Link between both infratentorial and supratentorial intracranial pressure burdens and final outcome in patients with infratentorial brain injury.

OBJECTIVE: Increased intracranial pressure (ICP) is most likely not being transmitted uniformly within the cranium. The ICP profiles in the supra- and infratentorial compartments remain largely unclear. Increased ICP in the cerebellum, however, is insufficiently captured by supratentorial ICP (ICPsup) monitoring due to compartmentalization through the tentorium. The authors hypothesized that additional infratentorial ICP (ICPinf) monitoring can be clinically valuable in selected patients. The aims of this study were to demonstrate the safety and feasibility of ICPinf monitoring and to investigate the influence of the ICPinf on clinical outcome in a real-world setting. METHODS: Fifteen consecutive patients with posterior fossa (PF) lesions requiring surgery and anticipated prolonged neurointensive care between June 2019 and December 2021 were included. Simultaneous ICPsup and ICPinf were recorded. ICP burden was defined as a 15-minute interval with a mean ICP > 22 mm Hg. The Glasgow Outcome Scale score was assessed after 3 months. RESULTS: The mean ICPinf was substantially higher compared with ICPsup throughout the entire period of ICP recording (16.08 ± 4.44 vs 10.74 ± 3.6 mm Hg, p < 0.01). ICPinf was significantly higher in patients with unfavorable outcome when compared with those with favorable outcome (mean 17.2 ± 4.1 vs 11.4 ± 3.5 mm Hg, p < 0.05). Patients with unfavorable outcome showed significantly higher ICPinf burden compared with those with favorable outcome (mean 40.6 ± 43.8 vs 0.3 ± 0.4 hours, p < 0.05). Neither absolute ICPsup nor ICPsup burden was significantly associated with unfavorable outcome (p = 0.13). No monitoring-associated complications occurred. CONCLUSIONS: Supplementary ICPinf monitoring is safe and reliable. There is a significant transtentorial pressure gradient within the cranium showing elevated ICPs in the PF. Elevated ICP levels in the PF were strongly associated with unfavorable neurological outcome irrespective of ICPsup values.

Time Course of Metabolomic Alterations in Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage.

Object: The aim of this study was to investigate metabolite levels in cerebrospinal fluid (CSF) in their time-dependent course after aneurysmal subarachnoid hemorrhage (aSAH) comparing them to patients harboring unruptured intracranial aneurysms. Methods: Eighty CSF samples of 16 patients were analyzed. The study population included patients undergoing endovascular/microsurgical treatment of ruptured intracranial aneurysms (n = 8), which were assessed for 9 days after aSAH. Control samples were collected from the basal cisterns in elective aneurysm surgery (n = 8). The CSF samples were consecutively collected with extraventricular drain (EVD) placement/intraoperatively, 6 h later, and daily thereafter (day 1-9). The endogenous metabolites were analyzed with a targeted quantitative and quality controlled metabolomics approach using the AbsoluteIDQ®p180Kit. Differences inbetween timepoints and compared to the control group were evaluated. Results: Numerous alterations of amino acid (AA) levels were detected within the first hours after bleeding. The highest mean concentrations occurred 1 week after aSAH. AA levels were continuously increasing over time starting 6 h after aSAH. Taurine concentration was highest briefly after aSAH starting to decrease already after 6 h (vs. day 1-9, p = 0.02). The levels of sphingomyelins/ phosphatidylcholines/ lysophosphatidylcholines/mono-unsaturated fatty acid chain were highly elevated on day 0 (compared to other timepoints or controls, p < 0.01) and decreased over the next several days to concentrations comparable to the control group. Carnitine concentrations were decreased after SAH (vs. day 7, p < 0.01), while they recovered within the next day. The Fischer ratio of branched-chain AA to aromatic AA was lowest immediately after SAH and increased in 7 days (p < 0.001). Conclusion: AA levels in CSF increased overtime and often differ from patients without SAH. There was a peak concentration of structural AA within the first 6 h after aneurysm treatment. Time-dependent alterations of CSF metabolites and compounds may elucidate pathophysiological processes after aSAH, providing potential predictors assessed non-invasively by routine lab testing.

Transcallosal, transchoroidal clipping of a hypothalamic collateral vessel aneurysm in Moyamoya disease.

Peripheral collateral vessel aneurysms in Moyamoya disease (MMD) remain difficult to treat due to their deep location, small size, and vascular fragility. We report the case of an aneurysm localized in the hypothalamus, which was rapidly increasing in size with repeated hemorrhage despite revascularization surgery. Aneurysm clipping was performed to prevent further progress and rerupture with favorable outcome. To our best knowledge, this is the first description of a hypothalamic aneurysm in MMD being clipped via a transcallosal, transchoroidal approach through the third ventricle.

IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice.

Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src homology 2-containing inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation. Intravenous immunoglobulin (IVIG) is a FDA-approved drug containing IgG. We hypothesized that IVIG will attenuate the ICH-induced mast cell activation via FcγRIIB/SHIP1 pathway, resulting in a decrease of brain inflammation, protection of the blood-brain-barrier, and improvement of neurological functions after ICH. To prove this hypothesis we employed the ICH collagenase mouse model. We demonstrated that while ICH induced mast cell activation/degranulation, IVIG attenuated post-ICH mast cell activation. Mast cell deactivation resulted in reduced inflammation, consequently attenuating brain edema and improving of neurological functions after ICH. Furthermore using siRNA-induced in vivo knockdown approach we demonstrated that beneficial effects of IVIG were mediated, at least partly, via SHIP1/PIP3 pathway. We conclude that IVIG treatment represents a promising therapeutic approach potentially able to decrease mortality and morbidity after ICH in experimental models.

"I am not afraid of death"-a survey on preferences concerning neurosurgical interventions among patients over 75 years.

INTRODUCTION: Treatment decisions in elderly patients with traumatic brain injury (TBI) are mainly determined by trauma severity and patient age. The aim of this study was to explore personal preferences of potential patients regarding life-prolonging neurosurgical interventions by interviewing ambulatory, autonomous elderly people. METHODS: One hundred consecutive patients older than 75 years frequenting the outpatient clinic of the Department of Neurosurgery were interviewed about their attitudes regarding the hypothetical case of an 81-year-old patient with TBI and a space-occupying acute subdural hematoma (aSDH) using a 21-point questionnaire. RESULTS: Fifty-one percent of the consulted persons declined life-prolonging surgical measures. If surgery was associated with physical disability, 68% of the people wished no surgery. In case of cognitive impairment after surgery, 91% were against any surgical intervention. The majority feared being a burden to relatives (76%) and becoming unable to master an independent life (75%). Four-fifths of the interviewed patients (82%) were not afraid of death. CONCLUSIONS: The majority of elderly patients only consent to surgical measures if no relevant disabilities are involved and if they can return to their previous life. These findings need consideration in case of life-threatening neurosurgical emergencies as well as in the surgical treatment of elderly patients in general.

Pharmacological Management Options to Prevent and Reduce Ischemic Hemorrhagic Transformation.

BACKGROUND: Hemorrhagic transformation (HT) is a common and natural complication after acute ischemic stroke. The only FDA-approved treatment so far for acute ischemic stroke is rapid reperfusion with recombinant tissue plasminogen activator (rtPA). Although it has been shown to exaggerate the risk and severity of HT and to be associated with increased morbidity and mortality. OBJECTIVE: The aim of this review is to discuss the multifactorial pathophysiology of hemorrhagic transformation, promising interventional targets, and pharmacological treatment options. RESULTS AND CONCLUSION: Understanding HT is essential to restore cerebral blood flow to ischemic brain by reperfusion therapy without causing this complication and additional brain injury. Therefore methods for the prevention and treatment of HT are needed. Although experimental studies showed promising results, clinical translation remains unsatisfactory to date.

Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy.

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future.