susceptibility-weighted imaging (SWI). Finally, we analyzed the images.
UNASSIGNED: According to clinical symptoms, we divided the 30 cases of HACE into 12 mild cases and 18 severe cases. There was no significant difference in sex, age, leukocyte, neutrophil, or glucose content between mild and severe HACE. The sensitivity and specificity of the MRI diagnosis were 100 and 100%, respectively, while the sensitivity and specificity of the CT diagnosis were 23.3 and 100%, respectively. The distribution range of deep and juxtacortical white matter edema was significantly larger in severe HACE than in mild HACE (p < 0.001). The corpus callosum edema distribution range in severe HACE was significantly larger than that in mild HACE (p = 0.001). The ADC value of the splenium of the corpus callosum was significantly lower in severe HACE than in mild HACE (p = 0.049). In mild and severe HACE, the signal intensity of the DWI sequence was significantly higher than that of conventional MRI sequences (T1WI, T2WI, FLAIR) (p = 0.008, p = 0.025, respectively). In severe HACE, seven cases showed bilateral corticospinal tract edema at the thalamic level, and SWI showed cerebral microbleeds (CMBs) in five cases, especially in the corpus callosum.
UNASSIGNED: MRI has more advantages than CT in the evaluation of HACE, especially in the DWI sequence. The white matter injury of severe HACE is more severe and extensive, especially in the corpus callosum, and some CMBs and corticospinal tract edema may also appear.

BACKGROUND: To assess the association between relevant brain computed tomography (CT) parameters at different time and neurological prognosis in adult comatose survivors after cardiac arrest (CA).
METHODS: A total of 94 CA patients who underwent early and late CT scans (within 24 h and 24 h to 7 d respectively after CA) between January 2018 and April 2020 were enrolled in this retrospective study. According to the Cerebral Performance Category (CPC) score at hospital discharge, the patients were divided into either a good outcome (CPC 1-2) group or a poor-outcome group (CPC 3-5). The grey-to-white matter ratio (GWR) and the proportion of cerebrospinal fluid volume (pCSFV) were measured. In predicting poor outcomes, the prognostic performance of relevant CT parameters was evaluated, and the comparison analysis (expressed as the ratio of parameters in late CT to those in the early CT) of different CT time was conducted.
RESULTS: Totally 26 patients were in the good-outcome group, while 68 patients were in the poor-outcome group. The putamen density, GWR, and pCSFV in late CT were significantly lower in the poor-outcome group (P<0.05). The ratios of GWR and pCSFV in the poor-outcome group were significantly decreased according to comparison analysis of different CT time (P<0.05), while there was no significant difference in the ratio of putamen density. GWR-basal ganglia <1.18 in late CT showed the best predictive value. The ratio of pCSFV <0.98 predicted unfavorable neurological outcomes with a sensitivity of 65.9% and a specificity of 93.8% (P=0.001).
CONCLUSIONS: Brain CT performed >24 h after CA may be a good choice as a neuroimaging approach to evaluating prognosis. To predict neurological prognosis, comparison analysis of different CT time can be used as another promising tool in comatose CA survivors.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) and a leading cause of morbidity and mortality in children. We aim to assess the frequency, clinical characteristics, biochemical findings, and outcomes of DKA at the onset of T1DM in young children and adolescents.
METHODS: This retrospective cohort study analyzed the medical records of patients ≤ 16 years old seen in the emergency department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between April 2015 and June 2019. The severity of DKA was classified according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) criteria.
RESULTS: Out of 207 patients with T1DM, 53 presented with DKA as a new onset. The mean age was 8.51 ± 3.81 years, with the majority being 5-10 years old (52.8%). Polyuria (98.1%), polydipsia (86.8%), weight loss (62.3%), and abdominal pain and vomiting (45.3%) were the most frequent symptoms. Mean random blood glucose was 424.09 ± 108.67 mg/dL and mean venous pH was 7.15 ± 0.36 mmol/L. Of patients, 66% had no associated complications, 24.4% had hypokalemia, 20.8% developed hypoglycemia, and 18.9% developed hyperchloremic metabolic acidosis. One patient had cerebral edema and coma. Based on metabolic acidosis, 24.5% had mild DKA, an equal percentage had severe DKA, and 9.4% had moderate DKA. Of patients, 88.7% were admitted to the pediatric ward and 15.1% to the intensive care unit.
CONCLUSIONS: A total of 25% of patients diagnosed with T1DM below the age of 17 years presented with DKA. No permanent disabilities or deaths were reported. Forming a registry dedicated to T1DM is needed to follow up on these patients, especially among school-age children, as well as aid in the development of future research locally.

UNASSIGNED: In moyamoya disease (MMD) with direct or combined revascularization, the initially hemodynamic recipient features are likely one of the main causes of acute hemodynamic disruption. Previous studies have explored the relationship between recipient diameter or flow velocity and postoperative complications, but there are still no optimal selection criteria with multiple potential recipient vessels. Cerebral edema is one of the most common radiological manifestations in the acute postoperative period. This study assessed the hemodynamic characteristics of cortex vessels related to postoperative cerebral edema.
UNASSIGNED: All patients who had undergone direct or combined revascularization with preoperative digital subtraction angiography (DSA) between 2019 and 2021 were eligible for inclusion in this study. The application of DSA was performed and regular radiological examinations were employed after surgery. DSA was analyzed with the hemodynamic features within chosen recipient vessels. Cerebral edema was identified as a low-density image on CT or high signaling in the MRI T2 phase. The recipient hemodynamic characteristics and demographic presentation, as well as clinical data, were retrospectively analyzed in this study.
UNASSIGNED: A total of 103 patients underwent direct or combined revascularization with preoperative DSA. The mean age of this enrolled cohort was 44.31 ± 10.386 years, in which bilaterally involved MMD accounted for the main part. The preliminary correlation analysis found preoperative disease period (p = 0.078), recipients observed in angiography (p = 0.002), and surgery on the left (p = 0.097) may be associated with cerebral edema. The following regression analysis confirmed low occurrence of cerebral edema was accompanied by recipients observed in angiography (p = 0.003). After subdividing by flow direction and hemodynamic sources, the incidence rate of anterograde direction, anterior sources, and posterior sources were significantly lower than undetected recipients.
UNASSIGNED: Cerebral edema is a common radiological manifestation in MMDs after surgery. In this study, the observation in angiography reliably identifies a variety of physiological or pathological recipient detection, flow direction, and hemodynamic sources in patients with MMD after revascularization, which indicates the selection strategy of potential recipients and highlights the importance of recipient observability in DSA. Meanwhile, vascular conditions determined by recipient hemodynamics meditate the occurrence of postoperative cerebral edema.