Neurophysiological Examinations as Adjunctive Tool to Imaging Techniques in Spontaneous Intracerebral Hemorrhage: IRONHEART Study

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease, which may lead to severe disability or even death. Although many factors may influence the outcome, neurophysiological examinations might also play a role in its course. Our aim was to examine whether the findings of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) can predict the prognosis of these patients.Methods: Between June 1 2017 and June 15 2021, 116 consecutive patients with ICH were enrolled prospectively in our observational study. Clinical examinations and non-Contrast computed tomography (NCCT) scan were done on admission for ICH; follow-up NCCT scans were taken at 14 ± 2 days and at 3 months ± 7 days after stroke onset. EEG and TMS examinations were also carried out.Results: Of the patients in the study, 65.5% were male, and the mean age of the study population was 70 years. Most patients had a history of hypertension, 50.8% of whom had been untreated. In almost 20% of the cases, excessive hypertension was measured on admission, accompanied with >10 mmol/L blood glucose level, whereas their Glasgow Coma Scale was 12 on average. Presence of blood in the ventricles or subarachnoid space and high blood and perihematomal volumes meant poor prognosis. Pathological EEG was prognostic of a worse outcome. With TMS examination at 14 days, it might be possible to estimate outcome in a univariate model and the absence, or reduction of the amplitude of the motor evoked potentials was associated with poor prognosis.Conclusion: Together with the clinical symptoms, the volume of bleeding, perihematomal edema (or their combined volume), and neurophysiological examinations like EEG and TMS play an important role in the neurological outcome of patients with ICH. This might affect the patients' rehabilitation plans in the future, since with the help of the examinations the subset of patients with potential for recovery could be identified.

Pretreatment of Sulfonylureas Reducing Perihematomal Edema in Diabetic Patients With Basal Ganglia Hemorrhage: A Retrospective Case-Control Study

Background: The sulfonylurea receptor 1–transient receptor potential melastatin 4 (SUR1–TRPM4) channel is a target key mediator of brain edema. Sulfonylureas (SFUs) are blockers of the SUR1–TRPM4 channel. We made two assessments for the pretreatment of SFUs: (1) whether it associates with lower perihematomal edema (PHE) and (2) whether it associates with improved clinical outcomes in diabetic patients who have acute basal ganglia hemorrhage.Methods: This retrospective case-control study was conducted in diabetic adults receiving regular SFUs before the onset of intracerebral hemorrhage (ICH). All of the patients received the clinical diagnosis of spontaneous basal ganglia hemorrhage. The diagnosis was confirmed by a CT scan within 7 days after hemorrhage. For each case, we selected two matched controls with basal ganglia hemorrhage based on admission time (≤5 years) and age differences (≤5 years), with the same gender and similar hematoma volume. The primary outcome was PHE volume, and the secondary outcomes were relative PHE (rPHE), functional independence according to modified Rankin Scale score and Barthel Index at discharge, and death rate in the hospital.Results: A total of 27 patients (nine cases and 18 matched controls), admitted between January 1, 2009 and October 31, 2018, were included in our study. There was no significant association between SFU patients and non-SFU patients on PHE volumes [15.4 (7.4–50.2 ml) vs. 8.0 (3.1–22.1) ml, p = 0.100]. Compared to non-SFU patients, the SFU patients had significantly lower rPHE [0.8 (0.7–1.3) vs. 1.5 (1.2–1.9), p = 0.006]. After we adjusted the confounding factors, we found that sulfonylureas can significantly reduce both PHE volume (regression coefficient: −13.607, 95% CI: −26.185 to −1.029, p = 0.035) and rPHE (regression coefficient: −0.566, 95% CI: −0.971 to −0.161, p = 0.009). However, we found no significant improvement in clinical outcomes at discharge, in the event of pretreatment of SFUs before the onset of ICH, even after we adjusted the confounding factors.Conclusion: For diabetic patients with acute basal ganglia hemorrhage, pretreatment of sulfonylureas may associate with lower PHE and relative PHE on admission. No significant effect was found on the clinical outcomes when the patients were discharged. Future studies are needed to assess the potential clinical benefits using sulfonylureas for ICH patients.

Perihematomal Edema After Intracerebral Hemorrhage: An Update on Pathogenesis, Risk Factors, and Therapeutic Advances

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.

Early Perihematomal Edema Expansion: Definition, Significance, and Association with Outcomes after Intracerebral Hemorrhage

Objective. To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). Methods. Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. Results. In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001 ). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70–10.60; p = 0.002 ). Conclusions. The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.

Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions.Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729).Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016–1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, β = 7.66 95% CI 0.26–15.07), black hole sign (P = 0.002, β = 18.93 95% CI 6.84–31.02), and initial ICH volume (P = 0.018, β = 0.20 95% CI 0.03–0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P &lt; 0.001, β = 21.62 95% CI 10.10–33.15).Conclusions: An increase of PHE volume &gt;7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.