Prognosticators of Functional Outcome After Supratentorial Minimally Invasive Intracranial Hemorrhage Evacuation With Tubular Retractor Systems.

BACKGROUND AND OBJECTIVES: Prognosticators of good functional outcome after minimally invasive surgical (MIS) intracranial hemorrhage (ICH) evacuation are poorly defined. This study aims to investigate clinical and radiographic prognosticators of poor functional outcome after MIS evacuation of ICH with tubular retractor systems. METHODS: Single-center retrospective review of adult (age ≥18 years) patients who underwent surgical evacuation of a spontaneous supratentorial ICH evacuation using tubular retractors from 2013 to 2022 was performed. Clinical and radiographic factors, such as antiplatelet/anticoagulant use, initial NIH Stroke Scale, ICH score, premorbid modified Rankin Scale (mRS), intraventricular hemorrhage (IVH) severity according to the modified Graeb scale, and preoperative/postoperative ICH volume, were collected. The main outcome was poor functional outcome, defined as mRS score of 4-6 within 1 year postoperatively. RESULTS: Eighty-eight patients were included. Clinical follow-up data were available for 64 (73%) patients. Of those, 43 (67%) had a poor functional outcome. On multivariate Cox regression, postoperative ICH volume ≥15 mL (hazard ratio [HR] = 2.46 [95% CI: 1.25-4.87]; P = .010) and higher modified Graeb score (HR = 1.04 [95% CI: 1-1.1]; P = .035] significantly increased the risk of poor functional outcome. Elevated postoperative ICH volume was predicted by the presence of lobar ICH (vs nonlobar, OR = 3.32 [95% CI: 1.01-11.55]; P = .043) and higher preoperative ICH volume (OR = 1.05 [1.02-1.08]; P < .001). A minimum of 60% ICH evacuation yielded an improvement in mRS 4-6 rates (HR 0.3 [95% CI: 0.1-0.8], P = .013). In patients without IVH and with a >80% ICH evacuation, the rate of mRS 4-6 was 42% compared with 67% in the whole patient sample ( P = .017). CONCLUSION: Increased IVH volumes and residual postoperative ICH volumes are associated with poor functional outcome after MIS ICH evacuation. Postoperative ICH volume was associated with lobar ICH location as well as preoperative ICH volume. These factors may help to prognosticate patient outcomes and improve selection criteria for MIS ICH evacuation techniques.

Assessment of Cerebral Autoregulation Using Invasive and Noninvasive Methods of Intracranial Pressure Monitoring.

BACKGROUND: Pulse amplitude index (PAx), a descriptor of cerebrovascular reactivity, correlates the changes of the pulse amplitude of the intracranial pressure (ICP) waveform (AMP) with changes in mean arterial pressure (MAP). AMP relies on cerebrovascular compliance, which is modulated by the state of the cerebrovascular reactivity. PAx can aid in prognostication after acute brain injuries as a tool for the assessment of cerebral autoregulation and could potentially tailor individual management; however, invasive measurements are required for its calculation. Our aim was to evaluate the relationship between noninvasive PAx (nPAx) derived from a novel noninvasive device for ICP monitoring and PAx derived from gold standard invasive methods. METHODS: We retrospectively analyzed invasive ICP (external ventricular drain) and non-invasive ICP (nICP), via mechanical extensometer (Brain4Care Corp.). Invasive and non-invasive ICP waveform morphology data was collected in adult patients with brain injury with arterial blood pressure monitoring. The time series from all signals were first treated to remove movement artifacts. PAx and nPAx were calculated as the moving correlation coefficients of 10-s averages of AMP or non-invasive AMP (nAMP) and MAP. AMP/nAMP was determined by calculating the fundamental frequency amplitude of the ICP/nICP signal over a 10-s window, updated every 10-s. We then evaluated the relationship between invasive PAx and noninvasive nPAx using the methods of repeated-measures analysis to generate an estimate of the correlation coefficient and its 95% confidence interval (CI). The agreement between the two methods was assessed using the Bland-Altman test. RESULTS: Twenty-four patients were identified. The median age was 53.5 years (interquartile range 40-70), and intracranial hemorrhage (84%) was the most common etiology. Twenty-one (87.5%) patients underwent mechanical ventilation, and 60% were sedated with a median Glasgow Coma Scale score of 8 (7-15). Mean PAx was 0.0296 ± 0.331, and nPAx was 0.0171 ± 0.332. The correlation between PAx and nPAx was strong (R = 0.70, p < 0.0005, 95% CI 0.687-0.717). Bland-Altman analysis showed excellent agreement, with a bias of - 0.018 (95% CI - 0.026 to - 0.01) and a localized regression trend line that did not deviate from 0. CONCLUSIONS: PAx can be calculated by conventional and noninvasive ICP monitoring in a statistically significant evaluation with strong agreement. Further study of the applications of this clinical tool is warranted, with the goal of early therapeutic intervention to improve neurologic outcomes following acute brain injuries.

Isofurans and Isoprostanes as Potential Markers of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study.

BACKGROUND: F2-Isoprostanes (F2-IsoPs) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications following subarachnoid hemorrhage (SAH). Platelet activation and vasoconstriction are attributed to these compounds. Elevated IsoF to F2-IsoPs ratios have been proposed as in vivo biomarkers of mitochondrial dysfunction. In this pilot study, we examined their performance as specific biomarkers for delayed cerebral ischemia (DCI) development following SAH. METHODS: Eighteen patients with SAH and six controls with normal neuroimaging and cerebrospinal fluid (CSF) analysis results underwent CSF sampling and abstraction of clinical, demographic, and laboratory data. Samples (two) of CSF were collected on day 1 and once on days 5-8 post bleed. F2-IsoP and IsoF assays were performed by gas chromatography/mass spectroscopy methods. Levels are expressed in median (interquartile range) for nonnormally distributed data. Repeated sample measurements were compared using the Wilcoxon signed-rank test, whereas the Mann-Whitney U-test was used for other nonnormally distributed data. RESULTS: Mean age was 61 ± 15.7 (SAH cases) versus 48 ± 10 (controls) years, and 80% of patients with SAH were women. Median Hunt and Hess score was 3 (2-4), and modified Fisher scale was 3 (3-4). Thirty nine percent of patients developed DCI. F2-IsoP were significantly higher in SAH cases than in controls [47.5 (30.2-53.5) vs. 26.0 (21.2-34.5) pg/mL]. No significant differences were observed in patients with or without DCI [41 (33.5-52) vs. 44 (28.5-55.5) pg/mL]. IsoF were elevated in the second CSF sample in nine patients but were undetectable in the remainder cases and all controls. Patients who developed DCI had significantly higher IsoF than those who did not [57 (34-72) vs. 0 (0-34) pg/mL]. Patients who met criteria for DCI had a significantly higher IsoF to F2IsoPs ratio on the late CSF sample [1.03 (1-1.38) vs. 0 (0-0.52)]. CONCLUSIONS: Preliminary findings from this study suggest that IsoF may represent a specific biomarker predicting DCI following SAH. Future studies to further explore the value of IsoF as biomarkers of secondary brain injury following SAH seem warranted.

Central Nervous System Fungal Infection-Related Stroke: A Descriptive Study of Mold and Yeast-Associated Ischemic Stroke.

OBJECTIVE: Central nervous system (CNS) ischemic events caused by fungal infections are rare, and clinical characteristics of these ischemic events are largely unknown. The objective of this manuscript is to highlight characteristics of fungal-related strokes and describe possible mechanistic differences between CNS mold and yeast infection-related strokes. METHODS: We report a single-center retrospective case series of all adult patients who presented with concurrent CNS fungal infection and stroke between 2010 and 2018. Patients believed to have a stroke etiology due to cardioembolic, atheroembolic, or strokes nontemporally associated with a CNS fungal infection and those with incomplete stroke workups were excluded from analysis. RESULTS: Fourteen patients were identified with ischemic stroke and concurrent CNS fungal infection without other known ischemic stroke etiology. Eight patients had a CNS yeast infection, and 6 had a CNS mold infection. All patients presented with recurrent or progressive stroke symptoms. Six patients were immune-compromised. Four patients admitted to intravenous drug use. All yeast infections were identified by cerebrospinal fluid culture or immunologic studies while all but one of the mold infections required identification by tissue biopsy. Leptomeningeal enhancement was only associated with CNS yeast infections, while basal ganglia stroke was only associated with CNS mold infections. CONCLUSION: Ischemic stroke secondary to CNS fungal infections should be considered in patients with recurrent or progressive cryptogenic stroke, regardless of immune status and cerebrospinal fluid profile. CNS yeast and mold infections have slightly different stroke and laboratory characteristics and should have a distinct diagnostic method. Depending on clinical suspicion, a thorough diagnostic approach including spinal fluid analysis and biopsy should be considered.

Rationale and Current Evidence for Testing Iron Chelators for Treating Stroke.

PURPOSE OF REVIEW: To discuss the mechanisms of iron regulation in the brain and the pathophysiological role of deregulation of iron homeostasis following a stroke, and to review existing evidence supporting the potential role of iron chelators in the treatment of ischemic and hemorrhagic stroke. RECENT FINDINGS: In recent years, accumulating evidence has highlighted the role of neuroinflammation in neurological injury after ischemic and hemorrhagic stroke, and that free iron is central to this process. Via the Fenton reaction, free iron catalyzes the conversion of superoxide ion and hydrogen peroxide into hydroxyl radicals, which promote oxidative stress. Advances in our understanding of changes in brain iron metabolism and its relationship to neuronal injury in stroke could provide new therapeutic strategies to improve the outcome of stroke patients. Pharmacological agents targeting brain iron regulation hold promise as potentially effective treatments in both ischemic and hemorrhagic stroke.

Effect of Age on Transcranial Doppler Velocities in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: It is not well understood whether age impacts transcranial Doppler (TCD) mean flow velocities (MFVs) in patients with aneurysmal subarachnoid hemorrhage (SAH) with or without delayed cerebral ischemia (DCI). The aim of our study was to analyze the behavior of TCD MFV during the first 7 days after SAH in patients of different ages and correlate them with the occurrence of DCI. METHODS: This study is a databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. We analyzed mean MFV of bilateral middle cerebral arteries (MCAs) in all patients enrolled in the study on days 1, 3 and 7. The correlation between age and TCD MFV was analyzed using a univariate linear regression model. RESULTS: Fifty-five patients were studied. Starting on the third day after the bleeding, increasing age was associated with slower MFVs. This trend was not affected by the interrogation of the right or left MCA. After correction to include only patients who developed DCI, the same findings persisted on days 3 and 7. CONCLUSION: Older age was correlated with a significant decrease on TCD velocities in patients with SAH, even after correction for patients who developed DCI.

Brain iron metabolism and brain injury following subarachnoid hemorrhage: iCeFISH-pilot (CSF iron in SAH).

INTRODUCTION: Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. METHODS: Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. RESULTS: A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. CONCLUSIONS: Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.

New developments in the treatment of intracerebral hemorrhage.

Understanding of intracerebral hemorrhage (ICH) pathophysiology and technological advances are now providing the opportunity to significantly reduce the morbidity and mortality associated with this debilitating type of stroke. As reviewed in this article, several ongoing clinical trials may transform the way this patient population is treated within the next 5 years. Although more research is needed, a new era for ICH management is beginning.

Binswanger disease--an update.

Binswanger disease is a common cause of vascular dementia in the elderly. This report up-dates the pathological and clinical findings, imaging identification emphasizing recent advances, and diagnosis of this condition.

Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results.

BACKGROUND AND PURPOSE: Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. METHODS: Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). CONCLUSIONS: This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Glucocorticoid therapy in neurologic critical care.

BACKGROUND: The pivotal role of inflammation and edema across the spectrum of central nervous system injury has driven extensive investigation into the therapeutic potential of glucocorticoids. OBJECTIVE: To review the experimental and clinical data relating to the efficacy and adverse effects of glucocorticoids in conditions encountered in critical neurologic and neurosurgical illness. DATA SOURCE: Search of MEDLINE and Cochrane databases, manual review of article bibliographies. DATA SYNTHESIS AND CONCLUSIONS: The efficacy of glucocorticoids is well established in ameliorating edema associated with brain tumors and in improving outcome in subsets of patients with bacterial meningitis. Despite frequently encouraging experimental results, clinical trials of glucocorticoids in ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury have not shown a definite therapeutic effect. The evidence supporting glucocorticoid therapy for spinal cord injury is controversial; however methylprednisolone continues to be widely employed in this setting.

Symptomatic and asymptomatic retinal embolism have different mechanisms.

PURPOSE: To investigate differences between symptomatic and asymptomatic retinal embolism regarding the frequency and source of cerebral microemboli. METHODS: Thirty-seven patients with transient monocular blindness or retinal infarction and 27 patients (29 eyes) with asymptomatic retinal embolism were prospectively enrolled. Patients underwent a transcranial Doppler study and noninvasive imaging of the cervical internal carotid arteries (ICA). The middle cerebral artery (MCA) ipsilateral to the affected eye was monitored for 30 minutes for microembolic signals (MES), which were saved and analyzed offline. Age-matched controls (n=15) had no history of retinal or brain ischemia, <50% ICA stenosis, and normal ophthalmologic examinations. RESULTS: MES were detected in 0/15 (0%) controls, 11/37 (30%) MCAs in the symptomatic group (P=0.02), and 3/29 (10%) MCAs in the asymptomatic group (P=0.54). Nine of 11 (82%) symptomatic eyes with MES had ipsilateral ICA stenosis of > or =50%, as compared with 0/3 (0%) eyes in the asymptomatic group with MES (P=0.03). Both MES and ICA stenosis of >50% were present in 9/37 (24%) cases in the symptomatic and in 0/29 (0%) cases of the asymptomatic group (P=0.0036). CONCLUSIONS: The frequency and potential source of cerebral microemboli in symptomatic and asymptomatic retinal embolism are different. Cerebral microemboli are more frequent in symptomatic patients and are associated with ICA stenosis.

Treatment of lipid disorders after stroke.

The efficacy of lipid disorder therapy for the primary and secondary prevention of coronary heart disease is established. There are, however, no completed studies specifically directed at reducing the risk of stroke with lipid therapy. Although observational cohort studies have failed to demonstrate an association between lipid disorders and stroke incidence, recently completed trials of subjects at risk for coronary heart disease have shown that statins and fibric acid derivatives reduce not only the risk of myocardial infarction and death, but also that of brain infarction and transient ischemic attacks. Lipid drugs are well tolerated and treatment complications are relatively low. It seems prudent to conclude that the stroke patient with an undesirable lipid profile who has a history of coronary heart disease should receive specific treatment for the lipid disorder. Recommendations are more problematic for stroke patients with lipid disorders but no history of coronary heart disease; most should receive therapy for primary prevention of heart disease. Lipid treatment trials focused on stroke risk reduction are urgently needed.