Impact of Carotid Siphon Calcification on the Course and Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Carotid siphon calcification (CSC) serves as a marker of atherosclerosis and therefore may influence the outcome after subarachnoid hemorrhage (aSAH). We aimed to analyze the impact of CSC on neurological outcomes, ischemia, and vasospasm. METHODS: A total of 716 patients with aSAH were treated between December 2004 and June 2016 in our central European tertiary neurovascular care center in Essen, Germany. CSC was recorded using the Woodcock scale (grades 0-3) on a computed tomography scan. Study end points included an unfavorable outcome at 6 months post-aSAH (modified Rankin Scale score ≥4), vasospasm, and early cerebral ischemia (72 hours) and delayed cerebral ischemia (delayed cerebral ischemia; >72 hours) in the follow-up computed tomography scans. The associations were adjusted for patients' baseline characteristics and secondary complications. Finally, within a subgroup analysis, patients with and without daily aspirin intake after endovascular aneurysm occlusion were compared. RESULTS: Increasing grades of CSC were associated with lower rates of vasospasm in the anterior circulation. Severe CSC (grade 3) was independently related to the risk of an unfavorable outcome (adjusted odds ratio [aOR], 4.06 [95% CI, 1.98-8.33]; P<0.001) and early cerebral ischemia (aOR, 1.58 [95% CI, 1.03-2.43]; P=0.035) but not delayed cerebral ischemia (aOR, 1.08 [95% CI, 0.67-1.73]; P=0.763). In the aspirin subgroup analysis, the negative effect of severe CSC on functional outcome remained significant only in aSAH cases without aspirin (aOR, 5.47 [95% CI, 2.38-12.54]; P<0.001). In contrast, there was no association between severe CSC and unfavorable outcomes among individuals with daily aspirin intake (aOR, 0.84 [95% CI, 0.59-4.21]; P=0.603). CONCLUSIONS: Our data suggest CSC as a cerebrovascular risk factor resulting in higher rates of early cerebral ischemia and unfavorable outcomes after aSAH. However, by increasing arterial stiffness, CSC might lower the probability of vasospasm, which could explain the missing link between CSC and delayed cerebral ischemia. Additionally, aspirin intake seems to potentially mitigate the negative impact of CSC on aSAH outcome. Further investigations are needed to confirm the observations from the present study.

Impact of thyroid hormone replacement therapy on the course and functional outcome of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling. OBJECTIVE: We aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH). METHODS: SAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders. RESULTS: 109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41-0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28-0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38-1.26, p = 0.227). CONCLUSION: SAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH.

Comparing radiographic scores for prediction of complications and outcome of aneurysmal subarachnoid hemorrhage: Which performs best?

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high morbidity and mortality proceeding from the initial severity and following complications of aSAH. Various scores have been developed to predict these risks. We aimed to analyze the clinical value of different radiographic scores for prognostication of aSAH outcome. METHODS: Initial computed tomography scans (≤48 h after ictus) of 745 aSAH cases treated between January 2003 and June 2016 were reviewed with regard to Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), and Claassen, Barrow Neurological Institute (BNI), Hijdra, original Graeb and Fisher scale scores. The primary endpoints were development of delayed cerebral ischemia (DCI), in-hospital mortality and unfavorable outcome (modified Rankin Scale score >3) at 6 months after subarachnoid hemorrhage. Secondary endpoints included the different complications that can occur during aSAH. Clinically relevant cutoffs were defined using receiver-operating characteristic curves. The radiographic scores with the highest values for area under the curve (AUC) were included in the final multivariate analysis. RESULTS: The Hijdra sum score had the most accurate predictive value and independent associations with all primary endpoints: DCI (AUC 0.678, adjusted odds ratio [aOR] 2.83; p < 0.0001); in-hospital mortality (AUC 0.704, aOR 2.83; p < 0.0001) and unfavorable outcome (AUC 0.726, aOR 2.91; p < 0.0001). Multivariate analyses confirmed the independent predictive value of the radiographic scales for risk of decompressive craniectomy (SEBES and Fisher score), cerebral vasospasm (SEBES, BNI score and Fisher score) and shunt dependency (Hijdra ventricle score and Fisher score) after aSAH. CONCLUSIONS: Initial radiographic severity of aSAH was independently associated with occurrence of different complications during aSAH and the final outcome. The Hijdra sum score showed the highest diagnostic accuracy and robust predictive value for early detection of risk of DCI, in-hospital mortality and unfavorable outcome after aSAH.

Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.

Small intracranial aneurysms of the anterior circulation: A negligible risk?

BACKGROUND AND PURPOSE: According to the International Study of Unruptured Intracranial Aneurysms, small (<7 mm) unruptured intracranial aneurysms (IAs) of the anterior circulation (aC) carry a neglectable 5-year rupture risk. In contrast, some studies report frequencies of >20% of all ruptured IAs being small IAs of the aC. This contradiction was addressed in this study by analyzing the rates and risk factors for rupture of small IAs within the aC. METHODS: Of the institutional observational cohort, 1676 small IAs of the aC were included. Different demographic, clinical, laboratory, and radiographic characteristics were collected. A rupture risk score was established using all independent prognostic factors. The score performance was checked using receiver operating characteristic curve analysis. RESULTS: Of all registered small IAs of the aC, 20.1% were ruptured. The developed small IAs of the aC (SIAAC) score (range = -4 to +13 points) contained five major risk factors: IA location and size, arterial hypertension, alcohol abuse, and chronic renal failure. In addition, three putative protective factors were also included in the score: hypothyroidism, dyslipidemia, and peripheral arterial disease. Increasing rates of ruptured IA with increasing SIAAC scores were observed, from 0% (≤-1 points) through >50% (≥8 points) and up to 100% in patients scoring ≥12 points. The SIAAC score achieved excellent discrimination (area under the curveSIAAC  = 0.803) and performed better than the PHASES (Population,Hypertension, Age, Size of the aneurysm, Earlier SAH from another aneurysm, Site of aneurysm) score. CONCLUSIONS: Small IAs of the aC carry a considerable rupture risk. After external validation, the proposed rupture risk score might provide a basis for better decision-making regarding the treatment of small unruptured IAs of the aC.

The value of ventricular measurements in the prediction of shunt dependency after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Chronic hydrocephalus requiring shunt placement is a common complication of aneurysmal subarachnoid hemorrhage (SAH). Different risk factors and prediction scores for post-SAH shunt dependency have been evaluated so far. We analyzed the value of ventricle measurements for prediction of the need for shunt placement in SAH patients. METHODS: Eligible SAH cases treated between 01/2003 and 06/2016 were included. Initial computed tomography scans were reviewed to measure ventricle indices (bifrontal, bicaudate, Evans', ventricular, Huckman's, and third ventricle ratio). Previously introduced CHESS and SDASH scores for shunt dependency were calculated. Receiver operating characteristic analyses were performed for diagnostic accuracy of the ventricle indices and to identify the clinically relevant cut-offs. RESULTS: Shunt placement followed in 221 (36.5%) of 606 patients. In univariate analyses, all ventricular indices were associated with shunting (all: p<0.0001). The area under the curve (AUC) ranged between 0.622 and 0.662. In multivariate analyses, only Huckman's index was associated with shunt dependency (cut-off at ≥6.0cm, p<0.0001) independent of the CHESS score as baseline prediction model. A combined score (0-10 points) containing the CHESS score components (0-8 points) and Huckman's index (+2 points) showed better diagnostic accuracy (AUC=0.751) than the CHESS (AUC=0.713) and SDASH (AUC=0.693) scores and the highest overall model quality (0.71 vs. 0.65 and 0.67), respectively. CONCLUSIONS: Ventricle measurements are feasible for early prediction of shunt placement after SAH. The combined prediction model containing the CHESS score and Huckman's index showed remarkable diagnostic accuracy regarding identification of SAH individuals requiring shunt placement. External validation of the presented combined CHESS-Huckman score is mandatory.

Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy.

Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients' prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3-6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3-6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome.

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery.

PURPOSE: Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. METHODS: We included 93 female patients who underwent BC BM surgery in our institution (2008-2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. RESULTS: The median TI was 45.0 months (range: 9-334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47-61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02-0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46-12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III-IV of BC (aOR 4.82, 95% CI 1.10-21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09-98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35-15.40, p = 0.015). CONCLUSIONS: Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

The occurrence of neuropathic pain following surgery of brainstem cavernous malformations.

BACKGROUND AND PURPOSE: This study aimed to assess the occurrence and significance of postoperative neuropathic pain (NP) in patients with surgically treated brainstem cavernous malformations (BSCMs). METHODS: Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. The relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL) and life satisfaction was evaluated. RESULTS: Six out of 74 patients (8%) suffered from NP. The Leeds Assessment of Neuropathic Symptoms and Signs scores ranged from 12 to 16 (mean 14.28 ± 1.6). Visual analog scale pain was 5.2 ± 2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (life satisfaction) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient- and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of six patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results. CONCLUSION: Our findings may help to raise awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non-familial disease.

BACKGROUND AND PURPOSE: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. METHODS: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. RESULTS: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. CONCLUSIONS: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome.

OBJECTIVE: Occurrence of brain metastases BM is associated with poor prognosis in patients with breast cancer (BC). Magnetic resonance imaging (MRI) is the standard of care in the diagnosis of BM and determines further treatment strategy. The aim of the present study was to evaluate the association between the radiographic markers of BCBM on MRI with other patients' characteristics and overall survival (OS). METHODS: We included 88 female patients who underwent BCBM surgery in our institution from 2008 to 2019. Data on demographic, clinical, and histopathological characteristics of the patients and postoperative survival were collected from the electronic health records. Radiographic features of BM were assessed upon the preoperative MRI. Univariable and multivariable analyses were performed. RESULTS: The median OS was 17 months. Of all evaluated radiographic markers of BCBM, only the presence of necrosis was independently associated with OS (14.5 vs 22.5 months, p = 0.027). In turn, intra-tumoral necrosis was more often in individuals with shorter time interval between BC and BM diagnosis (< 3 years, p = 0.035) and preoperative leukocytosis (p = 0.022). Moreover, dural affection of BM was more common in individuals with positive human epidermal growth factor receptor 2 status (p = 0.015) and supratentorial BM location (p = 0.024). CONCLUSION: Intra-tumoral necrosis demonstrated significant association with OS after BM surgery in patients with BC. The radiographic pattern of BM on the preoperative MRI depends on certain tumor and clinical characteristics of patients.

Size does matter: The role of decompressive craniectomy extent for outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In previous studies in patients with traumatic brain injury and ischemic stroke, the size of decompressive craniectomy (DC) was reported to be paramount with regard to patient outcomes. We aimed to identify the impact of DC size on treatment results in individuals with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The extent of DC in 232 patients with SAH who underwent bifrontal or hemicraniectomy between January 2003 and December 2015 was analyzed using semi-automated surface measurements. The study endpoints were course of intracranial pressure (ICP) treatment after DC, occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months (defined as modified Rankin scale score >3). The associations of DC size with the study endpoints were adjusted for DC timing, patient age, clinical and radiographic severity of SAH, aneurysm location, and treatment modality. RESULTS: The mean DC surface area was 100.9 (±45.8) cm2 . In multivariate analysis, a large DC (>105 cm2 ) was independently associated with a lower risk of cerebral infarcts (adjusted odds ratio [aOR] 0.30, 95% confidence interval [CI] 0.16-0.56), in-hospital mortality (aOR 0.28, 95% CI 0.14-0.56) and unfavorable outcome (aOR 0.51, 95% CI 0.27-0.98). Moreover, SAH patients with a small DC size (<75 cm2 ) were more likely to require prolonged (>3 days, aOR 3.60, 95% CI 1.37-9.42) and enhanced (aOR 2.31, 95% CI 1.12-4.74) postoperative ICP treatment. CONCLUSION: This is the first study showing the impact of DC size on postoperative ICP control and patient outcome in the context of SAH; specifically, a large craniectomy flap (>105 cm2 ) might lead to better outcomes in SAH patients requiring decompressive surgery.

Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) as a radiographic marker of clinically relevant intracranial hypertension and unfavorable outcome after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The severity of early brain edema (EBE) after aneurysm rupture was reported to be strongly associated with the risk of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Using the recently developed Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), we analyzed the predictors of EBE and its impact on complications related to intracranial pressure (ICP) increase after SAH and on poor outcome. METHODS: All consecutive SAH cases treated between January 2003 and June 2016 with assessable SEBES were included (n = 745). Data on demographic characteristics, medical history, initial severity of SAH, need for conservative ICP treatment and decompressive craniectomy, occurrence of cerebral infarctions and unfavorable outcome at 6 months (modified Rankin scale score > 2) were collected. Univariable and multivariable analyses were performed. RESULTS: Younger age (<55 years; adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 2.28-4.38), female sex (aOR 1.64, 95% CI 1.16-2.31), poor initial clinical condition (World Federation of Neurosurgical Societies score 4-5; aOR 1.74, 95% CI 1.23-2.46), presence of intracerebral hemorrhage (aOR 1.63, 95% CI 1.12-2.36), hypothyroidism (aOR 0.60, 95% CI 0.37-0.98) and renal comorbidity (aOR 0.29, 95% CI 0.11-0.78) were independently associated with SEBES (scores 3-4). There was an independent association between SEBES 3-4 and the need for conservative ICP treatment (aOR 2.43, 95% CI 1.73-3.42), decompressive craniectomy (aOR 2.68, 95% CI 1.84-3.89), development of cerebral infarcts (aOR 2.24, 95% CI 1.53-3.29) and unfavorable outcome (aOR 1.48, 95% CI 1.0-2.17). CONCLUSIONS: SEBES is a reliable predictor of ICP-related complications and poor outcome of SAH. Our findings highlight the need for further research of the impact of patients' demographic characteristics and comorbidities on the severity of EBE after SAH.

Pathophysiology of Intracranial Aneurysms: COX-2 Expression, Iron Deposition in Aneurysm Wall, and Correlation With Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: The pathophysiology of development, growth, and rupture of intracranial aneurysms (IAs) is only partly understood. Cyclooxygenase 2 (COX-2) converts arachidonic acid to prostaglandin H2, which, in turn, is isomerized to prostaglandin E2. In the human body, COX-2 plays an essential role in inflammatory pathways. This explorative study aimed to investigate COX-2 expression in the wall of IAs and its correlation to image features in clinical (1.0T, 1.5T, and 3.0T) magnetic resonance imaging (MRI) and ultra-high-field 7T MRI. METHODS: The study group comprised 40 patients with partly thrombosed saccular IAs. The cohort included 17 ruptured- and 24 unruptured IAs, which had all been treated microsurgically. Formaldehyde-fixed paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 (Dako, Santa Clara, CA; Clone: CX-294). We correlated Perls Prussian blue staining, MRI, and clinical data with immunohistochemistry, analyzed using the Trainable Weka Segmentation algorithm. RESULTS: Aneurysm dome size ranged between 2 and 67 mm. The proportion of COX-2 positive cells ranged between 3.54% to 85.09%. An upregulated COX-2 expression correlated with increasing IA dome size (P=0.047). Furthermore, there was a tendency of higher COX-2 expression in most ruptured IAs (P=0.064). At all field strengths, MRI shows wall hypointensities due to iron deposition correlating with COX-2 expression (P=0.022). CONCLUSIONS: Iron deposition and COX-2 expression in IAs walls correlate with signal hypointensity in MRI, which might, therefore, serve as a biomarker for IA instability. Furthermore, as COX-2 was also expressed in small unruptured IAs, it could be a potential target for specific medical treatment.

TET2 promotor methylation and TET2 protein expression in pediatric posterior fossa ependymoma.

Pediatric posterior fossa ependymoma (PF) is one of the most common brain tumors in children. Recently, two subtypes of PF were identified. PF-A has a dismal prognosis and shows a hypermethylation phenotype, whereas PF-B shows a great genomic instability. The ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene (TET2) has been linked to the regulation of DNA methylation. We analyzed TET2 promotor methylation and protein expression to assess the role of TET2 in PF. Medical records of all PF cases treated in our institution between 1993 and 2015 were evaluated regarding tumor histology, grade, tumor location, gender, age, tumor recurrence, distant metastasis, survival and time to progression. Subsequently, we analyzed TET2 promotor methylation using methylation-specific polymerase chain reaction. TET2 protein expression was assessed using immunohistochemistry. Low TET2 expression was detected in seven of 17 cases. There was an association between low TET2 expression and tumor recurrence (P = 0.049). A TET2 promotor methylation was detected in five of 10 cases. There was no association between the TET2 promotor methylation with recurrence, tumor grade or gender. TET2 promotor methylation and low TET2 expression was detected in a subgroup of PF. Our data show an association between low TET2 expression and tumor recurrence in PF.

Laboratory biomarkers of delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review.

Delayed cerebral ischemia (DCI) is a severe complication of subarachnoid hemorrhage (SAH). Clinical and radiographic features of SAH may be helpful in identification of individuals prone to DCI. The aim of this systematic review was to analyze the present evidence on predictive value of blood and cerebrospinal fluid (CSF) biomarkers of DCI after SAH. We systematically searched in PubMed, Scopus, Web of Science, and Cochrane Library databases for publications before July 15, 2018, reporting correlations between blood/CSF biomarkers and occurrence of DCI and/or vasospasm in SAH patients. Included studies underwent quality assessment according to QUIPS and STARD guidelines. Level of evidence (I-IV) for each of tested biomarkers was assessed according to GRADE guidelines. Of 2181 unique records identified in four databases, 270 original articles and 5 meta-analyses were included to this review. Of 257 blood and CSF parameters analyzed in 16.914 SAH patients, there was no biomarker with positive association with DCI/vasospasm showing level I evidence. Twenty-one biomarkers achieved level II evidence and could be confirmed as predictive biomarkers. In this review, six single nucleotide polymorphisms (for EET metabolic pathways, COMT, HMGB1, ACE, PAI-1 promoter, and Hp genes) and 15 non-genetic biomarkers (pNF-H, ADAMTS13, NPY, Copeptin, HMGB1, GFAP, periostin, Tau, BNP, NT pro-BNP, hs-TnT, PA-TEGMA, MPV:PLT, NLR, and PLR) were selected as predictive DCI biomarkers. We propose that a panel analysis of the selected genetic and protein biomarker candidates would be needed for further validation in a large SAH cohort.

A rare case of a completely thrombosed bilobed giant intracranial aneurysm of the anterior cerebral artery with spontaneous parent vessel thrombosis: case report.

BACKGROUND: A huge spherical intracranial mass can sometimes be misdiagnosed, due to the lack of typical radiographic features. Thrombosed giant intracranial aneurysms (GIAs) are an uncommon but still a possible differential diagnosis that must be kept in mind to guarantee the best surgical approach and resection of the lesion. We describe an extremely rare case of a huge bifrontal mass mimicking a cystic echinococcosis, in which the surgery unveiled a completely thrombosed GIA of the left anterior cerebral artery (ACA). CASE PRESENTATION: A 61-year-old patient complained about intermittent weakness of the right leg, mild holocephalic headache, beginning cognitive deficits and lethargy. Magnetic resonance imaging (MRI) showed a huge partially calcified and bilobed frontal mass with peripheral edema. Based on a time-resolved angiography with interleaved Stochastic trajectories MRI (TWIST-MRI), a vascular origin of the lesion was considered unlikely. Therefore, the surgery was performed under the suspicion of a cystic echinococcosis but revealed a bilobed GIA of the left ACA with a parent vessel thrombosis. Although only a limited left frontal craniotomy was performed, a proximal control of the parent vessel could be ensured, and the aneurysm was successfully clipped. The patient showed postoperatively no new neurological deficits. CONCLUSIONS: Completely thrombosed GIAs with parent vessel thrombosis are rare lesions that might be misdiagnosed if typical radiographic features are missing. Thus, in case of an intracranial spherical mass with signs of intralesional hemorrhage and mural calcifications, presence of a completely thrombosed GIA should be considered as a possible differential diagnosis.

Risk Factors for and Clinical Consequences of Multiple Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Multiple intracranial aneurysms (MIAs) are common findings of cerebral angiographies; however, MIA prevalence varies in different patient cohorts. We sought to elucidate risk factors influencing MIA prevalence and the clinical consequences. METHODS: We systematically searched PubMed, Scopus, Embase, and Cochrane Library databases for publications before January 15, 2017, reporting MIA prevalence and risk factors. We used random-effects meta-analysis and multivariate regression analysis to assess the impacts of individual, study, and population characteristics. RESULTS: We included 174 studies reporting on MIA (mean overall prevalence, 20.1%; range, 2%-44.9%) in 134 study populations with 86 989 intracranial aneurysm (IA) patients enrolled between 1950 and 2015. Studies from Europe and North America (P<0.001) and more recent enrolment years (P=0.046) were independently associated with higher MIA prevalence. In meta-analysis, MIA correlated with female sex (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.4-1.8), higher patient age (>40 years; OR, 1.6; 95% CI, 1.14-2.25), arterial hypertension (OR, 1.51; 95% CI, 1.17-1.94), smoking (OR, 1.89; 95% CI, 1.37-2.6) and familial IA (OR, 2.02; 95% CI, 1.47-2.77), and formation of de novo (OR, 3.92; 95% CI, 1.95-7.87) and growth of initial IA (OR, 3.47; 95% CI, 1.87-6.45). Risk of subarachnoid hemorrhage in MIA patients was higher only in longitudinal studies from Japan and Korea (OR, 2.08; 95% CI, 1.46-2.96). CONCLUSIONS: Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for MIA. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.

Vasospasm-related complications after subarachnoid hemorrhage: the role of patients' age and sex.

BACKGROUND: Outcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients' age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups. METHODS: All patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6 months (modified Rankin scale > 2). RESULTS: Nine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55-74, and ≥ 75 years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75 years in females). Therefore, SAH females aged between 55 and 74 years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822). CONCLUSION: After acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74 years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause. CLINICAL TRIAL REGISTRATION NUMBER: DRKS, Unique identifier: DRKS00008749.

Impact of 2 years of COVID-19 pandemic on preterm birth: Experience from a tertiary center of obstetrics in western Germany.

OBJECTIVE: To compare preterm birth rates and reasons before and during the COVID-19-pandemic using a monocentric, retrospective study. METHODS: Univariate analysis identified differences in rates and reasons for preterm birth and neonatal outcomes between the pre-pandemic period (January 1, 2018 to December 31, 2019) and during the pandemic (January 1, 2020 to December 31, 2021) among all births at our tertiary obstetrical center, the University Hospital of Essen. RESULTS: The cohort consisted of 6086 deliveries with 593 liveborn preterm singletons. During the pandemic, the incidence of preterm birth decreased (10.7% vs. 8.6%; odds ratio [OR] 0.79; 95% confidence interval [CI] 0.66-0.93). Spontaneous preterm birth (43.2% vs. 52.3%; OR 1.47; 95% CI 1.05-2.03), and placenta accreta spectrum disorder (3.7% vs. 8.2%; OR 2.36; 95% CI 1.15-4.84) were more common reasons for preterm birth. Placental dysfunction was a less common reason (34.1% vs. 24.3%; OR 0.62; 95% CI 0.43-0.90). Incidences of preterm premature rupture of membranes (28.13% vs. 40.25%; OR 1.72; 95% CI 1.12-2.43) and oligo-/anhydramnios (3.98% vs. 7.88%; OR 2.06; 95% CI 1.02-4.21) increased. Iatrogenic preterm birth decreased (54.5% vs. 49.5%; OR 0.81; 95% CI 0.58-1.13). Stillbirth rates did not change significantly. Among term births, there were fewer spontaneous deliveries (71.0% vs. 65.8%; OR 0.78; 95% CI 0.69-0.88), and more elective (12.3% vs. 15.1%; OR 1.26; 95% CI 1.07-1.50) and unplanned (9.3% vs. 10.9%; OR 1.19; 95% CI 0.98-1.45) cesarean sections. During the pandemic, more term newborns were admitted to neonatal intensive care (1.4% vs. 2.5%; OR 1.86; 95% CI 1.20-2.88). CONCLUSION: Our results, in line with data from other high-income countries, suggest that the likely reason for the decreased preterm birth rates is the underdiagnosis of pregnancy complications.