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 post-thrombectomy isolated subarachnoid hemorrhage on neurological outcomes in patients with anterior ischemic stroke - a retrospective single-center observational study.

PURPOSE: We aimed to investigate the impact of post-thrombectomy isolated subarachnoid hemorrhage (i-SAH) and other types of intracranial hemorrhage (o-ICH) on patient's neurological outcomes. METHODS: Stroke data from 2018 to 2022 in a tertiary care center were retrospectively analyzed. Patients with large vessel occlusion from ICA to M2 branch were included. Post-thrombectomy intracranial hemorrhages at 24 h were categorized with Heidelberg Bleeding Classification. Neurological impairment of patients was continuously assessed at admission, at 24 h, 48 h and 72 h, and at discharge. Predictors of i-SAH and o-ICH were assessed. RESULTS: 297 patients were included. i-SAH and o-ICH were found in 12.1% (36/297) and 11.4% (34/297) of patients. Overall, NIHSS of i-SAH patients at discharge were comparable to o-ICH patients (median 22 vs. 21, p = 0.889) and were significantly higher than in non-ICH patients (22 vs. 7, p < 0.001). i-SAH often resulted in abrupt deterioration of patient's neurological symptoms at 24 h after thrombectomy. Compared to non-ICH patients, the occurrence of i-SAH was frequently associated with worse neurological outcome at discharge (median NIHSS increase of 4 vs. decrease of 4, p < 0.001) and higher in-hospital mortality (41.7% vs. 23.8%, p = 0.022). Regardless of successful reperfusion (TICI 2b/3), the beneficial impact of thrombectomy appeared to be outweighed by the adverse effect of i-SAH. Incomplete reperfusion and shorter time from symptom onset to admission were associated with higher probability of i-SAH, whereas longer procedure time and lower baseline ASPECTS were predictive for o-ICH occurrence. CONCLUSION: Post-thrombectomy isolated subarachnoid hemorrhage is a common complication with significant negative impact on neurological outcome.

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.

Duration of Intracranial Pressure Increase after Aneurysmal Subarachnoid Hemorrhage: Prognostic Factors and Association with the Outcome.

OBJECTIVE: A rupture of the intracranial aneurysm is frequently complicated, with an increase of intracranial pressure (ICP) requiring conservative and/or surgical treatment. We ana- lyzed the risk factors related to the duration of pathologic ICP increase and the relationship be- tween ICP burden and the outcome of subarachnoid hemorrhage (SAH). METHODS: Consecutive cases with aneurysmal SAH treated at our institution between 01/2003 and 06/2016 were eligible for this study. Different admission variables were evaluated to predict the duration of ICP increase >20 mmHg in univariate and multivariate analyses. The association of the ICP course with SAH outcome parameters (risk of cerebral infarction, in-hospital mortali- ty, and unfavorable outcome at 6 months defined as modified Rankin scale >3) was adjusted for major outcome-relevant confounders. RESULTS: Of 820 SAH patients, 378 individuals (46.1%) developed at least one ICP increase re- quiring conservative and/or surgical management after aneurysm treatment (mean duration: 1.76 days, range: 1 - 14 days). In the multivariable linear regression analysis, patients' age (unstand- ardized coefficient [UC]=-0.02, p <0.0001), World Federation of Neurosurgical Societies (WFNS) grade 4-5 at admission (UC=0.71, p <0.004), regular medication with the angiotensin- converting enzyme (ACE) inhibitors (UC=-0.61, p =0.01), and presence of intracerebral hemor- rhage (UC=0.59, p =0.002) were associated with the duration of ICP increase. In turn, patients with longer ICP elevations were at higher risk for cerebral infarction (adjusted odds ratio [aOR]=1.32 per-day-increase, p <0.0001), in-hospital mortality (aOR=1.30, p <0.0001) and un- favorable outcome (aOR=1.43, p <0.0001). SAH patients who underwent primary decompres- sive craniectomy (DC) showed shorter periods of ICP increase than patients with a secondary decompression (mean: 2.8 vs 4.9 days, p <0.0001). CONCLUSION: The duration of ICP increase after aneurysm rupture is a strong outcome predictor and is related to younger age and higher initial severity of SAH. Further analysis of the factors impacting the course of ICP after SAH is essential for the optimization of ICP management and outcome improvement.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies.

PURPOSE: Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. METHODS: A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. RESULTS: A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). CONCLUSION: This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Addressing Challenges in Cerebral Aneurysm Management: Strategies to Enhance Patient Outcomes.

We are pleased to present a Special Issue dedicated to addressing the current challenges in the management of cerebral aneurysms (CA) [...].

Histopathological Diagnosis of Primary Central Nervous System Lymphoma after Therapy with Corticosteroids or Anticoagulants.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p = 0.049), it was only necessary in less than 10% of the cases with preoperative (but discontinued) corticosteroid treatment. Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p = 0.015). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p = 0.02). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for early surgical intervention. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after the discontinuation of CS remains a case-by-case decision. The effect of anticoagulation and dual antiplatelet therapy on diagnostic accuracy might have been underestimated and should be examined closely in future investigations.

Treatment Strategies for Glioblastoma in the Elderly: What Should We Focus on Compared to Younger Patients.

(1) Background: Although the incidence of glioblastoma (GB) has a peak in patients aged 75-84 years, no standard treatment regimen for elderly patients has been established so far. The goal of this study was to analyze the outcome of GB patients ≥ 65 years to detect predictors with relevant impacts on overall survival (OS) and progression-free survival (PFS). (2) Methods: Medical records referred to our institution from 2006 to 2020 were analyzed. Adult GB patients with clinical data, postoperative MRI data, and ≥1 follow-up investigation after surgical resection were included. The complete cohort was divided into a younger (<65) and an elderly group (≥65 years). Multiple factors regarding OS and PFS were scanned using univariate and multivariable regression with p < 0.05. (3) Results: 1004 patients were included with 322 (61.0%) male individuals in the younger and 267 (56.1%) males in the older cohort. The most common tumor localization was frontal in both groups. Gross total resection (GTR) was the most common surgical procedure in both groups, followed by subtotal resection (STR) (145; 27.5%) in the younger group, and biopsy (156; 32.8%) in the elderly group. Multivariate analyses detected that in the younger cohort, MGMT promoter methylation and GTR were predictors for a longer OS, while MGMT methylation, GTR, and hypofractionated radiation were significantly associated with a longer OS in the elderly group. (4) Conclusions: Elderly patients benefit from surgical resection of GB when they show MGMT promoter methylation, undergo GTR, and receive hypofractionated radiation. Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.

Longitudinal impact of intracerebral low-grade glioma disease on health-related quality of life.

BACKGROUND: The aim of this study was to assess health-related quality of life (HRQOL) before and after treatment for intracerebral low-grade glioma. METHODS: Patients with low-grade glioma who underwent surgical tumor removal between 2012 and 2018 were eligible for this study. All individuals and their closest relatives received thorough preoperative (

The influence of radiological tumor growth pattern on sino­nasal health in pituitary adenomas.

Pituitary adenomas are one of the most common mass lesions of the brain and are associated with a reduced quality of life. While transnasal and transsphenoidal endoscopic approaches are considered to deliver similar recovery rates for sino-nasal health (SNH), the impact of radiological tumor growth patterns on SNH has not been evaluated. In the present study, the influence of radiological tumor growth on SNH was examined before and after endoscopic transsphenoidal tumor resection. Patient data were prospectively collected between August 1, 2016 and August 31, 2022. The Knosp and Hardy classifications were used to dichotomize pituitary adenoma lesions into low- and high-graded lesions. SNH was assessed shortly before surgery and at follow-up examinations 3-6 months after operation using the Sino-Nasal Outcome Test for Neurosurgery (SNOT-NC) questionnaire. Fully completed SNOT-NC questionnaires were collected before and after surgery from a total of 101 patients. Independent t-tests showed significantly higher rates of deterioration after surgery in patients with Knosp low-graded lesions compared with those with high-graded tumors for the SNOT-NC total score P=0.048, nasal discomfort P=0.034, sleep problems P=0.024 and visual impairment P=0.042. Pre- and post-operative comparisons for the Knosp low-graded tumor cohort showed an increase of nasal discomfort (P=0.004), while the Knosp high-graded tumor cohort reported decreased visual impairment (P=0.016) after surgery. Assessing the Hardy classification, increased nasal discomfort was reported in patients with high-graded infrasellar tumors after surgery (P=0.046). Growth characteristics of pituitary adenomas based on Knosp and Hardy classifications may influence SNH. Patients with less invasive lesions were revealed to be more prone to experiencing a decrease in SNH, which went beyond the assumed deterioration of 1-3 months. These findings indicate the importance of detailed information regarding SNH as part of every pre-operative patient briefing.

Risk factors for poor outcome after aneurysmal subarachnoid hemorrhage in patients with initial favorable neurological status.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating diagnosis. A poor outcome is known to be highly dependent on the initial neurological status. Our goal was to identify other parameters that favor the risk of complications and poor outcome in patients with aSAH and initially favorable neurologic status. METHODS: Consecutive aSAH cases treated at our hospital between 01/2003 and 06/2016 with the initial World Federation of Neurosurgical Societies grades I-III were included. Data on demographic characteristics, previous medical history, initial aSAH severity, and functional outcome after aSAH were collected. The study endpoints were the occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months after aSAH (modified Rankin scale > 3). RESULTS: In the final cohort (n= 582), the rate of cerebral infarction, in-hospital mortality, and unfavorable outcome was 35.1%, 8.1%, and 17.6% respectively. The risk of cerebral infarction was independently related to the presence of acute hydrocephalus (adjusted odds ratio [aOR]=2.33, p<0.0001), aneurysm clipping (aOR=1.78, p=0.003), and use of calcium channel blockers concomitant to nimodipine (aOR=2.63, p=0.002). Patients' age (>55 years, aOR=4.24, p<0.0001), acute hydrocephalus (aOR=2.43, p=0.036), and clipping (aOR=2.86, p=0.001) predicted in-hospital mortality. Baseline characteristics associated with unfavorable outcome at 6 months were age (aOR=2.77, p=<0.0001), Fisher grades III-IV (aOR=2.81, p=0.016), acute hydrocephalus (aOR=2.22, p=0.012), clipping (aOR=3.98, p<0.0001), admission C-reactive protein>1mg/dL (aOR=1.76, p=0.035), and treatment intervals (aOR=0.64 per-5-year-intervals, p=0.006). CONCLUSIONS: Although cerebral infarction is a common complication in aSAH individuals with favorable initial clinical condition, >80% of these patients show favorable long-term outcome. The knowledge of outcome-relevant baseline characteristics might help to reduce the burden of further complications and poor outcome in aSAH patients who tolerated the initial bleeding event well.

The role of previous medical history and secondary complications for the outcome of aneurysmal subarachnoid hemorrhage in elderly patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) presents a devastating diagnosis for elderly individuals, resulting in high morbidity and mortality rates. The aim of the study was to analyze the impact of medical history and complications during SAH on the outcome of elderly patients. METHODS: Consecutive SAH cases aged ≥ 65 years old treated in our hospital between 01/2003 and 06/2016 were included (n = 218). Data on comorbidities, previous medication, initial severity, secondary complications, and the outcome were collected. Study endpoints were occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months after SAH. RESULTS: Cerebral infarcts were documented in 111 (51.2 % ) individuals. Multivariate analysis showed that angiographic vasospasm caused an increase (adjusted odds ratio [aOR] = 3.11, p = 0.022) in the risk of infarction, whereas aspirin treatment decreased (aOR = 0.25, p = 0.001) the risk of infarction. In turn, increasing age (aOR = 1.11, p = 0.002), intracranial hypertension (>20 mmHg, aOR = 3.32, p = 0.006) and acute kidney failure (aOR = 6.65, p = 0.035) during SAH were independently related to the risk of in-hospital mortality (n = 50; 22.9 % ). Finally, patients' age (aOR = 1.09, p = 0.022), high initial SAH burden (WFNS ≥ 4: aOR = 7.5, p < 0.0001; intraventricular hemorrhage: aOR = 4.38, p = 0.007), aneurysm clipping (aOR = 4.07, p = 0.018), and intracranial hypertension during SAH (aOR = 4.08, p = 0.006) were independent predictors of unfavorable outcome (n = 106/192; 55.5 % ). Previous medical history showed no negative impact on the severity, course and outcome of SAH. CONCLUSION: About half of elderly SAH patients face poor outcomes after aneurysm securing. The initial severity of and complications during SAH are the major contributors to poor treatment results. Our findings might help to optimize the treatment strategies.

Safety and function of programmable ventriculo-peritoneal shunt valves: An in vitro 7 Tesla magnetic resonance imaging study.

OBJECTIVE: The quantity of ultra-high field MRI neuroimaging studies has rapidly increased. This study tests function, safety, and image artifacts of two frequently implanted programmable ventriculo-peritoneal (VP) shunt valves in a 7T MRI system. METHODS: All tests were performed using a whole-body 7T MRI system. Three proGAV 2.0 and 3 CODMAN CERTAS® Plus programmable VP-shunt valves were tested in three steps. 1) Deflection angle tests close to the bore opening at the location of a static magnetic field gradient of 3-5 T/m. 2) Valves were fixed on a spherical phantom in 3 positions (a. lateral, b. cranial, c. cranial with 22.5° tilt anteriorly) and assessed for keeping the programmed pressure setting and reprogrammability. 3) Valves were fixed on the phantom and positioned lateral in a radiofrequency head coil. MRI scans were performed for both models, including MPRAGE, GRE and SE sequences. RESULTS: Deflection angles were moderate (13°, 14°, 13°) for the proGAV valves and close to critical (43°, 43°, 41°) for the CODMAN valves at the test location. Taking a scaling factor of 2-3 for the maximum spatial magnetic field gradient accessible to a patient within the magnet bore into account renders both valves MR unsafe regarding ferromagnetic attraction. The proGAV valves kept the pressure settings in all positions and were reprogrammable in positions a. and b. In position c., reprogrammability was lost. The CODMAN valves changed their pressure setting and reprogrammability was lost in all positions. MR image signal homogeneity was unaltered in the phantom center, artifacts limit the assessability of structures in close vicinity to the valves. CONCLUSION: Both tested programmable VP-shunt valves are MR unsafe for 7T systems. Novel programming mechanisms using permanent magnets with sufficient magnetic coercivity or magnet-free mechanisms may allow the development of programmable VP-shunt valves that are conditional for 7T MR systems.

Natural course of cerebral and spinal cavernous malformations: a complete ten-year follow-up study.

Knowledge of the bleeding risk and the long-term outcome of conservatively treated patients with cavernous malformations (CM) is poor. In this work, we studied the occurrence of CM-associated hemorrhage over a 10-year period and investigated risk factors for bleeding. Our institutional database was screened for patients with cerebral (CCM) or intramedullary spinal cord (ISCM) CM admitted between 2003 and 2021. Patients who underwent surgery and patients without completed follow-up were excluded. Analyses were performed to identify risk factors and to determine the cumulative risk for hemorrhage. A total of 91 CM patients were included. Adjusted multivariate logistic regression analysis identified bleeding at diagnosis (p = 0.039) and CM localization to the spine (p = 0.010) as predictors for (re)hemorrhage. Both risk factors remained independent predictors through Cox regression analysis (p = 0.049; p = 0.016). The cumulative 10-year risk of bleeding was 30% for the whole cohort, 39% for patients with bleeding at diagnosis and 67% for ISCM. During an untreated 10-year follow-up, the probability of hemorrhage increased over time, especially in cases with bleeding at presentation and spinal cord localization. The intensity of such increase may decline throughout time but remains considerably high. These findings may indicate a rather aggressive course in patients with ISCM and may endorse early surgical treatment.

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge.

A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients' treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Outcome after conservative or surgical treatment for new-onset epilepsy in children with cerebral cavernous malformation.

OBJECTIVE: This study aimed to investigate and compare the outcome of conservatively or surgically treated children with cerebral cavernous malformation (CCM) and new-onset CCM-related epilepsy (CRE) during a 5-year period. METHODS: In this observational monocentric cohort study, data were collected ambispectivley. Our database was screened for CCM patients treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging dataset, clinical baseline characteristics, and diagnosis of new-onset CRE were included. Definite seizure control was classified as International League Against Epilepsy class <2. Functional outcome was assessed using the modified Rankin Scale score. CRE patients were separated into two groups according to their treatment modality. Seizure control, intake of antiseizure medication, and functional outcomes were assessed. Systematic literature research was performed to identify other cases of new-onset CRE in children and to compare the collected data with published data. RESULTS: Thirty-nine pediatric CRE patients were analyzed. A total of 18 (46.1%) patients were conservatively treated, while 21 (53.8%) underwent surgical CCM removal. While the functional outcome was similar in both groups at the last follow-up, definite seizure control was better in the surgical group (77.8%) than in the conservative group (25.0%) both after 5-years of follow-up (p = 0.038), and at last follow-up with 85.7% versus 50% respectively (p = 0.035). We found substantially higher rates of discontinuation of antiseizure medication at the last available follow-up in patients undergoing surgical resection (p = 0.009). The systematic literature review identified 4 studies with a total of 30 additional children with early onset CRE. CONCLUSION: Surgical treatment of pediatric patients with new-onset CRE had higher rates of complete seizure control and early discontinuation of antiseizure medication than conservative treatment. Neurological outcomes of patients managed surgically or conservatively were comparable. These results encourage early surgical management of children with CRE even in the absence of pharmacoresistant epilepsy, but randomized control trials are urgently needed for further decision-making.

Location of Recurrences after Trimodality Treatment for Glioblastoma with Respect to the Delivered Radiation Dose Distribution and Its Influence on Prognosis.

BACKGROUND: While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor. METHODS: All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern. RESULTS: Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% (p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar (p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence (p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose (p < 0.0001). Survival from recurrence was improved after complete resection (p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials. CONCLUSIONS: Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted.

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.

Morphometric Study of the Initial Ventricular Indices to Predict the Complications and Outcome of Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Acute hydrocephalus is a common complication in patients with aneurysmal subarachnoid hemorrhage (SAH). Several ventricular indices have been introduced to enable measurements of ventricular morphology. Previously, researchers have showed their diagnostic value for various neurological disorders. In this study, we evaluated the association between ventricular indices and the clinical course, occurrence of complications and outcome of SAH. METHODS: A total of 745 SAH patients with available early admission computed tomography scans were included in the analyses. Six ventricular indices (bifrontal, bicaudate, ventricular and third ventricle ratios and Evans' and Huckman's indices) were measured. Primary endpoints included the occurrence of cerebral infarctions, in-hospital mortality and a poor outcome at 6 months. Secondary endpoints included different adverse events in the course of SAH. Clinically relevant cut-offs for the indices were determined using receiver operating curves. Univariate analyses were performed. Multivariate analyses were conducted on significant findings in a stepwise backward regression model. RESULTS: The higher the values of the ventricular indices were and the older the patient was, the higher the WFNS and Fisher's scores were, and the lower the SEBES score was at admission. Patients with larger ventricles showed a shorter duration of intracranial pressure increase > 20 mmHg and required decompressive craniectomy less frequently. Ventricular indices were independently associated with the parameters of inflammatory response after SAH (C-reactive protein in serum and interleukin-6 in cerebrospinal fluid and fever). Finally, there were independent correlations between larger ventricles and all the primary endpoints. CONCLUSIONS: The lower risk of intracranial pressure increase and absence of an association with vasospasm or systemic infections during SAH, and the poorer outcome in individuals with larger ventricles might be related to a more pronounced neuroinflammatory response after aneurysmal bleeding. These observations might be helpful in the development of specific medical and surgical treatment strategies for SAH patients depending on the initial ventricle measurements.

Regular medication as a risk factor for intracranial aneurysms: A comparative case-control study.

Background: Previous medical history strongly contributes to the genesis of intracranial aneurysms (IA). A possible impact of regular medication on the occurrence of abdominal aortic aneurysms has been reported. Aim: To evaluate the value of regular medication on the risk of development and rupture of IA. Methods: Data on medication use and related comorbidities were obtained from the institutional IA registry. A 1:1 age- and sex-matched patient sample was collected from the population-based Heinz Nixdorf Recall Study with individuals from the same area. Results: In the analysis comparing IA cohort (n = 1960) with the matched normal population (n = 1960), the use of statins (adjusted odds ratio, 1.34 [95% confidence interval 1.02-1.78]), antidiabetics (1.46 [1.08-1.99]), and calcium channel blockers (1.49 [1.11-2.00]) was independently associated with higher risk of IA, whereas uricostatics (0.23 [0.14-0.38]), aspirin (0.23 [0.13-0.43]), beta-blockers (0.51 [0.40-0.66]), and angiotensin-converting enzyme inhibitors (0.38 [0.27-0.53]) were related to lower risk of IA. In the multivariable analysis within the IA cohort (n = 2446), SAH patients showed higher drug exposure with thiazide diuretics (2.11 [1.59-2.80]), but lower prevalence of remaining antihypertensive medication-beta-blockers (0.38 [0.30-0.48]), calcium channel blockers (0.63 [0.48-0.83]), angiotensin-converting enzyme inhibitors (0.56 [0.44-0.72]), and angiotensin-1 receptor blockers (0.33 [0.24-0.45]). Patients with ruptured IA were less likely to be treated with statins (0.62 [0.47-0.81]), thyroid hormones (0.62 [0.48-0.79]), and aspirin (0.55 [0.41-0.75]). Conclusions: Regular medication might impact the risks related to the development and rupture of IA. Further clinical trials are required to clarify the effect of regular medication on IA genesis.