First neurological symptoms in degenerative cervical myelopathy: does it predict the outcome?

PURPOSE: Degenerative cervical myelopathy (DCM) is the most common non-traumatic cause of spinal cord dysfunction. Prediction of the neurological outcome after surgery is important. The aim of this study was to analyze the relationship between first symptoms of DCM and the neurological outcome after surgery. METHODS: A retrospective analysis over a period of 10 years was performed. First symptoms such as cervicobrachial neuralgia, sensory and motor deficits and gait disturbances were evaluated regarding the postoperative neurological outcome. The modified Japanese Orthopedic Association Score (mJOA Score) was used to evaluate neurological outcome. RESULTS: In total, 411 patients (263 males, 64%) with a median age of 62.6 ± 12.1 years were included. Cervicobrachial neuralgia was described in 40.2%, gait disturbance in 31.6%, sensory deficits in 19% and motor deficits in 9.2% as first symptom. Patients with cervicobrachial neuralgia were significantly younger (median age of 58 years, p = 0.0005) than patients with gait disturbances (median age of 68 years, p = 0.0005). Patients with gait disturbances and motor deficits as first symptom showed significantly lower mJOA Scores than other patients (p = 0.0005). Additionally, motor deficits and gait disturbance were negative predictors for postoperative outcome according to the mJOA Score. CONCLUSION: Motor deficits and gait disturbances as the first symptom of DCM are negative predictors for postoperative neurological outcome. Nevertheless, patients with motor deficits and gait disturbance significantly profit from the surgical treatment despite poor preoperative mJOA Score.

HER2 Receptor Conversion Is a strong Survival Predictor in Patients with Breast Cancer Brain Metastases.

BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs). METHODS: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics. RESULTS: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival. CONCLUSIONS: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Surgery for Degenerative Cervical Myelopathy: What Really Counts?

STUDY DESIGN: Retrospective study (data analysis). OBJECTIVE: The purpose of this study was to assess the role of different factors on postoperative outcome of patients with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Ongoing degenerative changes of DCM lead to progressive neurological deficits. The optimal timing of surgical treatment is still unclear, especially in patients with mild DCM. METHODS: Patients with DCM treated in our clinic between 2007 and 2016 were retrospectively analyzed. Pre- and postoperative neurological function was assessed by the modified Japanese Orthopaedic Association Score (mJOA Score) at different stages. The minimum clinically important difference (MCID) was used to evaluate the improvement after surgery. The comorbidities were recorded using the Charlson Comorbidity Index (CCI). Possible associations between age, sex, CCI, preoperative symptoms duration, high signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) with mJOA Score and MCID were analyzed using univariate analysis and multivariate regression models. Additionally, subgroup analysis was performed according to the severity of DCM (mild: mJOA Score ≥15 points; moderate: mJOA Score of 12-14 points; and severe: mJOA Score <12 points). RESULTS: The mean age of the final cohort (n = 411) was 62.6 years (range: 31-96 years), 36.0% were females. High SI on T2-weighted MRI was detected in 60.3% of the cases. In the multivariate analysis, patients' age (P = 0.005), higher CCI (P = 0.001), and presence of high SI on T2-weighted MRI (P = 0.0005) were associated independently with lower pre- and postoperative mJOA Score and postoperative MCID. Subgroup analysis revealed age and high SI on T2-weighted MRI as predictors of pre- and postoperative mJOA. However, symptom duration did not influence neurological outcome according to the severity of DCM. CONCLUSION: Surgery for DCM leads to significant functional improvement. However, better outcome was observed in younger individuals with lower CCI and absence of radiographic myelopathy signs. Therefore, DCM surgery, particularly before occurrence of high SI on MRI, seems to be essential for postoperative functional improvement regardless the above-mentioned confounders.Level of Evidence: 3.

Predictors of catheter-associated meningitis in pediatric patients after brain tumor surgery: A 10-year single center experience.

OBJECTIVE: To evaluate the incidence of catheter-associated meningitis (CAM) in a pediatric population receiving brain tumor surgery, and to identify the major risk factors involved. METHODS: We retrospectively analyzed the medical and radiological records of 205 pediatric patients who received 251 external ventricular drains (EVDs) between January 2008 and December 2017. All patients less than 18 years old who underwent cerebrospinal fluid (CSF) diversion in the course of brain tumor surgery were included. Patients with central nervous system infection (CNS) at the time of EVD insertion were excluded. RESULTS: A total of 99 patients receiving 107 EVDs met the study selection criteria. Among this population, the incidence of CAM was 19.2%. Median time-to-infection was 5 days. CAM prolonged the period of drainage in 57.9% of the cases. An extended ICU stay (>3 days) was statistically significantly associated with the occurrence of CAM. In the multivariate analysis, the presence of a high-grade CNS tumor was a predictor of an extended intensive care unit (ICU) stay. Furthermore, CSF leakage along the catheter tunnel was an independent predictor of CAM. CONCLUSION: Our data confirms CAM as a significant complication in the acute treatment of hydrocephalus associated with pediatric brain tumors. To limit the incidence of CAM, measures must be taken to prevent CSF leakage, particularly among patients with high-grade CNS tumors that are likely to stay longer in the ICU and need prompt postoperative radiotherapy and oncological treatment.

The predominant expression of cancer stem cell marker ALDH1A3 in tumor infiltrative area is associated with shorter overall survival of human glioblastoma.

BACKGROUND: ALDH1A3 is a cancer stem cell marker in neoplasms including glioblastoma (GBM). However, the comprehensive role of ALDH1A3 in GBM remains unclear. This study attempted to investigate the expression of ALDH1A3 in human GBM tissues and its association with clinical parameters. METHODS: Thirty primary GBM and 9 control were enrolled in this study. ALDH1A3 mRNA and protein expression levels were detected by RT2-PCR and western blot, respectively. Immunohistochemistry and immunofluorescence staining were performed to evaluate the regional and cellular expression manner of ALDH1A3. The association of ALDH1A3 expression with multiple clinical parameters was analyzed. RESULTS: ALDH1A3 protein level, but not mRNA level, in a subgroup of GBM was significantly higher than that in the control group. ALDH1A3 immunoreactivity was detected heterogeneously in individual GBMs. Fifteen of 30 cases showed a positive of ALDH1A3 immunoreactivity which was predominantly observed in the tumor infiltrative area (TI). Double immunofluorescence staining revealed a co-localization of ALDH1A3 with GFAP in glial-shaped cells and in tumor cells. ALDH1A3 immunoreactivity was often merged with CD44, but not with CD68. Moreover, ALDH1A3 expression was positively associated with the tumor edema grade and inversely with overall survival (OS) (median OS: 16 months vs 10 months), but with neither MGMT promoter methylation status nor Ki67 index in GBM. An upregulation of ALDH1A3 was accompanied by a reduced expression of STAT3ß and p-STAT3ß. CONCLUSIONS: Inter- and intra-tumoral heterogeneous expression of ALDH1A3 was exhibited in GBMs. A high immunoreactivity of ALDH1A3 in tumor infiltrative area was associated with shorter OS, especially in patients with MGMT promoter methylation. Our findings propose ALDH1A3 not only as a predictive biomarker but also as a potential target for personalized therapy of GBM.

The influence of subventricular zone involvement in extent of resection and tumor growth pattern of glioblastoma.

OBJECTIVES: Isocitrate dehydrogenase (IDH1/2) mutations and O6-alkylguanine DNA methyltransferase (MGMT) promoter methylations are acknowledged survival predictors in patients with glioblastoma (GB). Moreover, tumor growth patterns like multifocality and subventricular zone (SVZ) involvement seem to be associated with poorer outcomes. Here, we wanted to evaluate the influence of the SVZ involvement and the multifocal tumor growth on the extent of surgical resection and its correlation with overall survival (OS) and molecular characteristics of patients with GB. METHODS: Adult patients with primary GB who underwent surgery at our department between 2012 and 2014 were included. Preoperative magnetic resonance imaging findings were analyzed with regard to tumor location, presence of multifocality and SVZ involvement. The extent of surgical resection as well as clinical and molecular parameters was collected from electronic patient records. Univariate and multivariate analyses were performed. RESULTS: Two hundred eight patients were retrospectively analyzed, comprising 90 (43.3%) female individuals with a mean age of 62.9 (±12.26) years and OS of 10.2 months (±8.9). Unifocal tumor location was a predictor for better OS with a mean of 11.4 (±9.4) months (vs. 8.0 [±7.4] months, p=0.008). Affection of the SVZ was also associated with lower surgical resection rates (p<0.001). SVZ involvement revealed with 7.8 (±7.0) months a significant worse OS [vs. 13.9 (±10.1) months, p<0.001]. All six IDH1/2 wildtype tumors showed an unifocal location (p=0.066). MGMT promoter methylation was not associated with multifocal tumor growth (p=0.649) or SVZ involvement (p=0.348). Multivariate analysis confirmed independent association between the SVZ involvement and OS (p=0.001). CONCLUSION: The involvement of the SVZ appears to have an influence on a lower resection rate of GB. This negative impact of SVZ on GB outcome might be related to lesser extent of resection, higher rates of multifocality and greater surgical morbidity but not inevitably to IDH1/2 mutation and MGMT promoter methylation status.

Impact of optic canal decompression on visual outcome in subtotal resected skull base meningiomas.

BACKGROUND: Visual impairment (VI) due to neoplastic infiltration of the optic canal (OC) is frequently seen in skull base meningiomas representing a significant restriction in patients` quality of life. However, the delicate anatomy of this region often prevents gross total tumor resection. The aim of the present study was to evaluate the impact of intradural OC decompression and postoperative oncological procedure on preservation of visual acuity in subtotal resected skull base meningiomas. METHODS: A retrospective analysis of 31 consecutive patients (19 females, 12 males; mean age 53 [range 18-78]), treated in our institution between 01/2011- 09/2014 was performed. Patients` charts were analyzed with special respect to operative procedure, postoperative treatment and procedural impact on late visual function. RESULTS: Most patients (74.2%) had VI prior to surgery. A pterional craniotomy (97%) facilitated subtotal tumor removal in 71% of the patients with no intraoperative and a low rate (6.4%) of postoperative complications. Adjunctive radiotherapy was performed in 19.3% of the patients. Preoperative visual acuity was preserved or improved in 92% of the patients. Substantial tumor regrowth occurred in only 11.2% of the patients. CONCLUSIONS: Intradural decompression of the OC stabilizes visual function in subtotally resected skull base meningiomas. Moreover, adjuvant radiotherapy seems to further benefit visual outcome which has to be evaluated in further prospective studies.

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.

Treatment of Odontoid Type II Fractures in Octogenarians: Balancing Two Different Treatment Strategies.

OBJECTIVE: Demographic changes have led to a higher incidence of C-2 fractures, especially in elderly patients. For patients with type II fractures, treatment remains controversial, as discussed by Anderson and D'Alonzo, due to the rising morbidity and mortality rates for any treatment. The aim of this study was to compare conservative and surgical management in patients with type II C-2 fractures regarding outcomes, complications, and the mortality rate. METHODS: A retrospective analysis was performed of the medical records, X-rays, and/or computed tomography scans of patients ≥80 years of age with type II fractures who were admitted to our Department of Neurosurgery between January 1990 and December 2017. The success of treatment was evaluated 3 months after surgery. RESULTS: In total, 125 patients were included, of whom 98 were treated surgically and 27 were treated conservatively. Surgical treatment was successful in 90.8% of cases, while conservative treatment was successful in 70.0%. The in-hospital mortality was 14.29% and the 3-month mortality was 27.8% in the surgical group, compared to 3.7% and 20% in the conservatively treated group. The in-hospital complication rate was 22.4% in the surgically treated patients and 7.4% in the conservatively treated patients. CONCLUSION: Surgical treatment of type II fractures seemed to be associated with higher success and complication rates than conservative treatment. Nevertheless, 3-month mortality was comparable in both groups. Therefore, we conclude that surgical treatment for type II fractures in elderly patients is superior to conservative management, although conservative treatment remains a valuable option in elderly patients with severe comorbidities.

Association of Surgical Resection, Disability, and Survival in Patients with Glioblastoma.

OBJECTIVE: Extent of resection (EOR) and Karnofsky Performance Status (KPS) are at odds in glioblastoma (GBM) surgery, that is, the anticipated postoperative disability limits the EOR. This study analyzes the correlation of different surgical modalities with the resulting physical status and survival of patients with GBM. METHODS: A total of 565 patients with primary GBM were operated on in a single institution between 2006 and 2014. Possible surgical modalities comprised supratotal resection (SLR), gross total resection (GTR; ≥ 95% by volume), tumor debulking (TDB; ≤ 95% by volume), and stereotactic biopsy (SB). Pre- and postoperative KPS before and up to 4 weeks after surgery as well as overall survival (OS) rate were determined retrospectively. Hazard ratio (HR) and 95% confidence intervals were calculated using a Cox proportional hazards model. RESULTS: Median postoperative KPS was ≥ 70, irrespective of surgical modality. Mean OS was 12.5 months. Multivariate analysis revealed age ≥ 70 years (HR: 1.93), preoperative KPS < 70 (HR: 2.15), and unmethylation in MGMT promoter (HR: 1.27) as independent factors for worse OS. Regarding surgical modality, SB was associated with the worst survival (HR: 2.3) followed by TDB (HR: 1.36). SLR was inferior to GTR (HR: 1.27). CONCLUSION: Higher EOR in patients with GBM does not seem inevitably correlated with increasing functional impairment, but better survival, provided there is a balanced preoperative indication. Nevertheless, SLR does not seem to be superior to GTR. Whenever possible, maximal safe resection should be considered in patients with GBM, even if an EOR ≥ 95% is not possible.

Impact of Multifocality and Molecular Markers on Survival of Glioblastoma.

OBJECTIVE: Several parameters like extent of resection and MGMT promotor methylation in glioblastoma (GBM) are known to influence survival. Other elements like multifocality and proliferation indices are not commonly used. The aim of the present study was to analyze routinely and not routinely assessed prognostic markers for survival of patients suffering from GBM in a single center. METHODS: Adult cases with GBM operated at our institution were included in this survey. The association of age, Karnofsky performance status (KPS), MGMT promotor methylation, Ki67 proliferation index, IDH1/2 mutational status, and multifocality on overall survival (OS) was analyzed in univariate and multivariate cox regression models. RESULTS: We analyzed 565 patients with a mean age of 62.2 (18-84) years. Median OS was 12.5 months. MGMT promoter methylation and IDH 1/2 mutation were associated with significant better OS (P < 0.01). In 48 cases (8.5%), the tumor was localized in both hemispheres, which was associated with a significant worse OS than tumor infiltration of 1 hemisphere (P = 0.039). Mean Ki67 proliferation index increased to 18% when both hemispheres were infiltrated. Multivariate analysis for OS revealed IDH 1/2 wildtype (adjusted odds ratio [aOR] 4.3), higher age (aOR 4.2), unmethylated MGMT promotor (aOR 3.5), preoperative KPS score <70 (aOR 1.9), and multifocality (aOR 2.1) as independent parameters for worse survival. CONCLUSIONS: This study confirms well-known parameters like MGMT promoter methylation, IDH 1/2 mutational status, KPS, and age as independent prognostic factors for survival and reveals multifocality as further independent prognostic marker for survival. The dismal prognosis of multifocal involvement is associated with an increasing Ki67 proliferation index.

Degenerative Cervical Myelopathy in Higher-Aged Patients: How Do They Benefit from Surgery?

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common reason for spinal cord disease in elderly patients. This study analyzes the preoperative status and postoperative outcome of higher-aged patients in comparison to young and elderly patients in order to determine the benefit to those patients from DCM surgery. METHODS: A retrospective analysis of the clinical data, radiological findings, and operative reports of 411 patients treated surgically between 2007 and 2016 suffering from DCM was performed. The preoperative and postoperative neurological functions were evaluated using the modified Japanese Orthopedic Association Score (mJOA Score), the postoperative mJOA Score improvement, the neurological recovery rate (NRR) of the mJOA Score, and the minimum clinically important difference (MCID). The Charlson Comorbidity Index (CCI) was used to evaluate the impact of comorbidities on the preoperative and postoperative mJOA Score. The comparisons were performed between the following age groups: G1: ≤50 years, G2: 51-70 years, and G3: >70 years. RESULTS: The preoperative and postoperative mJOA Score was significantly lower in G3 than in G2 and G1 (p < 0.0001). However, the mean mJOA Score's improvement did not differ significantly (p = 0.81) between those groups six months after surgery (G1: 1.99 ± 1.04, G2: 2.01 ± 1.04, G: 2.00 ± 0.91). Furthermore, the MCID showed a significant improvement in every age-group. The CCI was evaluated for each age-group, showing a statistically significant group effect (p < 0.0001). Analysis of variance revealed a significant group effect on the delay (weeks) between symptom onset and surgery (p = 0.003). The duration of the stay at the hospital did differ significantly between the age groups (p < 0.0001). CONCLUSION: Preoperative and postoperative mJOA Scores, but not the extent of postoperative improvement, are affected by the patients' age. Therefore, patients should be considered for DCM surgery regardless of their age.

Liponeurocytoma: Systematic Review of a Rare Entity.

OBJECTIVE: Liponeurocytoma is a rare benign tumor of the central nervous system, which develops mainly in adult patients within the posterior fossa. The World Health Organization has categorized this entity in its last classification of 2016 as a benign grade II tumor. Histopathologic characteristics contain neuronal and variable astrocytic differentiation with foci of lipomatous distinction. Only a few case reports and case series have been reported and the knowledge of this tumor is limited. General treatment guidelines do not exist. The aim of this study was to analyze the literature to create treatment guidelines. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to search existing online databases between January 1, 1978 and May 15, 2018. RESULTS: A systematic review of the literature found 73 patients (40 female, 33 male) with liponeurocytoma, in 59 of whom (80.8%) the disease occurred in the posterior fossa. The Ki-67/MIB-1 proliferation index was described in 58 patients, showing a mean value of 3.73% ± 4.01%. Follow-up was performed in 49 patients, with a median length of 52.02 ± 50.52 months, showing tumor recurrence in 14 patients (28.57%). Tumor recurrence was observed in only 1 patient (1/12, 8.33%) after adjuvant radiotherapy, whereas tumor recurrence was seen in 13/29 patients (44.83%) who did not receive adjuvant radiotherapy. CONCLUSIONS: Liponeurocytomas are rare benign tumors, occurring mainly in the cerebellum. The therapy of choice is surgery. Postoperative radiotherapy seems to decrease the risk of tumor recurrence and should be offered to the patient.

Nonoperative management of C-2 dens fractures: Single center experience and review of the literature.

OBJECTIVE: The demographic change in the population leads to a rising number of patients presenting with fractures of the cervical spine, especially C-2, due to falls. With an increase of co-morbidities in these elder patients, the risk for intra- and postoperative complications is increased likewise. Thus, an alternative strategy instead of operative management of these fractures should be taken into account whenever possible. Conservative management of dens fractures in the elderly is still a subject of great controversy despite numerous studies on this topic. The aim of this study was to analyze the rate of successful osseous consolidation of C-2 fractures with conservative treatment by wearing a semi-rigid collar or halo thoracic vest without further surgical intervention. PATIENTS AND METHODS: We analyzed the medical records and CT-scan of the cervical spine of 254 patients with C-2 fractures retrospectively, who were admitted to our department between January 1990 and September 2015. Fractures were diagnosed by CT-scan of the cervical spine and classified according to the Anderson - D`Alonzo classification. 183 patients were submitted to surgery as treatment of choice. In 71 patients a conservative management with external immobilization was chosen. The latter group was subjected to study analysis. RESULTS: 71 patients (mean age 74.08 years ±â€¯16.06 years) were diagnosed with C-2 fractures (Typ I: 4; Typ II 36; Typ III: 31) and treated conservatively using a Philadelphia collar (n = 57), or a halo-thoracic vest (n = 14), respectively. 12 patients were lost to follow up and excluded from further analysis. Conservative treatment of the fractures was deemed successful when a bony consolidation of the fracture in follow-up CT scans was seen (45 of 59 patients; 76.3%). 20 patients with a Type II fracture (20/28, 71.4%) showed a successful ossification. In 14 patients (overall 23.7%; Typ I: 1 (7.14%), Typ II: 8 (57.14%), Typ III: 5 (35.71%)) external immobilization failed to achieve primary stability. These patients were submitted to consecutive surgery. CONCLUSION: From our data it can be concluded that elderly patients, presenting with non-dislocated Type II fractures of the axis without accompaining neurological deficits, will have a more than 70% chance for a bony consolidation by conservative management. Consolidation rates may be estimated even higher in Type I and III fractures. Therefore, we suggest that external immobilization might be a valuable option to treat elderly patients with these fractures under certain circumstances.

Intraventricular Hemorrhage Caused by Subarachnoid Hemorrhage: Does the Severity Matter?

OBJECTIVE: Aneurysm rupture might be accompanied by intraventricular hemorrhage (IVH), which is associated with poor outcome of subarachnoid hemorrhage (SAH). The aim of this study was to analyze risk factors and clinical impact of IVH severity. METHODS: A total of 995 consecutive patients with SAH treated at our institution between January 2003 and June 2016 were eligible for this study. Clinical and radiologic findings were correlated with the presence and severity of IVH assessed with the original Graeb score. RESULTS: A total of 487 patients with SAH (48.9%) presented with IVH (mean IVH severity, 5.48 points [±3.5]). IVH severity correlated with poorer initial clinical condition (World Federation of Neurosurgical Societies grade >3; P < 0.001), acute hydrocephalus (P = 0.001), and poor outcome at 6 months (modified Rankin Scale score >2; P < 0.001). The location of the ruptured aneurysm in the anterior cerebral artery independently predicted the occurrence (P = 0.007) and severity of IVH (P < 0.001). In turn, aneurysm size affected only the severity of IVH (P = 0.001) but not its occurrence (P = 0.153). Early complications of SAH occurring within 72 hours after the bleeding event (cerebral infarction [P = 0.043], early mortality [P = 0.001], and primary craniectomy [P = 0.043]) were independently associated with the severity of IVH. CONCLUSIONS: Severity of aneurysmal IVH is a strong contributor to initial severity and early complications of SAH. Patients with larger aneurysms, especially located in the anterior cerebral artery, are at particular risk of severe IVH in cases of aneurysm rupture.

Intraventricular mass lesions: Still a question of surgical approach?

BACKGROUND: Intraventricular mass lesions represent a small subgroup of intracranial neoplasms with various entities. The anatomy of the ventricular system is complex. Hence multiple surgical approaches are used. We sought to present a single center algorithm regarding surgical approach for intraventricular mass lesion. METHODS: We retrospectively reviewed the data of all patients operated in our institution due to a primary intraventricular tumor between 2011 and 2014. Descriptive statistics were used to evaluate clinical presentation, imaging, histology, surgical approach, complications, and clinical outcome. RESULTS: A total of 52 patients were included in this study comprising 28 (53.8%) female and 24 (46.2%) male patients. The median age was 43.5years. Lesions location in descending order were fourth ventricle (46.2%), lateral ventricles (28.8%) and third ventricle (25.0%). A telovelar approach was used for all lesions in the fourth ventricle. Cystic lesions of the third ventricle were predominantly operated endoscopically. The surgical approach to the lateral ventricle was transcallosal or transcortical depending on the exact location of the lesion inside the lateral ventricle. We achieved a gross total resection in 82.7% and observed perioperative complications in 19.2% of the patients. Permanent morbidity and mortality were low at 7.7% and 1.9%, respectively. CONCLUSION: This single center series reveals a predominately used approach for each part of the ventricular system depending on exact location and texture of the mass lesion.

Study of angiogenic signaling pathways in hemangioblastoma.

Hemangioblastoma (HB) is mainly located in the brain and the spinal cord. The tumor is composed of two major components, namely neoplastic stromal cells and abundant microvessels. Thus, hyper-vascularization is the hallmark of this tumor. Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau (VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor. The present study investigated the key players of multiple angiogenic signaling pathways including VEGF/VEGFR2, EphB4/EphrinB2, SDF1α/CXCR4 and Notch/Dll4 pathways in surgical specimens of 22 HB. The expression of key angiogenic factors was detected by RT2 -PCR and Western blot. Immunofluorescent staining revealed the cellular localization of these proteins. We demonstrated a massive upregulation of mRNA levels of VEGF and VEGFR2, CXCR4 and SDF1α, EphB4 and EphrinB2, as well as the main components of Dll4-Notch signaling in HB. An increase in the protein expression of VEGF, CXCR4 and the core-components of Dll4-Notch signaling was associated with an activation of Akt and Erk1/2 and accompanied by an elevated expression of PCNA. Immuofluorescent staining revealed the expression of VEGF and CXCR4 in endothelial cells as well as in tumor cells. Dll4 protein was predominantly found in tumor cells, whereas EphB4 immunoreactivity was exclusively detected in endothelial cells. We conclude that multiple key angiogenic pathways were activated in HB, which may synergistically contribute to the abundant vascularization in this tumor. Identification of these aberrant pathways provides potential targets for a possible future application of anti-angiogenic therapy for this tumor, particularly when a total surgical resection becomes difficult due to the localization or multiplicity of the tumor.

Time Is Brain! Analysis of 245 Cases with Decompressive Craniectomy due to Subarachnoid Hemorrhage.

OBJECTIVE: Decompressive craniectomy (DC) may become a life-saving measure for patients with subarachnoid hemorrhage (SAH). However, the benefit of early DC has not been shown yet. We aimed at identifying the clinical value of DC timing. METHODS: We retrospectively analyzed 245 patients with SAH who underwent DC between January 2003 and December 2015. The cohort was stratified into primary (at admission, n = 171) and secondary DC (n = 74). In addition, primary DC was subdivided into early (≤24 hours after ictus, n = 120) and delayed (n = 51). RESULTS: There was no difference between primary and secondary DC (65.5% and 74.3%, P = 0.1828) with regard to unfavorable outcome at 6 months after SAH (defined as modified Rankin scale >3). However, individuals with early primary DC presented with significantly better functional outcome than the remaining cohort (P = 0.014, odds ratio [OR] = 2.02) and even compared with the subgroup with delayed primary DC (P = 0.023, OR = 2.42). Among individuals with World Federation of Neurosurgical Societies Grade <5 at admission, the benefits of early DC were more impressive: lower rates of unfavorable outcome (P = 0.003, OR = 0.28), in-hospital mortality (P = 0.031, OR = 0.37), and cerebral infarctions (P = 0.028, OR = 0.38) on the follow-up computed tomography scans. CONCLUSIONS: Not the timing of DC indication (primary/secondary), but rather the actual time left between the ictus and DC is crucial for the functional improvement of patients with SAH requiring DC. Especially, individuals without the signs of severe early brain injury strongly benefit from early DC.

Simultaneous 11C-Methionine Positron Emission Tomography/Magnetic Resonance Imaging of Suspected Primary Brain Tumors.

INTRODUCTION: The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone. MATERIAL AND METHODS: Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging. RESULTS: Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone. CONCLUSIONS: The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved.

Critical analysis of anatomical landmarks within the sphenoid sinus for transsphenoidal surgery.

The transsphenoidal approach to the sellar region has been introduced more than a 100 years ago. It is the accepted standard operative corridor to pathologies of the pituitary gland and surrounding structures. There are anatomical landmarks within the sphenoid sinus that are used for orientation directing to the sella floor or the cavernous sinus. Yet, little data can be found on the consistency of these landmarks. It is the aim of this study to evaluate the reliability of these anatomical landmarks for the surgeon's orientation. A total of 245 computed tomography (CT) volume data sets of the cranium performed according to a standardized protocol were analyzed for study purposes. CT scans of the cranium of 125 patients admitted to the emergency room of our hospital receiving a trauma spiral according to the local protocol were employed as a control group when no pathology in the sellar region was observed. In addition, preoperative CT scans of a group of 120 patients diagnosed with pituitary adenomas between 2009 and 2013 were analyzed. Image analysis of the anatomical landmarks included the minimal intercarotid distance (ICD), diameter of the sphenoid sinus (DSS), direction of the septum sinuum sphenoidalium (SSS), and the distance between vomer and clivus (VCD). The overall mean ICD was 16.2 mm, with patients suffering from adenomas showing a mean ICD of 15.8 mm compared with an average 16.5 mm in the control group. DSS was equal for both groups (adenoma group: mean 31.5 mm; controls: mean 31.3 mm). Mean VCD was 27.9 mm in patients with pituitary adenomas compared with 26.7 mm in controls. A septum of the sphenoid sinus located in the midline was found in overall 23 % only. SSS was directed into the bony shield of the internal carotid artery in 28 % of underlying tumors and in 37 % of the control group. This is the first detailed description of landmarks of the sphenoid sinus based on a large radiologic-anatomical analysis of CT scans yielding a wide variation and high inconsistency of these landmarks. From out data, we suggest that the surgeon approaching the sphenoid sinus should handle the anatomical landmarks with care bearing their inconsistency in mind. A thorough planning of the procedure up front is highly recommended. Usage of a navigation system considering the bony structures might as well facilitate as steady the approach to the sellar region in some cases for the patient's sake.