Significant Systemic Insulin Resistance is Associated With Unique Glioblastoma Multiforme Phenotype.

Background: Some glioblastoma multiforme (GBM) are characterized by the presence of gemistocytes (GCs), a unique phenotype of reactive astrocytes. Certain GCs can be identified as neoplastic cells but these cells were also found to be associated with diabetes in non-neoplastic lesions of the central nervous system. Our aim was to find a correlation between insulin - resistance metabolic features and the presence of GCs in patients with newly diagnosed GBM. Methods: Medical records from histologically confirmed GBM patients were retrospectively extracted for different systemic metabolic variables. A statistic-based comparison was made between GBM, diabetic patients with and without GC. Patients with poorly controlled diabetes (ie, hemoglobin A1C ⩾ 8.0) were also compared between the 2 groups. Results: A total of 220 newly diagnosed GBM patients were included in our study. 58 (26.3%) patients had a history of diabetes mellitus type 2 (DM2) at the time of admission. The rate of poorly-controlled DM2 was nearly as twice in the GC-GBM group than in the non-GC GBM group (18.75% vs 9.5%; P = .130). In the DM2 cohort, the subgroup of GC-GBM was significantly associated with demographic and metabolic features related to insulin resistance such as male gender predominance (89% vs 50%, P = .073) and morbid obesity (weight ⩾85 kg: OR 6.16; P = .0019 and mean BMI: 34.1 ± 11.42 vs 28.7 ± 5.44; P = .034 for group with and without GCs, respectively). In the poorly-controlled DM2 group, none of the GC-GBM patients were using insulin prior to diagnosis, compared to 61.1% in the non-GC GBM patients (OR = 0.04, P = .045). Conclusion: Systemic metabolic factors related to marked insulin resistance (DM2, morbid obesity, male gender) are associated with a unique histologic phenotype of GBM, characterized by the presence of GCs. This feature is prominent in poorly-controlled DM2 GBM patients who are not using synthetic insulin. This novel finding may add to the growing data on the relevance of glucose metabolism in astrocytes and in astrocytes associated with high-grade gliomas. In GBM patients, a correlation between patients' metabolic status, tumor's histologic phenotype, tumor's molecular changes, use of anti-diabetic drugs and the respective impact of these factor on survival warrants further investigation.

Supratentorial hemangioblastoma: correlation between phenotype, gender and vascular territory affected.

Supratentorial hemangioblastomas are rare, vascular lesions. The presence of peri-tumoral cysts and edema has meaningful clinical, diagnostic and therapeutic implications. Nevertheless, the pathogenesis of both cyst and edema formation is not fully understood. This study sought to determine if the radiologic phenotype of supratentorial hemangioblastoma is affected by the different cerebral arterial circulations. Review of the English-language literature from 1973 to 2023 yielded 53 cases of parenchymal supratentorial hemangioblastomas eligible for analysis. Patients were divided by the vascular territorial distribution of the lesions: anterior circulation (n = 36) or posterior circulation (n = 17), and the groups were compared for demographic, clinical, radiologic and molecular variables. Univariate analyses yielded a significant difference between the groups in five variables. Cystic changes and "classic" radiological phenotype were associated with hemangioblastomas of the posterior circulation (OR = 0.19, p = 0.045 and OR = 0.287, p = 0.048, respectively), while female gender, significant peritumoral edema and purely solid phenotype were associated with hemangioblastomas of the anterior circulation (OR = 3.384, p = 0.045 and OR = 5.25, p = 0.05 and OR = 14.0, p = 0.015; respectively). On multivariate analysis, solid phenotype and female gender remained significantly associated with the anterior circulation (OR = 36.04, p = 0.014 and OR = 4.45, p = 0.045). The incidence of von-Hippel Lindau disease was higher in the anterior-circulation group. Cystic tumors were present in all females in the posterior-circulation group compared to 43.4% in the anterior-circulation group (OR = 20.714, 95% CI 1.061 to 404.122; p = 0.045). Based on historical cases of supratentorial hemangioblastoma, this study shows that different tumor phenotypes are associated with the different cerebral circulations. Gender was also associated with differences in tumor distribution and radiologic phenotype. These novel data may improve our understanding of unique vascular diseases of the central nervous system.

[THERAPEUTIC OPTIONS FOR BRAIN OLIGOMETASTASES: COMPARISON BETWEEN SURGICAL RESECTION, STEREOTACTIC RADIOSURGERY, WHOLE BRAIN RADIATION THERAPY AND COMBINED MODULES IN RELATION TO SURVIVAL, FUNCTION AND OTHER CONSIDERATIONS].

INTRODUCTION: Brain metastases (BM) are a leading cause of morbidity and mortality in patients with systemic cancer. In the last two decades, an enormous improvement in controlling extra-cranial disease has been achieved, positively affecting the overall survival of patients. However, this has led to an increased number of patients who live long enough to develop BM. In addition, technological improvements in neurosurgery and radiotherapy caused both surgical resection and stereotactic radiosurgery (SRS) to become an integral part of the armamentarium when treating a patient with 1-4 BM. These increased therapeutic possibilities and combination of therapeutic options such as surgical resection, SRS, whole brain radiation therapy (WBRT) and lately targeted molecular therapy, have led to an enormous amount of, yet sometimes confusing, published data.

Deep, spontaneous intracerebral hemorrhages: Clinical differences and risk factors associated with anterior versus posterior circulation.

BACKGROUND: spontaneous intracerebral hemorrhages (ICH) in different anatomical locations are considered different clinical entities, associated with different vascular etiologies. However, such a distinction between deep ICH in the posterior vs. the anterior circulation is not well documented. OBJECTIVE: to look for different demographic, clinical, laboratory and radiological variables in order to clarify any distinction between deep ICH of the posterior versus the anterior circulations. MATERIAL AND METHODS: Retrospective study on patients diagnosed with deep, spontaneous ICH at a single tertiary center. Patients were divided into two groups: posterior circulation (group 1) and anterior circulation (group 2). Computerized medical records were extracted for multiple variables. RESULTS: A total of 142 patients with deep ICH were included in the study; 54.9 % (n = 78) with posterior (group 1) and 45.1 % (n = 64) with anterior circulation hemorrhages (group 2). In group 1, 67.9 % (n = 53) of hemorrhages were in the cerebellum and 28.2 % (n = 22) in the thalamus. Patients in group 1 were older at time of hemorrhage (68.69 ± 11.66 vs. 64.95 ± 13.34, p = 0.073) and had nearly threefold increased rate of BMI≥ 35 (22.0 % vs. 8.6 %, p = 0.071). In multivariate analysis, use of anti-aggregates (OR=2.391; 95 % CI 1.082-5.285, p = 0.031) and past medical history of HTN (OR=2.904; 95 % CI 1.102-7.654, p = 0.031) were significantly associated with ICH of the posterior circulation. When excluding patients with thalamic hemorrhages, BMI ≥ 35 was also associated with significant risk of having a deep hemorrhage in the posterior circulation vs. the anterior circulation (OR=3.420; 95 % CI 1.011-11.574, p = 0.048). No significant differences were found between the two groups in terms of functional and survival outcomes. CONCLUSION: HTN, use of anti-aggregates and morbid obesity are associated with deep ICHs of the posterior circulation and should be considered significant risk factors for this major clinical event. The growing data on pathophysiology of distinct subgroups of ICH will provide useful tools that will aid in preventing and treating these neurological emergencies. Future epidemiological and clinical studies should use the distinction between ICH subgroups based on their anatomical location and vascular territories as accurately as possible in order to reach solid conclusions.

Neuropsychological assessments and cognitive profile mostly associated with shunt surgery in idiopathic normal pressure hydrocephalus patients: diagnostic and predictive parameters and practical implications.

BACKGROUND: Cognitive decline is a well-documented feature of idiopathic normal pressure hydrocephalus (iNPH) that can be reversible following cerebrospinal fluid tap tests (CSF-TT). The current gold standard for selecting iNPH patients for shunt surgery is measurable improvement in gait tests following CSF-TT. However, the diagnostic significance and predictive role of pre-surgical cognitive evaluations in probable iNPH patients is still controversial. PURPOSE: To find the neuropsychological (NPSY) tests and cognitive aspects mostly associated with shunt surgery in iNPH. MATERIAL AND METHODS: A retrospective comparison between probable iNPH patients who, after undergoing CSF-TT with gait and cognitive evaluations, ended up receiving a shunt (group 1) and probable iNPH patients who ended up with no shunt surgery (group 2). Differences in the diagnostic and predictive results of variety of NPSY tests at baseline, pre-CSF-TT, and post-CSF-TT were used for thorough statistical calculations. RESULTS: A total of 147 patients with probable iNPH were included. Of those, 58 (39.45%, group 1) patients underwent shunt surgery, while 89 (60.55%, group 2) did not. For the vast majority of the cognitive tests used, no statistically significant differences were found between the groups at baseline (pre-CSF-TT). Following CSF-TT, the "naming" component of the Cognistat test was the only single test to show statically significant difference in improvement between the two groups. Combining at least two tests led to increased levels of accuracy and specificity; however, the sensitivity remained < 50. The only two combinations that were associated with sensitivity ≥ 70 were either any improvement in the Cognistat test (p = 0.627) or any improvement in either its naming, memory, or judgment components (p = 0.015). CONCLUSION: Cognitive tests, even when combined to cover several cognitive aspects, are not sensitive enough to act as an independent reliable diagnostic and predictive tool, especially when relying on their scores as baseline. In order to avoid cumbersome and unnecessary tests to our patients and to reduce the number of patients who are denied proper treatment due to misdiagnosis, we recommend to use NPSY tests that examine the cognitive aspects of naming and memory, in addition to 2-3 tests for executive functions.

Gemistocytes in newly diagnosed glioblastoma multiforme: Clinical significance and practical implications in the modern era.

BACKGROUND: Gemistocytes (GCs) in low grade gliomas are associated with rapid growth and worse prognosis. However, their clinical significance in glioblastomas (GBM) is a matter of debate. AIM OF STUDY: To investigate the clinical significance of the presence of GCs in newly-diagnosed GBM patients in the modern era. METHODS: Computerized medical records from newly diagnosed GBM patients were retrospectively reviewed and extracted for demographic, clinical, radiological and pathological variables. Patients with at least 5% GCs of neoplastic cells were considered GC-GBM (group 1). All other cases were considered non-GC GBM (group 2). Group 1 was further divided into two subgroups: Low percentage GCs (group 1a, ≤ 20% GCs) and high percentage GC (group 1b, >20% GCs). RESULTS: A total of 220 patients with newly diagnosed GBM were included. 14.5% were defined as GC-GBM (group I, n = 32) and 85.5% were defined as non-GC GBM (group 2, n = 188). 8.5% had ≤ 20% GCs (group 1a, n = 19) and 5.9% had > 20% GCs (group 1b, n = 13). Groups were similar for most epidemiological and clinical variables. There was a trend toward worse prognosis in group 1b. Several distinguished radiological and molecular features were observed in group 1. CONCLUSION: GCs are found in minority of naïve, newly diagnosed, GBM cases in adults. They seem to carry minimal implications on daily clinical practice. Higher percentage of GCs is associated with distinct radiological features such as multifocality that might be correlated with decreased OS. High-percentage GC-GBMs are also associated with increased prevalence of isocitrate dehydrogenase (IDH) mutations.

Minimally Invasive Intracerebral Hematoma Evacuation Using a Novel Cost-Effective Tubular Retractor: Single-Center Experience.

BACKGROUND: Spontaneous intracerebral hematoma (ICH) is a common disease with a dismal overall prognosis. Recent development of minimally invasive ICH evacuation techniques has shown promising results. Commercially available tubular retractors are commonly used for minimally invasive ICH evacuation yet are globally unavailable. METHODS: A novel U.S. $7 cost-effective, off-the-shelf, atraumatic tubular retractor for minimally invasive intracranial surgery is described. Patients with acute spontaneous ICH underwent microsurgical tubular retractor-assisted minimally invasive ICH evacuation using the novel retractor. Patient outcome was retrospectively analyzed and compared with open surgery and with commercial tubular retractors. RESULTS: Ten adult patients with spontaneous supratentorial ICH and median preoperative Glasgow Coma Scale score of 10 were included. ICH involved the frontal lobe, parietal lobe, occipitotemporal region, and solely basal ganglia in 3, 3, 2, and 2 patients, respectively. Mean preoperative ICH volume was 80 mL. Mean residual hematoma volume was 8.7 mL and mean volumetric hematoma reduction was 91% (median, 94%). Seven patients (70%) underwent >90% volumetric hematoma reduction. The total median length of hospitalization was 26 days. On discharge, the median Glasgow Coma Scale score was 12.5 (mean, 11.7). Thirty to 90 days' follow-up data were available for 9 patients (90%). The mean follow-up modified Rankin Scale score was 3.7 and 5 patients (56%) had a modified Rankin Scale score of 3. CONCLUSIONS: The novel cost-effective tubular retractor and microsurgical technique offer a safe and effective method for minimally invasive ICH evacuation. Cost-effective tubular retractors may continue to present a valid alternative to commercial tubular retractors.

Deep versus Superficial Spontaneous Cerebellar Hemorrhages: Separated Vascular Etiologies with Different Clinical Consequences.

BACKGROUND: Spontaneous cerebellar hemorrhage (CH) is a critical neurosurgical event. It is usually categorized as a homogenous group under the general term of deep/nonlobar intracerebral hemorrhage. However, increasing evidence suggests it is composed of 2 subgroups, separated from each other by their anatomic location (deep vs. superficial), as well as by their vascular etiology (small vessel disease vs. cerebral amyloid angiopathy). OBJECTIVE: To identify any clinically significant differences between anatomically separated subgroups of CHs: deep versus superficial. METHODS: This is a retrospective study on patients who were diagnosed with spontaneous CHs at a single tertiary center. On the basis of the radiologic location of the hematoma, patients were divided into 2 groups: deep (group 1) and superficial (group 2). Computerized medical records were extracted for multiple variables. RESULTS: A total of 69 patients fulfilled the inclusion criteria. Fifty-three (77%) were in group 1, and 16 (23%) were in group 2. Having any vascular risk factor was associated with the highest odds ratio for having a deep CH. Morbid obesity (body mass index ≥30) and the use of antiplatelets were also associated with increased odds ratios. Group 1 is also associated with high prevalence of intraventricular hemorrhage, acute hydrocephalus, and less favorable outcome. CONCLUSIONS: This study supports the notion that CH is most likely a heterogenous condition, composed of 2 subgroups, separated from each other in terms of anatomic location, vascular etiologies, and clinical consequences. Further studies on large cohort of patients are needed in order to accurately define the subgroups of this life-threatening event.

Height in adolescence as a risk factor for glioma subtypes: a nationwide retrospective cohort study of 2.2 million subjects.

BACKGROUND: Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. METHODS: The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex. RESULTS: A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women. CONCLUSIONS: The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.

Multicentric non-enhancing lesions in glioblastoma: A retrospective study.

Glioblastoma (GBM) typically presents as a single lesion. Multicentric GBM are defined as well separated lesions on MRI (enhancing and non-enhancing). Multicentric GBM with non-enhancing lesions (MNE-GBM) are rarely described in literature. We aimed at describing the radiologic characteristics, treatment, and clinical course of those patients. The institutional neuropathological database was searched for GBM patients diagnosed between 1/1/2015 and 31/05/2018. All pre-operative MRI brain scans were reviewed to identify patients with MNE-GBM. Electronic medical records and follow-up MRI scans were reviewed to assess progression-free survival (PFS) and overall survival (OS). Out of 149 adult patients with newly diagnosed GBM, 12 met the inclusion criteria of MNE-GBM, all of them presented at least one enhancing lesion. Median follow-up for the MNE-GBM patients was 16.1 months. At last follow-up, all patients had recurrence (median PFS 7.6 months) and eleven patients had deceased. Median OS was 16.2 months (95% CI, 4.1-27.5). Eleven patients received radiotherapy concomitant with temozolomide as initial treatment. Radiation field included all the disease foci (enhancing and non-enhancing lesions) in 8 patients, five of them progressed within the non-enhancing lesion. Three patients did not receive radiation for the entire non-enhancing lesions, and two of them progressed within the non-irradiated areas. In conclusion, MNE-GBM is not rare, and has high risk of aggressive progression within the separate non-enhancing lesion.

Acute Presentation of Normal Pressure Hydrocephalus After Transcatheter Aortic Valve Implantation: A Novel Interaction Between the First and Third Circulations.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) negatively affects gait and cognition abilities and urine continence in the elderly. It is associated with systemic hypertension, although the exact pathophysiology is still unknown. A correlation to increased intracranial pulsatility and decreased compliance was suggested. Transcatheter aortic valve implantation (TAVI) is increasingly used in the treatment of severe AS. New-onset systemic hypertension affects some patients after TAVI. OBJECTIVE: To identify any association between aortic valve replacement and the development of NPH. METHODS: A cohort was created retrospectively of all patients who were evaluated for NPH with cerebrospinal fluid (CSF) tap test at a single institute during 2014-2019. Patients were reviewed for a past medical history of aortic valvular disease or aortic valve replacement. RESULTS: A total of 242 patients underwent evaluations for NPH. Of these patients, 133 were considered to have iNPH. Six patients underwent aortic valve replacement before the initial symptoms of NPH: 1 surgical and 5 TAVI. The time from aortic valve replacement to the initial NPH symptoms was <6 months in 3 patients (as low as 1 month in 2 of them). Two patients had functional improvement after CSF tap test and proceeded to receive a shunt, 4 and 6 months after TAVI, respectively. Two patients developed hypertension after TAVI. Pulse pressure increased by >10 mm Hg in 3 patients after TAVI. CONCLUSIONS: This is the first case series of symptomatic NPH after TAVI. In this unique subgroup, NPH symptoms can develop rapidly. Post-TAVI iNPH represents a novel interaction between the blood and CSF circulations.

A Review of the Neurosurgical Management of Brain Metastases During Pregnancy.

OBJECTIVE: Patients with pregnancy-associated secondary brain tumors (PASBT) are challenging to manage. Because no guidelines for the management of such patients currently exist, we performed a systematic review of the literature using PRISMA guidelines with a discussion of management from a neurosurgeon's perspective. METHOD: Systematic review of the literature using PRISMA guidelines from 1999 to 2018. RESULTS: We identified 301 studies of which 16 publications (22 patients reporting 25 pregnancies, 20 deliveries, 5 early terminations) were suitable for final analysis. The most frequent primary cancers were breast (8/22, 36.36%), skin (6/22, 27.27%), and lung (5/22, 22.73%). Four patients (18.18%) had neurosurgical procedures during their pregnancies. Five patients (22.73%) received neurosurgical resection after their pregnancies. Nine patients (40.91%) received radiation therapy and seven patients (31.82%) received chemotherapy during pregnancy while seven patients (31.82%) received chemotherapy and radiation after pregnancy. There was 1 fetal death (5%) out of 20 healthy deliveries. Five pregnancies (20%) were terminated in the first trimester due to a need for urgent neurosurgical intervention. CONCLUSION: Management of PASBT remains a challenging issue. Maternal and fetal risks associated with surgical resection and teratogenicity due to adjuvant therapy should be discussed in the context of a multidisciplinary team. Timing of surgery and the use of systemic chemoradiation depends on the gestational age (GA) of the fetus, extent, and control of the mother's primary and metastatic disease. Guidelines need to be established to help neuro-oncology teams safely and effectively manage this group of patients.

Height as a risk factor in meningioma: a study of 2 million Israeli adolescents.

BACKGROUND: Meningiomas are the most common primary central nervous system tumors. Potential risk factors include obesity, height, history of allergy/atopy, and autoimmune diseases, but findings are conflicting. This study sought to assess the role of the different risk factors in the development of meningioma in adolescents/young adults. METHODS: The cohort included 2,035,915 Jewish men and women who had undergone compulsory physical examination between 1967 and 2011, at age 16 to 19 years, prior to and independent of actual military enlistment. To determine the incidence of meningioma, the military database was matched with the Israel National Cancer Registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according to sex, body mass index (BMI), height, and history of allergic or autoimmune disease. RESULTS: A total of 480 subjects (328 females) were diagnosed with meningioma during a follow-up of 40,304,078 person-years. Median age at diagnosis was 42.1 ± 9.4 years (range 17.4-62.6). On univariate analysis, female sex (p < 0.01) and height (p < 0.01) were associated with risk of meningioma. When the data were stratified by sex, height remained a significant factor only in men. Spline analysis of the male subjects showed that a height of 1.62 m was associated with a minimum disease risk and a height of 1.85+ meters, with a significant risk. CONCLUSIONS: This large population study showed that sex and adolescent height in males (> 1.85 m) were associated with an increased risk of meningioma in adulthood.

Fulminant presentation of a SMARCB1-deficient, anterior cranial fossa tumor in adult.

BACKGROUND: Malignant atypical teratoid rhabdoid tumor (ATRT) usually develops in children. ATRTs are rare in adults, with only one case in the literature describing involvement of the anterior skull base. These primary intracranial tumors are characterized molecularly as SMARCB1 (INI1) deficient. Different types of such SMARCB1-deficient tumors exist in adulthood, usually in the form of extracranial tumors. Very few cases of such a new entity, named SMARCB1-deficient sinonasal carcinoma have been described with intracranial penetration and involvement of the anterior cranial fossa. CASE DESCRIPTION: A 36-year-old male presented with acute cognitive deterioration. Over few hours, he developed a fulminant herniation syndrome. Imaging showed a tumor in the anterior cranial fossa surrounded by massive brain edema. The tumor has destroyed the frontal bone with involvement of the nasal cavities and paranasal sinuses. The patient underwent emergent decompressive craniectomy and tumor debulking but could not be saved. Pathological analysis revealed a highly cellular tumor without rhabdoid cells but with areas of necrosis. Further immunohistochemical stains revealed that neoplastic cells were diffusely and strongly positive for epithelial membrane antigen and P63 and negative for SMARCB1 (i.e., loss of expression), confirming the diagnosis of sinonasal carcinoma. CONCLUSION: To the best of our knowledge, this is the first report of a fulminant presentation of a SMARCB1- deficient tumor in young adult, involving the anterior cranial fossa and the paranasal sinuses. The main differential diagnosis of aggressive, primary, intracranial SMARCB1-deficient tumors in adults includes ATRT, SMARCB1- deficient sinonasal carcinoma, rhabdoid meningioma, and rhabdoid glioblastoma. Atypical tumors involving the anterior skull base without a clear histopathological pattern should therefore be checked for SMARCB1 expression.

Chiari I malformation and pregnancy: a comprehensive review of the literature to address common questions and to guide management.

BACKGROUND: The optimal management of Chiari I malformation during pregnancy remains uncertain. Labor contractions, which increase intracranial pressure, and neuraxial anesthesia both carry the theoretical risk of brainstem herniation given the altered CSF dynamics inherent to the condition. Mode of delivery and planned anesthesia, therefore, require forethought to avoid potentially life-threatening complications. Since the assumed potential risks are significant, we seek to systematically review published literature regarding Chiari I malformation in pregnancy and, therefore, to establish a best practice recommendation based on available evidence. METHODS: The English-language literature was systematically reviewed from 1991 to 2018 according to PRISMA guidelines to assess all pregnancies reported in patients with Chiari I malformation. After analysis, a total of 34 patients and 35 deliveries were included in this investigation. Additionally, a single case from our institutional experience is presented for illustrative purposes but not included in the statistical analysis. RESULTS: No instances of brain herniation during pregnancy in patients with Chiari I malformation were reported. Cesarean deliveries (51%) and vaginal deliveries (49%) under neuraxial blockade and general anesthesia were both reported as safe and suitable modes of delivery. Across all publications, only one patient experienced a worsening of neurologic symptoms, which was only later discovered to be the result of a previously undiagnosed Chiari I malformation. Several patients underwent decompressive suboccipital craniectomy to treat the Chiari I malformation during the preconception period (31%), during pregnancy (3%), and after birth (6%). Specific data regarding maternal management were not reported for a large number (21) of these patients (60%). Aside from one abortion in our own institutional experience, there was no report of any therapeutic abortion or of adverse fetal outcome. CONCLUSIONS: Although devastating maternal complications are frequently feared, very few adverse outcomes have ever been reported in pregnant patients with a Chiari I malformation. The available evidence is, however, rather limited. Based on our survey of available data, we recommend vaginal delivery under neuraxial blockade for truly asymptomatic patients. Furthermore, based on our own experience and physiological conceptual considerations, we recommend limiting maternal Valsalva efforts either via Cesarean delivery under regional or general anesthesia or by choosing assisted vaginal delivery under neuraxial blockade. There is no compelling reason to offer suboccipital decompression for Chiari I malformation during pregnancy. For patients with significant neurologic symptoms prior to conception, decompression prior to pregnancy should be considered.

[IS ROUTINE CT SCAN NECESSARY AFTER THE REMOVAL OF BENIGN BRAIN TUMORS?]

AIMS: Determine if early CT evaluation is justified in patients operated on for benign brain tumors. BACKGROUND: Researchers have recently questioned the common practice of referring all patients after cranial surgery for CT scans to rule out silent complications. METHODS: The cohort included 257 consecutive patients who underwent surgical removal of a benign brain tumor in the years 2011-2016. The neuroradiology scans performed before and after surgery were reviewed. The postoperative findings considered significant were hemorrhage in ≥50% of the tumor bed, ischemic changes, worsening brain edema, and mass effect. The relationship of the CT findings with the neurological outcome and their effect on the clinical management were evaluated. RESULTS: No significant complications were found by CT in 247 patients (96%). In the remaining 10 patients (4%), CT showed increased brain edema in 5 and hemorrhage in 5. The clinical management was influenced by the CT findings in 6/10 patients. One had a temporary neurological deficit. None died or required a second operation. CONCLUSIONS: Elective patients operated on uneventfully for benign brain tumors rarely benefit from routine CT after surgery. In most cases, CT follow-up can be replaced by careful neurological monitoring. Exceptions to this rule may be based on clinical judgment and local resources.

Spinal meningiomas: 61 cases with predictors of early postoperative surgical outcomes.

BACKGROUND: Spinal meningiomas are benign, well-circumscribed and slowly-growing intradural tumors that compress the spinal cord. Hereby, a retrospective review of 61 spinal meningioma cases evaluated in terms of demographic, clinical, pathological and radiological features to predict the early postoperative functional outcomes. METHODS: Patients' records and MRI images of all the histologically confirmed spinal meningioma cases that underwent surgical resection at two university hospitals from January 2005 to June 2016 were retrospectively reviewed. Demographic data, clinical findings, radiological features and pathology reports were reviewed. Univariate and multivariate logistic regression analyses were used to evaluate the impact of each factor on the early 3-month post-surgical functional outcome. A receiver operating characteristic (ROC) curve was used to predict the power of the model. RESULTS: Sixty-one cases of spinal meningiomas were operated: 13 males (21%) and 48 females (79%). Mean age was 60.5 years and ranged from 24 to 92 years. Patients presented with back pain (57%), motor deficits (47.5%), sensory deficits (18%) and sphincteric dysfunction (11.5%). One case (1.6%) showed an additional extradural growth. There were 40 thoracic, nine cervical, five cervicothoracic, five thoracolumbar, and two lumbar cases. Only four cases (6.6%) showed atypical pathological features (WHO grade II). At 3-month follow-up, 46 patients (75.4%) had either functionally improved or remained stable. Fifteen patients (24.6%) had "worse" functional outcome. Three variables showed statistically significant odds ratio for improved outcomes (OR): pre-surgical motor deficit (OR=5; P=0.005); presurgical sensory disturbance (OR=3.5; P=0.026); pre-surgical myelopathy (OR=3.5; P=0.026). Multivariate analysis showed increased OR for cross-sectional ratio, pre-surgical myelopathy, pre-surgical radiculopathy and non-cervical location of tumor (1.59, 3.46, 3.2, 1.63/3.56, respectively). Although none has reached statistical significance (P>0.05), the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.74. CONCLUSIONS: The independent predictors of the early postoperative functional outcomes of spinal meningioma resections may include pre-surgical motor deficit, sensory deficit and myelopathy.

[DIFFUSE LOW GRADE GLIOMA: PERSONALIZED ADAPTATION OF SURGICAL RESECTION IN AN ERA OF TARGETED ONCOLOGICAL THERAPY].

INTRODUCTION: Diffuse low grade glioma (DLGG) is a primary, infiltrative brain tumor which grows slowly but steadily and eventually undergoes malignant transformation into a high grade glioma. Today, it is hard to generalize the treatment approaches for DLGG. Due to different genetic and clinical variables, there is a large gap in the treatment provided to different patients. This kind of gap requires personalized adaptation of the treatment for a long period. Although there has been significant progress in the molecular characterization of DLGG, we still lack an efficient oncological targeted therapy. On the other hand, during the past two decades, there has been a significant paradigm shift in the treatment of DLGG, with the current recommendation to perform a maximal safe resection as first line treatment. Our aspirations to preserve the high function abilities of these relatively young patients for a long period (median overall survival of 15 years), together with the intention to postpone the malignant transformation as late as possible, have led to increases in the prevalence of awake craniotomies for DLGG. In this surgical technique, the resection of the tumor is as wide as possible, according to its functional boundaries (and not its radiological - anatomical ones). This kind of resection allows us to preserve the functioning abilities of the patients while making a wide resection. This resection can be performed with full adaptation to the patient's will, as well as for the tumor's characteristics. The long-term treatment of patients with DLGG requires us to perform personalized adaptation in any therapeutic junction and in any case where the delicate balance between function of the patient and his oncological status needs to be preserved. This study reviews the different options for personalized treatment in DLGG and emphasize the importance of awake surgeries in these cases.

Accelerated growth of hemangioblastoma in pregnancy: the role of proangiogenic factors and upregulation of hypoxia-inducible factor (HIF) in a non-oxygen-dependent pathway.

Hemangioblastomas (HBs) are benign, highly vascular tumors, often characterized by loss of function of the von Hippel-Lindau (vHL) gene. They are the most common central nervous system tumor observed in vHL syndrome. Loss of function of the vHL gene creates a "pseudo-hypoxic" state, causing overactivation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-related pathways. In some cases, HBs can rapidly increase in size during pregnancy to then present acutely, which most frequently occurs after the 20th gestational week. These changes in size usually occur from enlargement of the cystic component of the HB. Due to their preferred location in the posterior fossa near critical structures as well as along the spinal cord, such cases can present with severe neurological deficits, requiring urgent surgical intervention in a multidisciplinary setting. However, the reasons for this acute flare-up during pregnancy remain poorly understood, as are the reasons why this occurs in only a subset of tumors. Unveiling the etiology for this clinical scenario can affect the treatment of HBs, as it will contribute to the understanding of the pathophysiology of such a transformation from a quiescent lesion to a symptomatic one, not only in the setting of pregnancy. Identifying the correct triggers and the conditions initiating and mediating this switch will enable us to develop preventive medications which should allow us to keep the tumor in its quiescent phase. In this pathophysiological review, we investigate the association between HB growth and pregnancy based on an analysis > 40 such published cases. We suggest that the proangiogenic state of pregnancy is the leading etiology for this striking association, and to support the argument, we discuss its potential impact on HIF overexpression in a non-hypoxic manner through activation of the PI3K/Akt/mTOR pathway by proangiogenic factors. Specifically, we discuss the involvement of placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR-1) in various pathologic processes that can lead to the formation and growth of peritumoral edema and cysts, which are the primary causes for the development of any symptoms in HB. Both PlGF and VEGFR-1 are expressed at increased levels during pregnancy, and both have been reported as part of various pathological processes, including angiogenesis and tumorigenesis. The unique feature that both do essentially not show any significant negative impact on regular physiological processes makes them attractive therapeutic targets since very little side effects are expected. Further research into the effects of anti-PlGF or anti-VEGFR-1 therapy in HB is therefore recommended.

Management of quadrigeminal arachnoid cyst associated with obstructive hydrocephalus: report on stereotactic ventricular - cystic stenting.

Quadrigeminal arachnoid cysts (QAC) are usually accompanied by a symptomatic obstructive hydrocephalus. Several endoscopic and surgical treatments exist; however, the critical location of these cysts further complicates treatment and usually more than one procedure is required. In this report, a 31 year old female with QAC and associated obstructive hydrocephalus was successfully treated with stereotactic placement of a permanent ventricular - cystic stent (intraventricualr - cystic catheterization) in single - session. Intraventricular - cystic stenting provides a long lasting communication between these two compartments, allowing persistent "physiologic" solution to this challenging condition.