Yosef Laviv

Unique features of pregnancy-related meningiomas: lessons learned from 148 reported cases and theoretical implications of a prolactin modulated pathogenesis.

Meningiomas are some of the most frequently encountered adult intracranial tumors. Dramatic flare ups in size may occasionally be observed during pregnancy, leading to complicated clinical scenarios, with profound effects and substantial risks for both the mother’s and the fetus’s well-being. Despite the fact that such changes have largely been attributed to progesterone-based mechanisms, recent studies have put this theory into question or defied it. In order to assess these particular tumors carefully and to try and clarify the pathophysiology of such pregnancy-related meningioma growth, an in-depth review of the pertinent literature was undertaken. Based on clinical, radiographic, and pathological data gathered from 148 reported cases, we have found several unique features characterizing these pregnancy-related meningiomas. The presence of such observed features was found to be of high statistical significance when compared to their expected prevalence in the general population and included the following: (1) parasellar location, (2) anterior circulation blood supply, (3) visual symptoms at presentation, (4) high rate of clear-cell and chordoid morphology. A hypothesis is developed that these features are related to hormonal influences of the pituitary gland, and we discuss that this may be due to elevated prolactin levels. We encourage further research to test this exciting new theory.

Lumbar disk herniation during pregnancy: a review on general management and timing of surgery

Study designNarrative review with case illustration.ObjectiveProvide an overview of existing management strategies to suggest a guideline for surgical management of lumbar disk herniation in pregnant women based on time of presentation.MethodsWe performed a narrative review on the topic using the PubMed database. A total of 63 relevant articles published after 1992 were identified, of which 17 fulfilled selection criteria.ResultsA total of 22 published cases of spine surgery for disk herniation during pregnancy were found in 17 studies on the topic. Prone positioning was reported in the majority of cases during the first and early second trimester. C-sections were performed prior to spine surgery in the prone position for the majority of patients operated during the third trimester. The left lateral position with continued pregnancy was preferred during the latter half of the second trimester when delivery of the fetus cannot yet be performed but surgery is indicated.ConclusionSpine surgery during pregnancy is a rare scenario but can be performed safely when needed if providers adhere to general guidelines. Surgical approaches and overall management are influenced by the stage of pregnancy.

Hypervascular Lesions of the Cerebellopontine Angle: The Relevance of Angiography as a Diagnostic and Therapeutic Tool and the Role of Stereotactic Radiosurgery in Management. A Comprehensive Review

BACKGROUND The cerebellopontine angle (CPA) is a narrowed skull base area containing important cranial nerves and vessels and bordering with eloquent areas of the posterior fossa. Tumors of the CPA are a heterogeneous group and can have extradural, intradural/extra-axial, or intra-axial origins. Their vascular supply changes depending on their anatomic origin. Symptomatic, large CPA tumors require surgical resection in order to prevent irreversible, severe neurological damages. However, its tight and strategical location make surgery in the CPA very challenging and require appropriate pre-surgical planning. Pre-surgical diagnosis is of great importance as it allows us to choose the optimal management for the particular patient. This is of further significance when encountering high-risk lesions such as hypervascular tumors. Neurosurgeons should utilize every available pre-surgical diagnostic modalities as well as neo-adjuvant treatments in order to reduce such risks. METHODS We review all reported cases of hypervascular lesions of the CPA and discuss the roles of angiography and stereotactic radiosurgery in their management. RESULTS Three lesions of the CPA can be considered as truly hypervascular: hemangioblastomas, hemangiopericytomas and paragangliomas. All lesions share many radiological features. However, each lesion has a different anatomical origin and hence, has a characteristic vascular supply. Pre-surgical angiography can be utilized as a diagnostic tool to narrow down the differential diagnosis of a vascular CPA lesion, based on the predominant supplying vessel. In addition, pre-surgical embolization at time of angiography will narrow the associated surgical risks. CONCLUSIONS Angiography is a crucial diagnostic and therapeutic tool, helping both in narrowing the presurgical differential diagnosis and in controlling intraoperative bleeding. Because of the high surgical risks associated with resection of vascular tumors in the CPA, noninvasive treatments, such as stereotactic radiosurgery, also may have a crucial role.

Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis related to or comparable with mechanisms seen in inflammatory pathways? Part II: angiogenesis- and inflammation-related molecular pathways, tumor-associated macrophages, and possible therapeutic implications: a comprehensive review

Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles. Remarkably, both tumors are also known to have a unique association with elevated protein concentrations in the cerebrospinal fluid (CSF), sometimes in association with a non-obstructive (communicating) hydrocephalus. Of the two, SGCT has been shown to be associated with a predisposition to CSF clotting, causing a debilitating recurrent shunt obstruction. However, the exact relationship between high protein levels and clotting of CSF remains unclear, nor do we understand the precise mechanism of CSF clotting observed in SGCT. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood–brain barrier. The two presumed underlying pathophysiological processes for that in the context of tumorigenesis are angiogenesis and inflammation. Both these processes are correlated to the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin pathway which is tumorigenesis related in many neoplasms and nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation pathways on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I described the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating hydrocephalus. Part II hereafter describes the different cellular and molecular pathways involved in angiogenesis and inflammation observed in both tumors and explores the existing metabolic overlap between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both tumors, inflammatory processes seem significantly more prominent in SGCT. Both SGCT and VS are characterized by different subgroups of tumor-associated macrophages (TAMs): the pro-inflammatory M1 type is predominating in SGCTs, while the pro-angiogenetic M2 type is predominating in VSs. We suggest that a lack of NF2 protein in VS and a lack of TSC1/TSC2 proteins in SGCT significantly influence this fundamental difference between the two tumor types by changing the dominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, the pro-inflammatory state of SGCT may also explain the associated tendency for CSF clotting. The underlying cellular and molecular differences observed can potentially serve as an access point for direct therapeutic interventions for tumors that are specific to certain phacomatoses or others that also carry such genetic changes.

Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis comparable with mechanisms seen in inflammatory pathways? Part I: historical observations and clinical perspectives on the etiology of increased CSF protein levels, CSF clotting, and communicating hydrocephalus: a comprehensive review

Phacomatoses are a special group of familial hamartomatous syndromes with unique neuro-cutaneous manifestations as well as disease characteristic tumors. Neurofibromatosis 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. Vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with NF2 and TSC, respectively. These tumors can present with obstructive hydrocephalus due to their location adjacent to or in the ventricles. However, both tumors are also known to have a unique association with an elevated protein concentration in the cerebrospinal fluid (CSF), sometimes in association with non-obstructive (communicating) hydrocephalus (HCP), the causality of which has been unclear. Furthermore, SGCTs have repeatedly been shown to have a predisposition for CSF clotting, causing debilitating obstructions and recurrent malfunctions in shunted patients. However, the exact relation between high protein levels and spontaneous clotting of the CSF is not clear, nor is the mechanism understood by which CSF may clot in SGCTs. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood–brain barrier. The two presumed underlying pathophysiologic mechanisms for that, in the context of tumorigenesis, are angiogenesis and inflammation. Both mechanisms are correlated to the Pi3K/Akt/mTOR pathway which is a major tumorigenesis pathway in nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I describes the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating HCP. Part II describes different cellular and molecular pathways involved in angiogenesis and inflammation in these two tumors and the correlation between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both VS and SGCT, inflammatory processes seem more prominent in SGCT. Both pathologies are characterized by different subgroups of tumor-associated macrophages (TAM): the pro-inflammatory, M1 type is predominating in SGCTs while pro-angiogenetic, M2 type is predominating in VSs. We suggest that lack of NF2 protein in VS and lack of TSC1/2 proteins in SGCT determine this fundamental difference between the two tumor types, by defining the predominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, a “pro-inflammatory state” of SGCT can be used to explain the observed associated enhanced CSF clotting process. These distinct cellular and molecular differences may have direct therapeutic implications on tumors that are unique to certain phacomatoses or those with similar genetics.

Proposal of a new radiological classification system for spinal meningiomas as a descriptive tool and surgical guide

OBJECTIVES 1) To provide neurosurgeons and radiologists with a new quantitative and anatomical method to describe spinal meningiomas (SM) consistently. 2) To provide a guide to the surgical approach needed and amount of bony resection required based on the proposed classification. 3) To report the distribution of our 58 cases of SM over different Stages and Subtypes in correlation to the surgical treatment needed for each case. 4) To briefly review the literature on the rare non-conventional surgical corridors to resect SM. PATIENTS AND METHODS We reviewed the literature to report on previously published cohorts and classifications used to describe the location of the tumor inside the spinal canal. We reviewed the cases that were published prior showing non-conventional surgical approaches to resect spinal meningiomas. We proposed our classification system composed of Staging based on maximal cross-sectional surface area of tumor inside canal, Typing based on number of quadrants occupied by tumor and Subtyping based on location of the tumor bulk to spinal cord. Extradural and extra-spinal growth were also covered by our classification. We then applied it retrospectively on our 58 cases. RESULTS 12 articles were published illustrating overlapping terms to describe spinal meningiomas. Another 7 articles were published reporting on 23 cases of anteriorly located spinal meningiomas treated with approaches other than laminectomies/laminoplasties. 4 Types, 9 Subtypes and 4 Stages were described in our Classification System. In our series of 58 patients, no midline anterior type was represented. Therefore, all our cases were treated by laminectomies or laminoplasties (with/without facetectomies) except a case with a paraspinal component where a costotransversectomy was needed. CONCLUSION Spinal meningiomas can be radiologically described in a precise fashion. Selection of surgical corridor depends mainly on location of tumor bulk inside canal.

Single–session, transarterial complete embolization of Galenic dural AV fistula

Galenic dural arteriovenous fistula (DAVF) represents a unique, hard to treat subgroup of tentorial DAVFs. We present an unusual case of hemorrhagic Galenic DAVF in a 54-year-old woman. The fistula drained directly to the vein of Galen through multiple feeders. Complete occlusion of the fistula was achieved through transarterial embolization. Deep venous drainage remained intact and the patient recovered well. To our knowledge, this is the first report on complete closure of hemorrhagic Galenic DAVF using transarterial embolization with complete obliteration of vein of Galen. The presence of nonfunctioning straight sinus may have contributed to the success of treatment and it may be considered as a predictive marker for endovascular embolization.

The Utility of Routine Intensive Care Admission for Patients Undergoing Intracranial Neurosurgical Procedures: A Systematic Review

BackgroundPatients who have undergone intracranial neurosurgical procedures have traditionally been admitted to an intensive care unit (ICU) for close postoperative neurological observation. The purpose of this study was to systematically review the evidence for routine ICU admission in patients undergoing intracranial neurosurgical procedures and to evaluate the safety of alternative postoperative pathways.MethodsWe were interested in identifying studies that examined selected patients who presented for elective, non-emergent intracranial surgery whose postoperative outcomes were compared as a function of ICU versus non-ICU admission. A systematic review was performed in July 2016 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist of the Medline database. The search strategy was created based on the following key words: “craniotomy,” “neurosurgical procedure,” and “intensive care unit.”ResultsThe nine articles that satisfied the inclusion criteria yielded a total of 2227 patients. Of these patients, 879 were observed in a non-ICU setting. The most frequent diagnoses were supratentorial brain tumors, followed by patients with cerebrovascular diseases and infratentorial brain tumors. Three percent (30/879) of the patients originally assigned to floor or intermediate care status were transferred to the ICU. The most frequently observed neurological complications leading to ICU transfer were delayed postoperative neurological recovery, seizures, worsening of neurological deficits, hemiparesis, and cranial nerves deficits.ConclusionOur systematic review demonstrates that routine postoperative ICU admission may not benefit carefully selected patients who have undergone elective intracranial neurosurgical procedures. In addition, limiting routine ICU admission may result in significant cost savings.

Granular cell tumor of the infundibulum: a systematic review of MR-radiography, pathology, and clinical findings

IntroductionGranular cell tumors (GCTs) of the infundibulum are rare in practice and literature, resulting in a lack of evidence-based standard of care. We present two characteristic cases from our institution and perform a systematic review of the existing literature to further elucidate the presentation of this tumor and guide management.MethodsA systematic literature search was conducted according to PRISMA guidelines, yielding 42 total individual reported GCTs suitable for evaluation. Available clinical presentation, magnetic resonance imaging (MRI) characteristics, pathology, surgical approaches, and outcomes were charted. We measured frequencies of clinical characteristics and performed an outcome comparison of open versus endoscopic surgical treatment.ResultsIn this pooled dataset, GCT incidence was higher in females than males (3:1). Clinical presentation peaked in the fourth decade with tumor-related symptoms. MRI appearance was characterized by T1 isointensity (50%) and T2 hypointensity or isointensity (52%) with gadolinium contrast enhancement (74%). Histopathology demonstrated positive staining for PAS, PAS-D, S100, CD68, and TTF1. In a simple uncontrolled analysis, patients who underwent endoscopic surgery experienced more symptom improvement (p = 0.006) and lower incidence of new diabetes insipidus postoperatively (p = 0.047) versus patients who underwent open microsurgery.ConclusionsThis first comprehensive review of GCTs of the infundibulum corroborates existing data and adds significant new MR-radiological information to the literature, notably a typical tumor appearance of T1 isointensity, T2 iso- to hypointensity, and gadolinium contrast enhancement. Future prospective studies should be conducted to validate our findings.

Primary Pituitary Fibrosarcoma with Previous Adenoma

BACKGROUND Pituitary sarcomas are rare clinical entities most often encountered as secondary neoplasms representing late sequelae of radiation therapy to the sellar region. Primary pituitary fibrosarcomas (PPFS), in contrast, are exceptionally rare tumors with very few cases described in the literature thus far. Herein, we present a case of PFFS and describe it in the context of the existing literature. CASE DESCRIPTION A 39-year-old woman presented with 2 months of headaches and rapidly progressive vision loss. She was found to have a 2.7-cm pituitary mass and initially underwent transnasal transsphenoidal resection from which pathology confirmed a pituitary adenoma. Eight months after surgery, she represented with vision changes and a recurrent tumor that postoperatively was found to be a primary fibrosarcoma with embedded adenoma remnants. On post-hoc examination of her original pathologic specimen, a prominent fibrous tissue component was suspected to be the source of her fibrosarcoma. CONCLUSIONS This is a rare case of PFFS that highlights the need for close surveillance in affected patients. Through this case, we review the existing literature and discuss both surgical management and aggressive adjuvant therapy of this rare disease entity.